Descargue version pdf gratis - Asociacion Medica de Puerto Rico
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Descargue version pdf gratis - Asociacion Medica de Puerto Rico
BOLETIN Year 107 Nbr. 03 July-September INDEX 3 President’s Message 5 Prevalence of Diabetes Mellitus in Human Immunodeficiency Virus positive Patients in Puerto Rico – San Juan City Hospital Experience 9 A Hispanic female patient with heartburn: A rare presentation of Paroxysmal Nocturnal Hemoglobinuria 13 Pleural Effusion In A Patient With Primary Sjögren’s Syndrome Successfully Treated With Corticosteroids 17 The Racial, Cultural and Social Makeup of Hispanics as a Potential Profile Risk for Intensifying the Need for Including this Ethnic Group in Clinical Trials Catalogado en Cumulative Index e Index Medicus Listed in Cumulative Index and Index Medicus No. ISSN-0004-4849. Registrado en Latindex -Sistema Regional de Información en Línea para Revistas Científicas de América Latina, el Caribe, España y Portugal 24 Usefulness Of Glucocorticoids In The Management Of Foreign Body Aspiration 29 Previous Exposure to Anesthesia and Autism Spectrum Disorder (ASD): A Puerto Rican Population-Based Sibling Cohort Study 38 Metastatic Ovarian Tumor Masquerading as Atypical Pneumonia 42 Diagnostic Studies for the Evaluation of Peripheral Artery Disease OFICINAS ADMINISTRATIVAS Asociación Médica de Puerto Rico 47 Endovascular Intervention in the Treatment of Peripheral Artery Disease 52 Non-Invasive Therapy of Peripheral Arterial Disease 58 Acondroplasia: Un Estudio Pionero Sobre Las Características Psicosociales Y Médicas De Una Muestra En Puerto Rico 66 Metabolic Changes After Roux-N-Y Bariatric Surgery In Hispanics 70 Obesity and premature coronary artery disease with myocardial infarction in Puerto Rican young adults 75 Peripheral Arterial Disease: Surgical Treatment 79 Epidemiology of Traumatic Peripheral Nerve Injuries Evaluated by Electrodiagnostic Studies in a Tertiary Care Hospital Clinic 85 POEMS Syndrome: A Rare Disease With A Challenging Diagnosis 89 The Prevalence Of Sexually Transmitted Infections On Teen Pregnancies And Their Association To Adverse Pregnancy Outcomes 95 Screening for Peripheral Arterial Disease 98 Difficult Diagnosis between B Cell Lymphoma and Classical Hodgkin’s Lymphoma 2015 PO Box 9387 SANTURCE, PR 009089387 Tel 787-721-6969 Fax: 787- 724-5208 secretaria@asocmedpr. org ANUNCIOS EN BOLETIN, WEBSITE y NEWSLETTER Tel.: (787) 721-6939 itsupport@asocmedpr. org Ilustración digital de cubierta y diseño gráfico realizados por Juan Laborde-Crocela en la Oficina de Informática de la AMPR. Impreso en los talleres gráficos digitales de la Asociación Médica de Puerto Rico - E-mail:itsupport@ asocmedpr.org 103 Membership PRMA BOLETIN | 1 Asociacion Medica de Puerto Rico Junta de Directores 2014/2015 Dra. Wanda G. Vélez Andújar Presidente Dr. Ricardo Marrero Santiago Presidente Electo Dr. Natalio J. Izquierdo Encarnación Presidente Saliente Dr. Luis A. Román Irizarry Tesorero Dra. Ilsa Figueroa Secretaria Dr. Arturo Arché Matta Vicepresidente Dr. Raúl A. Yordán Rivera Vicepresidente Dr. Jaime M. Díaz Hernández Vicepresidente Dr. Benigno López López Pres. Cámara Delegados Dr. Eliud López Vélez Vicepres. Cámara Delegados Dr. Gonzalo González Liboy Delegado AMA Dr. Rolance G. Chavier Roper Delegado AMA Dr. José L. Romany Rodríguez Delegado Alt. AMA Dr. Rafael Fernández Feliberti Delegado Alterno AMA Dra. Mildred R. Arché Pres. Distrito Central Dr. Pedro J. Zayas Santos Pres. Distrito Este Dra. Lilliana G. Silva Pres. Distrito Sur Dr. Luis J. Lugo Vélez Pres. Cjo de Política Pública y Legislación Dr. Rafael Rodríguez Mercado Pres. Junta Editora Boletín President’s Message The time has come for me to write my last message as Puerto Rico Medical Association President. My two years are about to be over. This is the time to look back, to review and plan ahead. Looking back, we knew well since 2013 that this present October 2015, was to bring profound changes in how medicine was to be practiced from then on. To mention a couple of the most significant changes, Centers for Medicare and Medicaid Services (CMS,) had decided that by the first day of the current month, all physicians must be using, and in a meaningful way, Electronic Health Records (EHR) besides implementing the ICD-10. The Health Insurance Companies also invested time and effort educating health providers to be well versed on the matter. In Puerto Rico, our government requested that all physicians caring for patients under the Government Health Program must comply with these requisites or will no longer be considered providers. These conditions brought such turmoil in the practicing physicians, that many of those that were close to the age of retirement, decided to close their offices. Right now, we must keep our eyes wide open for other consequences not foreseen, that most likely will surface. In Puerto Rico, there is an additional grievance. We are going through 2 | PRMA BOLETIN a shortage of physicians. Many physicians are moving back to the United States where they trained, or are not returning to Puerto Rico when they complete their medical training. Right now, we do not even have enough pediatricians to supply our necessities. And this is so hard to believe! In the 1980’s, when I went through my pediatrics training, no one would even think of the possibility that this could ever happen! These facts do not match the interest the Government has expressed of developing medical tourism…! Do not get me wrong, we are truly capable of giving “State of the Art” care to patients, as good as the best of the best in the United States of America. For the Spanish speaking population, we possess an additional asset for we are fully bilingual between both languages. Never the less, keeping our physicians at home, available, the patient care will be enhanced. The medical migration, considered by some as secondary, among other factors, to the recent tax laws…, makes the health tourism’s future look blurred! For the time being, let’s take a brief look at what the future might bring. By the time our next Boletin issue is published, Dr. Ricardo Marrero will be the President of the Puerto Rico Medical Association (PRMA). The ICD-10 will, undoubtedly, have been successfully implemented and the EHR’s should no longer be a barrier for any physician to care for patients. Certainly the data of these coming months of their implementation will be available and evaluated. This could give a more precise picture of what to be expected! and our future. PRMA is an Accreditor of providers’ that have a genuine interest in Continuous Medical Education (CME). We accredit providers by following the Essentials and Criteria of the Accreditation Council of Continuous Medica Education, ACCME. This commitment of education goes hand in hand with Boletin. As for Boletin, it will continue to be an excellent peer review scientific journal where physicians intraining and all medical researchers interested will be welcomed to publish their papers. PRMA is committed to the advancement of education and research for the benefit of physicians. Both the CME and Boletin allow us to be updated and enhance our knowledge, competence and performance for the benefit of our patients. Boletin has been continuously published since 1903; I believe we are in the best moment to say that it will be around for at least the next 112 years! Boletin is the jewel of the crown! Now, as the 85 th President of Puerto Rico Medical Association and the second women in charge, it is my turn to say good-bye! Wanda G Vélez Andújar, MD PRMA President In the meantime, Puerto Rico Medical Association (PRMA) will continue to work hard for physicians PRMA BOLETIN | 3 BOLETIN Médico-científico de la Asociación Médica de Puerto Rico AUTHORS INSTRUCTIONS We publish our magazine quaterly: january/march, april/june, july/september, october/december. You could publish your article if you sent it, at list, 3 months before dead lines (march 20, June 20, September 20 and December 20). You must sent your articule to: [email protected], writting the complete tittle in the SUBJECT of your email. DO NOT REPEAT REMITTANCES. You will receive an authomatic notification when your email arrive. Above email address is for articles remittances, only. Do not send questions or other kind of issues because we don’t have answer system on it. Take note you have to reference the place of your article were each ilustration have to be included, as follows: [fig 1]. PLEASE DO NOT EMBED YOUR ILUSTRATIONS IN THE ARTICLE PRESENTATION. The articule must contain: Tittle Specialty Authors Faculties ABSTRACT in english, and spanish, including keywords. TEXT in english REFERENCES in english Please, reference your text using numbers in brackets, as follows: (12), never use under or upper lines. Format: Tittle: ARIAL BLACK 14 Sub-tittle: ARIAL BLACK 11 Text: ARIAL 11 References: ARIAL 9 Paragraph: single Editor: Word (doc or docx), Open office (odt), or Adobe Acrobat (pdf) Ilustrations: pdf, tif, png, gif, jpg (hig definition) Your article will be evaluated by our BOARD OF EDITORS. Ask questions to [email protected], refering article title and author names. 4 | PRMA BOLETIN Prevalence of Diabetes Mellitus in Human Immunodeficiency Virus positive Patients in Puerto Rico – San Juan City Hospital Experience. Luis R. Hernández-Vázquez MD, José H. Martínez MD, Carmen Rivera-Anaya MD, José Laboy MD, Samayra Miranda MD, Paola Mancilla MD, Sharon Vélez MD. San Juan City Hospital Endocrinology Department. San Juan, Puerto Rico. ABSTRACT INTRODUCTION: The total number of patients with Human Immunodeficiency Virus(HIV) is 33 million, with 2.7 million new infections in 2007(1). Puerto Rico has an increasing prevalence trend of Diabetes Mellitus of 12.8% in 2010(3). As treatment of HIV continues to develop, and access to therapy improves, the incidence of HIV associated diabetes is bound to grow. We investigate the prevalence of Diabetes Mellitus and its associated risk factors in a determinate HIV positive population. MATERIALS AND METHODS: A retrospective study, reviewing the medical records of 146 HIV positive patients. The prevalence of DM was statistically measured and a Logistic Regression with Pearson X² Square and Fisher’s exact test was used to assess the association between DM and its risks factors. RESULTS: The prevalence of DM in the studied population was 13.7% (n=20). There were 59%(n=86) males, 43%(n=63) of patients treated with HAART, 46%(n=67) IVDA, the mean age was 47; with 29% older than 50 years old, and 68% of the patients had a BMI of less than 25. Gender, IVDA, HAART, BMI, and age were not associated as risk factors for the prevalence of DM in the studied population. DISCUSSION: Our data revealed a higher prevalence of DM in HIV infected patients. We observed no significant association between DM and its risks factors. This raises concern for yet unrecognized risk factors contributing to a higher prevalence of the disease in this population. Results of our study alert physicians on the importance of DM screening in the HIV positive patient population. INTRODUCTION The total number of patients with Human Immunodeficiency Virus is 33 million worldwide, with 2.7 million new infections in 2007(1). Prevalence of Diabetes Mellitus among adults in the United States ranges from 4.4 to 17.9 percent. Puerto Rico had an increased prevalence trend of Diabetes Mellitus of 12.8% in 2010(3). Patients with human immunodeficiency virus (HIV) and acquired immunodeficiency syndrome (AIDS) are increasing in number due to improved screening, earlier diagnosis, better methods of treatment, and greater accessibility to treatment, as well as acceptance of therapy. Diabetes Mellitus results from the autoimmune destruction of beta cells in the islets of Langerhans, insulin resistance or impaired insulin secretion. Concurrent use of opiates may alter beta cell function, while heroin addiction is associated with insulin resistance. Highly Active Antiretroviral Therapy (HAART) has also lead to an increase in metabolic dysfunction, including insulin resistance, diabetes dyslipidemia and lipodystrophy, especially in patients treated with protease inhibitors. As treatment of HIV continues to develop, and access to therapy improves, the incidence of HIV associated diabetes is bound to grow. This incidence has augmented with cumulative exposure to combination antiretroviral therapy, as shown in several research studies(1). For example the 130,151 person-years of follow-up (PYFU), in the Data Collection on Adverse Events of Anti-HIV Drugs (D:A:D) Study, Diabetes was diagnosed in 744 patients (for an incidence rate of 5.72 per 1,000). The aim of our study was to investigate the prevalence of Diabetes Mellitus and its associated risks factors in a determined HIV positive population. MATERIALS AND METHODS v A retrospective study reviewing medical records of 146 HIV positive patients admitted or evaluated at the San Juan City Hospital between the years 2007 to 2010. v For purposes of this study, a subject was considered to be diabetic if the provider documented PRMA BOLETIN | 5 The prevalence of DM in the study population was 13.7% (n=20), 0.9% higher than the general population, as demonstrated in Figure 1. Eighty six of the study population were males (59%), sixty three (43%) were treated with Highly Active Antiretroviral therapy, and lastly, sixty seven (46%) were intravenous drug abusers. The mean age was 47, ranging from 24 to 77 years. Of the 45 patients with a BMI over 25(kg/m²) six had Diabetes Mellitus for a thirteen percent prevalence rate (13%), while 13 of the 97 patients with a BMI under 25(kg/m²) had a similar Diabetes Mellitus prevalence rate (13%). Figure 2: BMI of HIV positive patients with Diabetes Mellitus 11% 10% 5% < 18 16% 58% 18 24.99 25 29.99 30 34.99 > 35 Figure 2 shows that sixty eight percent (68%) of HIV positive patients with Diabetes in our study have a normal Body Mass Index. Gender, intravenous drug abuse, HAART, BMI and age were not statistically significant risk factors for the prevalence of DM in the studied population, as disclosed in the data analysis in Table 1. DISCUSSION a diagnosis of DM in the chart or the subject was receiving a hypoglycemic and/or insulin-sensitizing agent(s). v All patients were older than 21 years of age. v Every subject had three identifiers to avoid duplication of data. v In every record we identified the patient’s gender, age, body mass index, history of intravenous drugs abuse, and HAART treatment. v The prevalence of DM was statistically measured and compared to that of the general population of Puerto Rico. 6 | PRMA BOLETIN STATISTICAL ANALYSIS v A Logistic Regression with Pearson X² Square and Fisher’s exact test was used to assess the association between DM and its most common risks factors such as gender, intravenous drug abuse (IVDA), age intervals, BMI, and Highly Active Antiretroviral Treatment in this population. RESULTS Of 146 HIV infected subjects, 20 were found to have Diabetes Mellitus. Our study revealed that the prevalence of Diabetes Mellitus in HIV-infected patients was slightly higher (13.7%) when compared to that of the general population of Puerto Rico (12.8%) Figure 1. Previous studies have demonstrated that different risks factors influenced the incidence of Diabetes Mellitus in HIV positive patients. Capeau et al. studied 1046 patients at 47 French clinical sites and found an association of the incidence of DiabetesMellitus in HIV positive patients with older age (hazard ratio = 2.13 when 40-49 years, hazard ratio = 3.63 when ≥50 years), overweight (hazard ratio Table 1: Factors associated with Type 2 diabetes mellitus (DM) in an HIV-infected pop- = 1.91 for a BMI 25-29 ulation1: Factors associated with Type 2 diabetes mellitus (DM) in an HIV-infected Table population kg/m(2), hazard ratio = 2.85 11Pearson Chi square test,22T test equal variances, 33Fisher proportion extended, 4Adust4 >30 kg/m(2)), waist-to-hip Pearson Chi square test, T test equal variances, Fisher proportion extended, Adusted by age, gender, and BMI ed by age, gender, and BMI ratio (hazard ratio = 3.87 for ≥0.97 male/0.92 female), DM+ DMp-value ORcrude(IC ORadjusted (IC time-updated lipoatrophy 4 n (%) n (%) 95%) 95%) (hazard ratio = 2.14) and short-term exposure to indiGender: navir (0-1 year: hazard ra8 (40.00) 78 0.41 (0.16, 0.38 (0.13, 1.13) Male tio = 2.53), stavudine (0-1 1 (61.90) 1.08) 0.064 year: hazard ratio = 2.56, 1-2 12 (60.00) 48 Ref. Ref. Female years: hazard ratio = 2.65) or (38.10) didanosine (2-3 years: hazard Age ratio = 3.16). Obesity is asso(years):: ciated with an increased risk 4 (20.00) 28 Ref. Ref. <36 for the development of Diabe1 (22.22) tes Mellitus even more than 0.384 gender, opioid abuse, and an8 (40.00) 28 0. 89 (0.21, 0. 80 (0.18, 37-45 tiretroviral drug therapy. (22.22) 3.85) 3.63) 46-50 4 (20.00) 51>+ 4 (20.00) mean 45±8 37 (29.37) 33 (26.19) 43±10 2 (10.53) 11 (57.89) 3 (15.79) 20 (16.26) 64 (52.03) 21 (17.07) 1 (5.26) 8 (6.50) BMI 0.500 2.35 (0.64, 8.66) 1.18 (0.27, 5.14) 2.27 (0.56, 8.96) 0.58 (0.12, 2.84) Ref. 0.62 (0.12, 3.14) 0. 83 (0.21, 3.26) 1.45 (0.27, 7.78) 0.58 (0.07, 5.00) 0.91 (0.22, 3.69) 1.37 (0.30, 6.39) 2 2 (kg/m ): <18 18-24.99 25-29.99 30-34.99 0.926 3 Ref. Butt AA et al. in the Veterans Aging Cohort Study compare the prevalence of DM in 3227 HIV-infected and 3240 HIV-uninfected individuals. He found that HIV-infected individuals had a lower prevalence of diabetes at baseline (14.9 vs. 21.4%, P < 0.0001). However when more risks factors as increasing age, minority race or higher BMI were present the odds ratio for the incidence of Diabetes Mellitus were greater among HIV infected Veterans(10). 0.91 (0.15, 5.47) Zhang et al. study four hundred fifteen patients of a lon2 10 0.46 (0.05, 4.43) 35> gitudinal data pooled from (10.53) (8.13) a multicenter clinical trial of 2 24.94±6.07 23.51±6.17 mean 0.34 combination antiretroviral regimens DM developed in 12 IVDA: patients, resulting in an inci1 10 (50.00) 57 1.21 (0.47, 1.983 (0.64, Yes 0.691 dence density of 2.62 per 100 (45.24) 3.11) 6.126) patient years (PYs). Impaired 10 (50.00) 69 Ref. Ref. No Fasting Glucose (IGF) was (54.76) diagnosed in 163 patients, HAART: resulting in an incidence den1 8 (40.00) 55 0.860 0.82 (0.28, 2.418) Yes sity of 35.64 per 100 PYs. 0.759 (43.65) (0.33, 2.25) This incidence of DM and IGF 12(60.00) 71 Ref. Ref. No was influenced by advancing (56.35) age, lower baseline CD4+ cell count, and higher baseline triglyceride BMI: Body Mass Index, IVDA: Intravenous Drug Abusers, HAART: Highly Active AntiretBMI: Body Mass Index, IVDA: Intravenous Drug Abusers, HAART: Highly Active Antiretroviral Treatment level. These paroviral Treatment tients were more likely coinp-value: p-value: Statistical Statistical Significance Significance << 0.05 0.05 fected with HBV compared OR:Odds OddsRatio Ratio OR: with patients who did not deIC:Interval Interval of of Confidence Confidence IC: velop DM or IFG(9). As in ou PRMA BOLETIN | 7 r study overall BMI was not predictive of DM or IFG. Although BMI is an established risk factor for DM in the general population. In Asia the affected individuals with Diabetes epidemic certainly have a lower BMI than the Western counterpart(9). No statistical association was found between the measure risks factors as age, gender, BMI, IVDA, and HAART with the prevalence of Diabetes in our study. In view of this discrepancy regarding the link between obesity and Diabetes found in our study population other risks factors must be entertained. Several bias should be considered in our study such as this is a retrospective study which may underestimate the prevalence of Diabetes due to incomplete medical records data gathering, the small sample size which influence the statistical power for correlations, and the inability to properly classify the Diabetes subtype. The high prevalence of Diabetes Mellitus in our study validates the importance to screen for DM in all HIV positive patients as one would do in the general population. Marshall J. Glesby, M.D., Ph.D. Glycemic Control in HIV-Infected Patients with Diabetes Mellitus and Rates of Meeting American Diabetes Association Management Guidelines. AIDS PATIENT CARE and STDs Volume 25, Number 1, 2011 Mary Ann Liebert, Inc. 6. Samaras, Katherine MBBS (Hons), PhD, FRACP. Prevalence and Pathogenesis of Diabetes Mellitus in HIV-1 Infection Treated With Combined Antiretroviral Therapy. JAIDS Journal of Acquired Immune Deficiency Syndromes:Volume 50(5)April 2009pp 499505. 7. TODD T. BROWN, MD, PHD1, KATHERINE TASSIOPOULOS, DSC, MPH2 RONALD J. BOSCH, PHD Association Between Systemic Inflammation and Incident Diabetes in HIV-Infected Patients After Initiation of Antiretroviral Therapy. Diabetes Care 33:2244–2249, 2010. 8. Calza L1, Masetti G, Piergentili B, Trapani F, Cascavilla A, Manfredi R, Colangeli V, Viale P. Int J. Prevalence of diabetes mellitus, hyperinsulinaemia and metabolic syndrome among 755 adult patients with HIV-1 infection. STD AIDS. 2011 Jan; 22(1):43-5. 9. Zhang C1, Chow FC, Han Y, Xie J, Qiu Z, Guo F, Li Y, Wang H, Li T. Multicenter cohort study of diabetes mellitus and impaired fasting glucose in HIV-infected patients in China. J Acquir Immune Defic Syndr. 2015 Mar 1; 68(3):298-303. 10. Butt AA(1), McGinnis K, Rodriguez-Barradas MC, Crystal S, Simberkoff M, Goetz MB, Leaf D, Justice AC; Veterans Aging Cohort Study. HIV infection and the risk of diabetes mellitus. AIDS. 2009 Jun 19; 23(10):122734. REFERENCES 1. Sanjay K. et al., Understanding Diabetes in patients with AIDS/HIV. Diabetology & Metabolic Syndrome 2011, 3:2. 1758-5996. 2. Jain MK et al., Hepatitis C is associated with type 2 Diabetes Mellitus in HIV-infected persons without traditional risk factors. HIV Medicine (2007), 8, 491-497. 3. Datos estadísticos de Diabetes en Puerto Rico. Programa para la prevención y control de la Diabetes. Departamento de Salud Gobierno de Puerto Rico. 1996-2010. 4. Jacqueline Capeau, Vincent Bouteloup , Francois Raffi , JeanPhilippe Bastard . Diabetes Mellitus in Treated HIV-Infected Patients: Incidence over Ten Years in 1,046 patients from the ANRS CO8 APROCO-COPILOTE Cohort. CROI 2011 March 2 Boston. 5. Michael J. Satlin, M.D.,1 Donald R. Hoover, Ph.D.,2 and 8 | PRMA BOLETIN Nota al Calce: Este estudio fue electo ganador del primer premio en investigación en el ACP Regional Clinical Vignettes and Research Poster Competition San Juan, PR. 2014. En adición se presentó como poster en el Endocrine Society National Annual Meeting, San Diego, California. 2015. RESÚMEN INTRODUCCIÓN: El número total de pacientes con el Virus de Inmunodeficiencia Humana (VIH) es de 33 millones, con 2.7 millones de nuevos casos en el 2007(1). Puerto Rico tiene una prevalencia de Diabetes Mellitus (DM) que va en incremento con 12.8% para el 2010(3). Este estudio investiga la prevalencia de Diabetes Mellitus y los factores de riesgo asociados en pacientes VIH positivo. METODOS Y MATERIALES: Estudio retrospectivo de revisión de expedientes médicos de 146 pacientes VIH positivos. Se mide la prevalencia de DM en la población y se utiliza regresión logística Pearson Chi-square y Fisher-exact test para determinar la asociación entre los pacientes con Diabetes Mellitus y sus factores de riesgo. RESULTADOS: La prevalencia de Diabetes en la población estudiada es de 13.7%. De los pacientes VIH positivo estudiados el 59% fueron hombres, 43% utilizan medicamentos antiretrovirales, 46% utilizan drogas intravenosas, la edad media fue de 47 años con un 29% de los pacientes mayores de 50 años y el 68% de los pacientes tiene un Índice de masa corporal menor de 25kg/m². Ninguno de los factores de riesgo estudiados fue estadísticamente significativo en la prevalencia de Diabetes. DISCUSION: Nuestro estudio revela una prevalencia mayor de Diabetes en la población VIH positivo. No encontrar una asociación estadística entre los factores de riesgo para Diabetes, nos provoca un interés en estudiar más a fondo esta población. La alta prevalencia de Diabetes Mellitus en nuestro estudio valida la importancia de evaluar los pacientes VIH positivo como se evalúa la población general. A Hispanic female patient with heartburn: A rare presentation of Paroxysmal Nocturnal Hemoglobinuria Abstract: Paroxysmal nocturnal hemoglobinuria (PNH) is a non-malignant, acquired clonal hematopoietic stem cell disease that can present with bone marrow failure, hemolytic anemia, smooth muscle dystonias, and thrombosis. We present a case of a 32 year-old-female, G2P2A0 with no past medical history of any systemic illnesses who refers approximately 2 months of progressively worsening constant heartburn with associated abdominal discomfort. CBC showed leukopenia (WBC 2.9 x 103 /μL) with neutropenia (segmented neutrophils 48%), macrocytic anemia (Hgb 6.1 g/dL, hematocrit 20%, MCV 113 fL) and thrombocytopenia (platelet count 59 x 109/L). Abdomino-pelvic CT scan revealed a superior mesenteric vein thrombosis, which was treated initially with low-molecular-weight heparin for full anticoagulation. Peripheral blood flow cytometry assays revealed diminished expression of CD55 and CD59 on the erythrocytes, granulocytes and monocytes. Paroxysmal nocturnal hemoglobinuria is a rare, clonal, hematopoietic stem-cell disorder whose manifestations are almost entirely explained by complement-mediated intravascular hemolysis. The natural history of PNH is highly variable, ranging from indolent to life-threatening. The median survival is 10 to 15 years, but with a wide range. Thrombosis is the leading cause of death, but others may die of complications of bone marrow failure, renal failure, myelodysplastic syndrome, and leukemia. Anticoagulation is only partially effective in preventing thrombosis in PNH; thus, thrombosis is an absolute indication for initiating treatment with Eculizumab. Nevertheless, bone marrow transplantation (BMT) is still the only curative therapy for PNH but is associated with significant morbidity and mortality. Index words: Paroxysmal nocturnal hemoglobinuria, PIG-A gene, glycosyl phosphatidylinositol (GPI)–anchored proteins, complement, eculizumab Corresponding author: Luis A. FigueroaJiménez, MD1**; Co-Authors: Amy Lee González-Márquez, MD2; Ricardo Alicea-Guevara, MD1; Mόnica Santiago-Casiano, MD2; Maryknoll de la PazLópez, MD2; Luis Negrón-Garcia, MD2; Luis Báez-Dίaz, FACP2; William Cáceres-Pérkins, FACP2 Academic Affiliations: Internal Medicine Department, San Juan City Hospital, San Juan, Puerto Rico. 2 Hematology–Medical Oncology Section, VA Caribbean Healthcare System and San Juan City Hospital, San Juan, Puerto Rico. 1 *Corresponding author: Luis A. Figueroa-Jiménez MD. Internal Medicine Department, San Juan City Hospital, CMMS #79 P.O. BOX 70344 San Juan, Puerto Rico 00936-8344. Email: [email protected] Introduction Paroxysmal nocturnal hemoglobinuria (PNH) is a non-malignant, acquired clonal hematopoietic stem cell disease that can present with bone marrow failure, hemolytic anemia, smooth muscle dystonias, and thrombosis.1 The disease arises from chronic and uncontrolled complement activation causing dysfunction in all 3 blood cell lines: red blood cells, white blood cells (both granulocytes and monocytes), and platelets.3 It is a rare disease, with a worldwide prevalence estimated in the range of 1–5 cases per million regardless of ethnicity; an increased prevalence is reported in some regions which also harbor higher incidence of aplastic anemia.5 The median age of presentation is 40 years, but the disease occurs in all age groups.2 We present the case of a 32 year-old-female with no past medical history of any systemic illnesses who presents with heartburn, abdominal discomfort and fatigue with associated occasional dizziness. Case history: This is the case of a 32 year-old-female, G2P2A0 with no past medical history of any systemic illnesses who refers approximately 2 months of progressively worsening constant heartburn with associated PRMA BOLETIN | 9 abdominal discomfort. Patient visited the emergency room on multiple occasions where she was treated for heartburn and gastritis with proton pump inhibitors and IV hydration without resolutionof her symptoms. She says changing her diet and avoiding precipitating foods did not help. Abdominal symptoms progressed to a point of being intolerable. She reports associated nausea and fatigue as well as an orange-colored morning urine which later progressed to Coca-Cola colored urine. Denies vomiting, fever, chills, melena, hematochezia or any other constitutional symptoms. Family history is non-contributory. Social history is only pertinent for occasional alcohol use and surgical history relevant for two cesarean delivery which required patient to receive blood transfusions, and cholecystectomy. Upon physical examination patient is noted to be hypotensive (BP: 100/63 mmHg) with no orthostatic changes and heart rate within normal range (HR: 83 bpm). Abdominal examination is remarkable for positive bowel sounds, soft and depressible, no tenderness, no guarding or rebound but slight abdominal discomfort on deep palpation diffusely. CBC showed leukopenia (WBC 2.9 x 103 /μL) with neutropenia (segmented neutrophils 48%), macrocytic anemia (Hgb 6.1 g/dL, hematocrit 20%, MCV 113 fL) and thrombocytopenia (platelet count 59 x 109/L). Patient was transfused 2 units of packed red blood cells. Other laboratories revealed elevated LDH levels 850 units/L, total bilirubin of 1.8 mg/dL and a reticulocyte count 15.4% consistent with hemolysis. Folate, Iron, Vitamin B12 levels were under normal limitis. Direct Coomb’s test resulted negative. Disseminated intravascular coagulation (DIC) panel was unremarkable with normal PT, PTT, INR, fibrinogen, fibrin split products and D-dimer. In view of history of persistent gastrointestinal symptoms an an abdominopelvic CT-scan was performed. Abdominopelvic CT-scan revealed a superior mesenteric vein thrombosis (Fig. 3) which was treated initially with low-molecular-weight 10| PRMA BOLETIN heparin for full anticoagulation and later changed to warfarin to maintain a therapeutic INR between 2.0 and 3.0. In order to assess etiology of pancytopenia a bone marrow aspirate and biopsy was done showing hypocellularity of 20% (Fig. 4). This is a young, healthy female with an interesting constellation of idiopathic thrombosis associated with pancytopenia and highly suspicious for paroxysmal nocturnal hemoglobinuria. Flow cytometry assays of peripheral blood revealed diminished expression of CD55 and CD59. A fluorescein-labeled proaerolysin variant (FLAER) identified a population with deficient levels of expression of glycosylphosphaditdylinositol linked antigens and anchor proteins on 81% erythrocytes, 80% granulocytes, and 75% monocytes. (Fig. 1-2) Discussion: Figure 1: Flow cytometry report: Populations with deficient GPI-Anchored proteins are identified (approximately 81%). Figure 2: Flow cytometry identifies a population with deficient levels of expression of glycosylphosphaditdylinositol linked antigens and anchor proteins on 81% erythrocytes, 80% granulocytes, and 75% monocytes Paroxysmal nocturnal hemoglobinuria is a rare, clonal, hematopoietic stem-cell disorder whose manifestations are almost entirely explained by complement-mediated intravascular hemolysis.2 The natural history of PNH is highly variable, ranging from indolent to life-threatening. The median survival is 10 to 15 years, but with a wide range.1 Thrombosis is the leading cause of death, but others may die of complications of bone marrow failure, renal failure, myelodysplastic syndrome, and leukemia.1 PNH is divided into three categories for a more focused approach: 1- Classical PNH, these patients have the characteristic symptoms of PNH with intravascular hemolysis, a cellular bone marrow and have no evidence of any other bone marrow pathology. 2- PNH in the setting of another specified bone marrow disorder; these patients have symptoms of intravascular hemolysis but also have, or have previously had, an underlying bone marrow abnormality such as aplastic anemia (AA) or myelodysplasia (MDS). 3- Subclinical PNH, these patients have no evidence of ongoing hemolysis.6 Figure 3: Abdomino-pelvic CTscan; revealed a superior mesenteric vein thrombosis Figure 4: Bone marrow biopsy and aspiration, remarkable for hypocellularity of 20%. PRMA BOLETIN | 11 no evidence of ongoing hemolysis.6 The disease originates from a multipotent hematopoietic stem cell that acquires a mutation of the PIG-A gene.1 Clinical manifestations of the disease arise secondary to the expansion and differentiation of the PIG-A mutant stem cell. The PIG-A gene product is required for the biosynthesis of glycophosphatidylinositol anchors, a glycolipid moiety that attaches dozens of proteins to the plasma membrane of cells.1 Consequently, the PNH stem cell and all of its progeny have a reduction or absence of glycosyl phosphatidylinositol (GPI)–anchored proteins.1 CD55 and CD59, are two of these proteins which are also complement regulatory proteins and fundamental to the pathophysiology of the disease when absent. CD55 inhibits C3 convertases and CD59 blocks formation of the membrane attack complex (MAC) by inhibiting incorporation of C9 into the MAC.1 The loss of complement regulatory proteins renders PNH erythrocytes susceptible to both intravascular and extravascular hemolysis, but it is the intravascular hemolysis that contributes to much of the morbidity and mortality from the disease.1 Free hemoglobin is released to the plasma due to intravascular hemolysis. This free plasma hemoglobin searches nitric oxide leading to depletion of nitric oxide at the tissue level which contributes to various PNH manifestations including esophageal spasm, male erectile dysfunction, severe fatigue, renal insufficiency, and thrombosis. Our patient had a PNH cell population of 80% of granulocytes. A history of even one thrombotic event is associated with a 5-fold to 10-fold higher risk of death for PNH patients.3 Therefore, it should be treated promptly with anticoagulation and depending on the location of the thrombus with thrombolytic therapy. Anticoagulation is only partially effective in preventing thrombosis in PNH; thus, thrombosis is an absolute indication for initiating treatment with eculizumab.1 Eculizumab is a humanized monoclonal antibody that targets complement protein C5 and inhibits terminal complement–mediated hemolysis associated with paroxysmal nocturnal hemoglobinuria (PNH).7 Eculizumab is highly effective in reducing intravascular hemolysis in PNH; it decreases or eliminates the need for blood transfusion, improves quality of life, and reduces the risk of thrombosis among both patients with classic PNH and those in whom PNH develops secondary to aplastic anemia.7 Treatment with Eculizumab was initiated in our patient and has been well tolerated, showing significant clinical improvement, with gradual decrease in LDH levels with no reported complications and no more transfusions required. Nevertheless, bone marrow transplantation (BMT) is still the only curative therapy for PNH but isassociated with significant morbidity and mortality.1 In conclusion, PNH is an unusual hematological disease that is easy to miss but impossible to ignore. To the The combination of nitrous oxide best of our knowledge this is the first depletion, complement-mediated PNH case reported in the medical litplatelet activation, and exposure of erature with initial presentation . the procoagulant interior of the red cell membranes makes PNH an ex- References: tremely hypercoagulable state.3 In Brodsky RA: How I treat paroxfact, thrombosis accounts for 40% 1. to 67% of the mortality from the dis- ysmal nocturnal hemoglobinuria, Blood June 2009;113 (26):6522-6527. ease.3 Venous thrombosis in PNH 25 2. Brodsky RA: Narrative Review: can occur anywhere, with the ab- Paroxysmal Nocturnal Hemoglobinuria: dominal veins (hepatic, portal, splen- The Physiology of Complement-Relatic, and mesenteric) and the cerebral ed Hemolytic Anemia, Ann Intern Med veins being the most common sites2. 2008;148:587-595. 3. Sharma VR, Talwalkar SS: Patients with a large PNH cell pop- Paroxysmal Nocturnal Hemoglobinuria: ulation (60% of granulocytes) seem Pathogenesis, Testing, and Diagnotobe at greatest risk for thrombosis.2 sis, Clinical Advances in Hematology & 12 | PRMA BOLETIN Oncology September 2013; 11(9): 2-10. 4. Raghupathy R, Derman O: Response of Paroxysmal Nocturnal Hemoglobinuria Clone with Aplastic Anemia to Rituximab, Case Reports in Hematology 2012; 2012:1-4. 5. Risitano AM, Rotoli B: Paroxysmal nocturnal hemoglobinuria: pathophysiology, natural history and treatment options in the era of biological agents, Biologics: Targets & Therapy 2008;2(2):205–222. 6. Kelly R, Richards S, Hillmen P, et al: The pathophysiology of paroxysmal nocturnal hemoglobinuria and treatment with eculizumab, Therapeutics and Clinical Risk Management November 18, 2009;5:911–921. 7. Nishimura J, Yamamoto M, Kanakura Y, et al: Genetic Variants in C5 and Poor Response to Eculizumab, N Engl J Med 2014;370:632-639. Resumen: Hemoglobinuria nocturna paroxismal es una enfermedad adquirida de un clon de células madres hematopoieticas que provienen de un origen no maligno. Esta entidad presenta con fallo de la médula osea, anemia hemolítica, distonia y trombosis. Presentamos un caso de una paciente de 32 años de edad, G2P2A0 con no historia médica pasada que refiere reflujos asociado con molestia abdominal por los últimos dos meses que ha ido gradualmente agravándose. El CBC inicial demostró una pancytopenia significativa (WBC 2.9 x 103 /μL con neutrofilos 48%, Hgb 6.1 g/dL, hematocrito 20%, MCV 113 fL y conteo de plaquetas 59 x 109/L). La Tomografίa Computarizada de abdomen demostró trombosis de la vena superior mesentérica tratado inicialmente con heparina. Pruebas de citometrίa de flujo de sangre periférica revelaron una disminución en la expresión de CD55 y CD59 en los eritrocitos, granulocitos y monocitos. Hemoglobinuria nocturna paroxismal es una entidad rara en cual sus manifestaciones clínicas son principalmente secundarias a hemólisis intravascular mediada por la cascada de complemento. Trombosis es la causa principal de muerte, pero también pacientes mueren de complicaciones tales como; fallo en la médula osea, fallo renal, síndrome mielodisplástico y leucemias. Eculizumab es la terapia de elección. Trasplante de médula osea puede ser curativo para pacientes con esta entidad pero esta asociado con una alta morbilidad y mortalidad. Pleural Effusion In A Patient With Primary Sjögren’s Syndrome Successfully Treated With Corticosteroids* ABSTRACT Sjögren’s syndrome is a systemic autoimmune disorder characterized by salivary insufficiency and lymphocytic infiltration of the exocrine glands. Bronchiolitis and bronchiectasis are common airway manifestations but interstitial pneumonitis, and lymphocytic interstitial pneumonitis may also occur. It rarely presents with pleuritis. We report a woman with primary Sjögren’s syndrome who developed pleuritis with moderately large effusions and antibody levels for SS-A and SS-B in the serum without evidence of infection, malignancy or other collagen diseases. After the initial treatment, daily administration of 20 mg of oral prednisone has effectively controlled the serious manifestations of the disease with minimal side effects. Franchesca del Pilar Cruz-Pérez*, MD, Armando Doval-Cortés, MD, Francisco Jaume-Anselmi, MD, FACP, José Ramírez-Rivera, MD, MACP Department of Internal Medicine, Hospital de la Concepción, San Germán, Puerto Rico Corresponding author: Franchesca Cruz Perez, MD Address: HC-2 Box 21404 Aguadilla Puerto Rico, 00603 Email: [email protected] *Presented in part at the American College of Physicians, Puerto Rico Chapter Clinical Vignettes Competition, November 15, 2014. normal limits. The initial chest radiograph showed blunting of the left costophrenic angle. She was admitted with the diagnosis of bronchitis. Levofloxacin 750 mg IV q daily was initiated. Index words: Sjögren’s syndrome, pleural efOn the third day of admission, fusion, corticosteroids, anti-SS-A/SS-B antidyspnea, cough and left pleuritbodies ic pain persisted. A chest film demostrated a moderate size left pleural effusion (Fig.1). A left pain of four days duration. thoracocentesis yielded 600 ml INTRODUCTION Sjögren’s syndrome was diag- of exudative fluid with 375mm3 Sjögren’s syndrome is a system- nosed two months before admis- of leukocytes were 83% were ic autoimmune disease charac- sion based on sicca complex, monocytes but no malignant terized by sicca complex due to positive results for anti-SS-A/ cells. Protein/albumin concenchronic inflammation in the lac- SS-B antibodies and biopsy find- tration and LDH values in the rimal and small salivary glands. ings in the minor salivary glands. fluid were 0.6 g/dL and 1.2 IU/L, Interstitial pneumonitis and tra- She took prednisone for two respectively. The tuberculin test cheobronchitis are the most com- months and stopped treatment was negative and the cardiac mon pulmonary manifestations one month before admission ejection fraction was 55%. Blood and pleural cultures showed no (1). We present a case of primary when leg edema developed. Sjögren’s syndrome associated On examination, the vital signs growth. Becasuse cough and with pleural effusion successfully were normal. No parotid gland shortness of breath persisted on treated with corticosteroids. enlargement was noted but dry the sixteenth day of admission eyes were evident. There was a second thoracocentesis was CASE REPORT no malar rash, joint inflamma- performed yielding 600ml of flution, swelling, tenderness or id. On the twenty-fifth day of hosA 69-year-old woman with arterial decreased range of motion. A pitalization the chest film and CT hypertension, arthralgias, xeroph- friction rub and fine inspiratory scan demonstrated once again thalmia and xerostomia for more crackles were noted at the bas- a significant increase of the left than 10 years was admitted to the es. The rest of the physical ex- pleural effusion. The inserted hospital with generalized malaise, amination, routine laboratory ex- chest tubes drained 350 ml/day low grade fever, productive cough aminations and the arterial blood of serosanguinous fluid. A left of clear sputum, and left pleuritic gases at room air were within pleural biopsy showed acute PRMA BOLETIN | 13 aibrinoid pleuritis with lymphocytic infiltration (Fig.2). The tumor markers and serological test for CMV, HSV, EBV and HIV were negative, laboratory evaluations for lupus erythematosus, anti-dsDNA and anti-Sm antibodies were also negative as well anti-Scl-70 for systemic sclerosis. The serum ANA titer was positive at 1:640. The anti-SSA and anti-SSB antibodies were at 50.1 eu/ml and 22.1 eu/ml (normal range <20.0 eu/ml), respectively. These serologic findings indicated that the pleural effusion was most likely a manifestation of Sjögren’s syndrome and a negative rheumatoid factor IgM and anti-CCP IgG suggested that the Sjögren’s syndrome was primary. Figure 1: Chest radiograph showing left pleural effusion before initiation of methylprednisolone therapy. Methylprednisolone 40 mg IV every 8 hours was started. The chest pain improved after 24 hours and the pleural drainage gradually decreased to less than 50 ml/day in the next 72 hours. Ten days after initiating methylpredinisolone therapy, the patient felt well and the chest radiograph showed a dramatic decrease in the pleural effusion (Fig.3). The patient was discharged on 40 mg of oral prednisone. Three months after discharge the prednisone dose was decreased to 20 mg daily. She has tolerated this dose with mininal side effects. Eight months after discharge the pleural effusion has not recurred. DISCUSSION Sjögren’s syndrome may be primary or secondary. The secondary form is associated with other collagen disorders such as rheumatoid arthritis, systemic lupus erythematosus, and scleroderma (2). In 2002 the American-European consensus group reviewed the classification criteria: Two subjective criteria; ocular and oral symptoms and four objective criteria; ocular and oral signs and histopathological and serological findings including antinuclear, anti-SS-A or anti-SS-B antibodies (2). The diagnosis of Sjögren’s syndrome requires at least four of the six criteria including histopathological or serological findings. Pleural effusion is an unusual pulmonary manifestation of primary Sjögren’s syndrome (5). Only six cases have been reported in the medical literature (table 1). Pleural effusion was an initial manifestation in only two cases (2). Pleural effusions result from the production of autoantibody, immune complexes and the activation of the complement cascade in the pleural cavity (1,3). In four of the six 14| PRMA BOLETIN Figure 2: The left pleural biopsy showed acute fibrinoid pleuritis (arrow) with lymphocytic infiltrations (arrowhead). Figure 3: Chest radiograph ten days after initiation of methylprednisolone therapy showing a significant decrease in the left pleural effusion. Table 1: Literature review of primary Sjögren’s syndrome complicated by pleural effusions. cases, anti SS-A and/or SS-B antibodies in the pleural effusion helped identify the cause of the effusion (1,7).Sjögren’s syndrome should be considered in the differential diagnosis of pleural effusions. Anti SS-A and SS-B antibodies should be measured routinely in cases of pleural effusions associated with autoimmune diseases to reach a rapid diagnosis and initiate appropriate therapy (7,9). The six cases reported had a good response to corticosteroids therapy, but recurrence occurred in five of the six cases during dose reduction (2). Corticosteroid therapy, initially at 30 to 40 mg/day, is an appropriate treatment (2). CONCLUSION: REFERENCES: Sjögren’s syndrome must be considered as a cause of pleural effusions of unknown origin. It is important to measure levels of anti SS-A and SS-B antibodies in patients with autoimmune disease on serum and pleural fluid for appropriate diagnosis and rapid treatment. The possibility that pleuritis may be associated with Sjögren’s syndrome, although rare, should be considered. 1. Teshigawara K1, Kakizaki S, Horiya M, Kikuchi Y, Hashida T, Tomizawa Y, Sohara N, Sato K, Takagi H, Matsuzaki S, Mori M. Primary Sjögren’s syndrome complicated by bilateral pleural effusion. Respirology 2008;13:155-158. 2. Go Makimoto et al. Bilateral Pleural Effusions as an Initial Presentation in Primary Sjögren’s Syndrome. Hindawi Publishing Corporation. Case Reports in Rheumatology, 2012;1:1-3. 3. H. Suzuki, P. Hickling, and C. B. A. Lyons, “A case of primary Sjögren’s syndrome, complicated by cryoglobulinaemic glomerulonephritis, pericardial and pleural effusions,” Rheumatology, 1996;35:72–75. 4. C Vitali et al. Classification criteria for Sjögren’s syndrome: a revised version of the European criteria proposed by the American-European Consensus Group. Ann Rheum Dis. 2002;61:554– 558. 5. M. P. Papathanasiou, S. H. PRMA BOLETIN | 15 Constantopoulos, and C. Tsampoulas, “Reappraisal of respiratory abnormalities in primary and secondary Sjogren’s syndrome. A controlled study,” Chest, 1986;9:370–374. 6. C. Baldini, R. Talarico, A. G. Tzioufas, and S. Bombardieri, “Classification criteria for Sjögren’s syndrome: a critical review,” Journal of Autoimmunity, 2012;39:9–14. 7. T. Ogihara, A. Nakatani, H. Ito et al., “Sjögren’s syndrome with pleural effusion,” Internal Medicine, 1995;34:811– 814. 8. S. H. Constantopoulos, C. S. Papadimitriou, and H. M. Moutsopoulos, “Respiratory manifestations in primary Sjogren’s syndrome. A clinical, functional, and histologic study,” Chest, 1985;88:226–229. 9. Tanaka A et al. A case of Sjögren’s syndrome with pleural effusion. Nihon Kokyuki Gakkai Zasshi. 2000;38:628-31. Resumen El síndrome de Sjögren es una condición autoinmune caracterizada por insuficiencia salivar e infiltrado linfocitico en las glándulas exocrinas. Bronquiolitis y bronquiectasia son manifestaciones comunes pero neumonitis intersticial y neumonitis linfocítica intersticial pueden también ocurrir. Reportamos una mujer con el síndrome de Sjögren primario que presentó con pleuritis, derrame pleural bilateral y niveles de anticuerpos para anti SS-A and SS-B en la sangre sin evidencia de infección, malignidad o de otra enfermedad autoinmune. Después del tratamiento inicial, una dosis diaria de 20 mg de prednisona ha sido efectiva en controlar las manifestaciones importantes de la enfermedad con mínimos efectos secundarios. estimado colega medico: la asociacion medica realiza periodicamente encuestas de opinion cuyos resultados son muy importantes para nuestra politica publica y gestion ante otras organizaciones. sus respuestas son imprescindibles para nosotros. The Racial, Cultural and Social Makeup of Hispanics as a Potential Profile Risk for Intensifying the Need for Including this Ethnic Group in Clinical Trials ABSTRACT Hypertension not only is the most frequently listed cause of death worldwide; but also a well-recognized major risk factor for cardiovascular disease and stroke. Based on the latest published statistics published by the American Heart Association, hypertension is very prevalent and found in one of every 3 US adults. Furthermore, data from NHANES 2007 to 2010 claims that almost 6% of US adults have undiagnosed hypertension. Despite this staggering statistic, previous US guidelines for the prevention, detection, and treatment of hypertension (The Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure 7 [JNC 7]), released in 2003, stated that; “unfortunately, sufficient numbers of Mexican Americans and other Hispanic Americans… have not been included in most of the major clinical trials to allow reaching strong conclusions about their responses to individual antihypertensive therapies.” However, the recently published JNC 8 offers no comment regarding recommendations or guideline treatment suggestions on Hispanics. The purpose of this article not only is to raise awareness of the lack of epidemiological data and treatment options regarding high blood pressure in the US Hispanic population; but also to make a case of the racial, cultural and social makeup of this ethnic group that places them at risk of cardiovascular complications related to hypertension. Key Words: Evidence-Based Medicine, diabetes, hypertension, Hispanics, Latinos, obesity, population studies, renal dysfunction. Angel López-Candales, MD*; Jaime Aponte Rodríguez, MD*; David Harris, MD Cardiovascular Medicine Division, Medical Sciences Campus, University of Puerto Rico School of Medicine* and the Division of Cardiovascular Health and Disease, University of Cincinnati College of Medicine, Cincinnati, OH Address all correspondence to: Angel López-Candales, MD, FACC, FASE Cardiovascular Medicine Division University of Puerto Rico School of Medicine Medical Sciences Building PO Box 365067 San Juan, Puerto Rico 00936-5067 [email protected] INTRODUCTION Numerous risk factors have been linked to the development of hypertension including age, ethnicity, family history of hypertension, genetic factors, lower education and socioeconomic status, obesity, tobacco use, psychosocial stressors, sleep apnea, and dietary factors (such as dietary fats, higher sodium intake, lower potassium intake, and excessive alcohol intake). 3 Diverse data from related individuals in the NHLBI’s FHS has also suggested that different sets of genes regulate blood pressure at different ages. 5 As already stated, racial and/or ethnic backgrounds not only dictate how prevalent HTN is among different groups of our population; 3 but also their response to treatment. 6 It is well known that Hispanics constitute the largest and fastest-growing minority population in the United States . 7 Furthermore, Hispanics are known to have a rate of uncontrolled HTN that significantly exceeds the rates observed among non-Hispanic whites. 8 Specifically, Puerto Rican Americans consistently have a higher hypertension-related death rate than all other Hispanic subpopulations and non-Hispanic whites. 9 The Hispanic medical community has waited with great anticipation the release of the new American Heart Association Statistics Committee and Stroke Statistics Subcommittee 2014 Update: 16| PRMA BOLETIN PRMA BOLETIN | 17 A Report from the American Heart Association. 10 For the surprise of most of the Hispanic medical community, the recommendations only provided an analysis of what is known and not known about BP treatment thresholds, goals, and drug treatment strategies to achieve those goals based on evidence from randomized controlled trials. As in previous guidelines and statements these recommendations aside from pointing out differences between black and nonblack populations do not provide specific guidelines for implementing the suggested treatment algorithm when treating Hispanics. 10 THE US HISPANIC POPULATION The American system of racial classification was first established on August 2, 1790 with the particular aim of identifying the majority free white population from black slaves and American Indian minority groups. Later it adopted variations to also include Asian-origin populations. 11, 12 In 1850, the U.S. Census Bureau relied on objective indicators, such as country of birth to identify persons of Mexican origin in its decennial counts. 13 Decades later, parent’s birthplace, mother tongue, or Spanish surname were also included to broaden the definition of what constitutes the Hispanic population within the US. It was not until a century later, in the 1950s, that the Census Bureau first published information on persons of Puerto Rican’s birth or parentage and tabulations on people of Cuban birth or parentage were then published in 1970. 13 Efforts to demarcate and differentiate the Hispanic population date back to the late 1960s 14 when in the context of surging civil rights activism and a new federal legislation (that required accurate statistical documentation of minority group disadvantages) numerous minority groups including some Mexican 18| PRMA BOLETIN American organizations pressed for better clinical data about their ethnically group. 15 It is important to clarify that the Nixon White House ordinance to add a Spanish-origin self-identifier on the 1970 census was only included in the “long form” and simply represented a 5% sample since 109 million copies of the “short form” had already been sent to press. 13 The late Nixon ordinance and the use of vague identifiers in the “short form” perpetuate the incorrect identification of the Hispanic group. Questions about Hispanic origin were not consistently found in every census until 1980. 16, 17 In fact, over the last 40 years the question on Hispanic origin has undergone numerous changes and modifications, with the aim of improving the quality of Hispanic origin data in the United States, Puerto Rico, and the U.S. Island Areas. 16, 17 Data from the 2010 Census provided us with great insights regarding the mosaic nature of our true ethnic identity as a nation. According to the 2010 Census, 308.7 million people resided in the United States on April 1, 2010, of which 50.5 million (16%) were of Hispanic or Latino origin. 16, 17 In order to have a better perspective of the significance of these numbers, the overall growth of the Hispanic population between 2000 and 2010 was 43%, which was four times the growth in the total population. 16, 17 Author Rubén G. Rumbaut in his script “The Making of a People,” examined the evolution of the Hispanic population as an ethnic group. Here he describes the historical origins and contemporary diversity of Hispanics; but also the social construction of the catchall “Hispanic” category. 13 Rumbaut further clarifies that “the browning of America,” is a clear misnomer. This misnomer was originally based on popular stereotypes of phenotypes presumed to characterize peoples of Latin American origin. 13 The author describes the Hispanic population, as an ethnic group, which is composed of individuals that differ significantly as a race, due to their diverse national origins. 13 To the future in the clinical management of hypertension, it is crucial to be reminded of the fact that Hispanics are composed of a myriad of ethnic groups within the “Hispanic or Latino” label. ( as shown in table 1). From this Census data it is clear that people from Mexican origin not only account for the largest ethnic group within the Hispanic population (31.8 million) in 2010; but also this Hispanic ethnic group is the one that has experienced the greatest increase in their individual population since 2000 (54%). 16, 17 In contrast, the second largest Hispanic ethnic group, Puerto Ricans, even though they have grown by 36% in the same time period; they have just increased from 3.4 million in 2000 to 4.6 million in 2010. 16, 17 However, a vast number of Hispanics are still included among Cubans, Dominicans as well as people from Central and South America. 16, 17 This rapid growth of today’s Hispanic population was initially attributed to migration patterns that started with Puerto Ricans after World War II; the exodus from Cuba created after the 1959 revolution instigated by Fidel Castro and the surge of immigration from Mexico and Latin America since 1970. 13 However, fertility has probably overtaken immigration as the drive of Hispanic population growth in the current decade. Hispanics as a whole are younger, poorer and less educated contributing to a rise in their numbers. 13, 18-21 Based on population estimates and projection analysis, the US population is expected to grow from 310 million to 439 million (42% increase) between 2010 and 2050. 22 During this time period, the nation will also become more racially and ethnically diverse, with the aggregate minority projected to become the majority by 2042. 22 In addition, the population is also expected to become much older, with nearly one in five U.S. residents aged 65 and older in 2030. 22 In 2050, 20% of the population aged 65 and over is projected to be Hispanic (up from 7% in 2010), with this sector projected to grow from 2.9 million to 17.5 million, a sixfold increase. 22 Since Hispanic population is projected to nearly triple, from 46.7 million to 132.8 million, from 2008 through 2050, the Census bureau expects that one in three US residents would be Hispanic; 23 therefore, we should be more knowledgable of the clinical makeup of this ethnic group. CLINICAL MAKEUP OF THE HISPANIC COMMUNITY Mortality from cardiovascular disease (CVD) is the leading cause of death among Hispanic individuals in the US. 24 Evidence also seems to suggest that CVD risk factors and disease rates may vary considerably among the different Hispanic groups. Unfortunately, existing research on CVD risk factors among Hispanic groups in the US has largely involved Mexican-American individuals; 24, 30-32 with only a few studies trying to examine differences in CVD risk factors among other Hispanics. Daviglus and associates examined the risk and protective factors for chronic diseases as part of the Hispanic Community Health Study/Study of Latinos (HCHS/SOL). In this study they quantified the morbidity and mortality of people from Cuba, Dominican Republic, Mexico, Puerto Rico, Central and South America. 37 Their study individual representation was as follows; Cuban (n =2201), Dominican (n = 1400), Mexican (n=6232), Puerto Rican (n=2590), Central American (n=1634), and South American backgrounds (n = 1022) all from ages 18 to 74 years. 37 The overall prevalence of hypercholesterolemia among men ranged from 48% (Dominican and Puerto Rican men) to 55% (Central American men). In women, the prevalence of hypercholesterolemia was 37% and ranged from 31% (South American women) to 41% (Puerto Rican women). 37 In their cohort analysis, about 37% of men were obese; ranging from 27% (South American) to 41% (Puerto Rican) while in women the overall prevalence of obesity was 43% being highest among Puerto Rican women. 37 With regards to diabetes, 17% of men and women had diabetes; ranging from 10% in South American men and women to 19% in Mexican men and women and Puerto Rican women. 37 About 26% of men were current smokers; with highest prevalence of smoking among Puerto Rican men and 32% of Puerto Rican women were current smokers. 37 Finally, 25% of men had hypertension being more prevalent among Dominican men. 37 In women, the prevalence of hypertension ranged from 16% (South American) to 29% (Puerto Rican). 37 The baseline results of this HCHS/ SOL study clearly demonstrate that a sizable burden of CVD risk factors exists among all Hispanic groups with prevalence of risk factors comparable or higher than those reported for non-Hispanic white individuals. 38, 39 Furthermore, the HCHS/SOL data also showed marked variation in CVD risk factor prevalence within the Hispanic population with some groups, particularly those with Puerto Rican background, experiencing strikingly high rates of individual adverse CVD risk factors or overall risk factor burden when compared with other Hispanic groups. Particularly Puerto Rican women have the highest prevalence in each of the major CVD risk factors. 37 In a separate study, Garza and colleagues found that a greater percentage of Puerto Rican island youth were overweight and obese when compared to corresponding US mainland youth. 40 They also reported that Puerto Rican youth (island residents) have a lower compliance with federal physical activity guidelines than mainland youth. 40 The study also noted that children of obese parents were more likely to be overweight/obese themselves than those with desirable weight parents. 40 This report on obesity is particularly troublesome given the known association between obesity and determinants of CVD risk. 41 It is well known that advanced grades of obesity are directly associated with multiple health hazards including arterial hypertension, coronary artery disease, heart failure and several other chronic disorders. 42 Hence, obesity has been considered as a poor prognostic parameter in terms of lifetime expectancy, increased morbidity and mortality. 44 HYPERTENSION Hypertension is a serious public health challenge in the United States, affecting approximately 30% of adults and increasing the risk for heart disease and stroke, the first and third leading causes of death in the United States. 45-47 People with hypertension have higher rates of mortality than people without hypertension, particularly of vascular mortality. 49, 50 Because of the high prevalence of this condition and the increased morbidity and mortality, health care costs are astronomical. In fact, the economic cost of hypertensive disease was estimated at $76.6 billion in 2010. 51 Additionally, the impact of this clinical entity is magnified by racial and ethnic disparities noted across the United States. PRMA BOLETIN | 19 52-55 Specifically, non-Hispanic blacks have been identified to be at a higher risk for hypertension and hypertension-related complications (e.g., stroke, diabetes, and chronic kidney disease) than non-Hispanic whites and Mexican Americans; 46, 52 but also hypertension occurs at a younger age among non-Hispanic blacks than Whites. 56 In contrast, the prevalence of hypertension was found to be comparable between Hispanics and non-Hispanic whites. 57-61 However, it is important to point out that a significant number of epidemiological studies related to hypertension regarding Hispanics in the United States have focused on Mexican-Americans from Southwestern United States. 57-65 When studies have tried to address hypertension prevalence among other Hispanic subgroups; conflicting results have been noted, likely in part due to differences in analytical approach and study design. 66-71 In addition, none of these studies have addressed the potential effect that ancestral origin has over Caribbean Hispanics when compared to Mexican-origin Hispanics. Particularly with regards to salt-sensitivity and its effect on hypertension. 72 The latter can in part explain the findings of the Northern Manhattan Study, which reported that hypertension was more common in non-Hispanic blacks and in a largely Caribbean population of Hispanics compared with non-Hispanic whites, with rates of 62%, 58%, and 43%, respectively. 73 In addition, data from the Multi-Ethnic Study of Atherosclerosis might also be explained using the same premise. This study revealed that the prevalence of hypertension among Hispanics of Caribbean origin approximated that of non-Hispanic blacks, while the prevalence in Mexican-origin Hispanics approximated that of non-Hispanic whites. 74 Finally, when analyzing the results reported by Hyman and associates, these investigators 20| PRMA BOLETIN noted that even though average 24-hour BP measurements were similar among non-Hispanic black, non-Hispanic white and Caribbean Hispanic hypertensives; an absence of the nocturnal dipping was more commonly seen in non-Hispanic blacks and among Caribbean Hispanic men. 75 groups might have a higher incidence of diabetes and hence the combination of diabetes and hypertension; but also the fact that hypertension increases the risk of cardiovascular complications in diabetic patients. 84 The fact that many patients with diabetes require combination therapy with multiple antihypertensive agents 85-87 might further affect compliIn a report by the National His- ance as a result of adverse social panic Medical Association the pressures that plague most Hisprevalence of selected conditions panics. 13, 18-21 among Hispanic adults (aged 20 years or older and group by race/ Since the US guidelines report ethnicity) versus non-Hispanic on prevention, detection, and whites was assessed. 76 In this treatment of HTN (The Seventh analysis of the national census Report of the Joint National Comand health databases compared mittee on Prevention, Detection, data from Puerto Rico to data re- Evaluation, and Treatment of corded from the following states High Blood Pressure 7 [JNC 7]) including Arizona, California, Col- released in 2003, it was clear as orado, Florida, Georgia, Illinois, stated in the final manuscript that Nevada, New Jersey, New Mex- “unfortunately, sufficient numbers ico, New York, Texas, and Virgin- of Mexican Americans, other Hisia. 76 The data was used from panic Americans...have not been the US Census July 2008; Be- included in most of the major clinhavioral Risk Factor Surveillance ical trials to allow reaching strong System (BRFSS) 2005, 2006, conclusions about their respons2007, 2008; National Health and es to individual antihypertensive Nutrition Examination Survey therapies.”1 In the years follow(NHANES) 2003–2006 and from ing this report, post hoc analyses the National Health Interview of major trials have particularly Survey (NHIS) 2007, 2008. 77- reported on Hispanic patients. 82 Using this unique snapshot of 88-92 the population studied the prevalence of hypertension among As stated by Ventura and associPuerto Ricans living in the is- ates, with the anticipated growth land was higher (33.6%) than in the Hispanic population in the that reported for non-Hispanic United States, it is critically imwhites (26.6%). 76 Concluding portant that every effort be made data published by the National to seek and enroll Hispanics in Health Interview Survey 2000- clinical trials. It is also important 2005, showed a wide variation in to increase awareness in recweighted unadjusted prevalence ognizing treatment options in of self-reported hypertension this sector of the population. 93 across Hispanic subgroups, with With this in mind, the 2014 Evioverall rates ranging from 12% dence-Based Guideline for the for Central/South Americans to Management of High Blood Pres24% in Puerto Ricans and 25% sure in Adults: Report from the for Cubans. 83 Additional find- Panel Members Appointed to the ings of this study also showed Eighth Joint National Committee that Puerto Ricans had the high- (JNC 8) were much anticipated. est self-reported prevalence of 10 Unfortunately, despite the diabetes (11%). 83 only two new things taken from JNC 8 are the new blood presDiabetes is of particular concern sure threshold for older adults 60 not only because some Hispanic years or older and for adults with chronic kidney disease or diabetes; there is no comment regarding recommendations or guideline treatment suggestions on Hispanics. 10 Therefore, this should serve as a call for action for all clinical researchers to be more sensitive with regards to the population profile of our country, but also to be more determinate in providing more comprehensive treatment guidelines for this high risk clinical entity. Even though tangential to our topic of discussion, recently published data from a retrospective propensity-matched study of patients with heart failure and reduced left ventricular ejection fraction who were on a beta-blocker, the use of angiotensin–converting enzyme inhibitors (ACEis) was associated with greater mortality reduction in Hispanic patients compared with African Americans and Whites. 94 This should probably encourage clinical researchers to investigate the pharmacokinetic response of different antihypertensive drugs among Hispanics. In conclusion, we believe that the very diverse racial, cultural and social makeup of each Hispanic subgroup poses a great challenge and Hispanics should not be dealt as a homogeneous but rather as a heterogeneous ethnic group in which diagnostic and therapeutic options might not apply similarly and more clinical data is urgently needed to offer more accurate interventions. REFERENCES 1. 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Hypertension and Antihypertensive Therapy in Hispanics and Mexican Americans Living in the United States. Postgraduate Medicine. 2011; 123: 46-57. 94. Eshtehardi P, Pamerla M, Mojadidi MK, Goodman-Meza D, Hovnanians N, Gupta A, Lupercio F, Mazurek JA, Zolty R. Addition of Angiotensin-converting enzyme inhibitors to Beta-blockers has a distinct effect on hispanics compared with african americans and whites with heart failure and reduced ejection fraction: a propensity score-matching study. J Card Fail. 2015; 21: 448-456. ABSTRACTO La hipertensión no es solamente la causa mas frecuente de muerte al redor del mundo, sino que también es un factor de riesgo para el desarrollo de enfermedades cardiovascular y derrame cerebral. Según las ultimas estadísticas por la Asociación Americana del Corazón, uno de cada 3 adultos en Estados Unidos tiene hipertensión. En adición, data de NHANES que cubre los años 2007 al 2010 identifica que aproximadamente 6% de la población Americana tiene hipertensión y no ha sido diagnostica y por ende tratada. Aun cuando estas estadísticas son impresionantes en la séptimo tratado del comité de Prevención, Detección, Evaluación y Tratamiento [JNC 7], publicado en el 2003 se menciono números insuficientes de Americanos Mejicanos y otros Hispanos no estaban bien representados para llegar a conclusiones definitivas con relación al diagnostico y tratamiento de esta raza. Desgraciadamente, en la mas reciente publicación del JNC 8, estos autores no ofrecieron ninguna recomendación o guía con relación al diagnostico o manejo de pacientes Hispanos. Es por eso que este articulo pretende no solamente el crear consciencia de la falta de datos vitales con relación a Hispanos , pero que exploramos como el perfil racial, cultural and social de esta raza Hispana contribuye a que la hipertensión sea una entidad clínica que se tome con cautela y se le el debido interés y reconocimiento por ser una causa principal de riesgo tanto cardiovascular como para derrame cerebral. PRMA BOLETIN | 23 Discussion Usefulness Of Glucocorticoids In The Management Of Foreign Body Aspiration Bryan L. Pagán Rivera, MD, Francisco Jaume Anselmi, MD, FACP, María Del Mar Torres, MD, Amaury Segarra MD, and Jose Ramirez Rivera, MD, MACP Department of Internal Medicine, Hospital de la Concepción Corresponding author: Bryan L. Pagán Rivera, MD Address: P.O Box 1642 San Germán Puerto Rico, 00603 Email: [email protected] Case report presented as a poster at Ponce Health Science University Annual Scientific Conference, May 30, 2015 Introduction Foreign body aspiration (FBA) is a potentially life-threatening event. Data from the National Security Council reported that approximately 20% of cases occur in patients older than 15 years of age. Glucocorticoids are occasionally used when a foreign body is completely encased in bulky and bleeding granulation tissue and the extraction is difficult or impossible. We present a 19-year-old man with pneumonia due to foreign body aspiration who spontaneously expelled a foreign body, one day after admission due to right lower lobe pneumonia and glucocorticoids administration. A healthy 19- year-old male media communications student with shortness of breath, cough productive of yellow sputum, fever and chills of 6 weeks duration. He was fixing a toy using his teeth at his sister’s birthday when he sneezed and felt that he swallowed something (this information was not available at the time of admission). One week later he was evaluated with the described symptoms and azithromycin 500 mg PO daily for 5 days was prescribed. The chest radiograph was normal. Six weeks later cough and episodic fever persisted and he visited his primary care physician. The chest radiograph showed a consolidating acinar density at the right lower lobe. He was referred to our Institution. He had one episode of asthma in his childhood. [Figure 1 and 2] The admission temperature was 39°C, pulse 144 beats, respiratory rate 20 and blood pressure 132/87 mmHg and respiratory rate 20. He was alert with mild dyspnea. The right lung showed monophonic expiratory wheezes with prolonged expiratory phase. The left lung was clear to auscultation. The rest of the physical examination was within normal limits. 24| PRMA BOLETIN Foreign body aspiration is more common in children than in adults with only 20 percent of cases occurring over the age of 15 years. The first case of FBA was reported in 1897, when a pork bone was extracted from a trachea using an esophagoscope (1). Risk factors for FBA in adults include age over 75 years, neurologic disorders, loss of consciousness, and alcohol or sedative use. Adults usually presents with cough in 81% of cases, hemoptysis, wheezing and dyspnea or the patient may remain asymptomatic. Imaging findings include unilateral, bronchiectasis, atelectasis, lobar consolidation and/or pleural effusion. Abstract Foreign body aspiration can be a life-threatening emergency. An aspirated solid or semisolid object may lodge in the larynx, trachea or other breathing airways. If the object is large enough to cause nearly complete obstruction of the airway, asphyxia may rapidly cause death. We report a 19-year old man admitted with right lower lobe pneumonia who spontaneously expelled a foreign body, one day after admission and glucocorticoids administration. Glucocorticoids should be considered in foreign body aspiration management because improvement of the inflammatory reaction may facilitate expontaneous expulsion or foreign body extraction The hematocrit was 41.7%, hemoglobin 14.3 g/dl, white cell count 19.4 x 103 mm3 (N 88.3%, L 8.8 %), Hgb 14.3 g/dl, Hct 41.7% and platelets 188 x103/mm3. The arterial blood while breathing room air: pH 7.45, CO2 28.3 mmHg, PO2 76.6 mmHg, HCO3 19.1 mmol/L and SaO2: 95.7%. The thorax CT scan confirmed a consolidating acinar density at the right lower lobe. [Figure 3]. He was admitted with the diagnosis of right lower lobe pneumonia. He was treated with ceftriaxone 2gm IV q 24 hrs, moxifloxacin 400 mg IV daily, acetaminophen 325 mg PO q 4-6 hrs PRN, methylprednisolone 60 mg IV q 8 hrs, ranitidine 20 mg IV daily and free flow therapy with levalbuterol 1.25 mg q 4 hrs. On the second day of admission, after an episode of violent cough a piece of rubber was expelled. Dyspnea and cough improved shortly thereafter. Arterial blood breathing at room air showed: PH 7.42, CO2 33 mmHg, PO2 85 mmHg, HCO3 21mmol/L and PaSO2 96.6%. [Figure 4] One day after he expelled the foreign body the white cell count decreased to 10.4 x103/mm3.. Two days after he expelled the foreign body, he was afebrile, there was no cough or shortness of breath and the lungs were clear. The blood cultures were negative. He was discharged with Levofloxacin 750 mg PO daily to complete 7 days of treatment. Fig. 1 - CXR within normal limits Fig. 2 - Repeated chest film three weeks later showed a consolidating acinar density at the right lower lobe. Just 20% of foreign body aspiration cases occur in patients > 15 years old and incidence increase in adults over the age of 75 years, with deaths from FBA peaking at age 85. One retrospective study from a single center reported the removal of 89 foreign bodies in adults over a 20 year period (2). Similarly, case series from the Mayo Clinic identified 60 adults diagnosed with FBA over a 33-year period and studies from a single center in Taiwan reported 43 cases over a 15-year period (3). Other investigation paper describes eight patients (two teenagers and six adults) who had chronic symptoms (haemoptysis, cough, recurrent pneumonia) caused by foreign body (FB) inhalation which went undetected for 3 months to 25 yr. The diagnosis of FB was made by radiography in one patient only. Computerized tomography visualized one FB (a beef bone), and bronchoscopy identified FB in another two patients. The remaining four cases were diagnosed at thoracotomy (4). Unexplained respiratory symptoms should warrants either a flexible or rigid a bronchoscopy PRMA BOLETIN | 25 to exclude foreign body aspiration despite negative history and normal chest radiography. Firg. 4 - CT scan confirmed an extensive consolidating acinar density at the right lower lobe suggesting a consolidating pneumonia. Fig. 5 - After an episode of violent cough a piece of rubber was expelled. When dealing with long-standing organic foreign bodies that induce formation of granulation tissue, case series report that the use of systemic glucocorticoids 12 h to 24 h before removal (5) may aid in extraction by reducing inflammation. Although this practice and dosing has not been validated in prospective trials, it often results in significant improvement of the inflammatory reaction and facilitates subsequent extraction as occurred in our case. Glucocorticoids have also been administered by intraluminal injection as reported in a case of a 67 year old woman with a peanut aspiration during a meal. Approximately 1 ml of TA was injected into the submucosal tissue of the bronchial obstruction without remarkable complications. Three days after the injection, the patient reported that the peanut was expectorated at lunchtime, although the expectorated peanut could not be confirmed unfortunately (6). Conclusion The use of glucocorticoids may be use in foreign body aspiration management because of the significant improvement of the inflammatory reaction and facilitation of subsequent foreign body extraction although practice and dosing has not been validated in prospective trials. It is also conclude that chronic, unexplained respiratory symptoms should warrant further investigation to exclude foreign body aspiration despite negative history and normal chest radiography as occur in our patient. 26| PRMA BOLETIN References Resumen 1. Killian G. Meeting of the society of physicians of Freiburg. December 17, 1897. Munchen Med Wschr.1989;45:378. 2. Casalini AG, Majori M, Anghinolfi M, et al. Foreign body aspiration in adults and in children: advantages and consequences of a dedicated protocol in our 30-year experience. J Bronchology Interv Pulmonol 2013; 20:313 3. Chen CH, Lai CL, Tsai TT, et al. Foreign body aspiration into the lower airway in Chinese adults. Chest 1997; 112:129. 4. al-Majed SA, Ashour M, al-Mobeireek AF, al-Hajjaj MS, Alzeer AH, al-Kattan K. Overlooked inhaled foreign bodies: Late sequelae and the likelihood of recovery. Respir Med. 1997;91:293–6 5. Banerjee A, Rao KS, Khanna SK, et al. Laryngo-tracheobronchial foreign bodies in children. J Laryngol Otol.1988;102:1029. 6. Toshiaki Niwa, , Atsushi Nakamura, Takashi Kato, Takeo Kutsuna, Ken Tonegawa, Ken Kato, Hiroki Morita, Makoto Itoh. Bronchoscopic intralesional injection of triamcinolone acetonide treated against bronchial obstruction caused by peanut aspiration La aspiración de un cuerpo extraño es una emergencia la cual pone en riesgo la vida de un paciente. Un objeto sólido o semi-sólido se puede alojar en áreas como la laringe o la tráquea causando así la muerte. En este caso presentamos un paciente de 19 años, admitido por neumonía, quien espontáneamente expulsó un cuerpo extraño un día después de su admisión y la administración de glucocorticoides. Los glucocorticoides deben ser considerados en el manejo de un paciente luego de la aspiración de un cuerpo extraño porque su actividad anti-inflamatoria facilita la extracción o la expulsion del mismo. estimado colega medico: la asociacion medica realiza periodicamente encuestas de opinion cuyos resultados son muy importantes para nuestra politica publica y gestion ante otras organizaciones. sus respuestas son imprescindibles para nosotros. historia de la medicina Con Alcmeón de Crotona, en el año 500 a. C., se dio inicio a una etapa basada en la tekhné (‘técnica’), definida por la convicción de que la enfermedad se originaba por una serie de fenómenos naturales susceptibles de ser modificados o revertidos. Ese fue el germen de la medicina moderna, aunque a lo largo de los siguientes dos milenios surgirán otras muchas corrientes (mecanicismo, vitalismo...) y se incorporarán modelos médicos procedentes de otras culturas con una larga tradición médica, como la china. A finales del siglo XIX, los médicos franceses Bérard y Gubler resumían el papel de la medicina hasta ese momento: «Curar pocas veces, aliviar a menudo, consolar siempre». La medicina del siglo XX, impulsada por el desarrollo científico y técnico, se fue consolidando como una disciplina más resolutiva, aunque sin dejar de ser el fruto sinérgico de las prácticas médicas experimentadas hasta ese momento: la medicina científica, basada en la evidencia, se apoya en un paradigma fundamentalmente biologicista, pero admite y propone un modelo de salud-enfermedad determinado por factores biológicos, psicológicos y socioculturales. PRMA BOLETIN | 27 ORIGINAL ARTICLE Previous Exposure to Anesthesia and Autism Spectrum Disorder (ASD): A Puerto Rican Population-Based Sibling Cohort Study Creagh O. MDA, Torres H. MDA, Rivera K. MDA, Morales-Franqui M. MDA, Altieri-Acevedo G. MDAC, Warner D. MDB ADepartment of Anesthesiology, University of Puerto Rico Medical Sciences Campus, San Juan Puerto Rico BDepartment of Anesthesiology, Mayo Clinic Rochester, Minnesota CCorresponding author: Gabriel Altieri-Acevedo MD- Department of Anesthesiology UPR, Medical Science Campus School of Medicine PO BOX 365067. Email: [email protected] ABSTRACT Background mantenemos control de sus cuidados Lograr un paciente saludable y en control surge de la visión interdisciplinaria de conectar, coordinar y proveer los servicios en el orden y momento precisos. Promovemos el manejo coordinado por la salud de nuestra gente. Autism Spectrum Disorder (ASD) is characterized by impaired social interaction and communication, and by restricted and repetitive behavior, that begins usually before a child is three years old.1 Researchers have shown that prevalence rates in the U.S. may be as high as 1 in 68.52 A number of studies have examined the effects of early exposure to anesthesia on brain development and subsequent impairment in neurocognitive function; yet, little is known about the possible effects of anesthetic agents on social-behavioral functioning. The association between exposure to anesthesia either in uterus, during the first years of life, or later and development of Autistic Spectrum Disorder (ASD) or its severity was determined in a retrospective population based cohort study. Objectives Identify if children who had previous exposure to anesthesia either in uterus, first years of life during their developing brain years, or later, are at risk of developing ASD and its severe form of the disease. Methods Data was obtained from structured interviews administered to a sample of 515 parents/guardians distributed in two groups: ASD = 262 children diagnosed with this condition and Non-ASD: 253 children (siblings of ASD group) without diagnosis (p=0.8069) when comparing exposure to anesthesia in uterus to subsequent severe form of ASD. Of the 262 ASD patients, 99 had exposure to anesthetics before their diagnosis, while in Non-ASD population, 110 had exposure to anesthesia, demonstrating no statistically significant association between both groups (p=0.2091). Out of 99 ASD patients exposed to anesthesia prior to their diagnosis, 72 were exposed before age 2. When compared to the 110 Non-ASD patients exposed to anesthesia, 86 had exposure during this developing brain period, which indicates no statistically significant association (p=0.4207). In addition, most of the ASD children exposed to anesthesia during developing brain were diagnosed with mild degree of the disorder when compared to ASD children without any previous exposure to anesthesia (p=0.9700) during the same period. When the exposure occurred after age 2, ASD children developed mild form of the disorder as compared with ASD children without any previous exposure to anesthesia (p=0.1699) in that period. Conclusions Children under early exposure to anesthesia in uterus, first 2 years of life, or later are not more likely to develop neither ASD nor severe form of the disorder. Index words: Anesthesia, Autism Spectrum Disorder, Puerto Rico. (95% confidence interval) that freely decided to participate and agreed to a consent form. Variables studied include: demographics, diagnosis and severity of ASD, exposure to anesthesia, method of childbirth, and age of exposure. Children less than 2 years of age were considered into have developing brain period. Data was analyzed using Chi-square or Fisher exact test. Results In contrast to nonASD group, most of the children within ASD group were male, 76% (p=0.0001). With regards to methods of childbirth, 64% of the ASD population were vaginal delivery (VD; Non-anesthesia exposure group) and 36% cesarean delivery (CD) compared to non-autistic population with 71% VD and 29% CD, which demonstrates no statistical difference between both groups (p=0.1113). Out of the 36% of ASD population that underwent CD, 7% were performed using general anesthesia and 93% regional anesthesia, while the 29% of the CD of nonASD, 5% were performed using general anesthesia and 95% regional anesthesia. This reveals no statistical significance (p=0.7569) with the development of ASD and the type of anesthesia used when comparing ASD with non-ASD patients. In view of severity of autism, in VD, 56% of ASD population had mild form of the disorder, 34% moderate, and 10% severe; while CD had a 54% mild form of the disorder, 33% moderate, and 13% severe. This shows no statistical association PRMA BOLETIN | 29 INTRODUCTION Autism Spectrum Disorder (ASD) is a social developmental disorder that has multiple biologic causes. This behavioral syndrome is unique to each individual, with a variety of symptoms ranging from social withdrawal, communication deficits, and stereotypic and repetitive behavior.3,4 The rates of ASD have increased almost 5 times more; among boys (1 in 42) than girls (1 in 189) in the past few years.5,6,7,8,52 In Puerto Rico, 1 of every 62 babies born have high probability of developing autism, compared to 1 in every 68 babies born in the United States.9,10, 52 The pathophysiology of these disorders remains unclear, but both environmental and genetic factors have been implicated. Its onset usually occurs in the first 2 years of life, where brain overgrowth occurs.1,4 Abnormal brain growth in autism causes aberrant neuronal connections and dysfunction that may lead to the development of autistic behaviors.4,11 Furthermore, laboratory studies have demonstrated that anesthetic agents have serious neurotoxic effects on infant mice and other animals, as well as blocking N-methyl-D-aspartate (NMDA) receptors and/or hyperactivate γ-aminobutyric acid type A (GABA) receptor, thereby causing increased number of brain cells undergoing apoptosis.12,13,14 Because GABAand NMDA- mediated neuronal activities are vital to mammalian brain development, these anesthetic agents could potentially hinder normal brain growth.15 While in humans, the formation of new synapses, neurogenesis, and rapid brain growth continues for up to 2 to 3 years after birth,16 thus being the developing brain stage, in small rodents such as mice and rats the brain developmental stage of a 7-dayold postnatal mouse or rat has 30| PRMA BOLETIN been considered equivalent to a human neonate of approximately 32 to 36 weeks gestation.17,18 Yet, the relation between animal data to clinical anesthesia practice is still unclear.15 Though research studies have showed that exposure to anesthetic agents provide an increased risk to the development of learning disabilities,19 behavioral, and developmental disorders,20 others have demonstrated no causal relationship between anesthesia and subsequent cognitive impairment.21 In the last decade, studies have been focused on the development of behavioral disorders, anesthesia, and neurotoxicity during early childhood. Satomoto et.al has studied abnormal social behaviors and deficits in mice, demonstrating that exposure of neonatal mice to inhaled sevoflurane could cause social behaviors that resemble autism.12 The purpose of this study was to determine and identify if children who had previous exposure to anesthesia, either in uterus, during their first years of life, or afterwards, are at risk of developing ASD or its severe form in population based sibling cohort. It has been argued consistently that laboratory findings in 7-day-old rodents provide evidence for human receptiveness to anesthesia-induced neurotoxicity from the third trimester of pregnancy up to the second year of life.15,22,23 By comparing exposed with non-exposed siblings, along with ASD versus non-ASD siblings, important variables of environmental surroundings such as home, education, neighborhood, and parenting techniques were controlled.24 METHODS Study Design and Patient Selection: The University of Puerto Rico Medical Sciences Campus Institutional Review Board approved this research protocol. A Siblings Cohort Study of children born in Puerto Rico formed the basis of this study. Participants were recruited through the Alianza de Autismo y Desórdenes Relacionados de Puerto Rico, organization which keeps records of autistic patients participating in it. Data was obtained from structured interviews administered to parents or guardians of a sample of 515 children. This data was distributed into two groups: ASD = 262 children diagnosed with this condition and Non-ASD: 253 children (siblings of ASD group) without diagnosis (hazard ratio estimates corresponding 95% confidence intervals) that freely decided to participate and agreed to an informed consent form. Children less than 2 years of age were considered to have a developing brain. Statistical Analysis: The primary risk factor for determining the incidence of ASD was exposure to anesthesia in children during their uterus, developing brain years (before age 2), or after two years of age. Preliminary analyses were performed to compare demographics, pregnancy, delivery method, diagnosis and severity of ASD, age of exposure, and type of anesthesia. Data collected was analyzed using Chi-square or Fisher exact test for categorical variables. In all cases, two-tailed P values less than 0.05 were considered to be statistically significant. RESULTS In our cohort study, 51% had ASD patients and 49% were control. Of the ASD group 76% were male and 24% of the female. Of the control group 50% were males and 50% female. No statistical association was found regarding methods of childbirth, with 64% of the ASD population had vaginal delivery (VD) and 36% cesarean delivery (CD), compared to non-autistic population with 71% VD and 29% CD (p=0.1113). From the 36% of the ASD population that their method of childbirth was by CD, 7% were performed under general anesthesia and 93% regional anesthesia. From the 29% of the Non-ASD population in which their method of childbirth was CD, 5% were performed under general anesthesia and 95% regional anesthesia. This demonstrated no statistical significance (p=0.7569) with the development of ASD between regional or general anesthesia when comparing ASD with Non-ASD groups. Furthermore, out of the 262 ASD patients, 99 (38%) had exposure to anesthetics before their diagnosis, while in Non-ASD population, 110 (43%) had exposure to anesthesia, which showed no statistically significant association between both groups (p=0.2091). Out of 99 ASD patients exposed to anesthesia prior to their diagnosis, 72 (73%) were exposed before age 2 during their developing brain years. When compared to the 110 Non-ASD patients exposed to anesthesia, 86 (78%) had exposure during this developing brain period, which proved no statistically significant association (p=0.4207). In addition, most of the ASD children exposed to anesthesia before diagnosis were diagnosed with mild degree of the disease when compared to ASD children without any previous exposure to anesthesia (p=0.9700). When the exposure occurred before age 2, ASD children developed mild form of the disease as compared with ASD children without any previous exposure to anesthesia (p=0.1699). The ASD population was evaluated for their severity of the disease according to their method of birth. Its severity was subdivided in mild, moderate, and severe. 56% of VD had a mild form of the disease, while 34% and 10% Figure 1 Figure 2 Figure 3 PRMA BOLETIN | 31 Figure 4 respectively had moderate and severe forms. 54% of CD had a mild form, 33% moderate, and 13 % severe. There was no statistical association (p=0.8069) when comparing early exposure to anesthesia to severity of ASD. Most of the ASD children exposed to anesthesia before diagnosis had a mild form of the disease when compared to ASD children without any previous exposure to anesthesia (p=0.9700). When the exposure occurred before age 2, ASD children developed mild form of the disease as compared with ASD children without any previous exposure to anesthesia (p=0.1699). DISCUSSION Figure 5 Figure 6 32| PRMA BOLETIN In this retrospective population based cohort of siblings, prevalence of ASD was three times more frequently seen in males than in females, with an average age of diagnosis at 3.5 years. This correlates with the DSM-IV diagnostic criteria for ASD present before age 3 25, and with the Centers for Disease Control report of ASD population, which showed a prevalence estimate higher among boys than girls.52 As defined in previous research, learning disabilities (LD) are typically diagnosed when children reach an age when academic expectations are clear, and a significant gap appears between those expectations and the child’s performance.27 In addition, ASD is a condition diagnosed by clinical criteria, usually being discovered around 3 years of age,28 and a predominance on male children.5,6,7,8,25 Our sample size of 515 children, 262 diagnosed with ASD and 253 non-ASD siblings from cohort group, was consistent with those of other investigators as to gather enough data for statistical analysis and to draw significant conclusions. Moreover, our sample size gives power to our study because it Puerto Rico has a prevalence in ASD that reflects until 17 years of age 11.58 cases per 10,000 habitants,9,29 which provides a high probability of detecting as significant if exposure to anesthesia is an independent risk factor for subsequently developing ASD. Previous studies compared 408 patients with autism, characterized the group by maternal smoking during early pregnancy, a cesarean section delivery, and small size for gestational age, and low APGAR scores, with other matched siblings, and no comparison between them was made, not able to address the influence of genetics or maternal environment.30 These environmental factors cause oxidative stress in genetically vulnerable individuals, which leads to impaired methylation and neurological deficits secondary to reductions in the capacity for synchronizing neural networks.31 We limited our confounding factors and variables, that are important but difficult to measure (such as home, family, neighborhood environment, educational system, ecological surroundings, and parenting approach) because our ASD and non-ASD population are siblings.24,32 Another study that compares a similar sample size to ours involved 465 subjects that were included as cases, among which 314 had autism spectrum disorder. Siblings of the cases and random population were compared with the cases on obstetric information obtained in Maternal and Child Health Research Database of Western Australia. The autistic group had significantly older parents and more likely to be firstborn, mothers that had greater frequency of threatened abortion, labor inductions, as well as experienced fetal distress through delivery by elective or emergency cesarean section. Also, mothers with offspring that had ASD had higher frequencies of anesthesia use during labor, specifically an Figure 7 Figure 8 Figure 9 Figure 10 epidural caudal anesthesia,21 which made us question even further if anesthesia during labor, or even afterwards during the developing brain years, could indeed increase the risk of developing ASD. Our results confirmed that there was no association between this exposure during uterus and subsequently developing ASD or an increased risk of developing a more severe form. A similar analysis was made in a cohort study involving 497 live births via CD (under general anesthesia N=193, and regional anesthesia N=304), where children exposed to general or regional anesthesia during CD were not more likely to develop LD compared to children delivered vaginally.33 Unfortunately, our data was scarce in CD under general anesthesia for us to make any statistical significant remarks, and according to Palanisamy et al. there is a consistently low incidence of CD performed with general anesthesia.34 This is due mainly because experts and most obstetric anesthesiologists agree that regional anesthesia has many advantages over general anesthesia, including safety, avoiding potentially difficult maternal airway and risk of pulmonary aspiration, maternal blood loss, postoperative pain control, and the fact that complications from general anesthesia for CD are a leading cause of anesthesia-related mortality.34,35,36,37 According to Chien LN, they found a significant correlation between CD under general anesthesia and ASD,53 therefore more studies are needed to explore the role of CD under general anesthesia in the ASD incidence. On the other hand, epidural analgesia for labor was considered insignificant in this study because of the very PRMA BOLETIN | 33 limited data available. Most of the patients required anesthesia rather than analgesia. The effects of early exposure to anesthesia on brain development and neurocognitive function has been examined in DiMaggio’s et al. retrospective cohort study. There was a significant association between anesthesia and hernia repair surgery with young children developing behavioral and developmental disorders.20 But the authors emphasized the need for more rigorous clinical research for long-term effects of this exposure. Anesthetic agents commonly used may contribute to toxic loads, deplete vitamin B12 and folate system, and affect methylation because of their neurotoxic effects. Specifically, nitrous oxide deactivates methionine synthase, which is an enzyme that catalyzes the confersion of homocysteine and methyltetrahydrofolate to methionine and tetrahydrofolate. This deactivation in patients with defects on the methylenetetrahydrofolate reductase (MTHFR) gene could result in increased homocysteine levels, increased oxidative stress, and activated NMDA glutamate receptors.38,39,40 All of these could contribute to inflammation, in addition to hematologic problems, neuropathy, and neurotoxic effects that subsequently put patients vulnerable to ASD. Also, there is increasing evidence that a large number of ASD children have underlying mitochondrial myopathies, also known as respiratory chain disorders or disorders of energy production. ASD children are at risk in procedures requiring anesthesia, like other children who have confirmed of clinically diagnosed mitochondrial disease. Although the use of halothane and nitrous oxide is not as common as it used to be, Herbert MR hypothesized that using similar chemicals and toxins may play a role in triggering or exacerbating manifestations of ASD. In the Olmsted 34| PRMA BOLETIN County Study, halothane and nitrous oxide were used primarily. Halothane is a very fat-soluble drug that is difficult for the liver to metabolize. Administering a fat-soluble toxin, followed by inhibition of DNA methylation, may result in learning disabilities.41 Exposure to anesthesia in our population was subdivided during the developing brain before 2 years of age and after 2 years. Several studies describe how neonatal exposure to anesthetics that block N-methyl-D-aspartate receptors and/or hyperactive γ-aminobutyric acid type A (GABA) receptors cause neuronal degeneration in the developing brain.42,43,44,45 Satomoto et al. later investigated and concluded that exposure to inhaled sevoflurane caused not only deficits in social behavior, but also learning disabilities in neonatal mice that resembled ASD.12 There is scarce data regarding the effects of anesthetic agents on social-behavioral functioning due to insufficient evidence to state that there are associations between the development of ASD or severity of the condition in children and early exposure to anesthesia during CD.46 This data demonstrated that, according to DSM-IV ASD classification of mild, moderate that depended on symptoms and social impairment present in each patient, exposure to anesthesia in any stage of the patient was not statistically significant. Anesthesia did not increase the risk of a more severe form of the disease. This study has a number of limitations which oblige to caution when interpreting our results. With retrospective study designs, recall bias and confounding remains an issue that can only be solved in prospective randomized studies, yet prospective studies take too much time to complete, with a minimum of four years between inclusion of infants in the study and ability to diagnose behavioral abnormalities.47 It would have been useful to include in our study more information about neonatal past medical history, including prenatal care of mothers, umbilical cord pH, APGAR scores, type and duration surgeries done to patients, including duration of anesthesia, diet (breast feeding versus formulas), and developmental milestones occurrence which could facilitate a multifactorial analysis of whether any combination of these with anesthesia increases the risk of developing ASD or any form of the disorder. Examination of the associations of exposure to anesthesia during labor and delivery and children’s subsequent learning disabilities offers an important public health investigation towards understanding the impact of labor and delivery variables on children’s neurodevelopment outcomes.25 Furthermore, various assumptions can be made with regard to the development of the condition. First, obstetric complications may present a compromised environment, to which offspring are exposed, and moreover influenced by environmental stimuli or particular genotypes vulnerable to the disorder. Second, the composition and number of genes could be responsible for the condition, in which siblings may show different degrees of the traits characteristics of the disorder. And finally, anesthetic agents used during a child’s developing brain years have not been shown, according to this data, to increase the risk of subsequently developing ASD or any severe form of the disease. CONCLUSION Children under early exposure to anesthesia in uterus, first 2 years of life, or later are not more likely to develop neither ASD nor severe form of the disorder. REFERENCES 1. O’Brien G, Pearson J. Autism and learning disability. Autism 2004; 8:12540. 2. Shattuck PT, Durkin M, Maenner M, et al. Timing of identification among children with an autism spectrum disorder: findings from a population-based surveillance study. J Am Acad Child Adolesc Psychiatry 2009; 48:474-83. 3. Silver WG, Rapin I. Neurobiological Basis of Autism. Pediatr Clin N Am 59 (2012) 45-61. 4. Adams JB, Baral M, Geis E, Mitchell J, Hensley A, Zappia I, Newmark S, Gehn E, Rubin RA, Mitchell K, Bradstreet J, El-Dahr JM. The Severity of Autism Is Associated with Toxic Metal Body Burden and Red Blood Cell Glutathione Levels. Journal of Toxicology. Volume 2009, Article ID 532640, 7 pages. 5. Lai D, Tseng Y, Hou Y, Guo H. 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Changes in brain weights during the span of human life: relation of brain weights to body heights and body weights. Ann Neurol. 1978;4:345-56. 17. Dobbing J. The alter development of the brain and its vulnerability. In: Davis Ja, Dobbing J, eds. Scientific Foundations of Paediatrics London, UK: Heinemann Medical. 1991:744-59. 18. Hagberg H, Peebles D, Mallard C. Models of white matter injury: comparison of infectious, hypoxic-ischemic, and excitotoxic insults. Ment Retard Dev Disabil Res Rev. 2002;8:30-8. 19. Wilder RT, Flick RP, Sprung J, Katusic SK, Barbaresi WJ, Mickelon C, Gleich SJ, Schroeder DR, Weaver AL, Warner DO. Early Exposure to Anesthesia and Learning Disabilities in a Population-Based Birth Cohort. Anesthesiology. 2009 April; 110(4):796804. 20. DiMaggio C, Sun LS, Kakavouli A, Byrne MW, Li G. A retrospective cohort study of the association of anesthesia and hernia repair surgery with behavioral and developmental disorders in young children. J Neurosurg Anesthesiol. 2009 October; 21(4):286-291. 21. Bartels M, Althoff RR, Boomsma DI. Anesthesia and Cognitive Performance in Children: No evidence for a Causal Relationship. Twin Research and Human Genetics. 2009 Jun;12(3): 246-253. 22. Olney JW, Young C, Woxniak DF, Jevtovic-Todorovic V, Ikonomidou C. Do Pediatric drugs cause developing neurons to commit suicide? Trends Pharmacol Scie. 2004;25:1359. 23. Jevtovic-Todorovic V. General anesthetics and the developing brain: friends or foes? J Neurosurg Anesthesiol. 2005;17:204-6. 24. DiMaggio C, Sun LS, Li G. Early Childhood Exposure to Anesthesia and Risk of Developmental and Behavioral Disorder in a Sibling Birth Cohort. Anesthesia & Analgesia. 2011 Nov; 113(5): 1143-51. 25. American Psychiatric Association. Diagnostic and statistical manual of mental disorders. Washington, DC, 4th Ed., text rev., 2000. 26. CDC. Prevalence of Autism Spectrum Disorders—Autism and Developmental Disabilities Monitoring Network, 14 Sites, United States, 2008. MMWR 2012; 61 (SS03);1-19. 27. Radcliffe J, Bellinger DC. Learning Disability in Children as an Outcome in Anesthesia and Analgesia Research. Anesthesia and Analgesia Editorial. June 2011. Vol 112:Num 6. 1262-64. 28. Glasson EJ, Bower C, Petterson B, de Klerk N, Chaney G, Hallmayer JF. Perinatal Factors and the Development of Autism. Arch Gen Psychiatry. June 2004. Vol 61:618-27. 29. Department of Health of Puerto Rico. Departamento de Salud Anuncia Resultados de Primera Encuesta de Prevalencia de Autismo en Puerto Rico. Press Announcement: 11 mar 2012. 30. Hultman CM, Sparen P, Cnattangius S. Perinatal complications as predictors of infantile autism. Epidemiology. 2002;13:417-423. 31. Deth R, Muratore C, Benzecry J, Power-Charnitsky VA, Waly M. How environmental and genetic factors combine to cause autism: A redox/methylation hypothesis. Neurotoxicology. Jan. 2008;29(1):190201. 32. Susser E, Eide MG, Begg M. Invited commentary: the use of sibship studies to detect familial confounding. Am J Epidemiol. 2010;172:537-9. 33. Sprung J, Flick RP, Wilder RT, Katusic SK, Pike TL, Dingli M, Gleich SJ, Schroeder DR, Barbaresi WJ, Hanson AC, Warner DO. Anesthesia for Cesarean Delivery and Learning Disabilities in a Population-Based Birth Cohort. Anesthesiology. August 2009;111(2):302-310. 34. Palanisamy A, Mitani AA, Tsen LC. General anesthesia for cesarean delivery at a tertiary care hospital from 2000 to 2005: a retrospective analysis and 10-year update. Int J Obstet Anesth. 2001 Jan;20(1):10-6. 35. Hughes SC, Levinson G, Rosen MA. Anesthesia for cesarean section. In: Shnider and Levison’s Anesthesia for Obstetrics (4th ed.) Philadelphia: Lippincott Williams & Wilkins; 2002: 201-36. 36. Russell IF. Regional anesthesia for operative delivery. In: Reynolds F. Ed. Regional Anaesthesia in Obstetrics: a Millennium update. London: Springer; 2002: 25566. 37. Laudenbach V, Mercier FJ, Rozé JC, Larroque B, Ancel PY, Kaminsky M, Breart G, Diemunsch P, Subtil D, Lejus C, Fresson J, Arnaud C, Rachet B, Burguet A, Cambonie G, Epipage Study Group. Anaesthesia mode for caesarean section and mortality in very preterm infants: An epidemiologic study in the EPIPAGE cohort. Int J Obstet Anesth. 2009 Apr;18(2):142-9. 38. Selzer RR, Rosenblatt DS, Laxova R, Hogan K. Adverse effect of nitrous oxide in a child with 5,10-methylenetetrahydrofolate reductase deficiency. New England Journal of Medicine. July 2003;349:45-50 39. Kalikiri PC, Sachan Gajraj Singh Sachan R. Nitrous oxide induced elevation of plasma homocysteine and methylmalonic acid levels and their clinical implications. The Internet Journal of Anesthesiology. 2004;Vol. 8 (2). 40. Baum VC. When nitrous oxide is no laughing matter: Nitrous oxide and pediatric anesthesia. Paediatric Anaesthesia. Sept 2007;17(9):824-30. 41. Herbert MR. Autism: A brain disorder or a disorder that affects the brain? Clinical Neuropsychiatry. 2005;2(6):354-79. 42. Bayer SA, Altman J, Russo RJ, Zhang X. Timetables of neurogenesis in the human brain based on experimentally determined patterns in the rat. Neurotoxicology. 1993;14:83144. 43. Olney JW, Tenkova T, Dikranian K, Qin YQ, Labruyere J, Ikonomidou C. Ethanol-induced apoptotic neurodegeneratino in the developing C57BL/6 mouse brain. Brain Res Dev Brain Res. 2002;133:115-26. 44. Rice D, Barone S JR. Critical periods of vulnerability for the developing nervous system: Evidence from humans and animal models. PRMA BOLETIN | 35 Environ Health Perspect. 2000;108:51133. 45. Dobbing J, Sands J. Comparative aspects of the brain growth spurt. Early Hum Dev, 1979; 3:79-83. 46. Gardener H, Spiegelman D, Buka SL. Perinatal and Neonatal Risk Factors for Autism: A Comprehensive Meta-analysis. Pediatrics 2011:128;344-55. 47. Kalkman CJ, Peelen L, Moons KG, Veenhuizen M, Bruens M, Sinnema G, de Jong TP. Behavior and Development in Children and Age at the Time of First Anesthetic Exposure. Anesthesiology. 2009 Apr; 110(4):805-12. 48. Dodds L, Fell DB, Shea S, Armson BA, Allen AC, Bryson S. The Role of Prenatal, Obstetric and Neonatal Factors in the Development of Autism. J Autism Dev Disord. 2011 Jul;41(7):891-902. 49. Flick RP, Katusic SK, Colligan RC, Wilder RT, Voigt RG, Olson M D, Sprung J, Weaver AL , Schroeder DR, Warner DO. Cognitive and Behavioral Outcomes After Early Exposure to Anesthesia and Surgery. PEDIATRICS 2011 Nov; 128 (5): 1053-1061. 50. Chung W, Park S, Hong J,Park S, Lee S, Heo J, Kim D & Ko Y. Sevoflurane exposure during the neonatal period induces long-term memory impairment but not autism-like behaviors. Pediatric Anesthesia 2015 Jun; doi:10.1111/ pan.12694. 51. Ko WR, Huang JY, Chiang YC, Nfor ON, Ko PC, Jan SR, Lung CC, Chang HC, Lin LY, Liaw YP. Risk of autistic disorder after exposure to general anaesthesia and surgery: a nationwide, retrospective matched cohort study. Eur J Anaesthesiol. 2015 May; 32(5):303-10. 52. Bajo J. Prevalence of Autism Spectrum Disorder Among Children Aged 8 Years — Autism and Developmental Disabilities Monitoring Network, 11 Sites, United States, 2010. CDC. MMWR. 2014. March; 63(SS02); 1-21. 53. Chien LN, Lin HC, Shao YH, Chiou ST, Chiou HY. Risk of autism associated with general anesthesia during cesarean delivery: a population-based birth-cohort analysis. J Autism Dev Disord. 2015 Apr;45(4):932-42. Resumen Trasfondo El trastorno del espectro autista (TEA) es caracterizado por incapacidad en la interacción social, en la comunicación, y por comportamiento restrictivo y repetitivo, que empieza antes de los 3 años de edad. Investigaciones demuestran que la prevalencia de esta condición en los EEUU es de 1 en 68 niños. Varios estudios han examinado los efectos de la exposición temprana a anestésicos en el desarrollo del cerebro y el deterioro en la función neuro-cognoscitiva; aún poco se sabe respecto a los posibles efectos de los agentes anestésicos en la función y el comportamiento social. La asociación entre la exposición a anestesia ya sea en útero, durante los primeros años de vida o luego en la vida y el desarrollo del trastorno del espectro autista o la severidad fue determinada en un estudio poblacional retrospectivo de cohorte 36| PRMA BOLETIN Objetivos Identificar si los niños que estuvieron expuestos a anestesia ya sea en útero, en el primer año de vida, o más tarde en la vida, están a riesgo de desarrollar trastorno del espectro autista y la severidad del mismo. Métodos Los datos fueron recopilados en entrevistas estructuradas administradas a una muestra de 515 padres/ guardianes distribuidos en dos grupos: TEA= 262 niños diagnosticados con esta condición y los no-TEA= 253 niños (hermanos de los pertenecientes a TEA) sin diagnostico de TEA (95% de intervalo de confianza) que voluntariamente decidieron participar y consintieron. Las variables en estudio son: la demografía, el diagnóstico y severidad de TEA, exposición a anestesia, método de parto y la edad a la que fue expuesto a anestesia. Resultados Contrario al grupo no-TEA, la mayoría de los niños en el grupo TEA fueron masculinos, 76% (p=0.0001). Con respecto al método de parto, el 64% de la población de TEA fueron dados a luz por medio de parto vaginal y el 36% fueron por cesárea en comparación a la población no-TEA la cual obtuvo un 71% de parto vaginal y 29% por cesárea, lo cual demuestra que no hay significancia estadística entre ambos grupos (p=0.1113). Del 36% de la población de TEA, que nacieron a través de cesárea, 7% se realizaron con anestesia general y 93% con anestesia regional, mientras en los no-TEA el 29% se le realizó cesárea en el cual 5% se le realizó la cesárea bajo anestesia general y 95% con anestesia regional. Se puede extrapolar que el desarrollo de TEA y el tipo de anestesia utilizado, cuando se comparan los grupos TEA con los noTEA, no es estadísticamente significativo (p=0.7569). En cuanto a la severidad del TEA, en parto vaginal, 56% de la población TEA tuvo la forma leve del trastorno, 34% moderada y 10% severa; mientras que en las cesáreas, 54% tuvo la forma leve del trastorno, 33% moderada, y 13% la severa. Esto demuestra Resumen Trasfondo El trastorno del espectro autista (TEA) es caracterizado por incapacidad en la interacción social, en la comunicación, y por comportamiento restrictivo y repetitivo, que empieza antes de los 3 años de edad. Investigaciones demuestran que la prevalencia de esta condición en los EEUU es de 1 en 68 niños. Varios estudios han examinado los efectos de la exposición temprana a anestésicos en el desarrollo del cerebro y el deterioro en la función neuro-cognoscitiva; aún poco se sabe respecto a los posibles efectos de los agentes anestésicos en la función y el comportamiento social. La asociación entre la exposición a anestesia ya sea en útero, durante los primeros años de vida o luego en la vida y el desarrollo del trastorno del espectro autista o la severidad fue determinada en un estudio poblacional retrospectivo de cohorte. Objetivos Identificar si los niños que estuvieron expuestos a anestesia ya sea en útero, en el primer año de vida, o más tarde en la vida, están a riesgo de desarrollar trastorno del espectro autista y la severidad del mismo. Métodos Los datos fueron recopilados en entrevistas estructuradas administradas a una muestra de 515 padres/ guardianes distribuidos en dos grupos: TEA= 262 niños diagnosticados con esta condición y los no-TEA= 253 niños (hermanos de los pertenecientes a TEA) sin diagnostico de TEA (95% de intervalo de confianza) que voluntariamente decidieron participar y consintieron. Las variables en estudio son: la demografía, el diagnóstico y severidad de TEA, exposición a anestesia, método de parto y la edad a la que fue expuesto a anestesia. Resultados Contrario al grupo no-TEA, la mayoría de los niños en el grupo TEA fueron masculinos, 76% (p=0.0001). Con respecto al método de parto, el 64% de la población de TEA fueron dados a luz por medio de parto vaginal y el 36% fueron por cesárea en comparación a la población no-TEA la cual obtuvo un 71% de parto vaginal y 29% por cesárea, lo cual demuestra que no hay significancia estadística entre ambos grupos (p=0.1113). Del 36% de la población de TEA, que nacieron a través de cesárea, 7% se realizaron con anestesia general y 93% con anestesia regional, mientras en los no-TEA el 29% se le realizó cesárea en el cual 5% se le realizó la cesárea bajo anestesia general y 95% con anestesia regional. Se puede extrapolar que el desarrollo de TEA y el tipo de anestesia utilizado, cuando se comparan los grupos TEA con los no-TEA, no es estadísticamente significativo (p=0.7569). En cuanto a la severidad del TEA, en parto vaginal, 56% de la población TEA tuvo la forma leve del trastorno, 34% moderada y 10% severa; mientras que en las cesáreas, 54% tuvo la forma leve del trastorno, 33% moderada, y 13% la severa. Esto demuestra que cuando se compara la exposición a anestesia en útero con la forma severa de TEA no se encuentra una significancia estadística (p=0.8069). De los 262 pacientes de TEA, 99 fueron expuestos a anestesia antes de su diagnóstico mientras, en los no-TEA 110 fueron expuestos a anestesia, demostrando que no hay asociación estadísticamente significativa entre ambos grupos (p=0.2091). De los 99 pacientes con TEA expuestos a anestesia antes de su diagnóstico, 72 fueron expuestos antes de los 2 años de edad. Cuando se compara con los 110 no-TEA expuestos a anestesia, 86 tuvieron exposición durante el periodo de su desarrollo cerebral, lo cual indica que no hay relación estadísticamente significativa (p=0.4207). Además, la mayoría de los niños con TEA expuestos a anestesia durante el periodo de desarrollo cerebral fueron diagnosticados con un grado menor del desorden en comparación con los niños con TEA sin exposición previa a anestesia (p-0.9700) durante el mismo periodo. Cuando la exposición ocurrió después de los 2 años de edad, los niños con TEA desarrollaron una forma leve del trastorno en comparación con los niños sin exposición previa a anestesia (p=0.1699) en dicho periodo. Conclusión Niños expuestos a anestesia en útero, en los primeros 2 años de vida o luego en la vida no son más propensos a desarrollar TEA ni la forma más severa del trastorno. Ahora que ya es miembro Disfrute de las ventajas: Descuentos en jornadas de educación médica y convenciones. Eventos especiales y sociales. Descuento del 10% en DISABILITY INCOME INSURANCE de * Newsletter semanal con toda la información que necesita. Usted es representado por una institución sin filiación política que actúa frente al gobierno, el parlamento y otras agencias. Institución que es dirigida y supervisada por usted a través de su Cámara de Delegados. Representante exclusiva ante la AMA, lo que nos permite representarlo ante cualquier agencia federal. Usted es sponsor de BOLETIN, la primer revista medico-científica de Puerto Rico. * Por más información: 787-758-2244 Para asociarse a la AMPR visite nuestro website www.asocmedpr.org o llame al (787) 721-6969 PRMA BOLETIN | 37 Metastatic Ovarian Atypical Pneumonia Tumor Ivonne Robles Cartagena, MDa*; América Robles Cartagena, MDa; Glorilee Delgado Flores, MD, MPHb; Pedro Monroig Quiles, MD, FCCPa; Fernando Cabanillas, MD, FACPa; Luis Báez, MD, FACPa; Luis Acabá, MD, FACPa; Luis Santos Reyes, MD, FACOGa; Rafael Vicens, MDa Auxilio Mutuo Hospital, San Juan, PR. Family Medicine Department, University of Puerto Rico, Medical Sciences Campus, San Juan, PR. *Corresponding author: Ivonne Robles Cartagena, MD- Auxilio Mutuo Hospital, Medical Education Office, PO BOX 191227, San Juan, PR 00919-1227. Email: [email protected]. a b Introduction Krukenberg tumor is a malignancy in the ovary from a primary lesion in the gastrointestinal tract and a metastatic signet ring cell adenocarcinoma to the ovary. Krukenberg tumor is uncommon, accounting for 1% to 2% of all ovarian tumors. In 1896, Friedrich Krukenberg (1871–1946), a German gynecologist and pathologist, described what he presumed was a new type of primary ovarian neoplasm (1, 2). The true metastatic nature of this lesion was established 6 years later. Stomach is the primary site in most Krukenberg tumor cases (70%). Carcinomas of colon, appendix, and breast (mainly invasive lobular carcinoma) are the next most common primary sites. Rare cases of Krukenberg tumor originating from carcinomas of the gallbladder, biliary tract, pancreas, small intestine, ampulla of Vater, cervix, and urinary bladder/ urachus have been reported (2, 4).The interval between the diagnosis of a primary carcinoma and the subsequent discovery of ovarian involvement is usually 6 months or less, but longer periods have been reported (3, 5). Case Description A 47 year old G3P3A0 female patient without any history of systemic illnesses who presented to her pneumologist’s private office with the complaint of dry cough, shortness of breath and fatigue during the day and some nights, causing night time awakenings, 3 weeks ago. Her symptoms limited her daily activities. On physical exam, upon chest auscultation bilateral decreased breathing sounds were heard with hyperresonance to percussion and a long expiratory phase. 38| PRMA BOLETIN Masquerading as Abstract Krukenberg tumor is a malignancy in the ovary from a primary lesion in the gastrointestinal tract and a metastatic signet ring cell adenocarcinoma to the ovary. Stomach is the most common primary site, but other organs can serve as a primary site. The lymphatic system is the most likely route for metastasis. CA 125 levels can be used for screening for early detection of ovarian metastasis as well as for monitoring the course of disease. The prognosis of Krukenberg tumor is poor and no curative treatment is currently available. Upon further examination, a chest X-ray was ordered which showed bilateral pleural effusions (see Figure A). She was sent to the ER by her pneumologist. There a Chest CT scan was performed and it was found that the patient had bilateral pleural effusions with an incidental finding of diffuse wall thickening of the stomach. This finding was worrisome for an underlying neoplasm or infectious process. Also left retropectoral and mediastinal AP window lymphadenopathy was noted. These findings were worrisome for metastatic lymphadenopathy from either the left breast, or from the stomach, given its worrisome appearance (see Figure B). A CT scan of the abdomen and pelvis was suggested by the radiologist. CT scan of the abdomen and pelvis was performed and showed a right lower quadrant 6.8 x 6.5 x 10.3 cm solid and cystic mass favored to the ovarian. In light of gastric wall thickening, this was suspicious for Krukenberg tumor arising from the stomach. Diffuse retroperitoneal, periaortic and mesenteric root adenopathy with associated haziness of the fat was also seen as well as perihepatic, perisplenic and bilateral paracolic gutter ascites. Bilateral pleural effusions with compressive atelectasis. Multiple bilateral parapelvic cysts were suspected (see Figures C, D, E and F). A PET SCAN was suggested by Oncologist. PET SCAN was performed and showed a mass in the right pelvis is FDG-avid (see Figure H). Figure A. Bilateral pleural effusions, right greater than left. Figure D. Abnormal circumferential wall thickening of the stomach and loss of the usual gastric fold pattern. Figure B. Bilateral effusions. Wall thickening of the stomach is noted. Figure C. Abnormal circumferential wall thickening of the stomach and loss of the usual gastric fold pattern Figure E. An irregular, heterogeneous mass in the right lower pelvis with mixed density PRMA BOLETIN | 39 Figure F. An irregular, heterogeneous mass in the right lower pelvis with mixed density. Figure H. Mass in the right pelvis is FDG-avid. Figure G. Computed tomographic image during CT guided percutaneous biopsy. After the findings obtained on the abdomen and pelvis CT scan, a CT guided biopsy of the pelvic mass with immunohistochemicals stains was performed (see Figure G). The surgical pathology report described that the tumor cells were positive for CK 7 and CK 20, and a diagnosis of adenocarcinoma with focal signet ring cell features was shown in the pelvic core biopsy. A thoracentesis was also performed for the 40| PRMA BOLETIN worsening of the pleural effusion which showed multiple clusters of cohesive epithelial cells with smooth borders, intracytoplasmic vacuolization and irregular hyperchromatic nuclear membranes, in a background of reactive mesothelial cells and blood positive for malignancy, consistent with carcinoma. Transvaginal sonogram was performed and showed right adnexal mass. Several laboratories were ordered and showed a very high level of CA 19-9 (7602 U/mL), CA-125 (7602 U/mL) and Alpha Feto Protein (12.28 ng/ mL). With all of these radiological and pathological findings a diagnosis of Krukenberg tumor is suggested. Discussion Krukenberg tumor is a malignancy in the ovary from a primary lesion in the gastrointestinal trac is found after metastasis to the ovaries and even worse if the primary tumor remains undetected References (1)Young R: From krukenberg to today: the ever present problems posed by metastatic tumors in the ovary: part I. Historical perspective, general principles, mucinous tumors including the krukenberg tumor. Adv Anat Pathol 2006, 13:205–227. (2)Duarte I, Llanos O. Patterns of metastases in intestinal and diffuse types of carcinoma of the stomach. Hum Pathol. 1981;12:237–242. (3)Yakusshiji M, Tazaki T, Nishimura H, Kato T. Krukenberg tumors of the ovary: a clinicopathological analysis of 112 cases. Acta Obstet Gynaecol Jpn. 1987;39: 479–485. (4)Willis RA. The Spread of Tumours in the Human Body. 3rd ed. London, England: Butterworths; 1973:222–226. (5)Wong PC, Ferenczy A, Fan L-D, McCaughey E. Krukenberg tumors of the ovary: ultrastructural, histochemical, and immunohistochemical studies of 15 cases. Cancer. 1986;57:751–760. Resumen El tumor de Krukenberg es una malignidad en el ovario que proviene de una lesión primaria en el tracto gastrointestinal o de otros órganos. El tumor de Krukenberg es un adenocarcinoma metastatico hacia ovario compuesto de “signet ring cells”. El sistema linfático es la ruta más común para que este tipo de tumor haga una metástasis. Los niveles del marcador CA-125 pueden ser utilizados para hacer una detección temprana del tumor de Krukenberg o para hacer un monitoreo del curso de la enfermedad. La prognosis del tumor de Krukenberg es pobre y no se ha establecido un tratamiento para esta enfermedad. Year 107 Nbr. 03 - 2 0 1 5 t and a metastatic signet ring cell adenocarcinoma to the ovary. Is very uncommon and accounts for 1% to 2% of all ovarian tumors. The stomach is the primary site of involvement for the majority of these tumors. Patients with Krukenberg tumor tend to be young, with an average age of 45 years old. Patient usually present with symptoms related to ovarian involvement such as abdominal pain and distention. The remainders of patients are asymptomatic. Ascites is usually present in 50% of the cases. It is well recognized that adenocarcinomas composed of signet ring cells of various organs tend to metastasize to the ovaries much more commonly than adenocarcinomas of other histologic types from the same sites. The rate of metastasis of gastric carcinoma to the ovaries has been a mystery for a long time, but it is now evident that retrograde lymphatic spread is the most likely route of metastasis as there are several evidences supporting this concept. Immunohistochemical evaluation may aid in distinguishing primary ovarian carcinomas from metastatic carcinomas. Whereas a CK 7 +/ CK 20+ immunophenotype (CK 20 positivity, in particular) favors a metastatic gastrointestinal carcinoma. CT SCAN usually reveals bilateral, solid ovarian masses but cystic masses can also occur. The interval between the diagnosis of a primary carcinoma and the subsequent discovery of ovarian involvement is usually 6 months or less, but longer periods have been reported. There is no established treatment for Krukenberg tumors. A national registry and prospective studies are needed to set a therapeutic approach for Krukenberg tumors in the hope of improving the survival rate. The prognosis of a Krukenberg tumor is poor with a median survival rate of 14 months since such metastasis signifies rapid cell growth and proliferation. The prognosis is poor if the primary tumor. B LETíN MÉDICO-CIENTÍFICO PUBLICACIÓN OFICIAL DE LA ASOCIACIÓN MÉDICA DE PUERTO RICO En temas de salud, mantenerse al día es una necesidad ineludible. DESCARGALO GRATUITAMENTE EN ASOCMEDPR.ORG Catalogado en Cumulative Index e Index Medicus Listed in Cumulative Index and Index Medicus No. ISSN-0004-4849. Registrado en Latindex Sistema Regional de Información en Línea para Revistas Científicas de América Latina, el Caribe, España y Portugal. PRMA BOLETIN | 41 Diagnostic Studies for the Evaluation of Peripheral Artery Disease Hector Banchs Viña, MD, Hector Claudio, MD, Marcel Mesa, MD, Angel López-Candales, MD University of Puerto Rico School of Medicine, Department of Medicine, Cardiology Section Cardiovascular Diseases Training Program Introduction In recent years the concept of atherosclerosis has evolved dramatically. First, the traditional clinical focus mainly limited to involvement of the coronary arteries has now expanded to embrace other arterial beds such as cerebrovascular and peripheral territories. 1-3 Second, the pathobiology of the atherosclerotic process has been replaced from an inevitable and relentless degenerative behavior to a more dynamic process involving numerous structural as well as metabolic components. 1-3 Third, the overall atherosclerotic burden not only has expanded well beyond our previous notion of traditional risks factors; but also is important to recognize that early manifestations of disease involvement may be recognized if appropriate diagnostic testing is used. 1-3 Consequently, the purpose of this review not only is to familiarize the reader with available non-invasive testing modalities routinely used for diagnosis of lower extremity atherosclerosis; but also to determine hemodynamic significance. In the following section we should describe in detail techniques such as physiologic testing, Duplex ultrasonography, CT and magnetic resonance imaging. Limb Pressure Measurements and Pulse Volume Recordings Peripheral arterial disease (PAD) is an important manifestation of atherosclerosis, with an estimated age-adjusted prevalence of approximately 13% in people older than 50 years. 4 Noninvasive vascular physiologic studies are indispensable tools in the initial evaluation and workup and post intervention follow-up.4 In this review, we describe a practical approach to the technique, interpretation, pitfalls, and limitations of these physiologic studies. We also provide an algorithmic approach for using these studies in the initial workup of patients 42| PRMA BOLETIN Abstract Atherosclerosis is a systemic disease that may affect multiple vascular territories including the coronary, cerebral and peripheral circulation. Peripheral arterial disease (PAD) is a common manifestation of atherosclerosis and has an important impact on quality of life as well as morbidity in affected individuals. The diagnosis of PAD can be challenging and the clinician must know the different methods available and the limitations of each of them. In this article we review noninvasive methods used in the diagnosis of PAD in detail as well as the indications for conventional invasive angiography. Index Words: Peripheral Artery Disease, Vascular Duplex Ultrasound, Pulse Volumetric Recording, Limb Pressure with suspected PAD. Limb segmental systolic blood pressure measurements and pulse volume recordings are used to confirm a clinical diagnosis of peripheral arterial disease (PAD) and further define the level and extent of the obstruction. In its simplest terms segmental limb pressures are compared with the highest arm pressure. The ankle pressures are used to calculate the ankle-brachial index (ABI) for each extremity. This is specifically accomplished by dividing each of the ankle pressures by the higher of the brachial artery pressures. 5 Based on this principle, a normal ABI is between 1.0 and 1.3 while ABI ≤ 0.97 is diagnostic of PAD with 99% specificity and 94% sensitivity. 6, 7 Despite this data, a cutoff ABI value of ≤ 0.90 have been conventionally used to diagnose PAD in the general population. Furthermore, a 20≥ mmHg reduction in pressures from arterial segment to the next is considered significant and indicates stenosis between the measured levels. It is important to be reminded that in healthy subjects, thigh pressures typically exceed the brachial artery pressure by approximately 30 mmHg. Therefore, when thigh pressures are low compared with arm pressure, the site of the stenosis is either the aorta or the ipsilateral iliac artery. On the other side of the spectrum, when ABI values are 1.3 or higher, this represents sever vascular calcification. In these cases, not only interpretation of the ABI measurement is unreliable; but also these values are associated with worse clinical outcomes. 8 Furthermore, in the presence of vascular calcification the toe brachial index (TBI) should be instead used. In this case, the pulse waveform is obtained from the great toe using photoplethysmography. 9 A normal TBI is 0.60 ± 0.17. 9 accordingly to the severity of the stenosis. 10 As the severity increases both this slope and amplitude are significantly decreased until a severe stenosis on PVR configuration resembles that of a tardus parvus waveform arterial signal. 10 Pulse waveforms can also be obtained using photoplethysmography in which signals are recorded using infrared light that measures the quantity of red blood cells in the cutaneous circulation rather than volume changes. Transcutaneous Oxymetry Since color absorbance bePulse Volumetric Record- tween oxygenated and deoxing Interpretation ygenated hemoglobin varies significantly; measurement of The same cuffs used to mea- color absorbance has been sure segmental pressures may invaluable to differentiate oxbe attached to a plethysmograph ygenated from deoxygenated and used to measure changes in blood. Specifically, oxygenated pulse volumes in each limb. Anal- blood absorbs more infrared ysis of a pulse volume waveform light. Therefore, the principle of allows assessment of arterial oxymetry simply relies on using flow. Since this test does not rely both an emitter and a receiver. on cuff occlusion, it is particularly It emits both red and infrared useful when assessing calcified lights. A photodetector, which is arteries. For the purpose of this routinely used in a finger or eartest, cuffs are inflated to a pre- lobe, then determines the ratio determined reference pressure of red to infrared light received (65 mmHg) level. The change in order to derive blood oxygenin volume in the limb segment ation. causes a corresponding change in pressure in the cuff throughout For transcutaneous oxymethe cardiac cycle. Interpretation try, one probe is placed on the of pulse volumetric recordings chest as a control to ensure that (PVR) requires calibration of the the oxygen tension is from 50 to amount of air in the cuff. 75 mmHg while a second probe is placed on the limb in the area PVR waveforms are recorded for of interest. 11 Measurements each limb segment and analysis are then obtained which is seis specifically based on evaluation quentially positioned from proxof the overall waveform shape, imal to distal segments of the signal and amplitude.10 A normal limb. A normal distal transcutaPVR waveform resembles the neous oxymetry reading should arterial contour configuration of approximate that of the chest. an arterial pressure signal that is 11-13 This particular technique composed of a sharp systolic up- is most often used to determine stroke followed by a downstroke the level of amputation. A value that contains a prominent notch. > 20 mmHg can predict healing In the case of a hemodynamical- at the site with 80% accuracy. ly significant stenosis, both the 12, 13. amplitude and slope are reduced Exercise Testing for Peripheral Arterial Disease Exercise is a well-known adjunctive physiologic test modality used in the assessment of patients suspected of having PAD. Not only it is useful in assessing functional capacity and distance patients with claudication are able to walk; bust also it is extremely useful in helping physicians clarify if leg symptoms are related to PAD. This is particularly relevant for patients with symptoms that are atypical for claudication as well as for those who have history of intermittent claudication, yet have a normal resting ABI’s value. With regards to relative contraindications to perform this test include rest lower extremity pain, disabling shortness of breath with exertion and unstable angina. Obviously, this test cannot perform in patients unable to walk on a treadmill. On a fasting patient, the constant load of the treadmill is performed at a speed of 2 miles per hour and an incline of 12%. Graded exercise protocols increase the grade and/or speed in 2 to 3 minute stages. The Gardner protocol is the most commonly used graded protocol to evaluate walking capacity. 14 It usually begins at 2 mph and an incline of 0% and the grade increases by 2% every 2 minutes. For evaluating PAD patients, the Bruce protocol is not employed because of the rapid rate of speed and incline limits the assessment of exercise capacity in claudication. Treadmill exercise for PAD assessment is terminated due to leg claudication, chest pain or is limited by other symptoms such as shortness of breath or fatigue. At this point, the patient lies down immediately and ankle pressures are obtained starting with the symptomatic leg, followed by the highest brachial pressure. Pressure measurements are repeated every 1 to 2 minutes until they PRMA BOLETIN | 43 return to baseline. Data record ed from this type of physiologic testing should include: • Length of time the patient was able to walk • Nature and location of patient’s symptoms • Reason for test discontinuation • Ankle pressures • Time required for the pressures to return to baseline With this information PAD is confirmed with a decrease in ABI of more than 20% immediately following exercise. Furthermore, the time before ankle pressure returns to normal is increased in more severe PAD cases, for example from 1 minute in mild PAD cases to 10 minutes in more severe disease involvement. Duplex Ultrasonography Even though description of the physical principles of ultrasonography are well beyond the scope of this article; it should suffice to state that this imaging modality not only allows for plaque characterization based on gray scale (B Mode) imaging, but also blood flow detection and hemodynamic estimation of stenosis based on Duplex determination of flow velocity. 15-17 Lower extremity ultrasound not only is accurate for diagnosis PAD when compared to angiography to detect significant stenosis in patients with symptomatic aorto-iliac and femoro-popliteal disease; 18 but also is routinely and a readily available portable imaging modality useful in: 19 • PAD diagnosis in the setting of claudication, limb pain, or ulcers • Routine follow up of patients who have undergone lower extremity revascularization • Planning therapy for known PAD • It allows localization and severity assessment of limb arterial stenosis 44| PRMA BOLETIN • Studies can be tailored to individual requirements and can be limited to a given arterial segment or extended to evaluate both lower extremities • Color Doppler is used initially to detect normal (laminar flow) or abnormal flow (turbulence and aliasing) states throughout the arterial segments or bypass grafts • Once an abnormal color flow state is identified, pulse Doppler is used to characterize degree of stenosis based on peak systolic velocities (PSV) and overall waveform analysis o Spectral broadening as the degree of stenosis worsens o A monophasic waveform pattern that loses its normal diastolic reverse flow component with severe stenosis o An arterial occlusion is suggested when there is: u Absence of flow in the arterial segment u In the absence of collateral vessels, high resistance waveforms signals are also identified u Tardus et parvus waveform • Peripheral arterial stenosis is categorized by pulsed wave Doppler examination as percentage reduction of luminal diameter that is mild (0 to 19%), moderate (20 to 40%), or severe (50% and greater). 19 Similarly, ultrasound is also very useful for overall surveillance and detection of disease recurrence in patients following endovascular interventions. 20 Duplex ultrasound is performed following interventions prior to discharge, 1, 3 and 6 months post intervention, then yearly. In these particular cases, color Doppler and pulsed-Doppler evaluations are focused proximal to the site of intervention, at the site of the intervention, and distal to it with special attention of the following: • Waveform analysis is used in a way similar to that used in native vessels; hence, alterations from a triphasic to monophasic signal on serial examinations suggests a developing stenosis 21 • Doubling of the PSV is consistent with hemodynamically significant stenosis 22, 23 radiation. Renal function must be evaluated prior to CTA since it may deteriorate with the administration of contrast material. Magnetic Resonance Imaging Contrast angiography remains the gold standard for vascular imaging and can aid in the evaluation of the arterial anatomy before a revascularization procedure. In some circumstances, as in acute ischemia, it is the primary imaging modality because it offers the benefit of intervention after the diagnostic images are obtained. Conventional angiography is also useful when the diagnosis is not clear and cannot be accurately made using noninvasive studies. Depending on the vessel to be imaged a femoral, axillary, brachial or radial arterial access may be used. Most invasive laboratories use digital subtraction techniques after contrast administration to enhance image quality and resolution. Contrast angiography is an invasive procedure that exposes the patient to ionizing radiation and other complications associated to the use of contrast material and arterial access. Thus it is important to thoroughly discuss with patients the potential risks of conventional angiography prior to the procedure. Magnetic resonance angiography (MRA) with three-dimensional image reconstruction is a powerful tool for the assessment of the aorta and peripheral arteries. The resolution of gadolinium enhanced MRA approaches that of conventional angiography. MRA is usually only performed if revascularization is being considered as the images permit precise planning for peripheral interventions. It is also useful in patients at risk of allergic, renal or other complications that may occur during conventional angiography. In patients with significant renal insufficiency the use of gadolinium is contraindicated due to the risk of developing nephrogenic systemic sclerosis. Computed Tomography Computed tomographic angiography (CTA) uses intravenous contrast to opacify and visualize the aorta and peripheral arteries. The development of multidetector CT scanners allows for cross sectional images with excellent spatial resolution, in shorter period of time while utilizing a reduced amount of contrast material. Three-dimensional reconstruction can further aid in identifying stenosed segments in the peripheral vasculature. The sensitivity and specificity of CTA in identifying significant stenosis is comparable to that of conventional angiography. When compared to MRA, CTA has the advantage in that it can be used in patients with metal medical hardware (stents, pacemakers, prosthesis, metal clips), but has the disadvantage of requiring contrast material and ionizing Contrast Angiography REFERENCES 1. Tellides G, Pober JS. Inflammatory and Immune Responses in the Arterial Media. Circ Res. 2015 Jan 16;116(2):312-322. 2. Pescetelli I, Zimarino M, Ghirarduzzi A, De Caterina R. Localizing factors in atherosclerosis. J Cardiovasc Med (Hagerstown). 2015 Jan 7. 3. Rafieian-Kopaei M, Setorki M, Doudi M, Baradaran A, Nasri H. Atherosclerosis: process, indicators, risk factors and new hopes. Int J Prev Med. 2014 Aug;5(8):927-46. 4. McCann TE, Scoutt LM, Gunabushanam G. A practical approach to interpreting lower extremity noninvasive physiologic studies. Radiol Clin North Am. 2014 Nov;52(6):1343-57 5. Pascarelli EF, Bertrand CA. Comparison of blood pressures in the arms and legs. N Engl J Med 1964; 270: 693. 6. Ouriel K, Zarins CK. Doppler ankle pressure: an evaluation of three methods of expression. Arch Surg. 1982 Oct;117(10):1297-1300. 7. Carter SA. Clinical measurement of systolic pressures in limbs with arterial occlusive disease. JAMA. 1969 Mar 10;207(10):1869-74. 8. Khaleghi M, Kullo IJ. Aortic augmentation index is associated with the ankle-brachial index: a community-based study. Atherosclerosis. 2007 Dec;195(2):248-53 9. Zierler RE. Doppler techniques for lower extremity arterial diagnosis. Herz. 1989 Apr;14(2):126-33. 10. Stein R, Hriljac I, Halperin JL, Gustavson SM, Teodorescu V, Olin JW. Limitation of the resting ankle-brachial index in symptomatic patients with peripheral arterial disease. Vasc Med. 2006 Feb;11(1):29-33. 11. Dowd GS. Predicting stump healing following amputation for peripheral vascular disease using the transcutaneous oxygen monitor. Ann R Coll Surg Engl. 1987 Jan;69(1):31-5. 12. Wutchert R, Bounameaux H. Determination of amputation level in ischemic limbs. Reappraisal of the measurement of TcPo2. Diabetes Care 1997; 20:1315-1318. 13. Poredos P, Rakovec S, Guzic-Salobir B. Determination of amputation level in ischaemic limbs using tcPO2 measurement. Vasa. 2005 May;34(2):108-12. 14. Gardner AW, Skinner JS, Cantwell BW, Smith LK. Progressive vs single-stage treadmill tests for evaluation of claudication. Med Sci Sports Exerc. 1991 Apr;23(4):402-8. 15. Lunt MJ. Review of duplex and colour Doppler imaging of lower-limb arteries and veins. J Tissue Viability. 1999 Apr;9(2):45-55. 16. Trusen A, Beissert M, Hahn D. Color Doppler US findings in the diagnosis of arterial occlusive disease of the lower limb. Acta Radiol. 2003 Jul;44(4):411-8. Review. 17. Androulakis AE, Giannoukas AD, Labropoulos N, Katsamouris A, Nicolaides AN. The impact of duplex scanning on vascular practice. Int Angiol. 1996 Dec;15(4):283-90. Review. 18. Leng GC, Whyman MR, Donnan PT, Ruckley CV, Gillespie I, Fowkes FG, Allan PL. Accuracy and reproducibility of duplex ultrasonography in grading femoropopliteal stenoses. J Vasc Surg. 1993 Mar;17(3):510-7. 19. Jager KA, Phillips DJ, Martin RL, Hanson C, Roederer GO, Langlois YE, Ricketts HJ, Strandness DE Jr. Non-invasive mapping of lower limb arterial lesions. Ultrasound Med Biol. 1985; 11: 515-521. 20. Kinney EV, Bandyk DF, Mewissen MW, Lanza D, Bergamini TM, Lipchik EO, Seabrook GR, Towne JB. Monitoring functional patency of percutaneous transluminal angioplasty. Arch Surg. 1991 Jun;126(6):743-7. 21. Ahn SS, Rutherford RB, Becker GJ, Comerota AJ, Johnston KW, McClean GK, Seeger JM, String ST, White RA, Whittemore AD, et al. Reporting standards for lower extremity arterial endovascular procedures. Society for Vascular Surgery/International Society for Cardiovascular Surgery. J Vasc Surg. 1993 Jun;17(6):1103-7. 22. Polak JF, Donaldson MC, Dobkin GR, Mannick JA, O’Leary DH. Early detection of saphenous vein arterial bypass graft stenosis by color-assisted duplex sonography: a prospective study. AJR Am J Roentgenol. 1990 Apr;154(4):857-61. 23. Polak JF, Karmel MI, Mannick JA, O’Leary DH, Donaldson MC, Whittemore AD. Determination of the extent of lower-extremity peripheral arterial disease with color-assisted duplex sonography: comparison with angiography. AJR Am J Roentgenol. 1990 Nov;155(5):1085-9. Abstracto La aterosclerosis es una enfermedad sistémica que puede afectar múltiples territorios vasculares incluyendo la circulación coronaria, cerebral y periferica. La enfermedad arterial periferica es una manifestación común de la aterosclerosis y afecta tanto la calidad de vida como la morbilidad y mortalidad de los pacientes afectados. El diagnóstico de la enfermedad arterial periferica es muchas veces retante y los médicos deben conocer las herramientas disponibles y las limitaciones de estas al momento de ordenar las diferentes pruebas diagnósticas. En este artículo repasamos los métodos no-invasivos utilizados para el diagnóstico de esta condición y las indicaciones para angiografía convencional. PRMA BOLETIN | 45 Para la Asociación Médica SU OPINIÓN es muy valiosa, responda a nuestras encuestas Primer Sondeo de Opinión de la Asociación Médica De Puerto Rico a través de MiOpiniónPR.com Endovascular Intervention in the Treatment of Peripheral Artery Disease Perfil clase médica puertorriqueña consultada Demograficos: Media 48 años, 60% masculino 40% femenino. Geográficos: 50% metropolitanas 50% no-metropolitanas Especialidades: 20 Ambitos de ejercicio de la profesión: 25% sector público 75% privado Hospitales de los encuestados: 27 33% de los encuestrados de la AMPR, 80% suscriptos a alguna revista profesional médica. 90% acepta planes médicos, entre ellos el 60% acepta Reforma. Resumen de resultados u La evaluación en torno a los planes médicos y sus servicios es significativamente homogénea entre un grupo con perfiles diversos. w 98% opinan que los planes médicos en la Isla pagan muy poco por el servicio médico. w 80% piensan que el pago de los planes médicos tarda demasiado. w Al 81% le molesta que los planes médicos objeten sus diagnósticos u objeten su peritaje. w 76% señalan que los planes médicos tardan demasiado en aprobar los servicios prescritos a sus pacientes. u Entre las variada gama de sugerencias vertidas por quienes participaron en el estudio para atender sus objeciones a los servicios y procedimientos de los planes médicos en PR, se destaca: w Un reclamo por más respeto al diagnóstico médico. w La necesidad de que se valore más la carrera de medicina y el peritaje al determinar la paga por servicio…que se pueda ser más justo en el pago y con más premura. w La necesidad de reducir la burocracia de los planes médicos. u En cuanto a la Reforma de Salud, las opiniones mayoritarias plantean que: w La posibilidad de que se sustituya el sistema actual por un sistema de universal de salud en el que se negocien las tarifas por servicio y el acceso a la salud sea más fácil y de mejor calidad. w Limita demasiado la intervención del especialista por su protocolo de referidos desde el generalista (66%). w Que los planes médicos no tengan fines de lucro y que su personal conozca más sobre la prestación de servicios médicos. w Califican para el servicio a mucha gente que califica o ya recibe plan privado de salud, cosa que sobre carga el sistema y lo drena fiscalmente (63%). w Que la clase médica esté mejor representada ante los planes médicos y ASES. w Opera en menoscabo de la salud de los pacientes porque (54%): w Los servicios de salud y medicinas que se ofrecen son limitados. w La aprobación de pruebas diagnósticas es muy lenta. 46| PRMA BOLETIN La mayoría de las opiniones vertidas en cuanto a cómo mejorar los servicios públicos de salud o de mejorar la Reforma coinciden en la necesidad de re-estructurarla por completo con una participación activa y efectiva de la clase médica y sus representantes, las escuelas de medicina y salud pública y los demás sectores vinculados (y conocedores) a los servicios de salud en Puerto Rico. En eso proceso, según la clase médica, los planes médicos no pueden tener el rol protagónico que los gobiernos le han concedido hasta el presente. Ver más en http://encuestas.miopinionpr.com/s3/ Asociacion-de-Medicos Abstract Endovascular therapy has emerged as an essential part of the management we can offer patients suffering from peripheral arterial disease. The AHA/ACCF guidelines deemed ballon angioplasty as a reasonable alternative for patients with limb threatening lower extremity ischemia who are not candidates for an autologus venous graft. Endovascular treatment is most useful for the treatment of critical limb ischemia and should ensure adequate proximal flow before engaging in interventions of distal disease.To increase procedure success rate, a thorough diagnostic evaluation is fundamental. This evaluation must take into account amount of calcium, no flow occlusion, length of occlusion, and presence of collaterals. There are different tools and procedure techniques available. Among these are the medicated ballon angioplasty and atherectomy by laser or high-speed drill, among others. Further studies may consolidate endovascular intervention as a safe and effective management for patients with lower extremity arterial disease and possibly cause a change in the actual practice guidelines. Index Words: Peripheral Artery Disease, claudication, endovascular therapy, percutaneous intervention Marian Couto, MD; Alejandro Figueróa, MD; Antonio Sotolongo, MD; MD; Reynerio Pérez, MD; José Martinez Ojeda, MD University of Puerto Rico School of Medicine, Department of Medicine, Cardiology Section Cardiovascular Diseases Training Program Introduction Percutaneous interventions provide symptomatic relief to patients with lower extremity peripheral arterial disease. These can be offered to patients whose claudication limits their ability to work or to perform other important activities. In addition, they can also be performed in patients who fail, or are predicted to fail to respond to exercise and pharmacologic therapy. The long-term success of these interventions depends upon the site and length of the lesion. Multifocal, long, calcific and eccentric stenosis/occlusions are best treated surgically. Atherosclerotic disease patterns in the lower extremities are classified by Trans Atlantic Inter-Society Consensus (TASC II) according to anatomy distribution and number and nature of lesions (stenosis, occlusion). Endovascular therapy has been proven to be an effective and safe management in a wide population of patients. Aortoiliac Interventions The infrarenal abdominal aorta and iliac arteries are one of the most common sites of chronic atherosclerosis, accounting for about one third of all symptomatic peripheral artery disease patients. In the past, this arterial segment was treated primarily surgically, but over the past decade, due to advances in technology and technique, the endovascular approach has become the treatment of choice for many of these patients (1). Patients with aortoiliac occlusive disease (AIOD) present most frequently with lifestyle limiting claudication. They usually present with thigh, hip or buttock pain with exertion. Due to the chronic nature of the disease, critical limb ischemia is rare in the absence of distal disease. The threshold for performing percutaneous intervention of aortoiliac occlusive disease is typically lower than from distal interventions due to better long term outcomes (2). PRMA BOLETIN | 47 In addition to this, when considering patients with multi level disease, specifically in the setting of critical limb ischemia, the ACC/AHA guidelines recommend that aortoiliac lesions be addressed first (2). When evaluating the aortoiliac anatomy and lesion complexity of a patient, the guideline from the TransAtlantic Inter-Society Consensus (TASC II) provides an algorithm that classifies lesions as A-D in order of increasing extent and intricacy (figure 1)(3). In general, endovascular therapy is the treatment of choice in TASC A-B lesions. Type C lesions should take patient’s preference and risk profile into consideration when making a decision. Type D lesions should be addressed surgically. Despite this, development of new technologies and techniques has led to increased use of endovascular therapy for extensive AIOD. A meta-analysis performed in 2010, that included 1711 patients with type C and D lesions, reported a technical success in 86-100% of patients (4). Four or five year primary patency rates ranged from 60% to 86% and 80 to 98%. The study concluded that experienced interventional physicians can perform extensive AIOD successfully and results are comparable to surgical repair. Selection of lesions for endovascular versus conservative therapy is not defined (2). In cases where the severity of a stenosis is uncertain, specifically in lesions between 50-75%, a trans-stenotic intra-arterial pressure measurement should be obtained. 48| PRMA BOLETIN A mean gradient more than 5mmHg or a peak systolic gradient of > 10mmHg is considered significant. AHA/ACC guidelines recommend against intervention in patients with no significant pressure gradient (2). Percutaneous revascularization at the aortoiliac segment generally involves percutaneous transluminal angioplasty (PTA) with or without stent placement. Stents can be used primarily or as an addition to PTA due to a residual diameter stenosis, persistent gradient or flow-limiting dissection (2). Comparing stenting to stand-alone PTA, the Dutch Iliac Stent Trial Study Group randomized patients with iliac artery occlusive disease to primary stent placement vs. PTA with selective stent placement. The study found that primary outcomes between the two groups were statistically non-significant (5). More recent studies, however, have shown primary stenting to be superior to selective stent placement in terms of acute success and long-term patency in TASC C and D aortoiliac lesions (6). The Stents Versus Angioplasty for the Treatment of Iliac Artery Occlusions (STAG) trial randomly assigned 112 patients with an iliac occlusion to PTA vs. primary stent placement. Technical success in the primary stenting group was higher, 94% vs. 84%, and major complications occurred less frequently (7). The most important limitation for stenting is in-stent restenosis resulting from neointimal hyperplasia (8). Covered stents may overcome this limitation by creating a barrier between the hyperplasia and arterial lumen. Studies like the Covered Versus Balloon Expandable Stent Trial (COBEST) demonstrate favorable results with covered stents, specifically in TASC C and D lesions (9). In addition to the iliac artery, PTA and stents have also been used to treat stenosis of the aortic bifurcation. To avoid plaque dislodgement or dissection, a “kissing balloon” technique is often used. In this technique, simultaneous balloon dilatation at the origin of both common iliac arteries is performed and usually followed with the placement of “kissing stents”. This procedure has good results with primary and assisted primary patency rates at five years of overall technical success rate 64.5 and 81.8 percent respec- was 88 percent; successful antively (10). gioplasty was higher for stenosis (91 percent) compared with The indications for aortoiliac en- occlusion (83 percent). Two-year dovascular therapy have gradu- patency rates ranged from 42 ally expanded over the last two to 58 percent (14). Restenosis, decades. Extensive and complex which accounts for loss of initial lesions, which at one point were patency, usually occurs within deemed too complicated for an the first six months. Progressive endovascular approach, are be- atherosclerosis at the lesion site ing treated at experienced cen- or elsewhere in the same vessel ters worldwide with good results. may also contribute to loss of paAn endovascular intervention tency. approach may prove of greater benefit for patients at high and/ In an effort to improve outcomes or intermediate risk for otherwise and prevent restenosis after PTA, surgical management. several modalities have been developed. However, only local Femoropopliteal Disease delivery of paclitaxel has been shown to improve outcomes. The femoropopliteal segment As seen in the THUNDER triimposes a treatment challenge al, which assigned patients with given its mobility. Balloon angio- femoropopliteal stenoses to plasty of this segment has a high treatment with paclitaxel-coated rate of restenosis and re-occlu- angioplasty balloons, uncoated sion, probably due to the nature balloons with paclitaxel dissolved of the lesion. Several modalities in the contrast medium, or unhave been developed in order coated balloons with contrast to minimize restenosis including solution containing no paclitaxel. medication coated balloon angio- The coated balloon group had a plasty, which has improved out- significantly lower rate of mean comes, and stenting, most widely late lumen loss (0.4 versus 2.2 used for longer lesions. These and 1.7 mm, respectively) as modalities may be combined with well as target lesion revascularatherectomy which involves the ization at six months (4 versus removal of plaque using physical 29 and 37 percent) (15). The primeans. Percutaneous angioplas- mary end point of late lumen loss ty (PTA) for femoropopliteal dis- at six months was also signifiease has a lower long-term pa- cantly less in the coated balloon tency rate compared with PTA for group (0.5 versus 1.0 mm) of the aortoiliac disease (13). A smaller FemPac trial, where patients unvessel diameter, long or eccentric dergoing angioplasty of femorocalcified lesions, arterial occlu- popliteal lesions were randomly sion, as well as poor distal runoff assigned to uncoated or pacliare among the factors affecting taxel-coated balloons catheters. the long-term patency, leading to The DEBELLUM (Drug-Eluting higher rate of restenosis follow- Balloon Evaluation for Lower ing PTA of the femoropopliteal Limb MUltilevel TreatMent), PACsegment. IFIER, and LEVANT trials also compared and demonstrated Long-term outcomes after bal- the efficacy of drug-eluting balloon angioplasty in the femoro- loons over conventional, uncoatpopliteal segment are not signifi- ed balloon angioplasty. In these cantly improved, as evidenced by studies, a significantly lower rate several studies. In a prospective of target lesion revascularization study evaluating the effective- and late lumen loss at six months ness of femoropopliteal PTA in was associated with the use of patients with claudication, the drug-eluting balloons. In addition, the IN.PACT SFA, which is a multicenter trial that randomly assigned patients with intermittent claudication or ischemic rest pain attributable to superficial femoral artery PAD to angioplasty with a paclitaxel-coated balloon or plain balloon, demonstrated that drug-coated balloons are superior to PTA and had a favorable safety profile for the treatment of patients with symptomatic femoropopliteal peripheral artery disease. Primary patency at one year was significantly higher for the drug-coated compared with plain balloon angioplasty (82.2 versus 52.4 percent), with lower rates of target lesion re-intervention (2.4 versus 20.4 percent). Despite the restenosis associated with PTA, a clear advantage to primary stenting has not definitively been demonstrated. In a meta-analysis that included only trials using contemporary flexible nitinol stents (four trials, 627 patients, 665 lesions), technical success was significantly higher in the primary stenting group compared with balloon angioplasty (95.8 versus 64.2 percent) (11). Longer lesions probably benefit from stenting however the type of stent (self-expanding metal stent, covered stents, drug-eluting stents, or biodegradable stents) remains controversial. The Vienna Absolute trial compared primary stenting with a self-expanding nitinol stent to PTA with adjunctive stenting in patients with severe claudication or chronic limb ischemia and superficial femoral artery stenosis or occlusion. The rate of restenosis was significantly lower with the nitinol stent on angiography at six months (24 versus 43 percent) and on duplex ultrasonography at one year (37 versus 63 percent)(18). The RESILIENT (Randomized study comparing the Edwards Self-expanding LifeStent versus angioplasty alone in Lesions iNvolving the SFA and/or Proximal PRMA BOLETIN | 49 Popliteal Artery) demonstrated better primary patency at one year for the group that had received stents compared with angioplasty alone (81.3 versus 36.7 percent)(20). On the other hand, the Femoral Artery Stenting Trial (FAST) found no advantage for stenting compared with PTA (19). The use of drug-eluting stents has been studied through the SIROCCO II and ZILVER PTX trials. The former compared sirolimus drug-eluting versus bare nitinol self-expanding stents and there were no significant differences in the rates of restenosis between the groups at two years (sirolimus group: 22.9 percent, bare stent: 21.1 percent)(21). The ZILVER PTX trial compared primary placement of paclitaxel drug-eluting stents with angioplasty in superficial femoral artery lesions. It demonstrated significantly improved rates for primary patency in the drug-eluting stent group (75 versus 27 percent) at two years and was associated with a sustained clinical benefit (22-23). The use of covered stents (stent grafts) remains controversial. It is theorized that these may be more resistant to neointimal hyperplasia and stent fracture. Heparin has been added to the surface of stent grafts to provide an additive antiproliferative or antithrombotic effect. However, failure raises concern as acute thrombosis associated with a covered stent may result in symptoms that are more severe than the symptoms that begot the initial intervention. Another therapeutic approach is atherectomy which involves the removal of plaque burden using physical or ablative means, such as laser, in a directional (proximal to distal) or rotational manner. It may be combined with angioplasty and stenting. Nonetheless, a definitive role for atherectomy for femoropopliteal occlusive disease has not been demonstrated. 50| PRMA BOLETIN Infrapopliteal Disease Once the angiography has taken place, the physician would usually consider percutaneous transluminal angioplasty (PTA). Initially balloon angioplasty was the gold standard therapy when dealing with infrapopliteal PAD. Early trials had reported no significant difference in outcome between PTA and bypass surgery in patients with CLI. Current guidelines by the American Heart Association recommend that “patients with limb-threatening lower extremity ischemia in whom autogenous vein conduit is not available, balloon angioplasty is reasonable to perform when possible as the initial procedure” (Class IIa, level of evidence B). Endovascular therapies for infapopliteal peripheroarterial disease (PAD) differ in several aspects from the management of disease in more proximal vessels, most notably when deciding when to intervene. PAD endovascular management is essentially limited to dealing with critical limb ischemia. Ischemic rest pain, ulceration and gangrene are accepted indications. This is a result of the difference in anatomical and comorbid conditions associated with infrapopliteal disease. PAD occurring at this level is typically seen in patients with a higher incidence of diabetes mellitus and chronic kidney disease, thereby leading As time has passed, guidelines a more diffuse and difficult to are lagging behind the current treat condition. practice. The field of percutaneous endovascular therapy has Prior to managing critical limb been rapidly advancing in the ischemia (CLI) secondary to in- past years, with new therapies frapopliteal disease, a good in- been developed to be used on flow must be obtained, therefore their own or in conjunction with more proximal disease should balloon angioplasty. One of the be initially addressed. Next, the most popular is atheroablative interventional cardiologist must atherectomy (orbital, laser or rotake into account the nature of tational atherectomy) that works the lesions, the amount of calci- by fragmenting the cholesterum, the presence of total occlu- ol plaque into smaller particles, sions and their lengths and the thereby attaining vessel patency. number of collaterals to adjust Excisional atherectomy is anothhis strategy. Many authors have er alternative that has a similar stated that establishing straight goal of debulking the lesion but line pulsatile flow to the foot is the instead of crumbling the plaque, goal of the intervention, but stud- it shaves it off. Atherectomy has ies have shown that the greater been postulated to be superior to the number of patent vessels PTA because it minimizes neoinafter percutaneous transluminal timal hyperplasia thereby leading angioplasty (PTA), the higher to less restenosis and plaque the likelihood of limb salvage. shift. Consequently, restoring patency of both tibial arteries is generally Also, drug eluting balloons were preferred over patency of the pe- recently approved after the DEroneal artery alone. Additionally, BATE-BTK study, by demonother studies have demonstrat- strating that they had far less ed that utilizing direct revascu- reocclusions than conventional larization guided by the different balloon angioplasty when manangiosomes (anatomic maps fed aging tibial vessel lesions. These by single arteries) have been the balloons are designed to release superior strategy. Still, no large paclitaxel into the media of the randomized clinical trials com- artery and reduce restenosis by paring one strategy to the other suppressing the proliferation of have been performed. smooth muscle cells. Even bare metal stents (BMS) have a small but essential role in infrapopliteal PAD. They have been recommended for management of flow limiting dissections caused by an endovascular intervention. Whatever therapy is used, the main goal is the improve wound healing and prevent amputations. Limb salvage is the priority, and studies have shown that longterm limb salvage rates are substantially greater than patency rates. The basic principle is that it takes higher levels of oxygen and nutrition to allow healing of ischemic tissue, since there are higher metabolic demands required for tissue healing than to maintain tissue integrity. Therefore, even if vessel patency is not present in the long term, the improved circulation that persisted for some time may allow resolution of non-healing ulcers and even avoid amputations. In conclusion there is as yet no clear consensus on the optimal approach. Therefore, high quality research demonstrating convincing clinical benefit of one form of treatment over another must be done and guidelines updated to further optimize patient care. References: 1. Bonvini R, Roffi M. Aortoiliac and common femoral endovascular interventions. Eurointervention. 2010 Jun;6(2): 288-9 2. Hirsch AT, Haskal ZJ, Hertzer NR, Bakal CW, Creager MA, Halperin JL, Hiratzka LF, Murphy WRC, Olin JW, Puschett JB, Rosenfield KA, Sacks D, Stanley JC, Taylor LM Jr., White CJ, White J, White RA. ACC/ AHA 2005 practice guidelines for the management of patients with peripheral arterial disease (lower extremity, renal, mesenteric, and abdominal aortic): a collaborative report from the American Association for Vascular Surgery/Society for Vascular Surgery, Society for Cardiovascular Angiography and Interventions, Society for Vascular Medicine and Biology, Society of Interventional Radiology, and the ACC/AHA Task Force on Practice Guidelines (Writing Committee to Develop Guidelines for the Management of Patients With Peripheral Arterial Disease). Circulation. 2006;113:e463– e654. DOI: 10.1161/ CIRCULATIONAHA.106.174526 3. Norgren L, Hiatt WR, Dormandy JA, et al. Inter-Society Consensus for the Management of Peripheral Arterial Disease (TASC II). J Vasc Surg 2007; 45 Suppl S:S5. 4. Jongkind V, Akkersdijk GJ, Yeung KK, Wisselink W. A systematic review of endovascular treatment of extensive aortoiliac occlusive disease. J Vasc Surg 2010. Nov;52(5):1376-83 5. Klein WM, van der Graaf Y, Seegers J, et al. Dutch iliac stent trial: long-term results in patients randomized for primary or selective stent placement. Radiology 2006 Feb;238(2):733-44 6. Ichihashi S, Higashiura W, Itoh H, et al. Longterm outcomes for systematic primary stent placement in complex iliac artery occlusive disease classified according to Trans-Atlantic Intersociety Consensis (TASC)-II. J Vasc Surg. 2011 Apr;53(4):992-9 7. Goode SD, Cleveland TJ, Gaines PA. Randomized clinical trial of stents versus angioplasty for the treatment of iliac artery occlusions (STAG trial). Br J Surg. 2013 Aug;100(9):1148-53 8. Bekken JA, Jongsma H, de Vries JP, Fioole B. Self expanding stents and aortoiliac occlusive disease: a review of the literature. Med Devices (Auckl). 2014; 7:99-105 9. Mwipatayi BP, Thomas S, Wong J, et al. A comparison of covered vs bare expandable stents for the treatment of aortoiliac occlusive disease. J Vasc Surg. 2011 Dec;54(6):156170 10. Abello N, Kretz B, Picquet J, et al. Longterm results of stenting of the aortic bifurcation. Ann Vasc Surg 2012 May;26(4): 521-6 11. Acin F, de Haro J, Bleda S, et al. Primary Nitinol Stenting in Femoropopliteal Occlusive Disease: A Meta-Analysis of Randomized Controlled Trials. J Endovasc Ther 2012; 19:585. 12. Gallagher KA, Meltzer AJ, Ravin RA, et al. Endovascular Management as First Therapy for Chronic Total Occlusion of the Lower Extremity Arteries: Comparison of Balloon Angioplasty, Stenting, and Directional Atherectomy. J Endovasc Ther 2011; 18:624. 13. Wilson SE, Wolf GL, Cross AP. Percutaneous Transluminal Angioplasty versus Operation for Peripheral Arteriosclerosis. Report of a Prospective Randomized Trial in a Selected Group of Patients. J Vasc Surg 1989; 9:1. 14. Matsi PJ, Manninen HI, Vanninen RL, et al. Femoropopliteal Angioplasty in Patients with Claudication: Primary and Secondary Patency in 140 Limbs with 1-3-year Follow-up. Radiology 1994; 191:727. 15. Tepe G, Zeller T, Albrecht T, et al. Local Delivery of Paclitaxel to Inhibit Restenosis During Angioplasty of the Leg. N Engl J Med 2008; 358:689. 16. Werk M, Langner S, Reinkensmeier B, et al. Inhibition of Restenosis in Femoropopliteal Arteries: Paclitaxel-Coated versus Uncoated Balloon: Femoral Paclitaxel Randomized Pilot Trial. Circulation 2008; 118:1358. 17. Tepe G, Laird J, Schneider P, et al. Drug-Coated Balloon versus Standard Percutaneous Transluminal Angioplasty for the Treatment of Superficial Femoral and Popliteal Peripheral Artery Disease: 12-Month Results from the IN.PACT SFA Randomized Trial. Circulation 2015; 131:495. 18. Schillinger M, Sabeti S, Loewe C, et al. Balloon Angioplasty versus Implantation of Nitinol Stents in the Superficial Femoral Artery. N Engl J Med 2006; 354:1879. 19. Krankenberg H, Schlüter M, Steinkamp HJ, et al. Nitinol Stent Implantation versus Percutaneous Transluminal Angioplasty in Superficial Femoral Artery Lesions Up to 10 cm in Length: The Femoral Artery Stenting Trial (FAST). Circulation 2007; 116:285. 20. Laird JR, Katzen BT, Scheinert D, et al. Nitinol Stent Implantation versus Balloon Angioplasty for Lesions in the Superficial Femoral Artery and Proximal Popliteal Artery: Twelve-Month Results from the RESILIENT Randomized Trial. Circ Cardiovasc Interv 2010; 3:267. 21. Duda SH, Bosiers M, Lammer J, et al. Drug-Eluting and Bare Nitinol Stents for the Treatment of Atherosclerotic Lesions in the Superficial Femoral Artery: Long-Term Results from the SIROCCO Trial. J Endovasc Ther 2006; 13:701. 22. Dake MD, Ansel GM, Jaff MR, et al. Paclitaxel-Eluting Stents Show Superiority to Balloon Angioplasty and Bare Metal Stents in Femoropopliteal Disease: Twelve-Month Zilver PTX Randomized Study Results. Circ Cardiovasc Interv 2011; 4:495. 23. Dake MD, Ansel GM, Jaff MR, et al. Sustained Safety and Effectiveness of Paclitaxel-Eluting Stents for Femoropopliteal Lesions: 2-year Follow-Up from the Zilver PTX Randomized and Single-Arm Clinical Studies. J Am Coll Cardiol 2013; 61:2417. 24. Capek P, McLean GK, Berkowitz HD. Femoropopliteal Angioplasty: Factors Influencing Long-Term Success. Circulation 1991; 83:I70. 25. Percutaneous Interventional Procedures in the Patient with Lower Extremity Claudication. www.uptodate.com Abstracto Las terapias endovasculares es actualmente parte esencial del manejo que se le ofrece a pacientes con enfermedad arterial periférica. Las guías actuales de la Asociación Americana del Corazón y la Fundación del Colegio Americano de Cardiología (AHA y ACCF por sus siglas en ingles) recomienda que “aquellos pacientes con isquemia que amenace la extremidad inferior en los que un puente con una vena autóloga no sea posible, angioplastia con balón es una alternativa razonable como procedimiento inicial cuando sea posible” (Clase IIa, nivel de evidencia B). Tratamiento endovascular para enfermedad infrapoplitea esta esencialmente limitado a resolver isquemia crítica y requiere la presencia de flujo adecuado en los vasos mas proximales. Para aumentar las posibilidades de que esta intervención sea efectiva es fundamental estudiar la naturaleza de las lesiones, tomando en cuneta la cantidad de calcio, la presencia de oclusiones totales, largo de oclusión(es) y el número de colaterales. Exciten distintos métodos y herramientas para llevar acabo esta intervención, pero aún no hay un consenso sobre cual es la terapia óptima. Nuevos estudios podrían consolidar la terapia endovascular en este campo y forzar un cambio en las guías actuales de tratamiento. PRMA BOLETIN | 51 Non-Invasive Therapy of Peripheral Arterial Disease José M. Marcial, MD; Reynerio Pérez, MD; Pedro Vargas, MD; Hilton Franqui-Rivera, MD University of Puerto Rico School of Medicine, Department of Medicine, Cardiology Section Cardiovascular Diseases Training Program INTRODUCTION Peripheral arterial disease (PAD) is a major cause of morbidity and mortality worldwide. This article focuses on non-invasive treatment of PAD, particularly lower extremity arterial disease (LEAD). The first portion of this article will deal with non-pharmacologic interventions (ie, lifestyle modification) whereas the second portion will deal with pharmacologic therapy. Pharmacologic therapy will be further divided in two main components: symptomatic relief and prevention of disease progression. NON-PHARMACOLOGIC INTERVENTIONS IN NON-INVASIVE MANAGEMENT OF PAD Risk factor modification can help to reduce disease burden of atherosclerosis and its complications. PAD being part of the spectrum of atherosclerotic disease, lifestyle modifications commonly used with patients with PAD are very similar to those applied in patients with coronary atherosclerotic disease (CAD). The following section summarizes the available evidence regarding ‘life-style’ modification in patients with PAD. Smoking cessation Tobacco smoking is unquestionably related to development of atherosclerosis and is in fact the strongest risk factor for the development of claudication [1, 2]. The severity of PAD has been demonstrated increase proportionally to the number of cigarettes smoked daily [3]. Moreover, a major amputation rate of 6–11% has been reported in patients with intermittent claudication who smoke compared with no major amputations in non-smokers [4]. Fortunately, complete and permanent smoking cessation is by far the most clinically and cost effective intervention in patients with atherosclerosis [5]. Smoking cessation has been associated with a rapid decline in the 52| PRMA BOLETIN Abstract Peripheral arterial disease (PAD) is a significant cause of morbidity and mortality worldwide. Lifestyle changes, like the cessation of the use of tobacco as well as a modification of dietary and exercise habits, can be the most cost-effective interventions in patients with PAD. Smocking cessation is the most important intervention, since it increases survival in these patients. Antiplatelet therapy is an essential component in the treatment of peripheral arterial disease (PAD) of the lower extremities. In addition to delaying arterial obstructive progression, these agents are most usefull in reducing adverse cardiovascular events such as non-fatal myocardial infarction (MI), stroke and vascular death. Mainstay of treatment continues to be aspirin monotherapy (75-325mg daily). Current treatment for lower extremity PAD is directed towards the relief of symptoms and improvement in QoL. The two agents which have consistently been found to be most efficient in achieving these goals are cilostazol and naftidrofuryl oxalate. Naftidrofuryl oxalate may emerge as the most efficient and cost-effective treatment for symptom relief. Index Words: Peripheral Artery Disease, claudication, antiplatelet therapy, life-style changes incidence of intermittent claudication. Furthermore, the risk of intermittent claudication for ex-smokers 1 year after quitting is approximately the same as that for non-smokers [6]. Patients who stop smoking have a twofold increase in their 5-year survival rate compared with those who continue to smoke [7]. Simple advice is usually not very effective in smoking cessation since it is a form of addiction. Special programs can aid in smoking cessation, however, patient insight and motivation remain the foundation. It is vital that PAD patients be convinced that their disease is related to smoking, as this may not be widely appreciated by the general public. Adjunctive treatments like nicotine replacement therapy and Bupropion, a norepinephrine, serotonin and dopamine neuronal uptake inhibitor, have been successful in increasing the likelihood of permanent smoking cessation [8]. Current guidelines by the American College of Cardiology Foundation (ACCF) and the American Heart Association (AHA) strongly advice in favor of aggressive smoking cessation counseling in all patients with PAD, including establishing a plan for quitting, pharmacologic therapy, and referral to smoking cessation programs [9]. Exercise Exercise training is an essential component in the management of symptomatic claudication in patients with PAD. However, it is important to emphasize that no studies have shown a survival benefit of exercise in these patients as they have in patients with CAD and chronic heart failure [10]. Nonetheless, it has been shown that the risk of PAD is inversely related to previous levels of physical activity suggesting a mechanistically protective effect of exercise [1]. Walking capacity has been demonstrated to increase by exercise training in patients with claudication [11]. For this reason, regular exercise coupled with risk factor modification -especially smoking cessation- is the cornerstone of conservative therapy for intermittent claudication. Exercise rehabilitation is associated with a positive impact on the quality of life and the functional status of the patient [12]. Classically, the two activities that are considered vital in supervised exercise programs are walking and step-climbing [13]. The ACCF/ AHA Guidelines strongly advice in favor of supervised exercise training programs for patients with PAD [9], usually in sessions of 30-45 minutes at least 3 times a week. Diet and weight loss A ‘Mediterranean’ type diet, which is rich in fruit, nuts, vegetables, fish and mono-unsaturated vegetable oils, has been demonstrated to significantly decrease the progression of coronary artery disease [14]. However, so far no studies have shown any overall benefit by dietary fat reduction or modification in patients with PAD [15]. Nevertheless, weight loss is recommended in obese patients with cardiovascular disease, including PAD. It is known that obesity adversely impacts cardiovascular hemodynamics, structure and function [16], as well as increases the prevalence of most cardiovascular diseases. Abdominal fat distribution, but not total body fat, is associated with PAD independently of coexisting cardiovascular risk factors [17]. The ATTICA epidemiological study showed that adherence to the Mediterranean diet was associated with 20% lower odds of having the metabolic syndrome, irrespective of age, sex, physical activity, lipids, and blood pressure levels [18]. Furthermore, lifestyle changes comprising reduced total and saturated fat intake and increased polyunsaturated fat and fiber intake have been shown to significantly reduce multiple metabolic and inflammatory parameters such as high-sensitivity C-reactive protein (hsCRP) [19]. Consistent with the view that PAD is yet another manifestation of cardiovascular inflammation, every effort in terms of lifestyle modifications should be undertaken when dealing with this devastating disease. Current ACCF/ AHA Guidelines do not include a specific recommendation regarding this intervention. PHARMACOLOGIC THERAPY FOR PREVENTION OF PROGRESSION OF PAD Antiplatelet agents are the cornerstone of pharmacologic therapy for prevention of progression of PAD. However, multiple other pharmacologic interventions, such as use of lipid-lowering therapy and antihypertensive drugs have been used in this population. Antiplatelet agents Antiplatelet treatment for lower extremity PAD has a dual role of slowing arterial disease progression to vessel occlusion and more importantly reducing the risk of future mayor cardiovascular adverse events. The Antithrombotic Trialists’ Collaboration performed a meta-analysis of 287 studies of antiplatelet agents versus control involving 135,000 patients evaluated the impact of antiplatelet agents in patients with high risk of occlusive vascular events. For patients with PAD (9,716 in 46 trials) -which included patients with intermittent claudication, peripheral artery grafting or angioplasty- the use of an antiplatelet agent showed a 23% reduction of serious vascular events such as non-fatal myocardial infarction, stroke and death from a vascular cause [20, 24]. Several agents were used in these studies including aspirin, ticlopidine and picotamide; with aspirin being the most commonly used agent. Several newer studies have shown mixed results regarding the effect PRMA BOLETIN | 53 of aspirin in prevention of serious cardiovascular events [9, 25-26]. Most of these studies included only asymptomatic PAD patients. This suggests that the benefit of an antiplatelet agent is stronger in symptomatic patients. For this reason, current ACCF/AHA Guidelines give a strong recommendation in favor of use of antiplatelet agents in patients with symptomatic PAD [9]. The use of antiplatelet agents in asymptomatic patients is reasonable for asymptomatic patients with an ankle-brachial index (ABI) below 0.90 and may be considered for asymptomatic patients with an ABI 0.91-0.99. The evidence of antiplatelet use for halting lower extremities arterial disease progression to vascular occlusion is less robust than the evidence for prevention of mayor cardiac adverse events. A subanalysis of the Antithrombotic Trialists’ Collaboration study [24] demonstrated that the use antiplatelet agents conferred a 43% risk reduction of vascular occlusion [27]. The use of an antiplatelet agent over a 19 month period resulted in a 92 per 1000 risk reduction in peripheral artery occlusion. Most of the data was from studies of patients with saphenous or prosthetic grafts, only one trial evaluated the patency of native arteries. Further categorizing the degree of peripheral artery disease, the use on antiplatelet agent provided a reduction in vascular occlusion in patients with intermittent claudication who were not submitted to invasive procedures (64% risk reduction), patients with previous peripheral grafts (38% risk reduction) and prior percutaneous peripheral angioplasty (47%), although the latter did not achieved statistical significance [28]. This study suggest a benefit of antiplatelet agents in peripheral artery disease progression. symptomatic PAD and those with prior revascularization or amputation at doses from 75-325 mg orally daily to reduce the risk of mayor vascular events such as myocardial infarction (MI), stroke and cardiovascular deaths [9, 27]. The use of aspirin at any dose results in 23% risk reduction in vascular events [24]. Monotherapy with aspirin in doses of 75-150 mg and 160-325 mg versus placebo conveyed a risk reduction of 32% and 26% respectively. In addition, addition of another antiplatelet agent such as dypiridamole or ticlopidine to aspirin therapy does not convey a significant risk reduction on mayor vascular events. Clopidogrel is a thyenopyridine derivative that binds to platelet’s adenosine diphosphate receptor and prevents platelet activation selectively and irreversibly. A 75mg daily dose of clopidogrel is a safe and effective alternative to aspirin for the risk reduction of MI, stroke or vascular death in symptomatic patients with PAD [9, 26]. The evidence for this therapy comes from the results of the Clopidogrel versus Aspirin in Patients at Risk of Ischemic Events (CAPRIE) trial [26]. A total of 19,185 patients with atherosclerotic vascular disease such as recent MI, recent ischemic stroke or symptomatic PAD were randomized to receive clopidogrel vs. aspirin therapy. The use of clopidogrel revealed an 8.7% relative risk reduction for cardiovascular events. Subgroup analysis demonstrated a 23.8% relative risk reduction of cardiovascular events in patients with PAD treated with clopidogrel vs aspirin [26]. Clopidogrel also showed less adverse events including severe gastrointestinal bleeding, non-fatal intracranial bleeding and hemorrhagic deaths, with the former being statistically significant. This single comparative study suggests that clopidogrel Aspirin is the antiplatelet agent has a better risk reduction and of choice for patients with safety profile than aspirin for the 54| PRMA BOLETIN management of PAD. However, aspirin remains the mainstay of therapy and dual antiplatelet therapy is not usually prescribed unless there are other compelling indications. The CHARISMA trial [27] evaluated the efficacy of combination therapy with clopidogrel and low dose aspirin versus aspirin monotherapy to reduce mayor vascular events in patients with either multiple atherothrombotic risk factors, documented CAD, documented cerebrovascular disease or documented symptomatic PAD. The results of this trial showed that combination clopidogrel and low-dose aspirin does not confer a significant risk reduction in the composite of primary end point of MI, stroke or death from cardiovascular causes versus monotherapy with lowdose aspirin. However, further analysis showed that patients with symptomatic or asymptomatic PAD had a statistically significant risk reduction of MI of 37% and rate of hospitalization for ischemic events of 19%. As per current ACCF/AHA Guidelines, combination therapy with aspirin and clopidogrel may be considered in symptomatic patients with lower extremity PAD [9]. Vorapaxar is a competitive and selective antagonist of protease-activated receptor 1 (PAR-1). PAR-1 is the main receptor interacting with thrombin on platelets. This antagonism produces a potent inhibition of thrombin-induced platelet aggregation [28]. Vorapaxar was approved by the FDA on May 2014, as an adjunctive therapy for the risk reduction of the combined endpoint of death, MI, stroke and urgent coronary revascularization in patients with history of myocardial infarction or PAD. The addition of vorapaxar to standard antiplatelet therapy has demonstrated a risk reduction in cardiovascular death, MI or stroke of 13% compared to placebo. The antithrombotic effect of vorapaxar comes at an expense of an increase of moderate or severe bleeding, especially intracranial bleeding. Due to this finding, vorapaxar is contraindicated in patients with prior ischemic or hemorrhagic stroke, transient ischemic attack or active pathological bleeding. Current ACCF/AHA Guidelines do not include a recommendation regarding this drug, as it was not commercially available at the time of their publication. Lipid-lowering therapy There is extensive evidence regarding benefit of lipid-lowering therapy for patients with atherosclerotic disease. Current ACCF/ AHA Guidelines strongly recommend the use of hydroxymethyl glutaryl coenzyme-A reductase inhibitor (statins) in all patients with PAD to achieve a target low-density lipoprotein (LDL) cholesterol level of less than 100 mg/dL. [9] Antihypertensive therapy Although there is no data regarding the effects of antihypertensive therapy on progression of PAD, ACCF/AHA Guidelines recommends achieving blood pressure control as per current guidelines for treatment of arterial hypertension. [9] Antihyperglycemic therapy Similarly, no controlled trials regarding the effects of glycemic control on progression of PAD have been published so far. However, it is generally recommended to follow current treatment guidelines for this condition, which is a major risk factor for development of PAD. PHARMACOLOGIC TREATMENT FOR SYMPTOMATIC RELIEF OF PAD Multiple pharmacological and natural medications have been studied with the goal of improving the quality of life of patients with PAD. The most common end-points in these studies were maximal walking distance (MWD) and pain-free walking distance (PFWD). Cilostazol Cilostazol is probably the most widely used medication for PAD in the US. It is a type III phosphodiesterase inhihibitor that suppresses platelet aggregation and causes direct arterial vasodilation [29]. The efficacy of cilostazol was studied in a meta-analysis involving 2,702 patients from 8 double-blinded, placebo-controlled trials. Patients were followed-up for 12-24 weeks. Cilostazol therapy was associated with increased MWD (67% vs. 50% from baseline) and PFWD (40% vs. 22% from baseline) [30]. These results hold true for all age groups over 40 years of age, gender, and presence or absence of diabetes mellitus (DM). Quality of life (QoL) assessment scores revealed significant improvement after initiation of cilostazol. Cilostazol was also associated with a decrease in triglycerides by 15.8% and an increased in high-density lipoprotein (HDL) cholesterol by 12.8%. Despite the well-documented efficacy of this product, it’s long-term effects are unclear, as no study has reported follow-up beyond 6 months [29]. Despite its anti-platelet effect, it is safe to combine with aspirin (ASA) since it will not cause an increase in bleeding time when compared to ASA monotherapy [31]. Cilostazol is contraindicated in patients with heart failure and is associated with increased mortality in this population [32]. the US. The proposed mechanism of action is through the up-regulation of glucose uptake and increase in adenosine triphosphate (ATP) levels. Several trials have consistently found naftidrofuryl to cause significant improvement in walking distance. An article review published in 2011 found five randomized controlled trials comparing naftidrofuryl to placebo for the treatment of lower extremity claudication [33]. Significant improvement in MWD was observed in one of the trials (158.7 m compared with 28.1 m for placebo). Four of the trials observed significant improvement in PFWD (mean differences in meters were 204.0, 158.2, 201.4 and 93.0 for those in the naftidrofuryl oxalate groups compared with 51.0, 29.9, 98.0 and 36.0 for those in the placebo group respectively). One study compared the relative efficacy of naftidrofuryl oxalate, cilostazol, and pentoxifylline [34]. The study was a non-double blinded network meta-analysis of systematic reviews including patients with intermittent claudication due to PAD, whose symptoms persisted despite a period of conservative management. Researchers found that patients on Naftidrofuryl had an increase in mean walking distance of 60% and PFWD of 49% when compared to placebo. Statistical differences were greater for naftidrofuryl when compared to cilostazol, which was associated with an improvement of only 25%. Naftidrofuryl oxalate was also found to be a more cost-effective therapy. No significant difference in rate of adverse effects was found between these agents. Based on these findings, the National Institute for Health and Care Excellence (NICE) recommends naftidrofuryl oxalate as first line therapy for intermittent claudication in people with peNaftidrofuryl Oxalate ripheral arterial disease for whom vasodilator therapy is considered Naftidrofuryl oxalate is a 5-hy- appropriate [33]. droxytryptamine-2-receptor antagonist not currently available in PRMA BOLETIN | 55 Other Agents Among other pharmacological agents that may improve patient symptoms are pentoxifylline, propionyl-L-carnitine, and ginko biloba. However, their efficacy has not been conclusively demonstrated. Pentoxifilline mechanism of action includes increased deformability of red blood cells and blood viscosity, and decrease platelet adhesion. Studies involving pentoxifilline vs. placebo have provided inconsistent result regarding its efficacy [35-37]. A small randomized double blinded study (n=79) compared the efficacy of pentoxifilline and cilostazol and found cilostazol was significantly better in improving claudication distance [38]. Claudication does not significantly improve with pentoxifilline when compared to a supervised exercise program or cilostazol [39]. Propionil-L-carnitine may improve claudication symptoms by increasing energy metabolism in ischemic muscle. One randomized double-blinded study compared demonstrated a significant improvement of MWD with propionil-L-carnitine (73 +/- 9% vs. 46 +/- 6% for placeb) but non-statistically significant improvement in walking distance from the time of claudication onset as compared to placebo [40]. Another study showed that patients with mild functional impairement (MWD >250m) do not benefit from propionil-L-carnitine [41]. Ginkgo biloba was postulated to improve claudication through its anti-oxidative properties and antithrombotic effects. In some studies comparing gingko biloba to placebo a trend towards improvement in absolute claudication distance with ginko biloba use has been observed, but no significant improvement has been reported [41-42]. The ACC/AHA guidelines concluded no clear benefit from 56| PRMA BOLETIN ginkgo biloba in the treatment of Task Force on Practice Guidelines. Circulation. 2011;124:2020-45. PAD [9]. INVESTIGATIONAL THERAPIES Other non-invasive therapies have been studied but so far they have failed to demonstrate consistent clinical benefit. These include antioxidants [43-44], such as gluthathiones and transsodium crocetinate; bosentan [45]; and even antichlamydial antibiotics [46-47]. The use of these agents is generally not recommended. References 1. Tornwall ME, Virtamo J, Haukka JK, Aro A, Albanes D, Huttunen JK. Prospective study of diet, lifestyle, and intermittent claudication in male smokers. Am J Epidemiol. 2000;151:892-901. 2. Meijer WT, Grobbee DE, Hunink MG, Hofman A, Hoes AW. Determinants of peripheral arterial disease in the elderly: the Rotterdam study. Arch Intern Med. 2000;160:2934-2938. doi:10.1001/ archinte.160.19.2934. 3. Drexel H, Steurer J, Muntwyler J, et al. Predictors of the presence and extent of peripheral arterial occlusive disease. Circulation. 1996;94:II199-I205. 4. Norgren L, Hiatt WR, Dormandy JA, et al. 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ACC/AHA 2005 Practice Guidelines for the management of patients with peripheral arterial disease (lower extremity, renal, mesenteric, and abdominal aortic): A collaborative report from the American Association for Vascular Surgery/Society for Vascular Surgery, Society for Cardiovascular Angiography and Interventions, Society for Vascular Medicine and Biology, Society of Interventional Radiology, and the ACC/AHA Task Force on Practice Guidelines (Writing Committee to Develop Guidelines for the Management of Patients With Peripheral Arterial Disease): Endorsed by the American Association of Cardiovascular and Pulmonary Rehabilitation; National Heart, Lung, and Blood Institute; Society for Vascular Nursing; TransAtlantic Inter-Society Consensus; and Vascular Disease Foun- dation. Circulation. 2006;113:e463–654. 21. Belch J, MacCuish A, Campbell I, et al. The prevention of progression of arterial disease and diabetes (POPADAD) trial: factorial randomised placebo controlled trial of aspirin and antioxidants in patients with diabetes and asymptomatic peripheral arterial disease. BMJ. 2008;337: a1840. 22. Catalano M, Born G, Peto R. Prevention of serious vascular events by aspirin amongst patients with peripheral arterial disease: randomized, double-blind trial. J Intern Med. 2007;261:276–84. 23. Fowkes FG, Price JF, Stewart MC, et al. Aspirin for prevention of cardiovascular events in a general population screened for a low ankle brachial index: a randomized controlled trial. JAMA. 2010;303:841–8. 24. Antithrombotic Trialists’ Collaboration. Collaborative meta-analysis of randomized trials of antiplatelet therapy for the prevention of death, myocardial infarction, and stroke in high risk patients. BMJ. 2002;324:71–86. 25. Antiplatelet Trialists’ Collaboration Collaborative overview of randomized trials of antiplatelet therapy—II: maintenance of vascular graft or arterial patency by antiplatelet therapy. Br Med J. 1994;308(6922):159–168. 26. CAPRIE Steering Committee. A randomised, blinded, trial of clopidogrel versus aspirin in patients at risk of ischaemic events (CAPRIE). Lancet. 1996;348:1329–39. 27. Cacoub PP, Bhatt DL, Steg PG, et al. Patients with peripheral arterial disease in the CHARISMA trial. Eur Heart J. 2009;30:192–201. 28. Morrow D. A., Braunwald E., Bonaca M. P., Ameriso S. F., Dalby A. J., Fish M. P., et al. (2012). Vorapaxar in the secondary prevention of atherothrombotic events. N. Engl. J. Med. 366, 1404–1413 29. Reilly MP, Mohler ER 3rd. Cilostazol: treatment of intermittent claudication. Ann Pharmacother. 2001;35(1):4856. 30. Thompson PD, Zimet R, Forbes WP, Zhang P. Meta-analysis of results from eight randomized, placebo-controlled trials on the effect of cilostazol on patients with intermittent claudication. Am J Cardiol. 2002;90(12):1314. 31. Abbas R1, Chow CP, Browder NJ, Thacker D, Bramer SL, Fu CJ, Forbes W, Odomi M, Flockhart DA. In vitro metabolism and interaction of cilostazol with human hepatic cytochrome P450 isoforms. Hum Exp Toxicol. 2000 Mar;19(3):17884. 32. NICE technology appraisal guidance 223. Cilostazol, naftidrofuryl oxalate, pentoxifylline and inositol nicotinate for the treatment of intermittent claudication in people with peripheral arterial disease. May 2011. 33. Stevens JW, Simpson E, Harnan S, Squires H, Meng Y, Thomas S, Michaels J, Stansby G. Systematic review of the efficacy of cilostazol, naftidrofuryl oxalate and pentoxifylline for the treatment of intermittent claudication. Br J Surg. 2012 Dec;99(12):1630-8. Epub 2012 Oct 3. 34. Rössner M, Müller R. On the assessment of the efficacy of pentoxifylline (Trental). J Med. 1987;18(1):1. 35. Hood SC, Moher D, Barber GG. Management of intermittent claudication with pentoxifylline: meta-analysis of randomized controlled trials. CMAJ. 1996;155(8):1053. 36. Salhiyyah K, Senanayake E, Abdel-Hadi M, Booth A, Michaels JA. Pentoxifylline for intermittent claudication. Cochrane Database Syst Rev. 2012;1:CD005262. 37. Surjit Singh, Harbinder Singh, Arvind Kohli, Vinod Kapoor, Gurjit Singh. Effects of cilostazole and pentoxifylline on claudication distance and lipid profile in patients with occlusive peripheral arterial disease: A comparative trial. Indian Journal of Thoracic and Cardiovascular Surgery June 2009, Volume 25, Issue 2, pp 45-48 38. Hiatt WR, Regensteiner JG, Hargarten ME, Wolfel EE, Brass EP. Benefit of exercise conditioning for patients with peripheral arterial disease. Circulation. 1990;81(2):602. 39. Brevetti G, Perna S, SabbáC, Martone VD, Condorelli M. Propionyl-L-carnitine in intermittent claudication: double-blind, placebo-controlled, dose titration, multicenter study. J Am Coll Cardiol. 1995;26(6):1411. 40. Brevetti G, Diehm C, Lambert D. European multicenter study on propionyl-L-carnitine in intermittent claudication. J Am Coll Cardiol. 1999;34(5):1618. 41. NicolaïSP, Kruidenier LM, Bendermacher BL, Prins MH, Stokmans RA, Broos PP, Teijink JA. Ginkgo biloba for intermittent claudication. Cochrane Database Syst Rev. 2013;6:CD006888. 42. NicolaïSP, Kruidenier LM, Bendermacher BL, Prins MH, Teijink JA. Ginkgo biloba for intermittent claudication. Cochrane Database Syst Rev. 2009. 43.Brass EP. Intermittent claudication: new targets for drug development. Drugs 2013; 73:999. 44. Violi F, Loffredo L, Mancini A, Marcoccia A. Antioxidants in peripheral arterial disease. Curr Drug Targets 2003; 4:651. 45. Luyt CE, Lepailleur-Enouf D, Gaultier CJ, et al. Involvement of the endothelin system in experimental critical hind limb ischemia. Mol Med 2000; 6:947. 46. Kaperonis EA, Liapis CD, Kakisis JD, et al. Inflammation and Chlamydia pneumoniae infection correlate with the severity of peripheral arterial disease. Eur J Vasc Endovasc Surg 2006; 31:509. 47. Vainas T, Stassen FR, Schurink GW, et al. Secondary prevention of atherosclerosis through chlamydia pneumoniae eradication (SPACE Trial): a randomised clinical trial in patients with peripheral arterial disease. Eur J Vasc Endovasc Surg 2005; 29:403. Abstracto La enfermedad arterial periférica (EAP, PAD en inglés) es una causa significativa de morbilidad y mortalidad en el mundo. Modificaciones en el estilo de vida como la cesación del uso de tabaco, cambios dietéticos y la actividad física pueden constituir la intervención más costo efectiva en los pacientes con PAD. Dejar de fumar es la intervención más importante ya que el uso de tabaco es el factor de riesgo con mayor impacto en el desarrollo de la claudicación y cuya cesación puede lograr un aumento en la sobrevida de estos pacientes. La terapia anti-plaquetaria es un componente esencial para el tratamiento de PAD de las extremidades inferiores. En adición a retrasar la progresión obstructiva arterial, estos agentes confieren una reducción de eventos cardiovasculares adversos como infarto al miocardio (IM) no fatal, apoplejía cerebral y muerte por causas vasculares. El tratamiento recomendado consiste en monoterapia con 75-325 mg de aspirina diario. El tratamiento actual para PAD se enfoca en obtener control de los síntomas y mejorar calidad de vida. Los dos agentes que han consistentemente demostrado mayor eficacia en estos dos renglones son cilostazol y oxalato de naftidrofurilo. Oxalato de naftidrofurilo es considerado por algunos expertos como el agente mas eficaz y costo efectivo para el tratamiento de PAD. PRMA BOLETIN | 57 Acondroplasia: Un Estudio Pionero Sobre Las Características Psicosociales Y Médicas De Una Muestra En Puerto Rico José Rodriguez-Gomez MD, MPH, PhDa, Ariadna Aldarondo BAb, Frances Vidot BAb, Ana Quiñones BAb, Maily Rivera MSWb, Eledy Cintrón BAb, Natalie González BAb, Rodolfo F. Trujillo MPHb, Nanet M. Lopez-Cordova, PsyDa, Natalia Colón BAb Abstract: La acondroplasia es la causa de enanismo más frecuente conocida en nuestra sociedad1. Se argumenta que esta condición es causada por un desorden autosómico dominante que genera una mutación en el gen que codifica para el receptor número tres del factor de crecimiento de fibroblastos mejor conocido como el FGFR32. Esta mutación es la más común manifestándose en la desproporción por baja estatura de los sujetos que la experimentan, cubriendo un 70% de los casos de enanismo en el mundo3. El Instituto Nacional de la Salud (NIH; por sus siglas en inglés) indican que esta condición ocurre 1 vez entre cada 15,000 a 40,000 nacimientos1. Las características fisiológicas de esta condición generan estatura desproporcionadamente disminuida, con acortamiento de las extremidades, hipoplasia en la mitad de la cara, macrocefalia, abultamiento frontal, ligamentos elásticos e hipotonía entre otras particularidades en el individuo4,5. Esta condición suele provocar dos problemas espinales usuales; cifosis toracolumbar y estenosis espinal lumbar. A través de múltiples estudios se ha encontrado que las complicaciones médicas asociadas a la acondroplasia incluyen: compresiones en la espina dorsal en la área cervical, discapacidades neurales e hidrocefalia debido a un foramen magnum pequeño, apnea del sueño, estenosis que por lo general se ve reflejada en problemas en la vejiga, deformidades en las extremidades inferiores que pueden causar dolor, retraso en desarrollo verbal por problemas auditivos y pérdida de audición6,7. This study explores the psychological wellbeing of twenty-two (n=22) adults with achondroplasia. The sample was composed of seven (n=7) males and fifteen (n=15) females between the ages of 21 and 75 (mean age=39.6). Each individual completed four self-administered questionnaires: the Beck Depression Inventory (BDI-II), the Beck Anxiety Inventory (BAI), the Beck Hopelessness Scale (BHS), and Derogatis Symptom Checklist-90-Revisited (SCL-90-R). They also filled out a socio-demographic questionnaire. We found that 31.8% of the sample reported at least one comorbid condition such as, hypertension, diabetes, rheumatoid arthritis, asthma, scoliosis, thyroid problems, neuropathy, psoriasis, gastritis and/or sleep apnea; 32% reported mild to severe depressive symptoms; 55% reported mild to severe symptoms associated to anxiety and 18% reported mild to severe symptoms associated with hopelessness; 22.7% reported mild to severe symptoms in at least one of the sub-scales in Derogatis Symptom Checklist-90-Revisited (SCL-90-R) particularly the obsessive-compulsive, paranoid and depressive subscales. Chi Square correlations (X2) were made to observe if there was interdependence between the socio-demographic variables and the administered tests. In general, no significant correlations were found between BDI-II, BAI, BHS, SCL-90-R and civil status, gender, income and age. However, a significant correlation was found between age and the somatization sub-scale of the SCL-90-R (rs = 0.510, p < 0.05). Our findings suggest that this particular sample is at risk for developing psycho-medical conditions. There is a marked lack of research in Puerto Rico associated to achondroplasia. The development of preventive and cultural sensitive interventions is suggested in order to protect and treat individuals with the condition. Estudios realizados fuera de Puerto Rico. Key words: Achondroplasia, Mental Health, Profile, Puerto Rico Faculty at Universidad Carlos Albizu, San Juan Campus, San Juan, Puerto Rico b Doctoral Program at Universidad Carlos Albizu, San Juan Campus, San Juan, Puerto Rico a INTRODUCCIÓN: El tema de la acondroplasia es mayormente 58| PRMA BOLETIN abordado desde diferentes perspectivas médicas, que incluyen en forma limitada investigaciones clínicas sobre la salud mental de las personas que padecen la condición. Algunos estudios han indagado en los niveles de ansiedad con pacientes con condroplasia y no específicamente acondroplasia8. En dicho estudio, 168 familias participantes completaron los inventarios de ansiedad “State-Trait” de Spielberg (que incluyen adultos y niños). Según los resultados, no se halló evidencia estadísticamente significativa de que la puntuación de ansiedad, para cualquiera de los sexos o grupo de edad fuera mayor que lo que se espera en la población general8. Sin embargo, unas particulares preguntas del instrumento se reportaban aumentadas en ambos sexos en comparación con la población general, siendo significativas más en las mujeres. De igual forma, en la revisión realizada se encontraron otras psicopatologías asociadas a discapacidad física entre ellas depresión. De hecho, Kilzieh et al. (2010)9, señalan que la discapacidad física es un elemento fuertemente asociado a la depresión, múltiples discapacidades físicas, como por ejemplo lo es la acondroplasia, pueden ser agentes causales de ansiedad y desesperanza. Estudios realizados Puerto Rico. en Se realizó una extensa revisión de literatura con el fin de identificar investigaciones referentes al tema de la acondroplasia en sujetos viviendo en Puerto Rico. Se utilizaron varias fuentes de búsqueda de datos en los últimos 40 años (i.e. Pubmed, Medline, ScienceDirect, Ovid), adicional a la búsqueda en bibliotecas académicas de diferentes universidades en Puerto Rico, utilizando los descriptores más comúnmente asociados a la condición. (i.e., enanismo, acondroplasia). No obstante, no se lograron identificar investigaciones referentes al estudio científico de la acondroplasia en la isla. Este hallazgo justificó la realización de esta investigación pionera con el propósito de compensar esta deficiencia. Se pretende estimular la investigación en el área, además de desarrollar conciencia sobre las posibilidades de ayuda a ser ofrecidas a dicha población. Justificación. El objetivo principal es crear un perfil de una muestra de personas con acondroplasia en Puerto Rico que incluye datos sociodemográficos e información psicológica. Método. Diseño El diseño de esta investigación es exploratorio descriptivo de carácter transversal con un acercamiento ex-post facto ya que el fin de la investigación es observar los fenómenos en su contexto natural para después analizarlos10. En este tipo de diseño estudiosos reconocen estudiar las posibles relaciones entre variables y describir estas tal y como ocurrieron sin la intervención de los investigadores11. De igual forma, se exploran grados de correlación entre variables de la muestra para identificar si existen o no. Este tipo de estudio nos ayuda a obtener información suficiente para tener la posibilidad de llevar a cabo una investigación más completa en algún tiempo futuro10. Muestra La muestra de investigación consistió de veinte y dos participantes escogidos por disponibilidad que padecen la condición. Los mismos eran residentes de Puerto Rico y mayores de 21 años. Esta investigación tiene la aprobación del IRB de la Universidad Carlos Albizu, salvaguardando así el bienestar de los sujetos bajo estudio. Los participantes fueron localizados a través del Capítulo Little People of Puerto Rico y su Presidenta, los cuales endosaron la investigación. Se procedió al reclutamiento con acercamientos directos, al igual que a través de la técnica de “bola de nieves”. En dicha técnica se realiza un contacto el cual a su vez refiere a otros sujetos para ser participes del estudio. El 31.8% de los participantes fueron hombres mientras que 68.2% de los participantes fueron mujeres. Las edades de los participantes fluctuaron entre 21 y 75 años de edad con un promedio de 39.6 años. Se encontró que un 59.1% (n=13) de los participantes se encuentra en la adultez temprana, un 36.4% (n = 8) en adultez intermedia y un 4.5% (n = 1) se encuentra en adultez tardía12. Con relación al estado civil se halló que el 54.5% de los participantes eran solteros/as, el 22.7% eran casados, el 13.6% eran divorciados, el 4.5% eran viudos/as, así mismo el 4.5% de los participantes convivían con un/a compañero/a. El 63.6% de los/as participantes no tienen hijos, mientras que el 36.4% de los participantes sí. La preparación académica de la muestra comprende desde grado elemental hasta estudios doctorales. Se encontró que 13.6% de los participantes alcanzaron hasta un grado educativo de escuela superior, el 22.7% alcanzaron hasta un curso técnico, el 18.2% alcanzaron créditos universitarios, el 22.7% alcanzaron un bachillerato, el 9.1% alcanzaron una maestría, el 4.5% alcanzaron un doctorado, y el 9.1% alcanzaron otros nivel educativos no determinados. Sobre el ingreso anual, se halló que el 65% de los participantes reportaron tener un ingreso anual de $10,000 o menos; el 5% entre $10,001 a $15,000; el 10% entre $15,001 a $20,000 y por último, el 18.2% de los participantes igual o mayor a $20,000. Cabe mencionar que la Oficina del Censo de los Estados Unidos utiliza unos PRMA BOLETIN | 59 umbrales específicos medidos en Tabla 1: Características socio-demográficas de la muestra cantidad de ingreso para determinar el estado de pobreza de los ciudadanos13. Para esto se toma Género 7 varones, en consideración la edad del ciu 15 féminas dadano, su ingreso, el tamaño de Edad Promedio 39.64 la familia y la cantidad de miemEstado Civil más prevalente Soltero/a bros menores de 18 años que Hijos 14 no, 8 sí forman parte de ésta14. Según Categorías de educación más prevalente Curso técnico / lo encontrado en nuestro estudio, Bachillerato un 75 porciento de la muestra Religión practicante más prevalente Católica está recibiendo un ingreso anual Categoría de ingresos más prevalente $10,000 o menos por debajo del umbral de pobreza Condiciones Medicas más prevalentes Hipertensión, Artritis (excluyendo al 9 porciento (n=2) Reumatoidea, Diabe- que no contestó el reactivo). Por es y Asma otro lado, se encontró que el 47.6% de los participantes eran puertorriqueños16. Dicho incatólicos, el 19% pertenecían a de acondroplasia. ventario toma entre cinco a diez una religión protestante, el 19% minutos para completarse. INSTRUMENTOS: no profesaban ninguna religión y el 14.3% profesaban otras deEl Inventario de Ansiedad de Se utilizaron cuatro inventarios nominaciones religiosas. para recopilar la información de Beck (BAI; 1993) es una escala De los participantes, 31.8% los participantes, el Inventario de que mide la severidad de la ansiereportaron tener algún tipo de Depresión de Beck – Segunda dad en adultos y adolecentes17. condición de salud, entre ellas, Edición (BDI-II), el Inventario de Consiste de 21 ítems que son calcondiciones relacionadas a es- Ansiedad de Beck (BAI), la Escala ificados en una escala de cuatro tatura baja, tales como, “acon- de Desesperanza de Beck (BHS) puntos que va desde 0 a 3. En droplasia, pseudo acondroplasia, y el “Symptom Checklist-90-Re- este caso, los valores sugeridos van de 0 a 7 para ansiedad mínidisplasia y enanismo”. De igual visited” de Derogatis. ma, de 8 a 15 para ansiedad leve, forma se reportaron condiciones de 16 a 25 para ansiedad modEl Inventario de Depresión relacionadas al sistema óseo que erada y de 26 a 63 para ansiede Beck – Segunda Edición (BDIreportaron los sujetos, se encontraron: problemas de discos, es- II, 1996) es un instrumento de dad severa18. En el año 2000, se coliosis, trauma lumbar, espon- auto-informe que mide la seve- diseñó un estudio en Puerto Rico dilitis anquilosante, osteoporosis, ridad de la depresión en adultos para “evaluar las característiartritis (reumatoide y psoriática), y adolescentes desde los trece cas psicométricas del Inventario y osteoartritis. Las condiciones años en adelante15. El inventario de Ansiedad Beck (BAI) en una relacionadas al sistema neural consta de 21 ítems los cuales se muestra de envejecidos puertorreportadas fueron: “neuropatía”, califican en una escala de 4 pun- riqueños” 18. En este, se realizó “epilepsia” y “dolores del cuerpo tos que va desde cero hasta tres. un “análisis estadístico para de(piernas)”. Sobre las condiciones La puntuación del Inventario es la terminar la consistencia interna relacionadas al sistema endo- suma total de las calificaciones, del inventario reportándose un crino los participantes indicaron por lo tanto, va desde un mínimo alfa de Cronbach de 0.9456; “lo padecer de: “tiroides”, “diabetes” de 0 hasta un máximo de 63. El que sugiere que el BAI tiene una e “hipoglucemia”. En términos manual de administración15 su- alta consistencia interna en una cardiológicos indicaron sufrir de giere como guía los valores de 0 muestra puertorriqueña de per“hipertensión”. En cuanto a condi- a 13 como depresión mínima, de sonas mayores de 60 años de ciones relacionadas al sistema 14 a 19 como depresión leve, de edad”18. El tiempo de adminisrespiratorio se reportaron “asma”, 20 a 28 como depresión modera- tración del BAI toma entre cinco “sinusitis” “alergias” y “apnea del da y de 29 a 63 como depresión a diez minutos para completarse. sueño”. Hubo participantes que severa. En el año 2006, investipadecían de “psoriasis” y “gastri- gadores puertorriqueños repor- La Escala de Desesperanza de tis”. Las condiciones de salud más taron que este inventario tiene Beck (1993) es una escala de auprevalentes en la muestra estudi- un coeficiente de confiabilidad in- to-informe que “mide tres aspecada fueron, hipertensión, artritis terna (alfa de Cronbach) de 0.89 tos principales de desesperanza: reumatoidea, diabetes y asma, según los datos recopilados en sentimientos sobre el futuro, pérlas cuales no difieren de la po- su estudio sobre este inventario dida de motivación y expectatiblación promedio sin la condición en una muestra de 410 ancianos vas”19. Consiste de 20 asevera 60| PRMA BOLETIN ciones contestadas con cierto o falso y “a cada aseveración se le asigna un valor de 0 o 1”19. Su resultado es la suma del valor de todos los ítems y fluctúa entre 0 a 20. Puede ser contestada por el participante en alrededor de cinco a diez minutos. El manual de administración sugiere los valores de 0 a 3 como desesperanza mínima, de 4 a 8 como desesperanza leve, de 9 a 14 como desesperanza moderada y de 15 hasta 20 como desesperanza severa19. En su estudio sobre la “conducta suicida en una muestra de pacientes diagnosticados con VIH/SIDA”, Vélez-Cruz encontró un coeficiente de confiabilidad de 0.83 para sus participantes puertorriqueñas20. El “Symptom Checklist-90-Revised” es un instrumento de auto-informe que “mide la angustia psicológica actual a través de un vistazo a los síntomas de los individuos y su intensidad”21. Consiste de 90 aseveraciones que reflejan posibles problemas de angustia psicológica contestada por el cliente. A través de este instrumentó se midió la “autopercepción de angustia psicológica en nueve dimensiones primarias de síntomas”21. Estas son: somatización, obsesión compulsión, sensibilidad interpersonal, depresión, ansiedad, hostilidad, ansiedad fóbica, ideas fóbicas y psicoticismo. Los resultados para las “nueve dimensiones de síntomas principales y los índices globales se convierten a ‘t-scores’ estandarizados utilizando tablas para el género y el grupo control apropiado. Las puntuaciones entonces se representan en un perfil”21. De acuerdo al estudio de Rosado-Medina, Rodríguez-Gómez y Altieri-Ramírez en una muestra de centenarios puertorriqueños el “Symptom Checklist-90-Revistited” muestra una consistencia interna adecuada con un alfa de Cronbach de 0.941, lo cual lo hace adecuado para ser utilizado en Puerto Rico. 22 RESULTADOS: En términos psicológicos se reportan los hallazgos divididos por condición tamizada acorde con los instrumentos utilizados. Los hallazgos demuestran que el 55% de los participantes reportaron síntomas entre leves a severos de ansiedad en el Inventario de Ansiedad de Beck, esto es, más de la mitad de la muestra (véase Tabla 2). reportaron síntomas entre leves a moderados de desesperanza (véase Tabla 4). Tabla 4: Escala de Desesperanza de Beck Nivel de Frecuencia % Desesperanza Mínima 18 81.8 Leve 2 9.1 Moderada 2 9.1 Total 22 100.0 En relación a los datos recopilados en el “SympNivel de Ansiedad Frecuencia Porciento tom CheckAnsiedad Mínima 10 45.5 list-90-Revisited” Ansiedad Leve 4 18.2 se observó, Ansiedad Moderada 7 31.8 dentro de los Ansiedad Severa 1 4.5 índices globales Total 22 100.0 de severidad de sintomatología psicológica, Nota. Se muestran las categorías a la cuales se asignaron que el 77.3% de la muestra no los participantes de acuerdo a la reportó síntomas acorde con las puntuación obtenida en el Inven- sub-escalas del instrumento. Sin tario de Ansiedad de Beck y las embargo, el 22.7% de la muestra frecuencias observadas en cada reportaron tener problemas entre leves y moderados. Las sub-esuna de ellas. calas de Obsesividad y ComEn términos del Inventario de pulsividad e Ideación Paranoide Depresión de Beck, el 32% de fueron de las más altas junto a los participantes reportaron sín- Depresión. Siendo la de Idetomas entre leves a severos de ación Paranoide una de las más importantes ya que tiene uno de depresión (véase Tabla 3). los porcentajes de activación más altos en combinación con Tabla 3: Inventario de Depresión de Beck la severidad. A continuación Nivel de Depresión Frecuencia Porciento se presenta el Depresión Mínima 15 68.2 índice global y Depresión Leve 4 18.2 los porcientos de Depresión Moderada 2 9.1 participantes que Depresión Severa 1 4.5 activaron alguna Total 22 100.0 de las sub-escalas con sus graNota. Se muestran las cate- dos de severidad del “Symptom gorías a las cuales se asignaron Checklist-90-Revisited” (véase los participantes, de acuerdo a la Tabla 5). puntuación obtenida en el Inventario de Depresión de Beck y las frecuencias observadas en cada CONTINÚA EN LA PRÓXIMA una de ellas. PÁGINA Tabla 2: Inventario de Ansiedad de Beck Según lo reportado en la Escala de Desesperanza de Beck el 18% de los participantes PRMA BOLETIN | 61 Tabla 5: Índices Globales y Subescalas del SCL-90-R de la muestra bajo estudio con sus grados de severidad SCL-90-R (sub-escalas) Global Somatizacion Obsesividad y compulsividad Sensitividad Interpersonal Depresión Ansiedad Hostilidad Ansiedad Social Ideación Paranoide Psicotismo % de la muestra 22.7 27.2 36.4 Personas Severidad de la muestra 5 Leve / moderado 6 Leve / moderado 8 Leve / moderado 27.2 6 Leve / severo 31.8 22.7 13.6 13.6 31.8 7 5 3 3 7 Leve / moderado Leve Leve / moderado Leve / moderado Leve / moderado / severo 13.6 3 Leve / moderado A continuación, se presenta en forma más detallada las sub-escalas activadas del SCL-90-R en la muestra. Al observar los datos se observó que en la sub-escala de Somatización el 72.7% de la muestra reporta no tener problemas. El 22.7 % de la muestra presentó tener problemas leves y el 4.5% de la muestra reportó tener problemas de manera moderada (véase Tabla 6). Al observar los datos por sub-escala se observó que en la de Sensitividad Interpersonal, el 72.7% de la muestra reporta no tener problemas. El 22.7 % de la muestra presentó tener problemas leves y el 4.5% de la muestra reportó tener problemas de manera moderada (véase Tabla 8). Tabla 6: Sub-escala de Somatización Tabla 8: Sub-escala de Sensitividad Interpersonal Nivel de severidad Frecuencia % Ningún Problema 16 72.7 Problema Leve 5 22.7 Problema moderado 1 4.5 Total (N=22) 22 100.0 Nivel de severidad Frecuencia % Ningún Problema 16 72.7 Problema Leve 5 22.7 Problema severo 1 4.5 Total (N=22) 22 100.0 En la sub-escala de Obsesividad y Compulsividad se observó que el 63.6% de la muestra reportó no tener problemas. Sin embargo, el 27.3 % de la muestra presentó tener problemas leves y el 9.1% de la muestra reportó tener problemas de manera moderada (véase Tabla 7). En la sub-escala de Depresión, el 68.2% de la muestra reportó no tener problemas. El 27.3 % de la muestra presentó tener problemas leves y el 4.5% de la muestra reportó tener problemas de manera moderada. (véase Tabla 9) Tabla 7: Sub-escala de Obsesividad y Compulsividad Tabla 9: Sub-escala de Depresión Nivel de severidad Frecuencia % Ningún Problema 14 63.6 Problema Leve 6 27.3 Problema moderado 2 9.1 Total (N=22) 22 100.0 62| PRMA BOLETIN Nivel de severidad Frecuencia % Ningún Problema 15 68.2 Problema Leve 6 27.3 Problema moderado 1 4.5 Total (N=22) 22 100.0 En la sub-escala de Ansiedad el 77.3% de la muestra reportó no tener problemas. El 22.7 % de la muestra presentó tener problemas leves (véase Tabla 10). Tabla 10: Sub-escala de Ansiedad Nivel de severidad Frecuencia % Ningún Problema 17 77.3 Problema Leve 5 22.7 Total (N=22) 22 100.0 En la sub-escala de Hostilidad, el 86.4% de la muestra reportó no tener problemas. El 9.1 % de la muestra presentó tener problemas leves y el 4.5% de la muestra reportó tener problemas de manera moderada (véase Tabla 11). Tabla 11: Sub-escala de Hostilidad Nivel de severidad Frecuencia % Ningún Problema 19 86.4 Problema Leve 2 9.1 Problema moderado 1 4.5 Total (N=22) 22 100.0 En la sub-escala de Ansiedad Social, el 86.4% de la muestra reportó no tener problemas. El 9.1% de la muestra presentó tener problemas leves y el 4.5% de la muestra reportó tener problemas de manera moderada (véase Tabla 12). Tabla 12: Sub-escala de Ansiedad Social Nivel de severidad Frecuencia % Ningún Problema 19 86.4 Problema Leve 2 9.1 Problema moderado 1 4.5 Total (N=22) 22 100.0 En la sub-escala de Ideación Paranoide, el 68.2% de la muestra reportó no tener problemas. El 18.2 % de la muestra presentó tener problemas leves, el 9.1% de la muestra reportó tener problemas de manera moderada y el 4.5% reportó un problema severo (véase Tabla 13). Tabla 13: Sub-escala de Ideación Paranoide Nivel de severidad Frecuencia % Ningún Problema 15 68.2 Problema Leve 4 18.2 Problema moderado 2 9.1 Problema severo 1 4.5 Total (N=22) 2 100.0 Se observó que en la sub-escala Psicotisismo, el 86.4% de la muestra reportó no tener problemas. El 9.1 % de la muestra presentó tener problemas leves y el 4.5% de la muestra reportó tener problemas de manera moderada (véase Tabla 14). Tabla 14: Sub-escala de Psicotisismo Nivel de severidad Frecuencia % Ningún Problema 19 86.4 Problema Leve 2 9.1 Problema moderado 1 4.5 Total (N=22) 22 100.0 Cuando se exploró la asociación entre el SCL-90-R y la edad no se identificó ningún tipo de asociación. No se observaron diferencias significativas a un nivel (p<.05) entre los resultados del BDI-II, BAI, BHS y SCL-90-R, correlacionados con el estado civil, género, ingreso y edad de los participantes. Sin embargo, se obtuvo una correlación significativa entre edad y la sub-escala de somatización del SCL-90-R (r = 0.510, p < 0.05), lo cual significa que a mayor edad mayores síntomas de somatización. CONCLUSIÓN: Más de la mitad de la muestra estudiada presentó niveles entre leves a severos de ansiedad, al igual que una tercera parte reportaron síntomas entre leves a severos de depresión, y aproximadamente una quinta parte de desesperanza. Cabe mencionar que estas patologías representan un gran reto de intervención clínica y la necesidad de prevención en las personas con acondroplasia. Estos hallazgos son importantes ya que confirman la información de PRMA BOLETIN | 63 estudios realizados en el que es importante el reconocer, no tan solo el aspecto médico de la condición sino, el aspecto psicosocial de la misma 24. Esta conclusión nos mueve a cuestionarnos para futuros estudios, cuál de los diversos factores y realidades biopsicosociales de las personas con acondroplasia les impacta más para que presenten esta sintomatología. De igual forma, los niveles de pobreza presentados por la muestra son factores de riesgo para el desarrollo de psicopatología. Según múltiples estudios se ha encontrado una asociación entre un nivel bajo socioeconómico y desordenes de salud mental comunes como la ansiedad y la depresión.24, 25 Cabe entonces reconocer la necesidad de proceder a desarrollar intervenciones para mejor las condiciones económicas de dichos sujetos. Quizás ha de considerarse los estigmas que pudiesen asociarse a su condición y que pueden actuar como factores limitantes en el desarrollo y ajuste adaptativo de esta población por mera ignorancia de aquellos/as que los creen. Los hallazgos de nuestro estudio demostraron que no había diferencias significativas entre las pruebas BDI-II, BAI, BHS y SCL-90-R, y las características sociodemográficas de estado civil, género, ingreso y edad de los participantes. Esto nos hace pensar que nuestra muestra, aún con sus posibles dificultades, según reportadas estas, tienden a ser bastantes resilientes, característica sumamente adaptativa y útil en la vida. Buscar una muestra más amplia de pacientes adultos con la condición de acondroplasia y continuar explorando desde diversas perspectivas los factores biopsicosociales que impactan el desarrollo y manejo de su condición en Puerto Rico, será un reto 64| PRMA BOLETIN para próximas investigaciones. Desarrollar un estudio interdisciplinario que pueda llevar un perfil de los infantes, niños y adolescentes diagnosticados con la condición de acondroplasia sería de mucha utilidad en el futuro, bajo la perspectiva de intervenciones preventivas y de sensibilidad cultural para esta población. De igual manera, desde la perspectiva académica y clínica recomendamos que a través de estos perfiles sobre la población con acondroplasia en la isla se pueda ir promoviendo el desarrollo de protocolos de manejo tanto a nivel médico como de otros profesionales de la salud. Este último aspecto dirigirá en el proceso de desarrollar más conocimiento en la isla para médicos y otros profesionales de la salud en general, de forma tal que puedan asistir más eficientemente en sus prácticas a pacientes con esta condición. También, recomendamos desde la perspectiva biopsicosocial intervenciones con las familias, cuya finalidad sea fortalecer a sus miembros y las interacciones con la comunidad. Finalmente, estos procesos de investigación ampliaran el conocimiento que se les pueda ofrecer a los/las estudiantes de áreas clínicas (i.e., estudiantes de medicina, y ciencias aliadas a la salud) en el área de salud mental y adiestramientos sobre cómo trabajar desde sus diversas perspectivas con personas que tengan la condición. Referencias: 1. U.S. National Library of Medicine Staff. Genetic Home Reference. U.S. National Library of Medicine. http:// ghr.nlm.nih.gov/condition=achondroplasia. Publicado en mayo de 2012.Accesado el 9 de septiembre del 2013. 2. Rodríguez CA, Isaza C, Pahajoa H. Achondroplasia among ancient populations of mesoamerica and South America: Ichonographic and Archeological Evidence. Colombia Médica. 2012; 43: 212-215. 3. Medline Plus Staff. Dwarfism. U.S. National Library of Medicine, National Institute of Health. http://www.nlm. nih.gov/medlineplus/dwarfism.html. Accesado en Agosto de 2013. 4. Thompson NM, Hecht JT, Bohan TP, Kramer LA, Davidson K, Brandt ME, y Fletcher JM. Neuroanatomic and Neuropsychological Outcome in School Age Children with Achondroplasia. American Journal of Medical Genetics (Neuropsychiatric Genetics). 1999; 88: 145-153. 5. Ireland PJ, McGill J, Zankl A, Ware RS, Pacey V, Ault J, Savarirayan R, Sillence D, Thompson EM, Townshend S, Johnston LM. Functional performance in young Australian children with Achondroplasia. Develomental Medicine y Child Neurology. 2011; 944-950. 6. Brinkmann G, Schlitt H, Zorowka P, & Spranger J. Cognitive skills in achondroplasia. American journal of medical genetics. 1993; 47(5): 800-8004. 7. Hoover-Fong JE, McGready J, Schulze KJ, Barnes H, & Scott CI. American journal of medical genetics. 2007; 143A (19): 2227-2235. 8. Hunter A GW. Some psychosocial aspects of nonlethal chondrodysplasias: II. Depression and anxiety. Am. J. Med. Genet. 1998; 78: 9–12. doi: 10.1002/ (SICI)10968628(19980616)78:1<9::AIDAJMG2>3.0.CO;2-N 9. Kilzieh N, Rastam S,Ward KD, Maziak W. Gender, depression and physical impairment: an epidemiologic perspective from Aleppo, Syria. Social Psychiatry and Psychiatric Epidemiology Journal. 2010; 45 (6): 595-602. doi: 10.1007/s00127-009-0076-7 10. Hernandez R, Fernandez C, Baptista M. Metodología de la investigación. (5ta ed.). Mexico: McGrawHill; 2010. 11. Kerlinger FN. Investigación del comportamiento. México: Interamericana; 1988. 12. Papalia D, Wendkos S, & Duskin R. Desarrollo Humano. México: Mc Graw Hill; 2010. 13. United States Census Bureau Staff. (2014). Poverty. United States Census Bureau. http://www.census.gov/ hhes/www/poverty/methods/definitions. html. Accesado en Octubre 2 de 2013. 14. United States Census Bureau Staff. (2014). Poverty Tresholds. United States Census Bureau. http://www.census.gov/hhes/www/poverty/data/threshld/index.html . Accesadp em Octubre 2 de 2013. 15. Beck AT, Steer R, y Brown G. BDI-II, Beck Depression Inventory: Manual 2nd ed. Boston (MA): Haracourt, Brace, & Company; 1996. 16. Rodríguez-Gómez JR, Dávila-Martínez MG y Collazo-Rodríguez LC. Factor structure of the Beck Depression Inventory-second edition (BDI-II) with Puerto Rican elderly. [Abstract]. Puerto Rico Health Sciences Journal. 2006; 25(2): 127-132. 17. Beck AT, y Steer R. Beck Anxiety Inventory Manual. San Antonio (TX): Psychological Corporation; 1993. 18. Rodríguez-Reynaldo M, Rodríguez-Gómez J y Lugo-Martínez M. Estudio de las características psicométricas del Inventario de Ansiedad Beck (versión al español) en una muestra puertorriqueña de edad avanzada [Disertación Doctoral]. Universidad Carlos Albizu, Recinto de San Juan en San Juan, Puerto Rico; 2000. 19. Beck AT, y Steer R. BHS, Beck Hopelessness Scale: Manual 2nd ed. San Antonio, TX: Psychological Corporation; 1993. 20. Vélez-Cruz I. El suicidio en una muestra de pacientes diagnosticados con elvirus de inmunodeficiencia adquirida en Puerto Rico [Disertación Doctoral] Universidad Carlos Albizu, Recinto de San Juan en San Juan, Puerto Rico; 2002. 21. Derogatis LR. Symptom Checklist-90-Revisited (tm) (SCL-90-R). http:// ip-50-63-173192.ip.secureserver.net:2060/eds/ detail?vid=4&sid=ab076541-c3e5471f-a0416917a77654c2%40sessionmgr10&hid=17&bdata=JnNpdGU9ZWRzLWxpdmU% 3d#db=c8h&AN=1997015732’. Publicado en 1997. Accesado en Septiembre de 2013. 22. Rosado-Medina JJ, Rodríguez-Gómez JR y Altieri-Ramirez G. Study on the resilience internal factors in a sample of Puerto Rican centenarians. Boletín de la asociación médica de Puerto Rico. 2012; 104(4): 17-25. 23. Adelson BM. Dwarfism: Medical and Psychosocial Aspects of Profound Short Stature. Baltimore: Johns Hopkins University Press; 2005. 24. Lund C, Breen A, Fisher AJ, Kakuma R, Corrigall J, Joska JA, Swartz L, & Patel V. Poverty and common mental disorders in low and middle income countries: A systematic review. Social science and medicine. 2010; 71: 517528. 25. Green MJ & Benzeval M. The development of socioeconomic inequalities in anxiety and depression symptoms over the lifecourse. Social psychiatry and psychiatric epidemiology. 2013; 48: 1951-1961. Resumen: a severo fueron respectivamente 32%, 55% y 18%. Se realizaron correlaciones de Chi cuadrado para observar si existía independencia entre las variables socio-demográficas y las pruebas administradas. En general, no se encontró ninguna correlación significativa entre BDI-II, BAI, BHS, SCL-90-R y estatus civil, género, ingreso y edad. No obstante, se encontró una correlación significativa entre edad y la sub-escala de somatización del SCL-90-R (rs = 0.510, p < 0.05). Existe necesidad extrema de estudiar esta población y sus particularidades, debido a la pocas investigaciones en Puerto Rico. Los principales hallazgos de salud abordan a reconocer a esta muestra en particular en un alto riesgo de condiciones psico-médicas. El desarrollo de intervenciones preventivas y sensitivas culturalmente son sugeridas en fin de proteger los individuos con acondroplasia. Se espera que los profesionales de la salud sean sensibles con esta población y sus necesidades. Este estudio pionero, el primero en Puerto Rico según nuestro conocimiento, explora el bienestar psicosocial de las personas con acondroplasia y sus características demográficas. La muestra fue de N=22 (7 hombres, 15 mujeres), entre las edades de 21 a 75 años (edad promedio= 39.6) y siendo soltero/a el estado civil más prevalente. Se administró el Inventario de Depresión de Beck (BDI-II), el Inventario de Ansiedad de Beck (BAI), la Escala de Desesperanza de Beck, el “Symptom Checklist-90-Revisited” de Derogatis (SCL90-R) y un cuestionario sociodemográfico para explorar el bienestar psicosocial de los participantes. Los hallazgos muestran que el 31.8% de la muestra reportó múltiples condiciones de salud tales como, hipertensión, diabetes, artritis reumatoidea, asma, escoliosis, problemas de tiroides, neuropatía, soriasis, gastritis y apnea del sueño. Los datos recopilados del Symptom Checklist-90-Revisited reportaron que el 77.3% de la muestra no Palabras clave: Acondroplaactivó ninguna sub-escala. Sin sia, salud mental, perfil, Puerto embargo, el 22.7% de la mues- Rico tra reportó problemas leves a moderados en todas las sub-escalas (especialmente en las sub-escalas de obsesividad-compulsividad, paranoide y depresión). En reacción al BDI-II, BAI and BHS, los porcentajes reportados entre leve Disability Income Insurance Designed especially for professionals, a Radious® disability income insurance policy helps you protect a portion of your income should you become too sick or hurt to work. Lets MassMutual help you get there. Members of Puerto Rico Medical Association gets a 10% of discount in new policies. CALL 787-758-2244 PRMA BOLETIN | 65 Metabolic Changes After Roux-N-Y Bariatric Surgery In Hispanics José Hernández-Gil de Lamadrid, MD; Juan J. Nieves-Rivera, MD; Laura Mora, BS; Lisa Corretjer, BS; Pablo I. Altieri, MD; Albert Suárez, MD; Héctor L. Banchs, M.D.; Jesús Muñiz, MD; Marie Ivelisse Soto, MS; Nelson Escobales, PhD; María Crespo, PhD Departments of Medicine-Surgery-Physiology University of Puerto Rico, San Juan, Puerto Rico Address of Reprints: Pablo I. Altieri, MD Box 8387 Humacao, Puerto Rico 00792 telephone: (787) 630-7638 Facsimile: (787) 725-6423 [email protected] INTRODUCTION During the past decades, the prevalence of obesity in the Unites States (US) has grown exponentially, representing a serious burden to our public healthcare system.(1,2,3) It is estimated that by 2030, if obesity trends continue unchecked in the US, obesity-related medical costs alone could rise by $48 to $66 billion a year.(4) Hispanics are no exception to this problem. The obesity prevalence in Hispanics has been reported to be at least 67%, compared to 32.8% and 44.1% in non-Hispanic whites, and African-Americans, respectively.(5) Obesity is defined by the World Health Organization (WHO) as a Body Mass Index (BMI) ≥ 30 kg/ m², and it is strongly associated with the development of type 2 diabetes mellitus (DM2), hyperlipidemia, stroke, arterial hypertension (HTN), obstructive sleep apnea (OSA), kidney disease, cancer, depression, coronary artery disease, and osteoarthritis, among many others. Furthermore, the association between excessive lipid storage in the form of obesity and increased proinflammatory states, insulin resistance, and endothelial dysfunction has long been recognized(6). Bariatric surgery has emerged as a novel alternative for patients with severe obesity who failed to lose weight by dieting, exercising, and pharmacotherapy. It is indicated in patients with a BMI ≥ 40 kg/m², or a BMI ≥ 35 kg/m² with comorbid conditions such as DM2, OSA, and arterial HTN.7 RouxN-Y is the most common type of bariatric procedure in the United States.(8) Other types of surgery available include adjustable gastric band, sleeve 66| PRMA BOLETIN ABSTRACT The objective was to describe the metabolic outcomes 12 months after bariatric surgery (Roux-N-Y) in morbidly obese Hispanic patients, and evaluate the correlation between weight loss and the observed changes. Medical records from a hundred-and-two Hispanic obese patients who underwent bariatric surgery were identified at the University of Puerto Rico (UPR) Hospital. The following variables were obtained before and 12 months after surgery: Body Mass Index (BMI), body weight, total cholesterol (TC), triglycerides, high density lipoprotein (HDL), low density lipoprotein (LDL), and fasting blood sugar (FBS). Ninety-seven percent of patients underwent Roux-N-Y surgery; 79.4% were females and 44% were diabetics. We observed statistically significant reductions (p<0.05) 12 months after surgery in: BMI -14.3(±6.2) kg/m2, weight -86.1(±34.4) lbs, TC -17.9(±32.4) mg/dL, triglycerides -28.7(±40.6) mg/dL, LDL-15.4(±30.6) mg/dL, and FBS -11.3(±23.5) mg/dL. HDL, instead increased +5.22(±12.9) mg/dL (p<0.0006). Gastric bypass surgery of the Roux-N-Y significantly improves the lipid profile and FBS levels in obese Hispanic patients. The poor correlation factor between weight loss and these variables suggests that other mechanisms, independent from weight loss, are responsible for these changes. gastrectomy, and biliopancreatic diversion.(7) Bariatric surgery has demonstrated to reduce cardiovascular risk factors such as DM2, metabolic syndrome, arterial HTN, and dyslipidemia.(9) It is associated with a lower incidence of cardiovascular events and a significantly reduced number of cardiovascular deaths in obese adults.(10) Obese Caucasians and African Americans have been already extensively studied. To our knowledge, there are no studies examining the metabolic outcomes after bariatric surgery in the Hispanic population. The purpose of the present study is to describe the changes in glycaemia and lipidemia in Hispanic patients undergoing bariatric surgery and the possible underlying mechanisms responsible for these changes. values below 0.05 were considered statistically significant. Statistical analyses were performed using Stata® for Windows release 12.0. The Spearman Rank Correlation Coefficient was used to determine linear associations between weight loss and changes in both FBS and lipids. The Institutional Review Board of the UPR Medical Sciences Campus approved the study. and in post-operatively follow up evaluation 12 months after surgery it was 33.3 ± 7.5 kg/m², for a mean reduction of 14.3 ± 6.2 kg/ m² (p<0.0001). All studied parameters are described in Table 1. Mean body weight pre-operatively 285.1 ± 62.0 lbs.; post-surgery 198.7 ± 54.4 lbs, for a mean reduction of 86.1 ± 34.4 lbs (p< 0.0001). Mean total cholesterol pre-operatively 169.6 ± 30.8 mg/dL; Our studied population’s mean post-surgery 151.8 ± 30.9 mg/ age was 39, and it consisted of dL, for a mean reduction of 17.9 79.4% female patients. The ma- ± 32.4 mg/dL (p<0.0001). jority underwent Roux-N-Y type bariatric surgery (97%), and the Mean triglyceride levels pre-oprest (3%) sleeve gastrectomy. eratively of 112.7 ± 47.3 mg/dL; We found that the mean pre-op- post-surgery 84.0 ± 22.9 mg/ erative BMI was 47.6 ± 9.1 kg/m², dL, for a reduction of 28.7 ± 40.6 RESULTS Table 1. The correlation factor between weight loss and changes in MATERIAL AND METHODS fasting blood sugar, cholesterol, HDL, and LDL POPULATION A retrospective cohort study was conducted in which 102 medical records dated from 2009 to 2011 were obtained. Demographic data and preoperative values of BMI (kg/m2), body weight (lbs), total cholesterol (mg/dL), LDL (mg/dL), triglycerides (mg/dL), HDL (mg/dL), and fasting blood sugar (FBS) (mg/dL) were analyzed from patients who underwent bariatric surgery at the University of Puerto Rico (UPR) Hospital in Carolina, Puerto Rico. Follow up values 12 months after surgery were obtained. STATISTICS Frequency distributions for categorical variables were utilized for study group description; comparison between paired measurements, pre and post-operatively, were obtained by student’s paired-samples t-test, or Wilcoxon matched-pairs signed-ranks test for continuous variables. Mean ± standard deviation (SD) expressed the descriptive data. For the interpretation of results, p PRMA BOLETIN | 67 (p < 0.0001). above study is consistent with there are hypertrophic changes similar, but not Hispanic-focused, occurring at the continuous segMean HDL pre-operatively in previously reported studies.(12) ment. These changes promote a 44.3 ± 10.4 mg/dL; post-surgery better absorption of nutrients by 49.5 ± 13.9 mg/dL, an increase Weight loss has been shown the individual intestinal epitheliof 5.22 ± 12.9 mg/dL (p<0.0006). to improve insulin sensitivity. It al cells. They also suggest that is believed to be secondary to Roux-N-Y surgery alters gut horMean LDL pre-operatively 101.4 weight loss-related reduction in mone levels: decreasing fasting ± 27.6 mg/dL; post-surgery in levels of tumor necrosis factor leptin and insulin, and increasing 86.2 ± 25.3 mg/dL, a reduction of alpha (TNF-alpha). This, in turn, peptide YY, enteroglucagon, and 15.4 ± 30.6 mg/dL (p < 0.0001) increases the phosphorylation of glucagon-like peptide-1 (GLP-1). the insulin receptor substrate-1 (16) Mean FBS pre-operatively 98.9 ± (IRS1) and the activity of the 25.0 mg/dL; post-surgery 87.6 ± phosphatidylinositol-3-kinase Gut microbiota population 20.6 mg/dL, a reduction of 11.3 ± (PI3K), which normalizes the change after bariatric is another 23.5 mg/dL (p<0.001) synthesis and translocation of possibility that could potentially glucose transporter-4 (GLUT4) explain the metabolic profile imThe Spearman’s Rank Correla- in the intestines.(13) Further- provement observed after these tion Coefficient was calculated more, gastric bypass reduces procedures. Obesity has been to determine linear association significantly the patient’s gastric recognized as one factor that between the studied variables fundus, causing a reduction in causes a disturbance in gut miand weight loss. The correlation ghrelin levels, and alterations in crobiota population.(17) Particfactor between weight loss and the enterohepatic axis, restoring ularly, an increase in the Firmicchanges in fasting blood sugar, insulin sensitivity, euglycaemia, utes and Lactobacillus species cholesterol, HDL, and LDL fluc- and B-cell glucose sensitivity. and a reduction in Bifidobactetuated between 0.1-0.5 (p>0.05). (14) These findings could poten- rium and Bacteroidetes species tially explain the improvement in have been found with weight glycaemia seen in our studied gain.18 Moreover, this change in DISCUSSION patients. gut microbiota may in turn influence gastrointestinal hormones In our study we have found that Weight reduction has traditional- such as peptide YY and choleglycaemia and lipidemia both im- ly been perceived to be a strong cystokinin(18), which could poprove in obese Hispanic patients contributor to the above described tentially influence the metabolic undergoing Roux-N-Y bariatric metabolic changes; however, we changes observed after bariatric surgery. This is supported by the have found a poor Spearman surgery, particularly Roux-N-Y. statistically significant reduction Rank Correlation Coefficient in TC, LDL and FBS, as well as when associating lipids and FBS Several studies are currently runthe increase in HDL 12 months changes with weight loss. This ning at our facilities. One of them post-surgery. To the best of our might suggest that weight loss is trying to assess the changes in knowledge, no previous study has not the sole responsibility intestinal microflora before and has ever before demonstrated for these changes. Saeidi, et al, after bariatric surgery (Roux-N-Y; these findings in the Hispanic performed Roux-N-Y surgery on sleeve gastrectomy) in a group population alone. We believe that 19 rats, and demonstrated an of Hispanic patients. Moreover, these changes observed after increased glucose uptake and a comparative study between bariatric surgery are secondary usage occurring secondary to an Roux-N-Y and sleeve gastrecto local alterations in lipid and up-regulation of glucose trans- tomy in this population is curglucose intestinal metabolism, porter-1 (GLUT1), independent rently being performed in order particularly in the Roux limb. of weight loss. Furthermore, they to determine which procedure Alexandrides TK, et al, demon- found that lipidemia improved af- is more successful in achieving strated that malabsorptive pro- ter bypass surgery due to mixed improvement in the Metabolic cedures, such as Roux-N-Y, pro- hyperplastic and hypertrophic Syndrome (MetS). Our experimote poor intestinal absorption of changes in the Roux limb, locally ence with sleeve gastrectomy lipids, and a partial interruption of affecting cholesterol metabolism has only shown a significant enterohepatic circulation of bili- when intestinal tissue exposes to change in weight, BMI reduction, ary salts, increasing their synthe- undigested nutrients.(15) Shaw and fasting blood sugar, although sis rate. Consequently, there is a et al described in another similar analysis is limited due to a small higher rate of cholesterol utiliza- study that after Roux-N-Y surgery group (10 P) of patients. No sigtion as a substrate.(11) The HDL there is villi atrophy occurring nificant changes were observed improvement observed in the at the bypassed segment, and in total cholesterol, HDL, LDL, 68| PRMA BOLETIN and triglycerides. The correlation between these changes with weight loss fluctuated between 0.1-0.5 (P. >0.05). The correlation was lower in the sleeve surgery. This raises the observation that the Roux-N-Y surgery will affect all the biochemical changes seen in MetS, while sleeve gastrectomy will only affect weight, BMI, and glycemic levels in a reduced proportion. In conclusion, glycaemia and lipidemia does improve with bariatric surgery, particularly Roux-N-Y, in Hispanics. Sleeve gastrectomy will probably have little effect in all the biochemical changes seen in a full MetS. More studies are required to fully understand how bariatric surgery really alters the local gastrointestinal metabolism of glucose and lipids, particularly at the Roux limb. REFERENCES (1) Finkelstein EA, Trogdon JG, Cohen JW, Dietz W. Annual Medical Spending Attributable to Obesity: Payerand Service-specific Estimates. Health Affairs 2009; 28(5): w822-831. (2) Colditz GA. Economic costs of obesity. Am J Clin Nutr 1992; 55:503S–507S. (3) Cawley J, Meyerhoefer C. The medical care costs of obesity: an instrumental variables approach. J Health Econ 2012; 31:219-30. (4) Wang CY, McPherson K, Marsh T, Gortmaker S, Brown M. Health and economic burden of the projected obesity trends in the USA and the UK. Lancet 2011; 378:815-25. (5) Cornier MA, Despres JP, Davis N, Grossniklaus DA, Klein S, Lamarche B et al. Assessing adiposity: A Scientific statement from the American Heart Association. Circulation 2011 Nov 1; 124(18): 1996-2019. (6) Shulman GI. Ectopic fat in insulin resistance, dyslipidemia, and cardiometabolic disease. N Engl J Med 2014 Sep 18;371(12):1131-41. (7) Snow V, Barry P, Fitterman N, Qaseem A, Weiss K; Clinical Efficacy Assessment Subcommittee of the American College of Physicians. Pharmacologic and surgical management of obesity in primary care: a clinical practice guideline from the American College of Physicians. Ann Intern Med 2005 Apr 5;142(7):525-31. (8) Tice, Jeffrey. Bariatric surgery for the treatment of type 2 diabetes mellitus. California Technology Assessment Forum 2012 Nov. 1-61. (9) Vest AR, Heneghan HM, Agarwal S, Schauer PR, Young JB. Bariatric surgery and cardiovascular outcomes: a systematic review. Heart 2012; 98 (24): 1763-1777. (10) Sjöström L, Peltonen M, Jacobson P, Sjöström CD, Karason K, Wedel H et al. Bariatric surgery and long-term cardiovascular events. JAMA 2012 Jan 4;307(1):56-65. (11) Alexandrides TK1, Skroubis G, Kalfarentzos F. Resolution of diabetes mellitus and metabolic syndrome following Roux-en-Y gastric bypass and a variant of biliopancreatic diversion in patients with morbid obesity. Obes Surg 2007 Feb;17(2):176-84. (12) Busetto L, Sergi G, Enzi G, Segato G, De Marchi F, Foletto M et al. Short term effects of weight loss on the cardiovascular risk factors in morbidly obese patients. Obes Res 2004;12(8):1256-63. (13) Smith U. Impaired (‘diabetic’) insulin signaling and action occur in fat cells long before glucose intolerance--is insulin resistance initiated in the adipose tissue? Int J Obes Relat Metab Disord 2002 Jul;26(7):897904. (14) Polyzogopoulou EV1, Kalfarentzos F, Vagenakis AG, Alexandrides TK. Restoration of euglycemia and normal acute insulin response to glucose in obese subjects with type 2 diabetes following bariatric surgery. Diabetes 2003 May;52(5):1098-103. (15) Saeidi N, Meoli L, Nestoridi E, Gupta NK, Kvas S, Kucharczyk J et al. Reprogramming of Intestinal Glucose Metabolism and Glycemic control in rat after gastric bypass. Science 2013 Jul 26; 341 (6144): 406-10. (16) Shaw D, Gohil K, Basson MD. Intestinal mucosal atrophy and adaptation. World Journal of Gastroenterology 2012 Nov 28; 18 (44): 6357-6375. (17) Chassaing B, Koren O, Goodrich JK, Poole AC, Srinivasan S, Ley RE et al. Dietary emulsifiers impact the mouse gut microbiota promoting colitis and the metabolic syndrome. Nature 2015 Mar 5; 519(7541):92-6. (18) Osto M, Abegg K, Bueter M, le Roux CW, Cani PD, Lutz TA. Roux en-Y gastric bypass surgery in rats alters gut microbiota profile along the intestine. Physiol and Behav 2013 Jul 2;119:92-6. ABSTRACTO: El objetivo es describir los resultados metabólicos, 12 meses después de la cirugía bariátrica (Roux-N-Y), en pacientes Hispanos mórbidamente obesos y evaluar la correlación entre pérdida de peso y los cambios observados. Se identificaron expedientes médicos de Ciento dos Hiispanos obesos sometidos a cirugía bariátrica en el Hospital de la Universidad de Puerto Rico (UPR). Las siguientes variables fueron obtenidas antes y 12 meses después de la cirugía: índice de masa corporal (IMC), peso corporal, colesterol total (CT), triglicéridos, lipoproteína de alta densidad (HDL), lipoproteína de baja densidad (LDL) y sangre en ayunas (FBS) de azúcar. Noventa y siete por ciento de los pacientes experimentaron la cirugía Roux-N-Y; 79,4% eran mujeres y 44% eran diabéticos. Se observaron reducciones estadísticamente significativas (p < 0.05) 12 meses después de la cirugía en: IMC-14.3(±6.2) kg/m2, peso-86.1(±34.4) kilos,-17.9(±32.4) TC mg/dL, triglicéridos-28.7(±40.6) mg/ dL, LDL-15.4(±30.6) mg/dL y FBS-11.3(±23.5) mg/dL. HDL, en cambio, aumentó +5.22(±12.9) mg/dL (p < 0.0006). La cirugía de bypass gástrico de Roux-N-Y mejora significativamente el perfil lipídico y niveles FBS en pacientes obesos Hispanos. El factor de correlación pobre entre la pérdida de peso y estas variables sugiere que otros mecanismos, independientes de la pérdida de peso, son responsables de estos cambios. PRMA BOLETIN | 69 Obesity and premature coronary artery disease with myocardial infarction in Puerto Rican young adults José M. Marcial, MD, and Pablo I. Altieri, MD Department of Medicine and Physiology, Medical Sciences Campus, University of Puerto Rico and Cardiovascular Center of Puerto Rico and the Caribbean Address Correspondence to: Pablo I. Altieri, MD - University of Puerto Rico - Medical Sciences Campus - Department of Medicine and Physiology - P.O. Box 365067 - San Juan, PR 00936-5067 - Email: [email protected] - Phone: (787) 6307638 - Facsimil: (787) 765-8471 Introduction: Coronary heart disease (CHD) is the leading cause of death in Puerto Rico and the United States. In 2010, the prevalence of CHD in Puerto Rico was 8%. (1) Many predictors have shown to confer a greater mortality in the setting of CHD and myocardial infarction. In particular, angiographic severity of coronary artery disease (CAD) has been shown to be a predictor of long-term adverse cardiovascular events and mortality as well as treatment costs. (2-3) Exploring the association between cardiovascular risk factors and angiographic severity or extent of CAD in young Puerto Rican adults who have suffered a myocardial infarction could elucidate which factors have the most impact on the progression of premature CHD in this unique population. The objective of this study was to evaluate the association between the cardiovascular risk profile and angiographic characteristics of young Puerto Rican adults who have suffered a myocardial infarction. Methods: This was a cross-sectional study which reviewed the medical records of young adults aged 21 to 35 years who underwent left cardiac catheterization in the Cardiovascular Center of Puerto Rico and the Caribbean during 2008 to 2012 due to myocardial infarction. Myocardial infarction was defined as hospital or physician records confirming a definite history of myocardial infarction and cardiac enzyme elevation. Patients without cardiac enzyme elevation documented on record were excluded from the study. Within the variables collected were age, gender, BMI, history of systemic hypertension, diabetes mellitus, dyslipidemia, tobacco use, family history of CHD and the use of drugs such as cocaine. In addition, angiographic data was retrieved 70| PRMA BOLETIN Abstract: A cross-sectional study examined adults aged 21 to 35 years who underwent left cardiac catheterization in the Cardiovascular Center for Puerto Rico and the Caribbean during 2008-2012 due to myocardial infarction. Demographic characteristics, clinical risk factors, and the extent of CAD were documented. Chi-square statistic or Fisher’s exact test was used to compare the distribution of demographic, clinical, and lifestyle characteristics across CAD extent. Polytomous logistic regression models were fitted to estimate the prevalence odds ratios (POR) with 95% confidence intervals (CI) for non-obstructive and obstructive coronary disease (OCD) compared with normal coronary anatomy. Statistical analyses were performed using Stata 11.0. Sixty-three (n=63) adults were evaluated (81% were men). The mean age was 31 ± 4 years. The most frequent clinical risk factors were history of tobacco use, hyper tension, and dyslipidemia. Obesity was present in 45.9% of subjects and OCD was present in 52.38% of subjects. Obesity and family history of CAD were significantly associated with OCD when adjusted by age. Obese patients had 5.94 times the possibility of having OCD than normal weight patients. Obesity was the most important treatable predictor of premature obstructive CAD in our young adult population. and it was categorized into 3 groups corresponding to the extent of CAD. Obstructive coronary artery disease (OCD) was defined as 70% or more occlusion in the right, left anterior descending or left circumflex artery, or a 50% or more occlusion of the left main artery. Non-obstructive coronary artery disease (NOCD) was defined as less obstruction than that of OCD, or any degree of obstruction in minor vessels. Normal coronary anatomy was defined as angiographically normal coronary arteries. IRB approval was attained for the performance of this study. Data from study participants was recorded in a database designed with the use of Research Electronic Data Capture (REDCap) software developed and supported by the Puerto Rico Clinical and Translational Research Consortium (PRCTRC). Chi-square statistic or Fisher’s exact test was used to compare the distribution of demographic, clinical, and lifestyle characteristics across CAD extent. Polytomous logistic regression models were fitted to estimate the prevalence odds ratios (POR) with 95% confidence intervals (CI) for non-obstructive and obstructive coronary disease compared with normal coronary anatomy. Statistical analyses will be performed using Stata for Windows release 11.0 (Stata Corporation, College Station, Texas). Results: Data chart review consisted of 63 medical records. An 81 % of the subjects were male and a 46% was obese (table 1). The mean age was 31 years. The most frequently present risk factors other than obesity were a history of hypertension, tobacco use and dyslipidemia (Table 2). Interestingly, a 30% of the subjects had a normal coronary anatomy and a 52% of the patients had OCD (table3). Results adjusted to polytomous logistic regression model demonstrated with statistical significance that patients 30 to 35 years of age were 7.71 times more likely to have OCD than patients from 21 to 29 years of age (Table 4). Table 5 shows statistically significant associations between clinical and demographic factors and the coronary artery disease severity adjusted by age. Obese patients were 5.94 times more likely to have OCD than those with a normal BMI (p=0.04). In addition, patients with family history PRMA BOLETIN | 71 cardiovascular diseases. We have recently reviewed the studies that support the idea of a milder phenotype of the metabolic syndrome and CHD in Hispanic versus non-Hispanic populations.(8) Similarly, it has been shown that black and Hispanic patients in the United States have a lower prevalence of CAD than their white, non-Hispanic counterparts when referred for evaluation of stable and unstable chest pain symptoms.(9) Cocaine and CAD of CHD were 19.48 times more likely to have OCD than patients without family history of CHD (p=0.02). There were no statistically significant associations between hypertension, diabetes mellitus, dyslipidemia and tobacco use, and the extension of coronary artery disease. Discussion: Ethnicity and premature CAD Our patients had a markedly higher frequency of normal coronary arteries (30%) upon index myocardial infarction than in other comparable studies, including the Coronary Artery Surgery 72| PRMA BOLETIN Study Registry (16% men and 21% women)(4), a study performed in Pakistan (6.7%)(5) and another in Poland (20%)(6). Myocardial infarction with normal coronary arteries usually occur in patients where risk factors for CHD are absent.(7) The young Puerto Rican adult population or Hispanics in general, as suggested by this study, may have a higher incidence of myocardial infarction with normal coronary arteries due to increased predisposition for coronary vasospasm, microvascular disease or enhanced thrombolytic mechanisms. Whichever the reason, it is known that there is ethnic variation in the expression of It is probable that the use of cocaine in our subjects was underreported. The prevalence of myocardial infarctions induced by cocaine is likely higher, especially in view of the high frequency of normal coronary anatomy found in these patients. The self-reported history of cocaine and marijuana use was present in 6.3% and 3.2% of our subjects, respectively. Toxicology was positive for cocaine in 3% of subjects; however, only 14.3% of the total subjects underwent drug toxicology. Furthermore, cocaine is cleared from the urine and blood in approximately 3 and 7 days respectively. Thus, the fact that cocaine use is not biochemically confirmed in an acute setting does not indicate that chronic use of the drug has not taken a toll on the cardiovascular system. The abuse of cocaine has been associated to serious coronary ailments of both an acute (i.e vasospasm) and chronic (i.e. atherosclerosis) nature, as well as to heart failure, cardiomyopathies, arrhythmias, aortic dissection, and endocarditis.(10) All these facts should be of particular concern in Puerto Rico, where the prevalence of this illicit drug use is high. Cocaine abuse may be placing a heavier burden on the cardio metabolic profile of our country than is traditionally perceived and further research into drug use and its association with cardiovascular disease in our population is imperative from a public health and economic standpoint. Obesity and premature obstructive CAD Obesity adversely impacts cardiovascular hemodynamics, structure and function(11), as well as increases the prevalence of most cardiovascular diseases. However, an “obesity paradox” has been noted in a variety of cardiovascular ailments, wherein a higher BMI has been reported as protective against cardiovascular events.(12) It has been shown that despite the fact that obesity increases the risk for developing CHD, at least overweight and mild obesity do not seem to adversely affect prognosis in older patients with established CHD.(13) It is currently unknown if obesity itself is a marker of improved nutrition in older populations or whether a low BMI is confounded by unexplained factors that promote mortality, such as frailty. It has also been documented that obese people tend to receive a more aggressive medical intervention. On the other hand, the risk of dying overall and from most major health causes has been associated to increasing BMI within the class III obesity group.(14) augmented neuro-hormonal activation, inflammation, pro-thrombosis and insulin resistance that may lead to high blood pressure, dyslipidemia, impaired glucose metabolism and endothelial dysfunction. This natural history of obesity may explain why obesity is more prevalent in our subjects than the other risk factors. Similarly, a recent study has shown that younger patients with heart failure are more likely to be obese than have other comorbidities such as diabetes mellitus, hypertension and stroke, likewise reflecting that these conditions occur beyond middle age.(16) In the United States, the total excess cost related to the current prevalence of adolescent overweight and obesity is estimated to be $208 billion in lost productivity secondary to premature morbidity and mortality.(17) The first large-scale data on body mass index (BMI) and cardiovascular disease risk factors among U.S. Hispanic/Latino adult populations demonstrated that the most severe class of obesity, a BMI greater than 40, was most common among young adults between 25 and 34 years of age. (18) In this group were looking for severe inflammation biomarkers and new cellular mechanisms for the resolution of inflammation termed in general resolvings and protectins. They have anti-inflammatory and pro-resolution properties.(19) In Puerto Rico, an alarmingly high prevalence of obesity has been estimated at 26.8% in elementary school children and 67% of the population is obese.20 It is imperative that risk factor management, especially lifestyle changes, exercise and healthy dietary habits be implemented at an early age, when the effects of obesity may be most damaging. This is the challenge of the Puerto Rico Government and the Health Department in the 2011 century.21 In our study, obesity was the only statistically significant “treatable or modifiable” predictor of premature obstructive CAD in young adults upon index myocardial infarction. Obesity is more prevalent than diabetes mellitus, hypertension, tobacco use and dyslipidemia in adolescent and pre-adolescent populations.(15) Thus, it is more than plausible that obesity holds a heavier and more detrimental cumulative burden on the coronary vasculature of our subjects than do the other risk factors that may have developed later in time. Indeed, obesity, especially central or abdominal obesity, is associated with Limitations Due to the infrequent nature of myocardial infarctions at a young age, an inherent limitation of our study naturally is a poor sample size. In addition, because the exposure and outcome were simultaneously assessed, there is generally no evidence of a temporal relationship between exposure and outcome. Thus, it is difficult to infer about causality. Lastly, results cannot be generalized to all subjects in Puerto Rico with CHD. Conclusion: The fight against the obesity epidemic should always remain a cornerstone in the prevention of cardiac disease. It may prove to be the best placed effort to ameliorate the rampant nature of CHD in the island of Puerto Rico. In addition, more resources should be spent in the exploration of cardiovascular disease in Puerto Ricans as it provides important and unique information for understanding the interrelationship between genetics, environment and culture in the modification of cardiovascular health. References: (1) Behavioral Risk Factor Surveillance System (BRFSS). 2006-2010 (2) Chilappa K, Aronow WS, Rajdev A, et al. Mortality at long-term follow-up of patients with no, nonobstructive, and revascularized 1-, 2-, and 3-vessel obstructive coronary artery disease. Med Sci Monit. 2010;16(5):RA120123. (3) Janardhanan R, Kenchaiah S, Velazquez EJ, et al. Extent of coronary artery disease as a predictor of outcomes in acute myocardial infarction complicated by heart failure, left ventricular dysfunction, or both. Am Heart J. 2006;152(1):183-189. (4) Zimmerman FH, Cameron A, Fisher LD, Ng G. Myocardial infarction in young adults: angiographic characterization, risk factors and prognosis (Coronary Artery Surgery Study Registry). J Am Coll Cardiol. 1995;26(3):654-661. (5) Shah SS, Noor L, Shah SH, et al. Myocardial infarction in young versus older adults: clinical characteristics and angiographic features. J Ayub Med Coll Abbottabad. 2010;22(2):187-190. PRMA BOLETIN | 73 Disability Income Insurance Designed especially for professionals, a Radious® disability income insurance policy helps you protect a portion of your income should you become too sick or hurt to work. Lets MassMutual help you get there. Members of Puerto Rico Medical Association gets a 10% of discount in new policies. CALL 787-758-2244 74| PRMA BOLETIN (6) Trzos E, Uznańska B, Rechciński T, Krzemińska-Pakuła M, Bugała M, Kurpesa M. Myocardial infarction in young people. Cardiol J. 2009;16(4):307311. (7) Chandrasekaran B, Kurbaan AS. Myocardial infarction with angiographically normal coronary arteries. J R Soc Med. 2002;95(8):398-400. (8) Marcial JM, Altieri PI, Banchs H, Escobales N, Crespo M. Metabolic syndrome among Puerto Ricans and other Hispanic populations. P R Health Sci J. 2011;30(3):145-151. (9) Shaw LJ, Shaw RE, Merz CN, et al. Impact of ethnicity and gender differences on angiographic coronary artery disease prevalence and in-hospital mortality in the American College of Cardiology-National Cardiovascular Data Registry. Circulation. 2008;117(14):1787-1801. (10) Schwartz BG, Rezkalla S, Kloner RA. Cardiovascular effects of cocaine. Circulation. 2010 Dec 14; 122(24):255869 (11) Alpert M.A.; Obesity cardiomyopathy: pathophysiology and evolution of the clinical syndrome. Am J Med Sci. 321 2001:225-236. (12) Lavie CJ, McAuley PA, Church TS, Milani RV, Blair SN. Obesity and Cardiovascular Diseases - Implications Regarding Fitness, Fatness and Severity in the Obesity Paradox. J Am Coll Cardiol. 2014. (13) Lavie C.J., Milani R.V., Artham S.M.; The obesity paradox, weight loss, and coronary disease. Am J Med. In press. ; 2009 (14) Kitahara CM, Flint AJ, Berrington de Gonzalez, A, et al. Association between Class III Obesity (BMI of 40–59 kg/m) and Mortality: A Pooled Analysis of 20 Prospective Studies. PLOS Medicine. July 8, 2014 (15) Kotchen TA. Obesity-related hypertension: epidemiology, pathophysiology, and clinical management. Am J Hypertens. 2010;23(11):1170-1178. (16) Wong CM, Hawkins NM, Jhund PS, et al. Clinical characteristics and outcomes of young and very young adults with heart failure: The CHARM programme (Candesartan in Heart Failure Assessment of Reduction in Mortality and Morbidity). J Am Coll Cardiol. 2013;62(20):1845-1854 (17) Go AS, Mozaffarian D, Roger VL et al; on behalf of the American Heart Association Statistics Committee and Stroke Statistics Subcommitte Heart disease and stroke statistics—2013 update on Overweight and Obesity: a report from the American Heart Association. Circulation. 2013;127:e6-e245. (18) Kaplan RC, Avilés-Santa ML, Parrinello CM, et al. Body mass index, sex, and cardiovascular disease risk factors among Hispanic/Latino adults: Hispanic community health study/study of Latinos. J Am Heart Assoc. 2014 Jul 9;3(4). (19) Serham CN, Chiang IV, Van Dyket. Nature reviews inmmunology 2008; 8:349-361. (20) Rivera-Soto WT, Rodríguez-Figueroa L, Calderón G. Prevalence of childhood obesity in a representative sample of elementary school children in Puerto Rico by socio-demographic characteristics, 2008. P R Health Sci J. 2010;29(4):357-363. (21) Department of Health of Puerto Rico Statistics (2010). Peripheral Arterial Disease: Surgical Treatment José Hernández Gil de Lamadrid, MD, Héctor Delgado Osorio, MD Abstracto: Abstract Se presenta un estudio transversal en el cual se examinaron los expedientes médicos de adultos entre 21 y 35 años de edad con angiografía coronaria realizada en el Centro Cardiovascular de Puerto Rico y del Caribe desde el 2008- 2012, después de sufrir un infarto de miocardio. Características demográficas, factores de riesgo clínicos y la extensión de enfermedad coronaria fueron documentados. Estas variables fueron ajustadas en modelos de regresión logística polítoma para estimar su asociación con la severidad de enfermedad coronaria, ya fuera enfermedad coronaria obstructiva (OCD) o no-obstructiva. Sesenta y tres sujetos fueron evaluados. Obesidad y OCD estaban presente en 45.9% y 52.3% de los sujetos, respectivamente. Además de obesidad, los factores de riesgo mas frecuentes fueron el uso de tabaco, hipertensión y dislipidemia. Solamente la obesidad y un historial familiar de enfermedad cardiovascular fueron significativamente asociados con la presencia de OCD (p <0.05). Ajustados por edad, los pacientes obesos tuvieron 5.9 veces la probabilidad de tener OCD que los pacientes de peso normal (p=0.04). La obesidad es el predictor modificable de enfermedad coronaria prematura más importante en nuestra población de adultos jóvenes Puertorriqueños. Peripheral arterial disease is a frequent under-diagnosed and poorly recognized clinical entity that can affect a great number of patients. Recognition of risk factors is crucial and a thorough evaluation of symptoms and use of diagnostic tools to better decide when an intervention is warranted. Lower extremity bypass surgery is one alternative method for treatment of PAD. It is indicated for type D and C lesions with low cardiac risk according to the TASC classification system. Preoperative assessment is imperative for every vascular procedure since it has been associated with major postoperative cardiovascular events; myocardial infarction being the most common. After excluding active disease, functional capacity and clinical risk predictors must be determined via METs and the Revised Cardiac Risk Index (RCRI), respectively. If a patient is considered to have a high cardiac risk, then noninvasive studies should be performed. Aspirin and a statin should be administered preoperatively and postoperatively. Clopidogrel can be utilized as an alternative if a contraindication to aspirin exists. Periodic follow up consisting of clinical evaluations assessing any return or progression of symptoms of claudication, presence of pulses, ankle-brachial index (ABI) measurement, and smoking cessation counseling should be performed in every patient after vascular surgery. University of Puerto Rico School of Medicine, Department of Medicine, Cardiology Section Cardiovascular Diseases Training Program Index Words: Peripheral Artery Disease, bypass surgery, vascular surgery Introduction Peripheral arterial disease (PAD), defined as a manifestation of diffuse atherosclerosis, is the leading cause of peripheral artery obstruction. The latter is a common but infrequently diagnosed disease process affecting millions of Americans. PAD represents a great healthcare burden and mainly afflicts smokers and diabetes mellitus type 2 (DM2) patients. Recognition of PAD is imperative among Puerto Ricans; particularly as the general profile of our population is afflicted with DM2 (12.8% vs 8.4% with patients from USA). Claudication is the main clinical manifestation of PAD and medical therapy remains as the most important treatment option. However, in certain cases either surgical or endovascular procedure may be considered, particularly if the patient is afflicted by1: x Functional disability that is lifestyle limiting. x Inadequate response to medical therapy and/or exercise rehabilitation. x The affected lesion has characteristics that permit adequate intervention with a high likelihood of success. Therefore, the aim of this article is to review current indications, as well as some preoperative, and postoperative care strategies commonly used in treating PAD patients in need of vascular surgery. Indications for Lower Extremity Bypass Surgery The Trans-Atlantic Inter-Society Consensus (TASC II) group developed a classification system in 2007 that describes different atherosclerotic disease patterns according to their anatomic distribution, as well as extent of the disease given by the number of lesions2. This classification scheme aids the examining physician in deciding which type of PRMA BOLETIN | 75 revascularization procedure is best suited. An endovascular approach is preferred for type A and B lesions, while a surgical approach should be instead considered for type D lesions and C lesions with low cardiac risk2. external iliac arteries. x Iliac stenosis in patients with abdominal aortic aneurysms requiring treatment and not candidates for endograft placement or other lesions requiring surgery. x Bilateral common iliac arteries occlusion x Bilateral stenosis of the external iliac artery measuring 3-10 cm and not involving the common femoral artery. x Unilateral occlusion of the external iliac artery that involves the origins of the internal iliac and/or the common femoral arteries. x Heavy calcified occlusion of a unilateral external iliac artery with or without involvement of origins of the internal iliac and/or common femoral arteries. It is currently debatable and less clearly outlined if patients younger than 50 years of age would benefit from surgical procedures given the lower patency rates and high frequency of graft revisions and replacements subsequently needed3. Additional studies addressing these patients are needed before more concrete guidelines can be formulated. x Femoropopliteal The following describes the classification components best treat- x Chronic total occlusion of ed by a surgical intervention: the common femoral artery or superficial femoral artery 1.Type C lesions x Chronic total occlusion of the popliteal artery and proximal xAortoiliac trifurcation vessels. x Femoropopliteal x Multiple stenotic or occlusive lesions totaling > 15 cm with or without heavy calcification x Recurrent stenosis or occlusion that needs treatment after two endovascular lesions. 2.Type D lesions xAortoiliac x Infrarenal-aortoiliac occlusion. x Diffuse disease involving the aorta and both iliac arteries requiring treatment. x Diffuse multiple stenosis involving the unilateral common iliac artery, external iliac artery, and common femoral artery. x Unilateral occlusion of common iliac artery and the external iliac artery. x Bilateral occlusion of both 76| PRMA BOLETIN Preoperative Care in Patients undergoing Vascular Surgeries Preoperative assessment before any vascular procedure is crucial as these patients are at high risk of developing perioperative complications, of which myocardial infarction is the most common culprit4. In fact, PAD is now recognized as a CAD equivalent and the prevalence of CAD in patients with PAD is reported to be 25%5. Obviously, once a vascular intervention is deemed emergent (<6 hours) or urgent (<6-24 hours), no further medical assessment is needed or required and the intervention should be performed without delay. Acute limb ischemia is defined as a sudden decrease in limb perfusion that represents a threat to limb viability. This condition is characterized by the 6 P’s: pain, pallor, pulselessness, poikilothermia, paralysis, and paresthesia. A 12 lead electrocardiogram (EKG) and a bedside evaluation should be performed with recommendations regarding postoperative care4. In cases of elective surgical intervention, the most important step is to determine if there is any active cardiovascular condition, such as unstable angina, heart failure, symptomatic valvular stenosis, or uncontrolled arrhythmias. In these cases, surgery should be postponed until the active cardiac condition is addressed6. For example, patients with decompensated or worsening CHF have an increased mortality and morbidity such as infections, pulmonary, and renal complications7. Once an active cardiovascular condition has been excluded, the cardiovascular risk should be calculated. History and physical examination are fundamental for this assessment; clinical risk predictors and functional capacity should be determined. Functional capacity is described as metabolic equivalents (METs), in which ≥ 4 METs indicate an acceptable functional capacity. Activities such as the ability to climb stairs or heavy work performance are equivalent to 4 Mets6. The most common utilized cardiac risk stratification tool is the Revised Cardiac Risk Index (RCRI)8. Six elements are included into this risk stratification tool: x Coronary Heart Disease (1 point) x Insulin dependent diabetes (1 point) x Creatinine > 2.0 (1 point) x Cerebrovascular disease (1 point) x High risk surgery (1 point) x Congestive heart failure (1 point) A patient with two or more of the above mentioned components is considered to be at high risk for cardiac events. Current guidelines recommend noninvasive stress testing in patients that will undergo high risk surgery with poor functional capacity and/or perioperative cardiac risk. Noninvasive tests include EKG stress test, dobutamine stress echocardiography, or myocardial scintigraphy4. Left heart catheterization and revascularization should not be performed if not indicated4. Other considerations regarding medical treatment for this type of procedure include ß-blockers, statins, and antiplatelet therapy. The use of perioperative beta blockers has been revised due to the inordinate increase in the risk of stroke9. Statins should be started or continued in patients undergoing vascular surgery. Aspirin should begin preoperatively with a dose between 75 to 100 mg daily and be continued afterwards in patients undergoing infra-inguinal bypass. Clopidogrel (75 mg daily) can be utilized as an alternative if a contraindication to aspirin exists. Aspirin and Clopidogrel are recommended for patients undergoing below the knee prosthetic graft bypass surgery for at least one year10. Vitamin K antagonists have been shown to be superior to antiplatelet agents in venous graft bypass surgeries; antiplatelet agents were shown to be superior in prosthetic graft bypass surgeries11. However, current guidelines have not yet recommended warfarin as part of treatment. Postoperative Care in Patients who underwent Vascular Surgery Postoperative follow up mainly consists of periodic clinical evaluations aimed for surveillance of symptom recurrence, patency of distal pulses, and ankle-brachial index (ABI) assessments. It is indispensable that patients continue abstaining from smoking as this is the most important and well documented intervention in the medical management of PAD. Arterial Duplex sonography is used when there is evidence of disease progression, symptom recurrence, or discrepancy between clinical data and physical examination. We will detail the surveillance approach after bypass in certain areas that warrant specific types of evaluation as per guidelines1. 1. Aortobifemoral bypass: measurement of ABI and periodic evaluation every 12 months. 2. Lower extremity bypass with an autogenous vein graft: arterial Doppler of the entire length of the graft must be performed; twice yearly periodic evaluation for at least two years. 3. Lower extremity bypass with a synthetic bypass graft: twice yearly evaluation for at least two years and. ABI measurement at rest. Arterial Doppler has not been found to be beneficial in synthetic bypass graft12. References 1. Hirsch et al. ACC/AHA 2005 Practice Guidelines for the management of patients with peripheral arterial disease (lower extremity, renal, mesenteric, and abdominal aortic): a collaborative report from the American Association for Vascular Surgery/Society for Vascular Surgery, Society for Cardiovascular Angiography and Interventions, Society for Vascular Medicine and Biology, Society of Interventional Radiology, and the ACC/AHA Task Force on Practice Guidelines (Writing Committee to Develop Guidelines for the Management of Patients With Peripheral Arterial Disease): endorsed by the American Association of Cardiovascular and Pulmonary Rehabilitation; National Heart, Lung, and Blood Institute; Society for Vascular Nursing; TransAtlantic Inter-Society Consensus; and Vascular Disease Foundation. Circulation. 2006;113(11):e463 2. Norgren et al. Inter-Society Consensus for the Management of Peripheral Arterial Disease (TASC II). Journal of Vascular Surgery. 2007 Jan;45 Suppl S:S5-67. 3. Reed et al. The impact of patient age and aortic size on the results of aortobifemoral bypass grafting. Journal of Vascular Surgery. 2003 Jun;37(6):121925. 4. Garg P. Preoperative Cardiovascular Evaluation in Patient Undergoing Vascular Surgery. Cardiology Clinics: Vascular Disease. February 2015; Volume 33, number 1: 139-150. 5. Hertzer et al. Coronary artery disease in peripheral vascular patients: a classification of 1,000 coronary angiograms and results of surgical management. Annals of Internal Medicine 1993:223-233. 6. Fleisher et al. 2014 ACC/AHA guidelines on perioperative cardiovascular evaluation and management for patients undergoing noncardiac surgery: a report of the ACC/AHA task force on practice guidelines. Journal of the American College of Cardiology. 2014 Dec 9;64(22):e77-137. 7. Maile et al. Worsening preoperative heart failure is associated with mortality and noncardiac complications, but not myocardial infarction after noncardiac surgery: a retrospective cohort study. Anasthesia and Analgesia. 2014 Sep;119(3):522-32. 8. Lee et al. Derivation and prospective validation of a simple index for prediction of cardiac risk of major noncardiac surgery. Circulation 1999;100: 1043-1049. 9. Wijeysundera et al. Perioperative blockade in Noncardiac Surgery: A Systematic Review for the 2014 ACC/ AHA Guideline on Perioperative Cardiovascular Evaluation and Management of Patients Undergoing Noncardiac Surgery. Journal of the American Collge of Cardiology. December 2014; 64(22):2406-2425. 10. Alonso-Coello et al. Antithrombotic therapy in peripheral artery disease: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest. 2012;141(2 Suppl):e669S). 11. Dorffler at al. Antithrombotic agents for preventing thrombosis after infrainguinal arterial bypass surgery. Cochrane Database Syst Rev 2003. 12. Lundell et al. Femoropopliteal-crural graft patency is improved by an intensive surveillance program: a prospective randomized study. Vasc Surg. 1995 Jan;21(1):26-33; discussion 33-4. Abstracto Enfermedad periferovascular es una entidad clínica pobremente reconocida y diagnosticada que puede afectar una gran cantidad de pacientes. Reconocimiento de los factores de riesgo es crucial y conlleva una evaluación exhausta de los síntomas con diferentes herramientas diagnósticas para así decidir que intervención es la más apropiada. La cirugía de puente de la extremidad baja es una de las alternativas disponibles para dicha enfermedad. Está indicada para lesiones tipo D y tipo C con bajo riesgo cardiaco de acuerdo a la clasificación PRMA BOLETIN | 77 TASC. La evaluación preoperatoria es imperativo para cualquier procedimiento vascular dado que se ha asociado con eventos cardiovasculares postoperatorios adversos, siendo el infarto al miocardio el más común. Una vez que una cirugía vascular es considerada emergente, un electrocardiograma y una evaluación física son lo único necesario para llevar a cabo dicha evaluación. Si la cirugía se considera electiva, el médico deberá determinar si alguna condición cardiovascular activa, como por ejemplo enfermedad coronariana aguda, fallo congestivo, arritmias cardiacas, o enfermedad valvular activa, están presente. De haber alguna condición activa, la cirugía deberá ser pospuesta. Al excluir una condición activa, la capacidad funcional y los predictores de riesgo clínico deben ser determinados por el “METs” y el Índice Revisado de Riesgo Cardiaco (IRRC). Si se determina que el paciente tiene alto riesgo cardiaco se deberá de realizar estudios no invasivos. Aspirina y estatina deberán de ser administradas pre y postoperatoriamente. Clopidogrel puede ser una alternativa si existe una contraindicación a la aspirina. Después de la cirugía, se deberá de realizar evaluaciones periódicas para determinar los siguientes: retorno o progresión de los síntomas de la claudicación, presencia de pulsos, el índice tobillo-braquial, y el cese de fumar cigarrillos. Éstas son trascendentales para cada paciente que lleve a cabo este tipo de cirugía. Por qué auspiciar • Es la primera revista médico científica de Puerto Rico, fundada en 1903. • Está indexada en Cumulative Index e Index medicus • Uno de los pocos recursos gratuitos para que nuestros residentes publiquen sus trabajos y obtengan sus licencias de especialidad. • Se distribuye gratuitamente en forma digital y hardcopy a todos los médicos, en oficinas médicas, hospitales y eventos de educación. • Puede ser descargada gratuitamente de nuestro website https://asocmepdr.org • Por tratarse de un recurso educativo y herramienta de investigación, es utilizada de manera continua por los profesionales de salud, muchos de los cuales las coleccionan. Original research Epidemiology of Traumatic Peripheral Nerve Injuries Evaluated by Electrodiagnostic Studies in a Tertiary Care Hospital Clinic Ruben Y Torres, MD1; Gerardo E Miranda, MD2 Abstract Objectives: Describe the etiology and frequency of traumatic peripheral nerve injuries (TPNI) in the electrodiagnostic laboratory of a tertiary care hospital. Methods: The charts of patients who underwent an electrodiagnostic study for a TPNI were revised. The main outcome measure was the frequency of each injury by anatomic location, involved nerve, mechanism, and severity. Results: 146 charts were included for a total of 163 injured nerves; 109 (74.7%) males and 37 (25.3%) females. The mean age was 33.6 years. The facial nerve and the brachial plexus followed by the ulnar nerve were more frequently involved. The ulnar, sciatic, median, radial nerve, and the lumbosacral plexus were more commonly injured by gunshot wounds, the brachial plexus by motor vehicle accidents, and the facial nerve by iatrogenic causes. The majority of the injuries were incomplete or partial (84.2% were incomplete and 15.8% complete injuries). Conclusions: TPNIs can lead to significant disability, but further investigation is needed to better understand their socioeconomic impact. Keywords: nerve injury, trauma, electrodiagnosis 78| PRMA BOLETIN 1 Resident Physician, 2Assistant Professor. 1-2Department of Physical Medicine, Rehabilitation and Sports Medicine, University of Puerto Rico School of Medicine. PO Box 365067, San Juan, PR 00936, Phone: 787-751-9625, Fax: 787-7541478, email: [email protected], miranda_gerardo@ yahoo.com Introduction Traumatic peripheral nerve injuries (TPNIs) are a major public health problem that can cause significant disability. (1) Their first epidemiologic description came during the American Civil War by the neurologist S. Weir Mitchell, providing the initial insight of such injuries. (2) In fact, historically wartime has provided many of the advances in the knowledge of TPNIs. (2) It is estimated that the number of TPNIs observed in military personnel will increase since more soldiers are surviving previously lethal attacks increasing the risk of residual injury. (2,3) Differentiating civilian and combat related cases is important because the etiology may vary. (2,3) Moreover, a population’s demographic characteristics, development level, and natural disasters (earthquakes) influence the injury distribution, cause, and severity. (4,5) The published literature about the epidemiology of TPNIs is limited. Among the few studies with comparable methodology were done in Brazil, Turkey, Canada, Pakistan, and the United Kingdom’s military personnel. (3,4,6-9) Common etiologic factors include motor vehicle accidents (MVA), penetrating injury, gunshot wounds (GSW), crush, compression, traction, ischemia, occupational, sport-related, and explosions. (1,3) The ulnar, median, and radial nerve along with the brachial plexus are more susceptible to injury in the upper limbs, while the sciatic and the deep peroneal nerve in the lower limbs. (3,4,6-10) Electrodiagnostic evaluation (EDX), encompassed by nerve conduction studies (NCS) and electromyography (EMG), is a reliable and useful method to localize and assess severity of a peripheral nerve injury. (1,2,6) Patients should be referred within 6 months after the trauma in order to help in the clinical decision while studies performed after 3 PRMA BOLETIN | 79 months of the trauma have more prognostic certainty. (1,11) The aim of this study was to assess and describe TPNI distribution pattern, mechanism, and severity in the patient population of the main medical center in Puerto Rico that had undergone an EDX evaluation. This study will add knowledge about the epidemiology of TPNIs specific to our population. Methods This study was approved by the Institutional Board Review (IRB) of the University of Puerto Rico Medical Sciences Campus. The medical charts of patients who had undergone an EDX study in the Department of Physical Medicine and Rehabilitation (PM&R) in the University District Hospital from 2004 to 2014 were revised. This institution is a tertiary care university teaching hospital in the mayor medical center in San Juan, Puerto Rico. Patients were referred from PM&R clinics, as well as from other specialists within the medical center and all regions of the country. The studies were performed by PM&R residents (Level II-IV) under direct supervision of an attending physician with more than 15 years of experience. The first EDX study performed at least 10 days post-injury in patients with TPNI was included for analysis. Exclusion criteria included incomplete patient information (demographics or trauma mechanism), presence of concomitant central nervous system injury (brain injury, spinal cord injury), inconsistency in the results and the diagnostic impression, or test limitations that resulted in the inability to rule out other pathologies. TPNI was defined as an acute injury to a major nerve from the root to the terminal nerve that included the facial nerve, brachial and lumbosacral plexus, 80| PRMA BOLETIN and the upper and lower limb peripheral nerves. Demographic information (age and gender) was collected from each chart. The main outcome measures were the frequency of each injury by anatomic location, specific nerve, mechanism or cause, and severity. The severity was divided into two categories: complete (total) or incomplete (partial). A complete injury was considered on the basis of an absent sensory nerve action potential (SNAP) and compound motor action potential (CMAP) after distal and proximal stimulation of the affected nerve on NCS; abundant spontaneous activity (fibrillations and/or positive sharp waves), and absence of voluntary recruitment of motor unit action potentials (MUAPs) on EMG. On the other hand, an incomplete injury had nerve conduction continuity on NCS with normal or reduced SNAP and CMAP when stimulating proximal to the lesion and normal or reduced SNAP and CMAP when stimulating distal to the injury; minimal spontaneous activity (fibrillations and/or positive sharp waves), and normal or decrease recruitment on EMG. The morphology of the MUAPs was not taken into account when categorizing severity. The data was analyzed with the Microsoft Excel programTM. Frequency description injury patterns and student t-test for gender differences were performed. Results A total of 1070 charts were revised of which 156 (14.5% of all studies) were done in patients with TPNI, and 10 studies were excluded from the data analysis. The patient population (n=146) included 109 (74.7%) males and 37 (25.3%) females. The mean age was 33.6 years (Figure 1) with a statistically significant gender age difference (32.2 males, 37.8 females; p=0.049). The anatomic areas affected were the upper extremities 73 (50%), lower extremities 40 (27.4%), and facial area 33 (22.6%). The left side was affected in 79 (54.1%) cases, the right side in 64 (43.8%), and both sides in 3 (2.1%). A total of 163 injured nerves were studied from 131 patients that suffered a single nerve injury, 13 injured two nerves, and 2 injured three nerves. Most injuries affected the facial nerve and the brachial plexus followed by the ulnar nerve (Figure 2). Injuries to more than one nerve often involved the median and ulnar nerves. In the male population the most common injured nerve was the ulnar nerve, while the facial nerve was injured more often in the females (Figure 3). Etiologic factors were described as mechanism of injury (Table 1). The ulnar, sciatic, median, and radial nerves, along with the lumbosacral plexus were more commonly injured by GSWs, the brachial plexus by MVAs, and the facial and accessory nerve secondary to iatrogenic causes, specifically tumor excision surgery complication (Figure 4). In terms of severity, there were 123 (84.2%) incomplete injuries and 23 (15.8%) complete injuries without a significant difference between genders. Our sample population was divided in three age groups: 13-25 years, 26-40 years, and >40 years for comparison (Table 2). The most common mechanism of injury in the age groups younger than 40 years of age were GSW and MVA, while those with >40 years of age were more frequently injured secondary to iatrogenic causes; being the facial nerve more often involved. Discussion TPNIs were more often observed in male adults younger than 40 years of age, specifically lesions to the brachial plexus and the ulnar nerve secondary to MVAs and GSWs, respectively. Nevertheless, injuries to the facial nerve were very common in an older sub-group of individuals, >40 years of age, mostly as a result of surgical complications. In our population TPNIs were very common, accounting for 14.5% of all the EDX studies reviewed. The incidence of TPNI in our laboratory may in fact be higher PRMA BOLETIN | 81 when considering that only 4559% of patients referred for an EDX study present abnormal findings. (12,13) (7-9) The brachial plexus seems to be at a higher risk of injury with this type of trauma. (6,8,10) Additionally, the ulnar nerve is more frequently affected by GSWs and direct penetrating injuries. (7,8) In the lower limbs, the sciatic nerve was more frequently injured due to GSWs, but in other series MVAs and iatrogenic causes were the main mechanism of injury. (7) Additionally, multi-nerve injuries more commonly involved the median and ulnar nerve, or the median, ulnar, and radial nerve. (7,8) Young male adults appear to be at a higher risk of sustaining a TPNI. Men are affected in 7192% of all cases. (4,6-9) The mean age in our population was 33.6 years, which is consistent with other studies, (6-9) except when considering TPNIs in military personnel where the mean age is 26.3 years. (3) It has been consistently reported that the majority of injuries occur in the economically productive 18-35 years age group therefore potentially adding to a country’s socioeconomic burden. (4,6-9) Among the studies reviewed only Ciarmitaro et al (6) and Eser et al (7) described iatrogenic causes as a trauma category accounting for 11.2% and 15% of the PNIs, similar to our finding of 11.1%. The most common iatrogenic cause of injury in our sample was tumor excision surgery affecting the facial nerve, while other reports demonstrated that intramuscular injections and orthopedic surgeries were more common, mostly involving the sciatic nerve injury. (6,7) Although the upper limbs were the most commonly affected body area in our sample, they only accounted for half (50%) of the injuries. This is a slight decrease in frequency when compared with other series: 73% in Italy, 77% in Turkey, 80% in Brazil, and 61% in Canada. (69) The main reason for this difference is that we included facial injuries in the anatomic area category, and they accounted for a high percentage of all the injuries (22.6%), which is significantly higher than previously reported (5%). (8) In terms of dexterity, the occurrence of left or right side lesions varies with the reported series. We found a higher incidence on the left side, but other reports show similar rates on either side, therefore no clinical significance has been found. (3,7-9) The frequency of specific location and injury mechanism of TPNIs may be influenced by several factors. The socioeconomic levels of the population or its involvement in war-related conflict are among these factors. (3,4,7) Different reports agree that the brachial plexus is commonly injured in MVAs, (6,8,10) while the ulnar nerve is involved in penetrating trauma, falls, GSWs, and 82| PRMA BOLETIN pedestrian accidents. (8) GSWs were responsible for the highest number of lesions in our population, similar to that reported by Babar in Pakistan. (4) Bullets present a dual threat of injury by direct trauma or indirect injury due to its cavitation effect. (14) Unfortunately Puerto Rico has a very high crime rate (homicide count= 26.5/100,000 habitants) (15) that could explain the elevated number of GSW related trauma in our population. Meanwhile, MVAs were the second most frequent cause of TPNIs in our sample, but the most common injury mechanism in multiple reports. The majority of injuries in our sample were incomplete or partial. However, since the EDX study in each patient was performed at variable post-traumatic time intervals and no follow up studies were included the severity may have been underestimated. The nerve injury severity classification scales proposed by Seddon (16) and Sunderland (17) are universally accepted, but only the former is often utilized in epidemiologic studies. It divides nerve injury, by increasing severity, into neuropraxia, axonotmesis, or neurotmesis; however, most cases present electrodiagnostic characteristics of mixed lesions. Therefore, we used a scale similar to Eser et al, (7) where injuries were divided into total (complete) or partial (incomplete) lesions. We estimate that most incomplete injuries are consistent with pure or mixed neuropraxia and partial axonotmesis, while complete injuries represent complete axonotmesis and neurotmesis. The latter was less common in our population and probably represents injuries with worse prognosis. In order to accurately classify nerve injuries the EDX evaluation needs to include ipsilateral proximal and distal nerve stimulation, and contralateral evaluation; as well as a complete EMG examination. (1) The importance of injury severity classification lies in its prognostic value and therapeutic intervention outcome. Therefore differentiating between neuropraxia, axonotmesis, and neurotmesis is essential, but it is time dependent, requiring follow-up EDX studies, as well as histologic evidence. This study has several limitations. First, the study is a retrospective chart analysis thus adherence to the inclusion criteria was important in order to minimize missing information. Secondly, injury severity classification was not determined using the universal scales (Seddon and/or Sunderland), although as described earlier in order to coincide with such scales follow up studies were needed. Lastly, several physicians in-training performed the EDX studies, although there was direct supervision by an attending physician. Conclusion TPNIs are more common among potentially economically productive individuals under 40 years of age. They can potentially lead to significant disability and have a negative socioeconomic impact in the population. EDX studies are very useful in detailing such injuries in order to make prompt clinical decisions and characterize prognosis. The reported etiology of these injuries varies in the literature, according to a population’s socio-demographic characteristics. However, further investigation is needed to better understand such injuries, specifically measure disability and their socioeconomic impact. References (1) Robinson LR. Traumatic injury to peripheral nerves. Muscle Nerve 2000 Jun;23(6):863-873. (2) Campbell WW. Evaluation and management of peripheral nerve injury. Clin Neurophysiol 2008 Sep;119(9):19511965. (3) Birch R, Misra P, Stewart MP, Eardley WG, Ramasamy A, Brown K, et al. Nerve injuries sustained during warfare: part I--Epidemiology. J Bone Joint Surg Br 2012 Apr;94(4):523-528. (4) Babar SM. Peripheral nerve injuries in a Third World country. Cent Afr J Med 1993 Jun;39(6):120-125. (5) Ahrari MN, Zangiabadi N, Asadi A, Sarafi Nejad A. Prevalence and distribution of peripheral nerve injuries in victims of Bam earthquake. Electromyogr Clin Neurophysiol 2006 JanFeb;46(1):59-62. (6) Ciaramitaro P, Mondelli M, Logullo F, Grimaldi S, Battiston B, Sard A, et al. Traumatic peripheral nerve injuries: epidemiological findings, neuropathic pain and quality of life in 158 patients. J Peripher Nerv Syst 2010 Jun;15(2):120-127. (7) Eser F, Aktekin LA, Bodur H, Atan C. Etiological factors of traumatic peripheral nerve injuries. Neurol India 2009 JulAug;57(4):434-437. (8) Kouyoumdjian JA. Peripheral nerve injuries: a retrospective survey of 456 cases. Muscle Nerve 2006 Dec;34(6):785-788. (9) Noble J, Munro CA, Prasad VS, Midha R. Analysis of upper and lower extremity peripheral nerve injuries in a population of patients with multiple injuries. J Trauma 1998 Jul;45(1):116-122. (10) Barman A, Chatterjee A, Prakash H, Viswanathan A, Tharion G, Thomas R. Traumatic brachial plexus injury: electrodiagnostic findings from 111 patients in a tertiary care hospital in India. Injury 2012 Nov;43(11):1943-1948. (11) Malikowski T, Micklesen PJ, Robinson LR. Prognostic values of electrodiagnostic studies in traumatic radial neuropathy. Muscle Nerve 2007 Sep;36(3):364-367. (12) Podnar S. Critical reappraisal of referrals to electromyography and nerve conduction studies. Eur J Neurol 2005 Feb;12(2):150-155. (13) Cocito D, Tavella A, Ciaramitaro P, Costa P, Poglio F, Paolasso I, et al. A further critical evaluation of requests for electrodiagnostic examinations. Neurol Sci 2006 Feb;26(6):419-422. (14) Samardzic MM, Rasulic LG, Grujicic DM. Gunshot injuries to the brachial plexus. J Trauma 1997 Oct;43(4):645-649. PRMA BOLETIN | 83 (15) United Nations Office of Drugs and Crime. UNODC Homicide Statistics 2013. 2013; Available at: http://www. unodc.org/gsh/en/data.html. Accessed 08/08, 2014. (16) Seddon HJ. A Classification of Nerve Injuries. Br Med J 1942 Aug 29;2(4260):237-239. (17) Sunderland S. Nerves and nerve injuries, 133–138. 2nd ed.: New York: Churchill Livingstone; 1978. Resumen Objetivos: Describir la etiología y frecuencia de las lesiones traumáticas a nervios periféricos en un laboratorio electrodiagnóstico de un hospital supraterciario. Metodología: Se revisaron los reportes de estudios electrodiagnóstico de pacientes con lesiones traumáticas a nervios periféricos. Las medidas principales fueron la frecuencia de cada lesión por su localización anatómica, el nervio afectado, el mecanismo y la severidad de la lesión. Resultados: 146 reportes fueron incluidos para un total de 163 lesiones a nervio periférico; 109 (74.7%) masculinos y 37 (25.3%) féminas. La edad promedio fue de 33.6 años. El nervio facial y el plexo braquial, seguidos por el nervio ulnar fueron más frecuentemente afectados. El nervio ulnar, ciático, mediano, radial, y el plexo lumbo-sacro se lesionan comúnmente por heridas de bala, el plexo braquial por accidentes de vehículos de motor y el nervio facial por causas iatrogénicas. El 84.2% fueron lesiones incompletas y el 15.8% completas. Conclusiones: Lesiones traumáticas a nervios periféricos pueden llevar a una discapacidad significativa, pero más investigación es necesaria para profundizar en la magnitud de su posible impacto socio-económico. Palabras claves: lesión a nervio, trauma, electrodiagnóstico 84| PRMA BOLETIN Case Report POEMS Syndrome: A Rare Disease With A Challenging Diagnosis SJR (SCImago Journal Rank) indicator It expresses the average number of weighted citations received in the selected year by the documents published in the selected journal in the three previous years. Abstract A complex conglomerate of symptoms, signs, and abnormalities are present with POEMS syndrome, making the diagnosis, management and follow-up a challenge. Recognizing the disease early on may be difficult. Many patients are initially misdiagnosed as having others disorders, for example: multiple myeloma. There is no standard treatment for patients diagnosed with POEMS syndrome. Glorilee Delgado Flores, MD, MPHa*, América Robles Cartagena, MDb, Ivonne Robles Cartagena, MDb, Armando Muñiz, MDb, Fernando Cabanillas, MD, FACPb, Rafael Vicens, MDb Family Medicine Department, University of Puerto Rico, Medical Sciences Campus, San Juan, PR. Auxilio Mutuo Hospital, San Juan, Puerto Rico. *Corresponding Author: Glorilee Delgado Flores, MD, MPH 133 Ciudad del Lago, Trujillo Alto, PR 00976-5492. Email: [email protected] a b Introduction POEMS syndrome is listed as a rare disease by the Office of Rare Diseases of the National Institute of Health. The exact incidence is unknown due to the complexity of the clinical manifestations that are multisystemics (1, 2). It commonly presents in the fifth to sixth decade and 63% of cases are seen in males. POEMS syndrome is rarely reported in Latin America. POEMS syndrome was first described in 1938 but is not until 1980 that the acronym “POEMS” was suggested for this disorder, representing the following constellation of findings: polyneuropathy, organomegaly, endocrinopathy, monoclonal protein and skin changes (3, 4). POEMS syndrome is listed as a “rare disease” by the Office of Rare Diseases of the National Institutes of Health and affects less than 200,000 people in the US population (3). A high level of suspicion is needed to avoid unfortunate outcomes. Case Description A 32-year-old male with a past Figure A. Hemamgiona Figure B. Hyperthricosis medical history of hypertension, restrictive cardiomiopathy, pericarditis, congestive heart failure, chronic liver disease, hepatorenal syndrome, chronic renal failure, and nephrotic syndrome and a family medical history that includes his mother which has a diagnosis of SLE, that came to the ER due to nausea, severe vomiting, diarrhea and general malaise. On Physical Examination, skin manifestations such as clubbing, hypertrichosis, white nails, hemangiomas and hyperpigmentation were visible (see Figures A, B, C, and D). Dry oral mucosa was seen. Decreased PRMA BOLETIN | 85 Figure C. White nails Figure D. Hyperpigmentation involving the extremities. Patient started to have visual changes and the presence of increased intracranial pressure with papilledema, increase CSF glucose, protein and opening pressure were found. Additional laboratories showed proteinuria, monocytosis, thrombocytosis, microcytic and hypochromic anemia. On serum immunofixation, IgA lambda monoclonal gammopathy was demonstrated. On urine immunofixation, lambda, kappa, IgA and IgG expression were increased. On PET scan films and other radiologic studies including Chest X-ray, CT SCAN, MRI, osteosclerotic bone lesions were evidenced (see Figure H). Endocrinopathies such as hypothyroidism and hypoparathyroidism were also present. Patient refers chest pain, shortness of breath, abdominal distention, peripheral edema and volume overload in the form of pleural effusions, pericardial effusions, severe and recurrent ascites (see Figure I) and peripheral edema were found. Based on all of these findings we confirmed the diagnosis of POEMS SYNDROME. Discussion Figure E. Abdominal Distention breathing sounds bilaterally and a 2/6 holosystolic murmur were found. On abdominal inspection was noted a globous abdomen (see Figure E) and at abdominal palpation, visceromegaly in the form of hepatosplenomegaly was noted and confirmed by abdominal sonogram (see Figures F and G). During the neurological examination foot drop, peripheral edema, symmetric decrease of muscle strength, muscle wasting, generalized weakness and 86| PRMA BOLETIN decrease deep tendon reflexes over the lower extremities were evidenced. Upon further questioning, patient referred an extensive past history of multisystemic findings that goes back to the year 2006. Some of these findings included weight loss, fatigue, weakness, bone and joint pain. Due to bone and joint pain, an electromyography was done and showed symmetric sensorimotor neuropathy POEMS syndrome is a rare disorder that is characterized by the presence of different features, divided into mandatory, major and minor criteria. By definition all patients with POEMS syndrome have peripheral neuropathy and a monoclonal plasma cell disorder of the IgA lambda light chain type, as mandatory criteria. One major criteria that is required in order to diagnose this rare disorder is osteosclerotic bone lesions. Six minor criteria are recognized in POEMS syndrome which includes endocrine abnormalities, skin changes, organomegaly, thrombocytosis/polycythemia, papilledema, extravascular volume overload. The cause of POEMS syndrome is unknown, although chronic overproduction of pro-inflammatory and other cytokines appears to be a major feature of this disorder. The exact incidence is unknown due to the complexity of the clinical manifestations. Patients with a diagnosis of POEMS syndrome frequently have a family medical history of Systemic Lupus Erythematosus. POEMS syndrome was first described in 1938 with sensorimotor peripheral neuropathy, hyperpigmentation, elevated cerebrospinal fluid protein, and a solitary plasmacytoma. Eighteen years later two patients presented with peripheral neuropathy, hyperpigmentation, elevation of cerebrospinal fluid protein, and plasmacytomas with new bone formation. But is not until 1980 that the acronym “POEMS” was suggested for this disorder, representing the following constellation of findings; polyneuropathy, organomegaly, endocrinopathy, monoclonal protein and skin changes. POEMS syndrome is listed as a “rare disease” by the Office of Rare Diseases of the National Institutes of Health and affects less than 200,000 people in the US population. There is no standard treatment for this syndrome. In general, the mode of therapy is based on whether the patient has limited or widespread sclerotic bone lesions. For patients with POEMS syndrome and one to three bone lesions, radiation therapy is employed. Young patients with widespread osteosclerotic lesions and rapidly progressive neuropathy should be manage using high dose melphalan with autologous hematopoietic cell transplantation. With this approach 75 percent of patients have some response. References (1)Dispenzieri, Angela. (2012). POEMS syndrome: Update on diagnosis, risk-stratification and management. American Journal of Hematology, 87:805-814 Figure F. Hepatomegaly Figure G. Splenomegaly Figure H. Cardiomegaly and Osteosclerotic Bone lesions 2)Dispenzieri, Angela. (2012). How to treat POEMS Syndrome. Blood, 119 (24) (3) Milanov I, Georgiev D. Polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy and skin changes (POEMS) syndrome. Can J Neurol Sci. 1994;21:60-63. (4) Soubrier MJ, Dubost JJ, Sauvezie BJ. POEMS syndrome: a study of 25 cases and a review of the literature. French Study Group on POEMS syndrome. Am J Med. 1994;97:543-553. PRMA BOLETIN | 87 A cross sectional study The Prevalence Of Sexually Transmitted Infections On Teen Pregnancies And Their Association To Adverse Pregnancy Outcomes Resumen Un conglomerado muy complejo de síntomas, signos y anormalidades están presentes en el Síndrome de POEMS, haciendo el diagnostico en una etapa temprana, manejo y seguimiento de la enfermedad un verdadero reto para la comunidad médica. Debido a la gran complejidad de signos y síntomas, el Síndrome de POEMS podría ser confundido con otras enfermedades como por ejemplo Mieloma Múltiple. No se ha establecido un tratamiento estándar para los pacientes que son diagnosticados con esta enfermedad. ABSTRACT Figure I. Ascites Introduction: Based on our population data, the teen pregnancy rate and the prevalence of sexually transmitted infections (STIs) reported during pregnancy are worrisome. STIs appear to pose a threat to pregnancy outcomes including preterm birth (PTB), neonatal low birth weight (NLBW) and premature rupture of membranes (PROM). The objective of this study is to determine the prevalence of STIs in pregnant teens and the association of this variable to adverse pregnancy outcomes. Methods: We performed a cross sectional study to assess the prevalence of STIs among pregnant teens during a 4-year period at our institution. Birth outcomes such as gestational age at delivery, PROM and NLBW were analyzed and compared with adults. Results: In the four years of our study, teen pregnancy rate fluctuated from 21.7% in 2010 to 16.8% in 2013. The rate of STIs for adult and teen pregnancies was similar, 21% and 23%, respectively. Chlamydia was the most common STI (67.3%) for both groups. PTB was more prevalent among adults affected with STIs than teens, 13.8% and 11.5%, respectively. NLBW was similar among teens and adults with STIs. PROM complicated 9.1% of teen pregnancies with STIs, compared to 6.7% in adults. CALL (787) 696-1520 88| PRMA BOLETIN Conclusion: There was no significant correlation between the STIs and adverse pregnancy outcomes on teen pregnancies for our population, except for PROM. This age group is associated with a high-risk sexual behavior and poor adherence to treatment. They would benefit from efforts to prevent unintended pregnancies and infectious diseases. Zaskia M. Rodriguez Gonzalez, MD; Karla Leavitt, MD, FACOG; Jose Martin, MD, FACOG; Erika Benabe, MD, FACOG; Josefina Romaguera, MD, MPH, FACOG; Ivette Negrón, MS Obstetrics and Gynecology Department San Juan City Hospital Introduction The behavior that put adolescents at risk for pregnancy also put them at risk for sexually transmitted infections (STIs). STI incidence and prevalence are higher among adolescent females 13 to 19 years of age. They are particularly high among those who are pregnant (1). Chlamydia trachomatis (C. trachomatis) has recently emerged as the most frequently diagnosed STI. There is a concern for the identification of the infection and the education of the patients (2). An estimated three million cases are diagnosed annually in the United States. The most common STI is generally asymptomatic in nature, and is often transmitted to infants through infected mothers. STIs appear to pose a threat to pregnancy, since it is associated with preterm birth (PTB) (3) and neonatal low birth weight (NLBW) (4). In a recent study, 4,208 pregnant patients were diagnosed with Trichomoniasis, N. Gonorrhea or C. trachomatis within the first 7-8 months of pregnancy. Nine percent of these patients delivered preterm. Of the three infections, C. trachomatis was more strongly associated with PTB and infections occurring later in pregnancy (5). The presence of an STI represents correctable risk for the pregnant adolescent (6). C. trachomatis infection is widely prevalent among this population. A previous study showed that among 267 pregnant adolescents from 12 to 17 years old who were screened for C. trachomatis before giving birth, 24% of girls tested positive. In 39% of the patients, treatable STIs were identified. Some of the patients tested negative in the initial screening and then tested positive in the following screening, showing that high-risk sexual behavior may continue during pregnancy in adolescents (7). PRMA BOLETIN | 89 In Puerto Rico, according to the Puerto Rico Department of Health, women have a fourfold risk of infection with an STI among men (8). For example in the same period of our study from 2010 to 2013, an average of 4,822 female patients per year were affected with C. trachomatis compared to an average of 1,141 male patients per year. The age group most commonly affected in our country is the teen population and young adults being 2024 years old the most affected in both sexes (8). From experience with our population, the pregnancy rate in teenagers is alarming. However, according to CDC the 2013 preliminary birth rate for teenagers was 26.6 for 1,000 women aged 15-19 years, down 10 % from 2012. This represents an historical low for the nation. This data is reassuring but could be due to an overall decrease in fertility rate since 2007 (9). Similar to the increased prevalence of C. trachomatis in adolescent and young adult women in the general population, the highest prevalence rate in pregnancy occurs in adolescents and young adult women (10). This is the result of high-risk behavior, including unprotected sex with multiple partners, which can result in adverse pregnancy outcomes for the expectant teenager and her newborn. Infections with STIs may be associated with preterm labor, and sepsis in the mother and pneumonia, conjunctivitis, congenital malformation, and sepsis in the neonate (6). Among others, C. trachomatis has statistical associations with adverse pregnancy outcome since, in certain circumstances, it may lead to chorioamnionitis, prematurity and growth retardation (11,12). The subjects were patients who delivered at San Juan City Hospital during 2010-2013. We searched our Institutional database for all pregnant patients delivered and identified those with reported STIs. We gathered data including patient age group (teens and adults), STI status, gestational age at delivery and pregnancy complications such as NLBW, PROM or PTB. This data was compared to demonstrate any tendency of complications and its association to a specific age group. Frequencies and distributions were analyzed. Specific STIs were identified and the prevalence of each one was described. Parity, medical interventions to avoid PTB and obstetric or maternal indications to preterm delivery such as hypertensive disorders, diabetes mellitus, fetal malpresentation or growth restriction were not considered. PROM was determined by rupture of membranes before cervical dilation and/or the presence of uterine contractions. Results From the 1,050 teen patients tested, 243 teen patients had STI’s (23%). The most common STI was C. trachomatis reported in 810 (67.3%) cases followed by Herpes simplex virus, which was reported in 157 patients (13.1%). The other STIs prevalent in our population were Syphilis, HIV, Hepatitis, Gonorrhea and HPV. Premature delivery affected 135 teen patients (18.3%) and 601 adults (81.7%). Among the 243 teens affected with STIs, 28 delivered prematurely (11.5%). Among the 807 teen patients not affected with STIs, 107 had premature deliveries (13.3%). For the adults, 21% were affected with STIs. Premature delivery affected 601 patients (14.2%) of the total population of adult patients. From the adults with STIs, 123 patients delivered prematurely (13.8%) and from the adults without STIs, 478 delivered prematurely (14.3%). Premature rupture of membranes (PROM) complicated 103 teen pregnancies through 2010 to 2013 (9.8%). Among teen patients with STIs, 22 patients were complicated with PROM (9.1%). Those not affected by STIs, had PROM in 81 cases (10%). Eight percent of the adults had PROM. Adult patients with STIs had PROM in 60 cases (6.7%). Adult patients without STIs had PROM in 304 cases (9.1%). From 2010 to 2013, a total of 5,272 births took place in the San Juan City Hospital. Of the total births, 1,050 (19.9%) were teens and 4,222 (80.1%) were adults. A total of 1,132 (21.5%) patients with STIs delivered at San Juan City Hospital between 2010 and 2013. Of these patients, 243 (23.1%) were teens and 889 pa- Lastly, neonatal low birth weight tients (21.1%) were adults. affected 156 teen pregnancies (14.9%). Thirty of these patients Of the total deliveries, 736 were had STIs (12.3%). And, 126 teens preterm deliveries (14.0%), 4,528 without STIs had NLBW infants term deliveries (85.9%) and 8 (15.6%). The adults had NLBW post term deliveries (0.20%). Of in 660 cases (15.6%). Adults with the preterm deliveries, 135 were STI had neonates with NLBW in adolescent patients (18.3%) and 116 cases (13%). Adults without 601 were adult patients (81.7%). STIs had a NLBW percentage Of the term deliveries, 915 were rate of 16.3% or 544 cases. adolescent patients (20.2%) Methods and 3,613 were adult patients Conclusion (79.8%). The 100% of the post This was a retrospective cross term deliveries were adult pa- In Puerto Rico, there has been a sectional study IRB approved. tients. worrisome increase in STIs. 90| PRMA BOLETIN Generally, our population does not seek medical attention for this problem either because of shame or due to the usual asymptomatic course of most of the STIs. Unfortunately a screening tool for STIs is not widely accessible and it is when pregnant, as part of their prenatal care, that most of the patients are aware of their STI status and get treated. The teen population is affected due to risky sexual behavior and multiple sexual partners. In our study 23% of patients affected with STIs were teens compared to a 21% of adults. Although not a significant difference between these two groups, it showed a trend toward teen patients. For example, in 2012, 25% of teens were affected with STIs compared to a 19.7% of adults. The rate of preterm deliveries in teen patients with STIs was 18.5% compared to a 21.9% of the teen patients that reached term. According to this data, in our population, pregnant adults with STIs were more affected by PTB than pregnant teens. Also, the overall rate of prematurity was greater in the adult population rather than the teen population, 14% and 12% respectively. This can be associated to previous history of preterm births, multiparity or other risk factors associated to increasing age. Premature deliveries rate in Puerto Rico for 2013 was 15% (13). This raise concern and although the rate of premature deliveries has been steadily decreasing since 2006 (12), the national goal of 9.6% for 2020 is far to reach. This problem has to be approached by the respective authorities and the factors that put these patients at risk, need to be addressed. At our institution, we are making efforts to decrease the premature delivery rate and this is evidenced by a decline in the incidence of premature deliveries since 2010 from 15% to 11.6% in 2013. PRMA BOLETIN | 91 From our study, we concluded that 13.2% of the teens without STIs had premature delivery compared to 11% of the patients with STIs. Therefore, we can not assume that STIs are directly associated to preterm delivery on our teen population. PROM yield similar results with 9% of the teen pregnant patients with and without STIs been affected by PROM. Therefore, having an STI did not put our teen patient group at risk for PROM. However, when comparing the adult population with the teens, the lather had higher rates of PROM in all categories. For example, PROM rate was higher in pregnant teens with STIs (9%) than in the adult group with STIs (6%). This shows a trend of teen patients with STIs 92| PRMA BOLETIN to be more at risk to have PROM than the adults in our population. Lastly, low birth weight neonates affected the 14.8% of the teen population. Teen patients with STIs were affected in 12.3% of cases and teen patient without STIs were affected in 15.6% of cases. Therefore, infection with STI was not a significant risk for NLBW in this population either. Compared to adults, neonates from teen mothers were less affected by low birth weight. This could mean that this age group is not at risk of low birth weight regardless of their STI status. Discussion Our intention was to depict an image of the teen pregnancy model in our institution, focusing on prevalence of sexually transmitted infections in this population. We were very interested to demonstrate if this risk factor posed a threat to the overall pregnancy outcome specifically on PTB, PROM and NLBW. We concluded that our pregnant population is mainly composed of adult patients. According to our data, STIs were more prevalent among teen patients. This raise concern and requires aggressive interventions to educate this population to safer sex practices and to promote monogamy and abstinence among this younger patients. Screening tools would be useful to aid Obstetricians and Gynecologists to target affected patients and offer treatment at a young age to eradicate the disease. Also, The American College of Obstetricians and Gynecologists supports the use of expedited partner therapy in accordance with CDC guidelines as a method for preventing reinfection of patients with gonorrhea and chlamydia when their partners are unable or unwilling to otherwise seek medical care (17). This is of benefit in order to prevent reinfection and obtain greater cure rates among women. An untreated STI and the reinfection associated to unprotected sex and untreated sexual partners can be linked to co-infection with other STIs like HPV, HSV and HIV. This can result in worrisome outcomes and serious health issues such as genital warts, squamous cell cancer of cervix, cervical dysplasia and immunocompromised patients. Also, babies of untreated mothers can have further complications on the neonatal period such as NICU admission and neurological sequelae. Pregnancy is a great opportunity to diagnose and treat these patients and their partners to improve pregnancy outcomes for the mother and her child. Premature delivery is undoubtedly a factor that contributes to neonatal morbidity and mortality. Also, the associated longterm complications of prematurity pose a high stressor to parents and caregivers. Is therefore that the American College of Obstetricians and Gynecologists (14) have issued several resources to aid physicians on decision-making regarding delivery timing and evidence based indications to premature delivery taking into account the best interest of the mother and the baby. This is a topic of debate and through literature review we found an association to preterm delivery and other adverse pregnancy outcomes on patients affected with STIs. While there are protocols, efforts and interventions to reduce recurrent preterm delivery on patients with certain risk factors, it would be beneficial to optimize these efforts by empowering the treatment of patients affected with STIs and decrease further the risk factors of premature delivery. Our study did not demonstrate a strong association of STIs to premature delivery in our population. The rate of preterm delivery on patients with STIs was the same although the teen population was more affected with STIs. The primary hypothesis of our investigation is therefore not confirmed. This could be accounted due to the limited number of subjects on our study period, small teen population and/or decrease in the number of teen pregnancies as reflected around the country. In bigger tertiary centers and with a greater teen population, specifically C. trachomatis was associated directly to preterm delivery. We did not specify the most common STI associated to preterm delivery but we did a simple analysis of the most common STIs on our population being C. trachomatis the most common. Also, underestimation of STIs could be a probable limitation in our study, because patients without adequate prenatal care, who probably did not benefit of screening for STIs during pregnancy, were not excluded form our study. Parity, medical interventions to avoid PTB and obstetric or maternal indications to preterm delivery such as hypertensive disorders, diabetes mellitus, fetal malpresentation or growth restriction were not considered. Premature rupture of membranes, pose a threat to the mother and the baby resulting in high maternal morbidity and neonatal mortality. It is associated to previous history of PROM and also to maternal genitourinary tract infections. On our population, PROM was more common on teen patients. Also, PROM was more prominent on teen patients with STIs than on adult patients. Besides the presence of STIs to correlate for this outcome there is also an increased rate of vaginal infections such as bacterial vaginosis and vaginal candidiasis, which can contribute to the increased PROM rate on these patients (15). However, we did not evaluate our population for the presence of infections other than a positive result during the prenatal care and/or history of STIs. We neither evaluate the cure rates and their association to adverse pregnancy outcomes, treatment adherence or neonatal infections such as infectious keratoconjutivitis, pneumonia, respiratory assistance or admission to NICU. This could also influence the pregnancy outcome given cure rates and adherence to treatment will evidently have a better outcome than an undertreated patient. Neonatal low birth weight was another variable of interest in our study given it contributes to morbidity and is a common reason for neonatal admission to NICU. Low birth weight was not associated to STI on the teen group. In fact, low birth weight was more prevalent in teens without STIs than on teens affected by STIs. Therefore, we can assume that there are other risk factors as low maternal weight and malnutrition, substance abuse and smoking (16) among others that can contribute to neonatal low birth weight. References 1.Berman SM, Hein K. Adolescents and STDs. In: Sexually transmitted diseases, 3rd ed. Holmes KK, et al. eds. New York: McGraw-Hill, 1999:129–42. 2. López-Cepero R, Flares JA, Romaguera J. Knowledge of chlamydia trachomatis assessed in a Puerto Rican medical student population. P R Health Sci J 2011; 30: 18-21. 3. Babin V, Ojanlatva, A. The impact of chlamydia infections on teen mothers and their children. J Sch Health 1986; 56:17-9. 4. Johnson HL, Ghanem KG, Zenilman JM, Erbelding EJ. Sexually transmitted infections and adverse pregnancy outcomes among women attending inner city public sexually transmitted diseases clinics. Sex Transm Dis 2011; 38: 167-71. 5. Donders GG, Desmyter J, De Wet DH, Van Assche FA. The association of gonorrhoea and syphilis with premature birth and low birthweight. Genitourin Med 1993; 69: 98-101. 6. Mann JR, McDermott S, Gill T. Sexually transmitted infection is associated with increased risk of preterm birth in South Carolina women insured by Medicaid. J Matern Fetal Neonatal Med 2010; 23: 563-8. 7. Gittens LN, Nichols RR, Apuzzio JJ. Epidemiology of sexually transmitted diseases among pregnant adolescents. Infect Dis Obstet Gynecol 1994; 1: 216219. 8 . DS de Puerto Rico, División de Prevención de ETS/VIH/SIDA, Oficina de Vigilancia de ETS, 2007-2013. 9. Oh MK, Cloud GA, Baker SL, Pass MA, Mulchahey K, Pass RF. Chlamydial infection and sexual behavior in young pregnant teenagers. Sex Transm Dis 1993; 20: 45-50. 10. Birth: Preliminary data for 2013. National Vital Statistics Report. May 29, 2014. Volume 63, number 2. 11. Niccolai LM, Ethier KA, Kershaw TS, Lewis JB, Ickovics JR. Pregnant adolescents at risk: sexual behaviors and sexually transmitted disease prevalence. Am J Obstet Gynecol 2003; 188: 63-70. 12. Donders GG, Moerman P, De Wet GH, Hooft P, Goubau P. The association between Chlamydia cervicitis, chorioamnionitis and neonatal complication. Arch Gynecol Obstet. 1991;249(2):79-85. 13. www.march of dimes.org/report card PRMA BOLETIN | 93 14. Practice bulletin: Prediction and prevention of preterm birth. 2012. ACOG 15. Klein LL, Gibbs RS. Infection and preterm birth. Obstet Gynecol Clin North Am 2005;32:397–410. 16. Polakowski LL, Akinbami LJ, Mendola P. Prenatal smoking cessation and the risk of delivering preterm and small-for-gestational-age newborns. Obstet Gynecol 2009;114:318–25. 17. Expedited partner therapy in the management of Gonorrhea and Chlamydia by Obstetricians-Gynecologists. Committee Opinion Number 506, Sept 2011. RESUMEN Introducción: Basado en la data de nuestra población, la tasa de embarazo en adolescentes y la prevalencia de enfermedades de transmisión sexual (ETS) durante el embarazo son preocupantes. Las ETS imponen un riesgo al embarazo incluyendo parto prematuro, ruptura prematura de membranas y bajo peso al nacer. El objetivo de este estudio es determinar la prevalencia de ETS en adolescentes embarazadas y su asociación a resultados adversos asociados al embarazo. Métodos: Realizamos un estudio transversal para determinar la prevalencia de ETS en adolescentes embarazadas durante 4 años en nuestra institución. Los resultados del parto como edad gestacional al nacer, ruptura prematura de membranas y bajo peso al nacer fueron analizados y comparados con las pacientes adultas. Resultados: Durante nuestro estudio, el embarazo en adolescentes fluctuó entre un 21.7% en 2010 a un 16.8% en el 2013. La tasa de ETS para embarazadas adultas y adolescentes fue similar, 21% y 23% respectivamente. Clamidia fué la ETS más común para ambos grupos (67.3%). El parto prematuro fué más prevalente en las adultas afectadas por ETS que en las adolescentes, 13.8% y 11.5%, respectivamente. Las adultas y las adolescentes fueron similarmente afectadas por bebés de bajo peso al nacer. La rupture prematura de membranas complicó un 9.1% de los embarazos en pacientes adolescentes afectadas por ETS, comparado con un 6.7% de las adultas. Conclusión: No hubo una correlación significativa entre las ETS y resultados adversos asociados al embarazo en adolescentes embarazadas para nuestra población, excepto para ruptura prematura de membranas. Esta población tiene un comportamiento sexual de alto riesgo y de pobre adherencia al tratamiento. Por lo tanto, se beneficiarían de esfuerzos para prevenir embarazos no deseados y la transmission de enfermedades infecciosas. Su Anuncio Aquí... Screening for Peripheral Arterial Disease Abstract Lower extremity peripheral artery disease is a manifestation of systemic atherosclerotic disease, which affects over 8 million Americans and conveys a significant health burden globally. Although PAD can be asymptomatic and subclinical, it is associated with a reduction in functional capacity and quality of life when symptomatic, and, in its most severe form, is a major cause of limb amputation. Peripheral arterial disease (PAD) commonly results from progressive narrowing of arteries in the lower extremities. Previous studies have shown that PAD is associated with a significantly elevated risk of cardiovascular disease morbidity and mortality. This is the reason screening is crucial for diagnosis and prevention of future adverse cardiovascular events. The most common etiology is atherosclerosis, although other disease process like inflammatory, immune, and hypercoagulable disorders can cause signs and symptoms of arterial insufficiency. When recognized early and appropriately managed, complications that lead to limb loss can be minimized. All patients should have a comprehensive history taken and be examined for PAD, but patients with risk factors should be specifically examined which is currently suboptimal in our daily practice. Introduction (787) 721-6969 94| PRMA BOLETIN Camargo-Arias, Edinson MD, Aponte-Rodriguez, Jaime MD, Banchs-Pieretti, Hector MD, FACC, Altieri-Nieto, Pablo I. MD, FACC University of Puerto Rico School of Medicine, Department of Medicine, Cardiology Section Cardiovascular Diseases Training Program Index Words: Peripheral Artery Disease, Claudication, Limb Ischemia from progressive narrowing of arteries in the lower extremities. Previous studies have shown that PAD is associated with a significantly elevated risk of cardiovascular disease morbidity and mortality. This is the reason screening is crucial for diagnosis and prevention of future adverse cardiovascular events. The most common etiology is atherosclerosis, although other disease process like inflammatory, immune, and hypercoagulable disorders can cause signs and symptoms of arterial insufficiency. When recognized early and appropriately managed, complications that lead to limb loss can be minimized. All patients should have a comprehensive history taken and be examined for PAD, but patients with risk factors should be specifically examined which is currently suboptimal in our daily practice. Risk factors for peripheral arterial disease Age • • Age 70 years Age 50-69 years with a history of smoking or diabetes Age 40-49 with diabetes and at least 1 other risk factor for atherosclerosis Lower extremity peripheral artery disease is a manifestation of systemic atherosclerotic disease, which affects over 8 million Americans and conveys a significant health burden globally. Although PAD can be asymptomatic and subclinical, it is associated with a reduction in functional capacity and quality of life when symptomatic, and, in its most severe form, is a major cause of limb amputation. • Peripheral arterial disease (PAD) commonly results Smoking - Most powerful risk predictor of PAD. Race - African Americans (men and women) and Hispanic American Women Family History - First-order relative with an abdominal aortic aneurysm or PAD PRMA BOLETIN | 95 Other Risk factors - Coronary artery disease, carotid artery disease, renal artery disease, diabetes and impaired glucose tolerance, hypertension, hyperlipidemia, hyperhomocysteinemia, chronic kidney disease, specially end-stage renal disease, elevated C-reactive protein, Leriche syndrome, cardiac arrhythmias, hypercoagulable state, obesity. Symptoms & Signs of PAD Symptoms of PAD depend upon the location and severity of stenosis and can be completely absent or range from mild extremity pain with moderate-to-severe exertion to limb-threatening ischemia. Claudication - The patient may complain of fatigue, aching, numbness, weakness, or heaviness in muscles, or pain of lower extremities with exertion. The primary and secondary sites of discomfort should be recorded, as well as the amount of exertion needed to develop the symptoms. Segments affected by claudication correlate with level of obstruction, as fallows: Buttock and Hip Claudication Seen in aortoiliac disease. The pain is aching in nature, usually presents immediately with or without weakness of the hip or thigh on walking, and subsides immediately with rest. Pulses in one or both groins are diminished, and males may present with impotence. consistently reproduced with ex- • Category 1: Mild claudiercise and quickly relieved with cation rest. • Category 2: Moderate claudication Foot Claudication - Isolated foot • Category 3: Severe clauclaudication is uncommon and dication represents PAD of the tibial and Grade II peroneal vessels. • Category 4: Rest pain Grade III Rest Pain - Any pain of the ex- • Category 5: Minor tissue tremities at rest and its associ- loss not exceeding ulcer of the ation with the upright or recum- digits of the foot bent positions should be carefully • Category 6: Major tissue evaluated. Ischemic rest pain is loss; severe ischemic ulcers or suspected if pain at rest occurs in frank gangrene the foot, toes, or instep and is aggravated by extremity elevation Fontaine classification of and improved by a dependent peripheral artery disease position. Almost always, ischemic rest pain worsens with leg Stage I: Asymptomatic exercise. Pain is usually worse at Stage II: Claudication night and is relieved by placing in Stage IIA: Claudication at a disa dependent position. Rest pain tance greater than 200 m strongly suggests PAD. Stage IIB: Claudication at a distance less than 200 m Ulcers - Ulcers are any poorly Stage III: Rest pain healing or non-healing wounds Stage IV: Necrosis and / or ganof the legs or feet. These can be grene of the limb caused by PAD or peripheral venous disease. Physical Examination Inspecting the skin Skin Changes - Thin, shiny, and brittle skin, thick opaque nails, Color - may be black from hehair loss on legs and bluish/black mostasis or brown from hemosiddiscoloration of the extremities erin deposition. Acute limb ischmay be caused by peripheral emia presents as a white limb venous disease or PAD. Pallor (extreme pallor) especially when or cyanosis while leg elevated is compared with other limb suggestive of PAD. Trophic skin changes – thin, Impotence - Severe symptomatic atrophic skin on the foot and lowbilateral aortoiliac PAD almost al- er extremity that shows pallor ways causes erectile dysfunction with elevation and rubor (redin men. Leriche syndrome is the ness) with dependency of the triad of claudication, absent or foot suggestive of ischemic PAD. diminished femoral pulses, and Distal hair loss and hypertrophic erectile dysfunction. nails are also seen with PAD. Thigh Claudication - Obstruction in the common femoral artery may cause claudication in the thigh, calf, or both. Classification of PAD by Symptoms Calf Claudication - This is the most common presentation. Rutherford classification Claudication in the upper two- of peripheral artery disthirds of the calf is usually caused ease by superficial femoral obstructive disease. In the lower third of the Grade 0 calf, it is usually caused by pop- • Category 0: Asymptomliteal PAD. It presents as an in- atic creasingly aching pain that is Grade I 96| PRMA BOLETIN Skin integrity and ulcers – these may be venous or arterial. Venous ulcers usually tend to be painless unless they have superimposed infection, whereas arterial ulcers are painful. Gangrene – wet or dry Varicose vein – presence of any varicose veins seen best with the patient standing upright. Palpation Temperature – starting distally, compare both extremities at similar levels with the back of the hand. A cool extremity suggests poor circulation and PAD. Palpate varicose veins – If thrombophlebitis is present, veins will be hard and painful to touch. Pitting edema – This should be tested for in dependent locations such as the dorsum of the foot and if present on the shins. If the patient has been in bed for a long period of time, the sacrum should be checked. Pulse – Brachial, radial, ulnar, femoral, popliteal, dorsalis pedis, and posterior tibial sites should be checked. Also palpate the carotid and abdomen for aorta. Pulse intensity should be assessed and recorded numerically as shown below. Pulse intensity scoring 0 = Absent 1= Diminished 2= Normal 3= Bounding Auscultation Check both femoral arteries for the presence of bruits, specially if patient has had a recent cannulation of the femoral artery or vein, as a bruit will suggest a possible arteriovenous fistula or a pseudoanuerysm. Pseudoaneurysm usually occur within 7 days after the sheath removal. Other examinations Capillary Refill – Should be less than 2 seconds in normal patients. Blood Pressure – Check blood pressure in both arms and legs especially for asymmetry as it helps in identifying the level of obstruction. Ankle-Brachial Pressure Index – This may be unreliable in patients with calcified arteries in the calf or those with extensive edema, in which case the toe-brachial pressure index should be performed. References 1. Selvin, E., Erlinger, T. P. Prevalence of and risk factors for peripheral arterial disease in the United States: results from the National Health and Nutrition Examination Survey, 1999-2000. CIRCULATION. 2004; 110(6):738-743. 2. Murabito, J. M., D’ Agostino, R. B., Silbershatz, H., st al. Intermittent claudication. A risk profile from The Framingham Heart Study. CIRCULATION. 1997; 96(1):44-49 3. Eric B. Rosero, MD, Katherine Kane, MD, G Patrick Clagett, MD, and Carlos H. Timaran MD, Dallas Texas. A systemic review of the limitations and approaches to improve detection and management of peripheral arterial disease in Hispanics. Elsevier; SOCIETY OF VASCULAR SURGERY 2009; 27s-35s. 4. Elizabeth Selvin, MPH; Thomas P. Erlinger, M.D., MPH. Prevalence of and Risk Factors for Peripheral Arterial Disease in the United States. Vascualr Medicine CIRCULATION. 2004, 738743. 5. Kenneth Ouriel, Seminar; Peripheral Arterial Disease. THE LANCET. Vol 358 October 13, 2001. 1257-1265. 6. Yoshimitsu Soga, MD, Osamu Lida, MD, Mitsuyoshi Takahaera, MD, Keisuke Hirano, MD, Kenji Suzuki, MD, Daizo Kawasaki, MD, Yusuke Miyashita, MD, Taketsugu Tsuchiya, MD. Two-Year Life Expectancy in Patients With Critical Limb Iscemia. JACC Vol.7 N0.12, 2014; 1444-1449 7. Writing Group Members, 2005 Writing Committee Members, ACCF/ AHA Task Force Members, 2011 ACCF/ AHA focused update of the guideline for the management of patients with peripheral artery disease; a report of the American College of Cardiology Foundation/ American Heart Association Task Force on practice Guidelines. CIRCULATION 2011; 124:2020-2045, doi;101161/ CIR.0b013e31822e80c3. 8. Manesh R. Patel, MD, Michael S. Conte, MD, Donald E. Cutlip, MD, Nabil Dib, MD,k Patrick Geraghty, MD, William Gray, MD, William R. Hiatt, MD, Mami Ho, MD, PHD, Koji Ikeda, PHD, Fumiaki Ikeno, MD, Michael R. Jaff, DO, W. Schuyler Jones, MD, Masayuki Kawahara, MD, Robert A. Lookstein, MD, Roxana Mehran, MD, Sanjay Misra, MD, Lars Norgren, MD, Jeffrey W. Olin, MD, Thomas J. Povsic, MD, PHD, Kenneth Rosenfield, MD, John Rundback, MD, Fadi Shamoun, MD, James Tcheng, MD, Thomas T. Tsai, MD, Yuka Suzuki, PHD , Pascal Vranckx, MD, Bret N. Wiechmann, MD, Christopher J. White, MD, Hiroyoshi Yokoi, MD, Mitchell W. Krucoff, MD JACC , State of the Art Review. Evaluation and Treatment of Patients With Lower Extremity Peripheral Artery Disease. Vol. 65. NO 9, 2015, 931-941. Abstracto Enfermedad arterial periférica de las extremidades inferiores es una manifestación de la enfermedad aterosclerótica sistémica, que afecta a más de 8 millones de estadounidenses y transmite una carga importante para la salud a nivel mundial. Aunque PAD puede ser asintomática y subclínica, se asocia con una reducción en la capacidad funcional y calidad de vida cuando sintomático, y, en su forma más grave, es una causa principal de amputación de extremidades. La enfermedad arterial periférica (PAD) comúnmente resulta de estrechamiento progresivo de las arterias de las extremidades inferiores. Estudios anteriores han demostrado que PAD se asocia con un riesgo significativamente elevado de morbilidad y mortalidad de la enfermedad cardiovascular. Esta es la razón crucial para el diagnóstico y la prevención de futuros eventos cardiovasculares adversos. La etiología más común es la aterosclerosis, aunque otro proceso de la enfermedad como trastornos inflamatorios, inmunológicos, y de hipercoagulabilidad pueden causar signos y síntomas de insuficiencia arterial. Cuando es diagnositicada temprano y se trata adecuadamente, las complicaciones que conducen a la pérdida de extremidades se pueden minimizar. Todos los pacientes deben tener una historial completo y examen fisico para PAD, pero los pacientes con factores de riesgo se deben examinar específicamente que actualmente todos sabemos que es subóptima en nuestra práctica diaria. PRMA BOLETIN | 97 Case Report and Review of Literature Difficult Diagnosis between B Cell Lymphoma and Classical Hodgkin’s Lymphoma Yaixa Rentas Torres, MDa*, Joshua L. Rodríguez-López, MS IVb, Maria Valentin, MDa, Hector Silva, MDa Internal Medicine Residency Training Program Hospital Episcopal San Lucas-Ponce School of Medicine and Health Science Consortium Poster Presentation in the ACP chapter of Puerto Rico b School of Medicine, Ponce Health Sciences University, Puerto Rico *Estancias de Santa Rosa 2 Calle Roble Villalba, PR 00766-8000. Email: [email protected] a Introduction Although primary mediastinal large B-cell lymphoma and classic Hodgkin lymphoma of nodular sclerosis type are distinct disease, they share several clinical characteristics and biologic features (1). However, overlap in biologic and morphologic features has been identified (2). For this reason, there are mediastinal lymphomas that not fit in either category. These types of lymphomas are recognized as mediastinal gray zone lymphomas. Gray zone lymphomas are lymphatic tumors that cannot be assigned to a defined lymphoma entity due to morphological, clinical, or genetic reasons (3). As a defining criterion they present with features of two overlapping entities or features that are intermediate (3). The World Health Organization classifies them as “B-cell lymphoma, unclassifiable, with features intermediate between diffuse large B-cell lymphoma and Hodgkin lymphoma” (4). Primary mediastinal large B-cell lymphoma and classic Hodgkin lymphoma of nodular sclerosis share many common clinical characteristics, and have been reported sequentially in the same patient and as composite lymphomas, in the same anatomic site (5-6). Frequently, they present with an anterior mediastinal mass involving the thymus gland and supraclavicular lymph nodes in young women (7). Mediastinal gray zone lymphomas present similarly, however, they are more common in males (7). Also, extranodal involvement is rare, but there have been cases reported with extranodal lesions and no evidence of mediastinal involvement (8). Our case regards a young Hispanic female with mediastinal involvement. 98| PRMA BOLETIN vision, orthopnea, dyspnea on exertion, shortness of breath, epigastric pain, nausea, vomiting, muscle weakness, loss of consciousness, and back pain. Clinical Course Abstract Although primary mediastinal large B-cell lymphoma and classic Hodgkin lymphoma of nodular sclerosis type are distinct disease, they share several clinical characteristics and biologic features. However, there are mediastinal lymphomas that not fit in either category. These types of lymphomas are recognized as mediastinal gray zone lymphomas. Gray zone lymphomas are lymphatic tumors that cannot be assigned to a defined lymphoma entity due to morphological, clinical, or genetic reasons. In this report, we present a case of a 22 year-old-Hispanic-female diagnosed with B-cell lymphoma, unclassifiable, with features intermediate between diffuse large B-cell lymphoma and Hodgkin lymphoma. Index words: B-cell lymphoma; diffuse large B-cell lymphoma; gray zone lymphoma; Hodgkin lymphoma Case History This is a case of a 22 year-old-Hispanic-primigravida with a past medical history of bronchial asthma, endometriosis, and gastritis that presents to the hospital with seven month history of productive cough, fatigue, and nausea. The patient gave birth in January 2014, and started with the cough two weeks after giving birth. The cough was initially alleviated with antitussive. As the months passed the cough persisted and she started presenting back pain, fatigue, anorexia, nausea, and vomiting. The patient went several times to the Emergency Room (ER), but always was discharged on anti-inflammatory medications. In June, 2014 the patient noted inflammation of the left posterior cervical nodes and left supraclavicular nodes. The lymph nodes were neither painful nor hot. She arrived to the ER because of worsening of symptoms, including: productive cough, fatigue, 35 pounds weight loss in the last three months, anorexia, general malaise, fever, blurry In the beginning the patient came to our institution due to respiratory problems and was thought to have acute bronchitis. Intravenous antibiotics and respiratory therapies were started. The chest x ray and chest CT done initially were highly suspicious for a lymphoma (see Figure 1 & 2). Biopsy studies from cervical nodes shows prominent nucleoli and basophilic cytoplasm (see Figure 3). A final diagnosis of large B-cell Lymphoma with features favoring thymic large B-cell lymphoma was done because of the clinical presentation. However, immunohistochemistry revealed a B-cell lymphoma, unclassifiable, with features intermediate between diffuse large B-cell lymphoma and classical Hodgkin lymphoma (see Figure 3). Figure 1: Chest X-Ray Prominence of upper mediastinum. Blunting of the left costophrenic angle suggestive of pleural effusion At clinic a bone marrow was made that showed mild hypocellular marrow with no definitive evidence of lymphoma, cytogenetic analysis revealed a normal female karyotype without apparent clonal aberrations and the flow cytometry report revealed a bone marrow with no immunophenotypic evidence of lymphoma. Whole Body Figure 2: Chest CT scan with IV contrast PET/CT scan done showed mul- Extensive mediastinal, hilar, and left suprahilar lymphadenopathy tiple matted areas of lymphade- suggestive of malignancy. Small left pleural effusion with atelectatic nopathy on the neck, chest and infiltrate in the left lower lobe celiac axis compatible with active to pathologists and oncologists as “Gray Zone Lymphoma” (GZL) infiltrative disease. Figure 1: Chest X-Ray because because it shares characteristics Patient has already received its differential diagnosis has di- of both classic Hodgkin’s lymphotreatment with cyclophospha- rect implications for management mas and large B-cell lymphomas. mide, doxorubicin, vincristine, strategies (9). The rarity of these Recently (last decade) this type of prednisone (CHOP) and rituximab cases, contribute to a poorer out- lymphoma has been documentshowing noticeable improvement. come in life quality, treatment, ed as distinct entity, and actually there are no define treatment. Her symptoms has succeed and and prognosis of these patients. GZL treatment is challenging due she has been stable. As suggested by literature to disease heterogeneity, lack of this is an uncommon case of data regarding prognostication Discussion lymphoma (considered rare), and no standard guidelines for This case illustrates a challenge some authors has named it management (10). PRMA BOLETIN | 99 The term “Gray Zone Lymphoma” was firstly used in 1998 at the “Workshop on Hodgkin’s disease and related diseases” to designate lymphomas at the border of cHL and other entities. This term was then further extended to lymphomas with overlapping features between BL (Burkitt lymphoma) and DLBCL. The 2008 updated WHO classification of Tumors of the Hematopoietic and Lymphoid Tissues proposed to assign these gray zone lymphomas to provisional categories called B-cell lymphomas unclassifiable with features intermediate between DLBCL and cHL and B-cell lymphomas unclassifiable with features intermediate between DLBCL and BL (11). Figure 3. Pathology of the cervical lymph node biopsy Nodular infiltration by large atypical lymphoid cells with large nuclei and nucleoli. Tumor necrosis is present. Delicate fibrotic bands and spindled atypical lymphoid cell are noted. Figure 4. Immunohistochemical Analysis. a) Positive CD20 stain, b) Positive CD79a stain, c) Positive CD15 stain (partial), d) Positive CD30 stain, e) Positive PAX-5 stain, f) Positive CD45 stain (partial), g) Spindled lymphoid cells with fibrotic bands, H&E, h) Sheets of large atypical cells, H&E 100| PRMA BOLETIN Both classical Hodgkin lymphoma and primary mediastinal B-cell lymphoma are two well-established clinicopathological entities. DLBCL is a heterogeneous group of tumors consisting of large, transformed B cells with prominent nucleoli and basophilic cytoplasm, a diffuse growth pattern and a high proliferation fraction (12). Tumor cells in DLBCL generally express pan B cell antigens (CD19, CD20, CD22, CD79a), as well as CD45. Fifty to 75 percent of tumors express surface or cytoplasmic monoclonal immunoglobulin (Ig), most often of the IgM isotype. Expression of CD30 is present in approximately 25 percent of cases (particularly the anaplastic variant) and is associated with more favorable disease. Uncommonly, DLBCLs express CD5, a finding associated with more aggressive disease and worse prognosis (12). Twenty-five to 80 percent of DLBCL in various studies express B cell leukemia/lymphoma 2 (BCL-2) protein. Approximately 70 percent express B cell lymphoma 6 (BCL-6) protein. Other markers that are commonly expressed include CD10 (30 to 60 percent of cases) and MUM1/IRF4 (35 to 65 percent of cases) (12). In this case there were expression of CD20, CD79a and CD45 (see Figure 3). This kind of lymphoma is also associated with genetic abnormalities the karyotype of our patient was normal. The clinical management of these patients is actually challenge for clinicians because each one require different therapies. Due to the rarity of the disease and the complexity of diagnostic criteria, the optimal therapy for these patients remains unclear. Some studies suggested that patients might benefit better from therapy designed for aggressive B-cell non Hodgkin lymphoma than those applied to patients with cHL (11). In conclusion, we presented a case of a 22-year-old woman who develop B-cell lymphoma, unclassifiable, with features intermediate between diffuse large B-cell lymphoma and classical Hodgkin lymphoma (by immunohistochemistry), which is a uncommon case of lymphoma. References 1. Dunleavy K, Grant C, Eberle FC, Pittaluga S, Jaffe ES, Wilson WH. Gray zone lymphoma: better treated like Hodgkin lymphoma or mediastinal large B-cell lymphoma? Curr Hematol Malig Rep 2012 Sep; 7(3): 241-7. 2. Traverse-Glehen A, Pittaluga S, Gaulard P, et al. Mediastinal gray zone lymphoma: the missing link between classic Hodgkin’s lymphoma and mediastinal and large B-cell lymphoma. Am J Surg Pathol. 2005 Nov; 29(11): 1411-21. 3. Ott MM, Horn H, Rosenwald A, Ott, G. Grey zones lymphomas: limitations of the classification of aggressive B-cell lymphomas. Pathologe 2013 May; 34(3): 225-32. 4. Swerdlow SH, Campo E, Harris NL, et al. WHO classification of tumours of haematopoietic and lymphoid tissues. Lyon: IARC; 2008. 5. Eberle FC, Salaverria I, Steidl C, et al. Gray zone lymphoma: chromosomal aberrations with immunophenotypic and clinical correlations. Mod Pathol. 2011 Dec; 24(12): 1586-97. 6. Jaffe ES, Zarate-Osorno A, Medeiros LJ. The interrelationship of Hodgkin’s disease and non-Hodgkin’s lymphomas—lessons learned from the composite and sequential malignancies . Semin Diagn Pathol. 1992 Nov; 9(4): 297-303. 7. Eberle, F. C., Rodriguez-Canales, J., Wei, L., et al. Methylation profiling of mediastinal gray zone lymphoma reveals a distinctive signature with elements shared by classical Hodgkin’s lymphoma and primary mediastinal large B-cell lymphoma. Haematologica 2011; 96(4): 558–566. 8. Iwaki N, Sato Y, Kurokawa T, et al. B-cell lymphoma, unclassifiable, with features intermediate between diffuse large B-cell lymphoma and classical Hodgkin lymphoma without mediastinal disease: mimicking nodular sclerosis classical Hodgkin lymphoma. Med Mol Morphol 2013 Sep; 46(3): 172-6. 9. Gabriela Gualco, Yasodha Natkunam and Carlos E Bacchi. The spectrum of B-cell lymphoma, unclassifiable, with features intermediate between diffuse large B-cell lymphoma and classical Hodgkin lymphoma: a description of 10 cases. Modern Pathology (2012) 25, 661–674 10. Gray Zone Lymphoma: A Retrospective Multicenter Analysis of Clinical Characteristics, Treatment, Outcomes and Prognosis. Retrieved from WEB http://www.researchtopractice.com/5MJCASH2014/6/6# 11. Sylvia Hoeller and Christiane Copie-Bergman. Grey Zone Lymphomas: Lymphomas with Intermediate Features. Advances in Hematology. Volume 2012, Article ID 460801, 7 pages doi:10.1155/2012/460801 12. Epidemiology, clinical manifestations, pathologic features, and diagnosis of diffuse large B cell lymphoma. Retrieved from WEB http://www.uptodate.com/contents/ epidemiology-clinical-manifestations-pathologic-features-and-diagnosis-of-diffuse-large-b-cell-lymphoma?source=search_result&search=b+cell+lymphoma+and+Classical+Hodgkin+lymphoma&selectedTitle=1~150 13. 9 Gualco G, Natkunam Y, Bacchi CE. The spectrum of B-cell lymphoma, unclassifiable, with features intermediate between diffuse large B-cell lymphoma and classical Hodgkin lymphoma: a description of 10 cases. Modern Pathology 2012 May; 25(5): 661-74. 14. 10 Wilson WH, Pittaluga S, Nicolae A, et al. A prospective study of mediastinal gray-zone lymphoma. Blood 2014 Sep 4; 124(10): 1563-9. 15. Epidemiology, clinical manifestations, pathologic features, and diagnosis of diffuse large B cell lymphoma. Retrieved from WEB http://www.uptodate.com/contents/ epidemiology-clinical-manifestations-pathologic-features-and-diagnosis-of-diffuse-large-b-cell lymphoma?source=machineLearning&search=between+diffuse+large+B+cell+lymphoma+and+classical+Hodgkin+lymphoma&selectedTitle=1~150& sectionRank=3&anchor=H5#H5 16. Primary mediastinal large B cell lymphoma. Retrieved from WEB http://www.uptodate.com/contents/ primary-mediastinal-large-b-cell-lymphoma?source=search_result&search=Primary+mediastinal+large+B+cell+lymphoma.&selectedTitle=1~16 17. Omar Nadeem, MD, Diana O Treaba, MD, Jorge J Castillo, MD, and James N Butera, MD. Grey Zone Lymphoma, Unclassifiable With Features Intermediate Between Diffuse Large B-Cell Lymphoma and Classical Hodgkin Lymphoma: Better Results With CHOPLike Regimens Resumen Se presenta un caso de una fémina de 22 años de edad que desarrollo un raro tipo de linfoma. Clasificado como un linfoma de células B, no clasificable con características intermedias entre linfoma grande de células B y linfoma clásico de Hodgkin. Como es sugerido por la literatura este es un tipo de linfoma poco común y algunos autores lo llaman “linfoma de la zona gris” lo cual le da una designación a estos tipos de linfomas que caen en el borde entre linfomas clásico de Hodgkin y otras entidades. El tratamiento para linfomas de la zona gris es un reto debido a lo heterogénea que es la enfermedad, la poca data que hay en relación al pronóstico y que no hay unas guías estándares de manejo. Hasta el momento la paciente ha sido tratada con cyclophosphamide, doxorubicin, vincristine, prednisone (CHOP) and rituximab y ha mejorado notablemente. PRMA BOLETIN | 101 TRITION NU E DU N NutrEd C AT I O “UNA” IDENTIFY EDUCATE ACT MALNUTRITION impacts PHYSICAL HEALTH, DAILY FUNCTION, INDEPENDENCE & RECOVERY from illness, injury and surgery. 14-15 Starting at age 40, adults lose on average 8% of muscle mass each decade. The rate of muscle loss increases to 15% per decade after the age of 70.3-6 Up to 1OF 2 OUT elderly people are at risk for malnutrition.1-2 $ 45% THE IMPORTANCE OF NUTRITION INCREASES WITH INJURIES & ILLNESSES Nutrition care can improve health outcomes and cut healthcare costs.7 At least of patients who fall down in the hospital are malnourished. 13 1 in 3 people enter the hospital malnourished with even more becoming malnourished during their stay. 8-11 Demasiado bueno para ser verdad, ¿no? Pero hay un paso que puede ayudar a protegerte de otra enfermedad seria, la pulmonía neumocócica. La vacuna PREVNAR 13®. Malnourished patients have 3x the risk of surgical site infections 12 Nutrition is everyone’s responsibility 1. Kaise MJ, et al. J Am Geriatr Soc. 2010;58:1734-1738 2. Izawa S, et al. Clin Nutr. 2006;25:962-967 3. Grimby GB, et al. Acta Physiol Scand. 1982;115:125 4. Larsson L, et al. J Appl Physiol. 1979;46:451 5. Flakoll P, et al. Nutrition. 2004;20:445-451 6. Baier S, et al. J Parenter Enteral Nutr. 2009;33:71-82 7. Phillpson TJ, et al. Am J Manag Care. 2013;19:121-128 8. Coats KG, et al. J Am Diet Assoc. 1993;93:27-33 9. Giner M, et al. Nutrition. 1996;12:23-29 10. Thomas DR, et al. Am J Clin Nutr. 2002;75:308-313 11. Braunschweig C, et al. J Am Diet Assoc. 2000;100:1316-1322 12. Fry DE, et al. Archives of Surgery. 2010;145:148-51 13. Bauer JD, et al. J Hum Nutr Diet. 2007;20:558-564 14. Norman K et al. Clin Nutr. 2008;27:5-15. 15. Elia M, Russell C. Combating Malnutrition: Recommendations for action. Report from the Advisory Group on Malnutrition, Led by BAPEN. 2009. Redditch, BAPEN. ©2015 Abbott Laboratories Inc. APR-150307 LITHO en P.R ¿Y SI UN “PUSH UP” PUDIERA AYUDAR A PROTEGERTE DE UNA ENFERMEDAD DEL CORAZÓN? ¿Mayor de 50 años? Tu riesgo de contraer pulmonía neumocócica es más alto. Es una enfermedad grave que podría llevarte al hospital. Los síntomas incluyen tos, fiebre, dolor de pecho y dificultad para respirar. Una dosis de la vacuna PREVNAR 13 ® puede ayudar a protegerte. Aun si has sido vacunado con otra vacuna contra la pulmonía, PREVNAR 13 ® puede ayudar a proveer protección adicional. No se ha estudiado la eficacia de PREVNAR 13 ® administrada menos de 5 años después de otra vacuna contra la pulmonía. Pregúntale a tu proveedor de salud si PREVNAR 13 ® es adecuada para ti. INDICACIONES PARA PREVNAR 13® • Prevnar 13® es una vacuna aprobada para adultos de 50 años y mayores para la prevención de la pulmonía neumocócica y la enfermedad invasiva causada por 13 cepas de Streptococcus pneumoniae (1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F y 23F). Esta indicación se basa en respuestas inmunes a la vacuna • Prevnar 13® no es 100% efectiva y solo ayudará a proteger contra las 13 cepas incluidas en la vacuna • Se desconoce la efectividad cuando se aplica en menos de 5 años después de una vacuna antineumocócica polisacárida INFORMACIÓN IMPORTANTE DE SEGURIDAD • No se debe dar Prevnar 13® a ninguna persona con un historial de reacción alérgica grave a cualquier componente de Prevnar 13® o de cualquier vacuna que contenga el toxoide diftérico • Puede ser que los adultos con sistemas inmunológicos debilitados (ejemplo: Infección de VIH, leucemia) tengan una respuesta inmune reducida CUMPLE CON ESTO HOY. • En adultos, las respuestas inmunes a Prevnar 13® se redujeron cuando se dio con la vacuna contra la gripe de temporada • En adultos, los efectos secundarios comunes fueron dolor, enrojecimiento o hinchazón en el área de la inyección, limitación de movimiento del brazo, fatiga, dolor de cabeza, dolor en los músculos, dolor en las coyunturas, apetito disminuido, escalofríos o erupción • Pregúntale a tu proveedor de salud sobre los riesgos y beneficios de Prevnar 13®. Solo un proveedor de salud puede decidir si Prevnar 13® es adecuada para ti Se te anima para que informes sobre los efectos secundarios negativos de las vacunas a la Administración de Drogas y Alimentos de los EE. UU. (FDA, por sus siglas en inglés) y a los Centros para el Control y la Prevención de Enfermedades (CDC, por sus siglas en inglés). Visita www.vaers.hhs.gov o llama al 1-800-822-7967. Por favor ve los Datos Importantes para Prevnar 13 ® en la siguiente página. PREVNAR 13 es una marca registrada de Wyeth LLC. Fabricado por Wyeth Pharmaceuticals Inc. Comercializado por Pfizer Inc. PSA723004-01 © 2015 Pfizer Inc. Todos los derechos reservados. Febrero del 2015 Las nuevas recomendaciones para las dos vacunas contra la pulmonía por neumococo – en secuencia y con intervalos precisos Por Johnny Rullán, MD, FACPM El 4 de septiembre 2015 se publicaron las nuevas recomendaciones del Advisory Committee on Immunization Practices (ACIP) con respecto al uso secuencial de las 2 vacunas para prevención de pneumococo, la 13-valente conjugada (PCV13, Prevnar-13 de Pfizer Inc.) y la 23-valente polisacarida (PPSV23, Pneumovax 23 de Merck & Co., Inc). Para una persona inmunocompetente que recién cumple 65 años de edad y nunca ha sido vacunado contra pneumococo, la recomendación del ACIP es vacunar oportunamente primero con PCV13 y luego de pasado un año aplicar la vacuna PPSV23. A partir de las dos dosis secuenciales, esta persona no necesita ponerse más dosis contra el pneumococo. Para una persona inmunocompetente que ya cumplió 65 años y fue vacunado previamente con PPSV23, esta persona deberá recibir una dosis de la vacuna PCV13 a partir de por lo menos un año de la vacunación con PPSV23. A partir de las dos dosis secuenciales, esta persona no necesita ponerse más dosis contra el pnéumococo. Para una persona inmunocompetente que recibió PPSV23 antes de edad 65 años y que ahora tiene 65 años o más, deberá recibir una dosis de PCV13 siempre y cuando haya pasado un año o más de la dosis de PPSV23 y al año siguiente deberá recibir una segunda dosis de PPSV23 siempre y cuando hayan pasado 5 años de la dosis 1 de PPSV23. A partir de las tres dosis secuenciales, esta persona no necesita ponerse más dosis contra el pneumococo. Para personas inmunocompetentes de cualquier edad que tengan lo siguiente: fuga de fluído cerebrospinal, implantes de cochlea, asplenia anatómica o functional; o, por otro lado, para personas inmunocomprometidas (HIV, fallo renal crónico, síndrome nefrótico, leucemia, línfoma, miéloma múltiple, enfermedad de hodgkins, transplante de órgano sólido, inmunosupresión iatrogénica, congenital o adquirida, malignidad generalizada), la secuencia es de una dosis de PCV13 primero y luego PPSV23 a las 8 semanas. Ese intérvalo tan corto se hace para minimizar la ventana de enfermedad invasiva pneumocóccica causada por serotipos que sí se incluyen en la vacuna PPSV23 (cerca de 40% de la enfermedad invasiva tiene serotipos únicamente incluídos en la vacuna PPSV23). Las regulaciones del Centro para Servicios de Medicare y Medicaid (CMS) del 11 de mayo del 2015 cubren la administración de dos vacunas diferentes con un intervalo de por lo menos un año para personas de 65 años en adelante. Esta cubierta de CMS es por parte B de Medicare Fee for Service (FFS) y es libre de co-pago o deducibles. Los planes Medicare Advantage (MA), que representan el 75% de los pacientes de Puerto Rico, vienen obligados a cubrir servicios cubiertos bajo Medicare FFS. O sea, los estándares de la medicina en Puerto Rico basados en las recomendaciones del ACIP (que tienen peso medicolegal en Puerto Rico) y en las regulaciones de CMS, dictan que toda persona de 65 años o más deberá recibir dos o mas dosis de vacuna pneumocócica en una secuencia PCV13-PPSV23, PPSV23-PCV13 o PPSV23-PCV13-PPSV23 según dicte su historial previo y las dosis secuenciales serán de un año o de 8 semanas según las guías del ACIP descritas arriba. Si se aplican las dosis secuenciales en los intervalos descritos por ACIP, entonces los planes MA de Puerto Rico que tengan accesibles en sus formularios ambas vacunas secuenciales estarán cumpliendo con los estándares de la medicina que se practica en Puerto Rico. De lo contrario, si no tienen dosis secuenciales en su formulario o no siguen el intervalo recomendado por ACIP y regulado por CMS, están poniendo innecesariamente a sus médicos primarios en riesgo médicolegal. Tómemos nota de los cambios del 2015 para así cumplir el triple objetivo de mejor salud colectiva, brindando servicios de cuido con calidad y a un costo razonable. Más vale precaver que tener que remediar. 1902