El índice de fragilidad y sus características en ensayos clínicos aleatorizados de diabetes mellitus / The Fragility Index and its characteristics in randomized clinical trials of diabetes mellitus

Resumen Introducción: para valorar la robustez de los resultados se ha propuesto una herramienta llamada el Índice de Fragilidad (IF), esta se define como el mínimo número de pacientes que se tienen que cambiar de "No eventos" a "Eventos" en el grupo de intervención para que un resultado estadísticamente significativo pase a no significativo, evidenciando que entre menor sea el IF, los resultados serán más frágiles. Diferentes autores han encontrado que la significancia de los resultados de muchos Ensayos Clínicos Controlados (ECA) dependen de pocos eventos. El objetivo del estudio fue evaluar el IF de los ECA en diabetes mellitus de cinco de las revistas médicas de mayor impacto a nivel mundial. Metodología: se realizó búsqueda electrónica en PubMed, para identificar ECA en Annals of Internal Medicine, BMJ, The Lancet, The New England Journal of Medicine y JAMA. Se revisaron los ECA en pacientes con diabetes mellitus o prediabetes y se calculó el IF para cada desenlace según el método descrito por Walsh et al, usando tablas de contingencia 2x2. Se planeó usar el coeficiente de correlación de Spearman para evaluar la correlación entre el IF y el tamaño de la muestra, el número de eventos, el valor de p y el tiempo de seguimiento. Se evaluó la significancia de todos los resultados con un valor de p<0,05. Resultados: la mediana del IF fue 11, y en tres estudios (7,3%) se encontró que el resultado no era estadísticamente significativo después de recalcular la p con el test exacto de Fisher. Se encontró relación directa leve entre el número de eventos y el IF (Rho= 0,343, p= 0,02) y correlación moderada inversa entre el valor de p y el IF (Rho= -0,632, p= 0,000). No se encontró correlación estadísticamente significativa entre el tamaño de muestra, tiempo de seguimiento y pérdidas con el IF. Conclusiones: en los ECA sobre diabetes, los resultados estadísticamente significativos dependen de pocos eventos, evidenciado por un bajo valor en el IF, los valores de esta medición están relacionados de forma directa con el número de eventos, e inversa con el valor de p.

Abstract Introduction: to evaluate the robustness of the results, a tool called the Fragility Index (FI) has been proposed, which is defined as the minimum number of patients that have to be changed from "No events" to "Events" in the intervention group to change a statistically significant to nonsignificant result. Showing that among a lower Fragility Index, the results of the trial will be less robust or more fragile. Different authors have found that the significance of the results of many controlled clinical trials (RCTs) depend on very few events. The objective of the study is to evaluate the FI of controlled clinical trials in diabetes mellitus in five of the general medical journals with the greatest impact factor worldwide. Methods: an electronic search was conducted in PubMed to identify randomized clinical trials in The Annals of Internal Medicine, BMJ, The Lancet, The New England Journal of Medicine and JAMA. Clinical trials were reviewed with diabetic or prediabetic patients and the FI was then calculated for each outcome according to the method described by Walsh et al, using 2x2 contingency tables. A priori was planned to use the Spearman correlation coefficient to evaluate the direct correlation between the Fragility Index and sample size, number of events, p-value and follow-up time. The significance of all the results was evaluated with a value of p <0.05. Results: the median Fragility Index was 11, and in three studies (7.3%) the result were not statistically significant after recalculating the p value with Fisher's exact test. A slight direct relationship between the number of events and the Fragility Index (Rho = 0.343, p = 0.02) was found and a moderate inverse correlation was observed between the p value and the FI (Rho = -0.632, p = 0.000 ). No statistically significant correlation was found between sample size, follow-up time and losses with the FI. Conclusions: in controlled clinical trials on diabetes, we found that the statistically significant results depend on a few events, evidenced by a low value in the Fragility Index. The values of this measurement are related to the number of events and negatively to the p value.

Prevalencia y manejo de anemia en enfermedad inflamatoria intestinal en un centro de referencia en Colombia / Prevalence and treatment of anemia in inflammatory bowel disease in a Colombian reference center

Resumen Introducción: la anemia es la complicación más frecuente en enfermedad inflamatoria intestinal (EII). El objetivo de este estudio fue determinar la prevalencia, asociaciones y tratamiento de la anemia en EII en nuestro medio. Materiales y métodos: se analizaron de forma retrospectiva datos de pacientes adultos con EII del Hospital Pablo Tobón Uribe en Medellín, Colombia, que consultaron desde 2001 hasta febrero de 2019. Se emplearon frecuencias absolutas y relativas. Para comparar dos proporciones se utilizó la prueba de chi cuadrado de independencia y se estimó el Odds ratio (OR). Resultados: se documentaron 759 pacientes con EII, de los cuales 544 (71,6 %) presentaron colitis ulcerativa (CU); 200 (26,3 %), enfermedad de Crohn (EC), y 15, EII no clasificable (1,9 %). En total, 185 (24,4 %) pacientes con EII presentaron anemia, que es menos frecuente en CU que en EC (22,2 % frente a 32,5 %, respectivamente; OR: 0,684; IC: 0,456-0,96; p = 0,03). Los pacientes con CU extensa (54,1 %) tenían más anemia que aquellos con CU no extensa (46,3 %) (OR: 4,4; IC: 2,6-7,4; p = 0,001); lo mismo se observó al comparar la CU grave (66,1 %) con la no grave (32,3 %) (OR: 4,95; IC: 2,87-8,51; p = 0,000). En la EC, los pacientes con comportamiento no inflamatorio (B2, B3: 73,9 %) presentaron más anemia en comparación con aquellos con comportamiento inflamatorio (B1: 26,2 %) (OR: 0,35; IC: 0,18-0,67; p = 0,000). 44,3 % de los pacientes no recibió tratamiento, 19,5 % recibió hierro oral, 20,0 % recibió hierro intravenoso y 16,2 % fue transfundido. Conclusiones: la anemia es una complicación frecuente de la EII en nuestro medio (24,4 %). A pesar de las guías internacionales, el tratamiento es subóptimo en nuestro medio.

Abstract Introduction: Anemia is the most frequent complication of inflammatory bowel disease (IBD). This study aims to determine the prevalence, connection, and treatment of anemia in IBD in a local context. Materials and Methods: This retrospective study was conducted at The Pablo Tobon Uribe Hospital, in Medellín (Colombia) with adult patients who (were admitted) came for consultation from 2001, until February 2019. Absolut and relative frequencies were calculated. The Chi square test of independence was applied for comparing two proportions and the odds ratio (OR) was estimated. Results: A total of 759 IBD patients were enrolled, 544 (71.6%) with ulcerative colitis (UC); 200 (26.3%) Crohn's disease (CD), and 15 (1.9%) with non-classifiable IBD. In total, 185 (24,4 %) IBD patients had a diagnosis of anemia, that is less frequent in UC patients that in CD patients (22,2 % versus 32,5 %, respectively; OR: 0,684; CI: 0,456-0,96; p = 0,03). Extensive UC patients (54,1 %) had a more recurrent level of anemia than non-extensive UC (46,3 %) (OR: 4,4; CI: 2,6-7,4; p = 0,001); the same result was observed when severe UC (66,1 %) was compared with UC non-severe (32,3 %) (OR: 4,95; CI: 2,87-8,51; p = 0,000). In the analysis of CD, patients with a non-inflammatory response (B2, B3: 73,9 %) had a more recurrent level of anemia than patients with an inflammatory response (B1: 26,2 %) (OR: 0,35; CI: 0,18-0,67; p = 0,000). 44,3 % of the total number of patients received treatment, 19,5 % received oral iron, 20,0 % received intravenous iron, and 16,2 % received a blood transfusion. Conclusions: In our context, Anemia is a common complication in IBD cases (24,4 %). Despite the existence of international guidelines, the treatment in our context is not optimal.

Caracterización y prevalencia de manifestaciones extraintestinales en una cohorte de pacientes con enfermedad inflamatoria intestinal en Medellín (Colombia) / Characterization and prevalence of extraintestinal manifestations in a cohort of patients with inflammatory intestinal disease in Medellin, Colombia

Introducción: Las manifestaciones extraintestinales (MEI) son frecuentes en pacientes con enfermedad inflamatoria intestinal (EII). Nuestro objetivo es caracterizar y determinar la prevalencia de MEI en nuestra cohorte de pacientes con EII. Pacientes y métodos: Se realizó un estudio retrospectivo en pacientes adultos con EII del Hospital Pablo Tobón Uribe en Medellín (Colombia). Se consideraron MEI articulares, colangitis esclerosante primaria (CEP), oftalmológicas y dermatológicas. Se emplearon frecuencias absolutas y relativas. Para comparar 2proporciones se utilizó la prueba χ2 de independencia y se estimó el odds ratio (OR). Resultados: Nuestro registro cuenta con 759 pacientes con EII, 544 presentaban CU (71,6%), 200 EC (26,3%) y 15 EII no clasificable (1,9%). Del total, 177 pacientes con EII (23,3%) presentaron MEI, 123 de 544 (22,6%) con CU y 53 de 200 (26,5%) con EC (OR: 0,81; IC 95%: 0,55-1,17; p=0,31). En cuanto al tipo de MEI, las articulares fueron las más frecuentes (13,5%), más en EC que en CU (20,0 vs. 11,3%; OR 1,94; IC 95%: 1,25-3,00; p=0,0037). Los pacientes con EII y MEI utilizaron más anticuerpos contra el factor de necrosis tumoral (anti-TNF) que aquellos sin MEI (43,5 vs. 18,5%; OR 3,38; IC 95%: 2,31-4,90; p=0,0001). Conclusiones: La prevalencia de MEI en nuestra cohorte es alta (23,3%) y el tipo más frecuente es la articular. Los anti-TNF son más utilizados cuando coexisten EII y MEI. Nuestro estudio aporta información valiosa sobre la asociación de MEI y EII en Latinoamérica.(AU)

Introduction: Extraintestinal manifestations (EIMs) are frequent in patients with inflammatory bowel disease (IBD). Our objective is to characterize and determine the prevalence of MEIs in our cohort of patients with IBD. Patients and methods: A retrospective study was carried out in adult patients with IBD at the Pablo Tobón Uribe Hospital in Medellín. Colombia. Articular MEIs, primary sclerosing cholangitis (PSC), both ophthalmological and dermatological, were considered. Absolute and relative frequencies were used. The Chi square test of independence was used to compare 2proportions and the odds ratio (OR) was estimated. Results: Our registry has 759 patients with IBD, 544 present UC (71.6%), 200 CD (26.3%) and 15 unclassifiable IBD (1.9%); 177 patients with IBD (23.3%) presented EIMs, 123 of 544 (22.6%) with UC and 53 of 200 (26.5%) with CD (OR: 0.81, 95% CI: 0.55-1.17, P=0.31). Regarding the type of EIMs, the articular ones were the most frequent (13.5%), more in CD than in UC (20.0 vs. 11.3%, OR 1.94, 95% CI: 1.25-3.00, P=0.0037). Patients with IBD and EIMs used more antibodies against tumor necrosis factor (anti-TNFs), compared to those without EIMs (43.5 vs. 18.5%, OR 3.38, 95% CI: 2.31-4.90, P=0.0001). Conclusions: The prevalence of EIMs in our cohort is high (23.3%) and the most frequent type is joint. Anti-TNFs are most used when IBD and EIMs coexist. Our study provides valuable information on the association of EIMs and IBD in Latin America.(AU)

Recomendaciones para reumatólogos sobre el manejo farmacológico durante la emergencia sanitaria por COVID-19: opinión de un grupo de expertos / Recommendations for rheumatologists on pharmacological management during the COVID-19 health emergency: Expert group opinion

RESUMEN La enfermedad por Coronavirus 2019 (COVID-19) es una pandemia inesperada que ha pro vocado un estado de emergencia y que ha generado cambios drásticos en los protocolos de atención clínica. Para su tratamiento se ha descrito el papel de algunos medicamen tos usados habitualmente en artritis reumatoide, lupus eritematoso sistémico y otras enfermedades autoinmunitarias sistémicas. Debido a ello, existe un inminente riesgo de desabastecimiento, por lo cual el objetivo de esta revisión narrativa y opinión de expertos es formular recomendaciones generales clínicas y administrativas sobre el manejo de pacien tes ambulatorios con enfermedad autoinmunitaria o inflamatoria sistémica en el contexto de la pandemia por COVID-19.

ABSTRACT Coronavirus 2019 (COVID-19) is an unexpected pandemic that has caused a state of emergency, as well as generating drastic changes in clinical care protocols. Some drugs commonly used in rheumatoid arthritis, systemic lupus erythematosus, and other systemic autoimmune diseases have been described for its treatment. Therefore, there is an imminent risk of shortages. The aim of this narrative review and expert opinion is to present general recommendations on the clinical and administrative management of outpatients with autoimmune or systemic inflammatory disease, in the context of the COVID-19 pandemic.

Trends in the epidemiology of inflammatory bowel disease in Colombia by demographics and region using a nationally representative claims database and characterization of inflammatory bowel disease phenotype in a case series of Colombian patients.

ABSTRACT: The incidence of inflammatory bowel disease (IBD) is on the rise in Latin America. The aims of this study were to examine epidemiologic trends of IBD in Colombia by demographics, region, urbanicity, and to describe the IBD phenotype in a large well-characterized Colombian cohort.We used a national database of 33 million adults encompassing 97.6% of the Colombian population in order to obtain epidemiologic trends of IBD using International Classification of Diseases 10codes for adults with ulcerative colitis (UC) and Crohn disease (CD). We calculated the incidence and prevalence of UC and CD from 2010-2017 and examined epidemiologic trends by urbanicity, demographics, and region. We then examined the IBD phenotype (using Montreal Classification), prevalence of IBD-related surgeries, and types of IBD-medications prescribed to adult patients attending a regional IBD clinic in Medellin, Colombia between 2001 and 2017.The incidence of UC increased from 5.59/100,000 in 2010 to 6.3/100,000 in 2017 (relative risk [RR] 1.12, confidence interval (CI) (1.09-1.18), P < .0001). While CD incidence did not increase, the prevalence increased within this period. The Andes region had the highest incidence of IBD (5.56/100,000 in 2017). IBD was seen less in rural regions in Colombia (RR=.95, CI (0.92-0.97), p < .01). An increased risk of IBD was present in women, even after adjusting for age and diagnosis year (RR 1.06 (1.02-1.08), P = .0003). The highest IBD risk occurred in patients 40 to 59 years of age. In the clinic cohort, there were 649 IBD patients: 73.7% UC and 24.5% CD. Mean age of diagnosis in CD was 41.0 years and 39.9 years in UC. UC patients developed mostly pancolitis (43%). CD patients developed mostly ileocolonic disease and greater than a third of patients had an inflammatory, non-fistulizing phenotype (37.7%). A total of 16.7% of CD patients had perianal disease. CD patients received more biologics than UC patients (odds ratio: 3.20, 95% CI 2.19-4.69 P < .001).Using both a national representative sample and a regional clinic cohort, we find that UC is more common in Colombia and is on the rise in urban regions; especially occurring in an older age cohort when compared to Western countries. Future studies are warranted to understand evolving environmental factors explaining this rise.

Characterization and prevalence of extraintestinal manifestations in a cohort of patients with inflammatory intestinal disease in Medellin, Colombia. / Caracterización y prevalencia de manifestaciones extraintestinales en una cohorte de pacientes con enfermedad inflamatoria intestinal en Medellín (Colombia).

INTRODUCTION: Extraintestinal manifestations (EIMs) are frequent in patients with inflammatory bowel disease (IBD). Our objective is to characterize and determine the prevalence of MEIs in our cohort of patients with IBD. PATIENTS AND METHODS: A retrospective study was carried out in adult patients with IBD at the Pablo Tobón Uribe Hospital in Medellín. Colombia. Articular MEIs, primary sclerosing cholangitis (PSC), both ophthalmological and dermatological, were considered. Absolute and relative frequencies were used. The Chi square test of independence was used to compare 2proportions and the odds ratio (OR) was estimated. RESULTS: Our registry has 759 patients with IBD, 544 present UC (71.6%), 200 CD (26.3%) and 15 unclassifiable IBD (1.9%); 177 patients with IBD (23.3%) presented EIMs, 123 of 544 (22.6%) with UC and 53 of 200 (26.5%) with CD (OR: 0.81, 95% CI: 0.55-1.17, P=0.31). Regarding the type of EIMs, the articular ones were the most frequent (13.5%), more in CD than in UC (20.0 vs. 11.3%, OR 1.94, 95% CI: 1.25-3.00, P=0.0037). Patients with IBD and EIMs used more antibodies against tumor necrosis factor (anti-TNFs), compared to those without EIMs (43.5 vs. 18.5%, OR 3.38, 95% CI: 2.31-4.90, P=0.0001). CONCLUSIONS: The prevalence of EIMs in our cohort is high (23.3%) and the most frequent type is joint. Anti-TNFs are most used when IBD and EIMs coexist. Our study provides valuable information on the association of EIMs and IBD in Latin America.

Puntaje de tinción ocular en pacientes con diagnóstico de síndrome de Sjögren en una institución de salud en Medellín, Colombia / Ocular staining score in patients diagnosed with Sjögren syndrome in a health institution in Medellín, Colombia

RESUMEN Introducción: El síndrome de Sjögren es una enfermedad autoinmune asociada a múltiples factores, tanto genéticos como ambientales, que afecta principalmente a las glándulas salivales y lagrimales con infiltración celular de estas, lo cual causa síntomas secos. Con frecuencia se describe la queratoconjuntivitis sicca y sus complicaciones. Sus criterios clasificatorios han cambiado a lo largo de los años por la diversidad de los órganos implicados y los espectros clínicos de la enfermedad. Hoy se cuenta con parámetros clínicos y paraclínicos para su identificación; uno de estos, el puntaje de tinción ocular ocular staining score (OSS, por sus siglas en inglés), estandarizado a partir de la cohorte SICCA. Objetivo: Describir los hallazgos en la evaluación ocular, el resultado de las pruebas que hacen parte del OSS y las características clínicas de los criterios clasificatorios en pacientes con síndrome de Sjögren en el servicio de consulta externa de reumatología de un hospital universitario en el noroccidente colombiano. Método: Se condujo un estudio observacional, descriptivo y de corte transversal. Se describieron las características de los criterios clasificatorios del síndrome de Sjögren, incluyendo el puntaje de tinción ocular durante un año. Se realizaron las pruebas clínicas y tinciones oculares estandarizadas, evaluando características de la superficie ocular, producción lagrimal y tinciones con verde lisamina y fluoresceína sobre la conjuntiva y la córnea. Según los hallazgos se asignó una puntuación a cada parámetro para evaluar positividad, de acuerdo con el estándar clasificatorio. Las variables cualitativas se expresaron por medio de frecuencias absolutas y relativas y las cuantitativas como mediana y rango intercuartílico (P25-P75), según la distribución de los datos. Se empleó el paquete estadístico Epidat, versión 4.2. Resultados: Se incluyeron 28 pacientes. Los síntomas de ojo seco estuvieron presentes en el 89,2% de ellos; un 96,4% tuvo hallazgos positivos en el examen ocular y el 78,5% alcanzó un puntaje a favor de los criterios clasificatorios en la evaluación del OSS. La mediana del OSS fue 6,14; los anticuerpos anti-Ro fueron positivos en un 57,1%. Conclusión: La evaluación ocular por medio de pruebas objetivas es un método sencillo y reproducible en los pacientes con síndrome de Sjögren. Los índices más afectados fueron aquellos de disminución en la producción lagrimal. Las tinciones oculares no tuvieron una relación directa con la positivad de anticuerpos ni del factor reumatoide.

ABSTRACT Introduction: Sjögren's syndrome is an autoimmune disease associated with multiple genetic and environmental factors. It mainly affects the salivary and lacrimal glands with cellular infiltration leading to dry eye symptoms, with keratoconjunctivitis sicca and its complications often being described. Its classification criteria have changed over the years, due to the diversity in the organs involved and clinical spectrum of the disease. Today, there are clinical and para-clinical parameters for its identification. One of these is the ocular staining score (OSS), standardised from the SICCA cohort. Objective: To describe the findings in the ocular evaluation, the results of the tests of the OSS, and the clinical characteristics of the classification criteria in patients with Sjögren syndrome in the outpatient service of Rheumatology Outpatient Department a university hospital in north-western Colombia. Methods: An observational, descriptive, cross-sectional study was conducted. The characteristics of the Sjögren syndrome classification criteria were described, including the OSS score for one year. Clinical tests and standardised ocular stains were performed, evaluating characteristics of the ocular surface, tearproduction, and lissamine green and fluorescein stains on the conjunctiva and cornea, assigning, according to the findings, a score to each parameter in order to assess positivity according to the classification standard. The qualitative variables were expressed by means of absolute and relative frequencies, and the quantitative ones as the median and interquartile range (P25-P75), according to the distribution of the data. Epidat statistical package, version 4.2, was used. Results: A total of 28 patients were included. Dry eye symptoms were present in 89.2%, 96.4% had positive findings in the eye examination, and 78.5% had a score on the OSS according to the classification criteria. The median OSS was 6.14, and anti-Ro antibodies were positive in 57.1%. Conclusion: Eye evaluation by objective tests is a simple and reproducible method in patients with Sjögren's syndrome. The most affected indices were those of a decrease in tearproduction. The ocular stains did not have a direct relationship with the positivity of antibodies, nor rheumatoid factor.

Biomicroscopic Findings and Management of Anterior Stromal Necrosis After Long-term Implantation of Intacs.

PURPOSE: We sought to evaluate the visual, refractive, and biomicroscopic findings pre- and posttreatment of observed anterior stromal necrosis (ASN) after long-term Intacs intracorneal ring segment (ICRS) implantation. DESIGN: Consecutive interventional case series. METHODS: All consecutive patients implanted with Intacs ICRS at a single center by 1 of the authors between October 2006 and October 2011 with a minimum follow-up time of 5 years were included. All Intacs were implanted using the Prolate system console and instrumentation from Addition Technology Inc (Chicago, Illinois, USA). The slit lamp, refractive, and visual findings and the management of those patients are described in detail. The primary outcome measures included the size of the epithelial defect overlying the Intacs body, the intended implantation depth measured by high-magnification slit lamp photography, and the management of the cases described in detail. The percentage of eyes with ASN out of those that reached the 5-year follow-up is reported. RESULTS: One hundred twenty-seven eyes (84 patients) were implanted with 215 ICRSs during the study period, and 77.16% (98/127) eyes had a follow-up of ≥5 years, out of which 9 eyes (7 patients) had ASN corresponding to at least 9.18% (95% confidence interval 4.29%-16.72%). The mean ± standard deviation time between implantation and ASN diagnosis was 10.5 ± 1.3 years. CONCLUSION: After 5 years of implantation, INTACS-treated eyes could present with an ASN over the ICRS body. Longer-term follow-up of patients implanted with INTACS is important to monitor if this complication keeps occurring over time.

Human Epidermal Growth Factor Receptor 2-Positive Breast Cancer Is Associated with Indigenous American Ancestry in Latin American Women.

Women of Latin American origin in the United States are more likely to be diagnosed with advanced breast cancer and have a higher risk of mortality than non-Hispanic White women. Studies in U.S. Latinas and Latin American women have reported a high incidence of HER2 positive (+) tumors; however, the factors contributing to this observation are unknown. Genome-wide genotype data for 1,312 patients from the Peruvian Genetics and Genomics of Breast Cancer Study (PEGEN-BC) were used to estimate genetic ancestry. We tested the association between HER2 status and genetic ancestry using logistic and multinomial logistic regression models. Findings were replicated in 616 samples from Mexico and Colombia. Average Indigenous American (IA) ancestry differed by subtype. In multivariate models, the odds of having an HER2+ tumor increased by a factor of 1.20 with every 10% increase in IA ancestry proportion (95% CI, 1.07-1.35; P = 0.001). The association between HER2 status and IA ancestry was independently replicated in samples from Mexico and Colombia. Results suggest that the high prevalence of HER2+ tumors in Latinas could be due in part to the presence of population-specific genetic variant(s) affecting HER2 expression in breast cancer. SIGNIFICANCE: The positive association between Indigenous American genetic ancestry and HER2+ breast cancer suggests that the high incidence of HER2+ subtypes in Latinas might be due to population and subtype-specific genetic risk variants.

BRAF and TERT mutations in papillary thyroid cancer patients of Latino ancestry.

Papillary thyroid cancer (PTC) is the second most commonly diagnosed malignancy in U.S. Latinas and in Colombian women. Studies in non-Latinos indicate that BRAF and TERT mutations are PTC prognostic markers. This study aimed to determine the prevalence and clinical associations of BRAF and TERT mutations in PTC Latino patients from Colombia. We analyzed mutations of BRAF (V600E) and TERT promoter (C228T, C250T) in tumor DNA from 141 patients (75 with classical variant PTC, CVPTC; 66 with follicular variant PTC, FVPTC) recruited through a multi-center study. Associations between mutations and clinical variables were evaluated with Fisher exact tests. Survival was evaluated with Kaplan-Meier plots. Double-mutant tumors (BRAF+/TERT+, n = 14 patients) were more common in CVPTC (P = 0.02). Relative to patients without mutations (n = 48), double mutations were more common in patients with large tumors (P = 0.03), lymph node metastasis (P = 0.01), extra-thyroid extension (P = 0.03), and advanced stage (P = 6.0 × 10-5). In older patients, TERT mutations were more frequent (mean age 51 years vs 45 years for wild type TERT, P = 0.04) and survival was lower (HR = 1.20; P = 0.017); however, given the small sample size, the decrease in survival was not statically significant between genotypes. Comparisons with published data in US whites revealed that Colombian patients had a higher prevalence of severe pathological features and of double-mutant tumors (10 vs 6%, P = 0.001). Mutations in both oncogenes show prognostic associations in Latinos from Colombia. Our study is important to advance Latino PTC precision medicine and replicates previous prognostic associations between BRAF and TERT in this population.

[SHTLV-I/II seroprevalence in blood donors of Hospital Pablo Tobón Uribe Blood Bank during the period 2014-2015].

INTRODUCTION: The human-T cell lymphotropic virus is a retrovirus with various types known so far. HTLV-I and HTLV-II are of clinically importance as they cause different diseases such as adult T-cell leukemia/lymphoma, tropical spastic paraparesis, and human T-lymphotropic virus type I-associated myelopathy (HAM). OBJECTIVE: To estimate the prevalence of presumptive and confirmatory reactivity to HTLV-I/II in blood donors of Hospital Pablo Tobón Uribe Blood Bank between 2014 and 2015. MATERIALS AND METHODS: The information was obtained from the Hospital Pablo Tobón Uribe Blood Bank database. We analyzed age, sex, place of origin, and place of residence of donors, and the reactivity using the screening test (ELISA) as well as the confirmatory test (immunoblot). RESULTS: The donor population studied included 6,275 men and 8,148 women, for a total of 14,423 donors recruited between March 1, 2014, and June 30, 2015. Of all tested donors, 25 were positive for HTLV-I/II by the screening test (ELISA). After performing the confirmatory test (immunoblot), only nine patients were positive for HTLV-I/II (36%), of whom eight were reactive to HTLV-I (32%) and one to HTLV-II (4%), for a global seroprevalence of 0.06% (CI 95%: 0.10-0.25). CONCLUSIONS: Our findings were consistent with those found in similar studies in non-endemic areas of the country and with those from studies at international level reported in the literature.

Seroprevalencia de los virus linfotrópicos de células T humanas de tipos I y II en donantes del Banco de Sangre del Hospital Pablo Tobón Uribe, entre 2014 y 2015 / HTLV-I/II seroprevalence in blood donors of Hospital Pablo Tobón Uribe Blood Bank during the period 2014-2015

Resumen Introducción . El virus linfotrópico humano de células T (HTLV) es un retrovirus del cual se conocen varios tipos, entre ellos el HTLV-I y el HTLV-II, los cuales son de importancia clínica por ser los causantes de diferentes enfermedades, como la leucemia y el linfoma de células T del adulto, la paraparesia espástica tropical y la mielopatía asociada al HTLV. Objetivo . Obtener la prevalencia de las reacciones presuntiva y confirmatoria de los virus HTLV-I y HTLV-II en los donantes del Banco de Sangre del Hospital Pablo Tobón Uribe de Medellín, entre el 2014 y el 2015. Materiales y métodos . La información se obtuvo de la base de datos del Banco de Sangre del Hospital Pablo Tobón Uribe. Se analizaron la edad, el sexo y el lugar de procedencia y de residencia de los donantes, así como la reacción en la prueba de tamización (ELISA) y en la prueba confirmatoria (inmunoblot). Resultados . La población de donantes estudiados incluyó a 6.275 hombres y 8.148 mujeres, para un total de 14.423 donantes reclutados entre el 1° de marzo de 2014 y el 30 de junio de 2015. De ellos, 25 resultaron positivos para HTLV-I o HTLV-II en la prueba de tamización (ELISA). En la prueba confirmatoria (inmunoblot), nueve (36 %) pacientes fueron positivos para el HTLV-I o HTLV-II , y de ellos ocho (32 %) lo fueron para el HTLV-I y uno (4 %) para el HTLV-II; la seroprevalencia global fue de 0,06 % (IC95% 0,10-0,25). Conclusiones . Los hallazgos del estudio concordaron con los de estudios similares en áreas no endémicas del país y con los de los estudios consultados a nivel internacional.

Abstract Introduction: The human-T cell lymphotropic virus is a retrovirus with various types known so far. HTLV-I and HTLV-II are of clinically importance as they cause different diseases such as adult T-cell leukemia/lymphoma, tropical spastic paraparesis, and human T-lymphotropic virus type I-associated myelopathy (HAM). Objective: To estimate the prevalence of presumptive and confirmatory reactivity to HTLV-I/II in blood donors of Hospital Pablo Tobón Uribe Blood Bank between 2014 and 2015. Materials and methods: The information was obtained from the Hospital Pablo Tobón Uribe Blood Bank database. We analyzed age, sex, place of origin, and place of residence of donors, and the reactivity using the screening test (ELISA) as well as the confirmatory test (immunoblot). Results: The donor population studied included 6,275 men and 8,148 women, for a total of 14,423 donors recruited between March 1, 2014, and June 30, 2015. Of all tested donors, 25 were positive for HTLV-I/II by the screening test (ELISA). After performing the confirmatory test (immunoblot), only nine patients were positive for HTLV-I/II (36%), of whom eight were reactive to HTLV-I (32%) and one to HTLV-II (4%), for a global seroprevalence of 0.06% (CI 95%: 0.10-0.25). Conclusions: Our findings were consistent with those found in similar studies in non-endemic areas of the country and with those from studies at international level reported in the literature.

[Effect of antenatal spiramycin treatment on the frequency of retinochoroiditis due to congenital toxoplasmosis in a Colombian cohort].

INTRODUCTION: Gestational toxoplasmosis is frequent and severe. There is still debate about the benefits of treatment against ocular manifestations in the newborn. Spiramycin treatment is used for this purpose, unfortunately prenatal diagnosis is sometimes delayed and pregnant women are not treated. OBJECTIVE: To describe the relationship between treatment with spiramycin during pregnancy in mothers with gestational toxoplasmosis and development of ocular toxoplasmosis in newborns. MATERIALS AND METHODS: We conducted a descriptive study of a case series. We evaluated a prospective cohort of patients diagnosed with gestational toxoplasmosis during three years at the Retinology Service at the Clínica Universitaria Bolivariana in Medellín. RESULTS: Gestational toxoplasmosis was found in 23 mothers; 15 (65%) were treated during pregnancy with 3 g per day of spiramycin, eight (35%) patients were untreated. In the treated group just one newborn developed ocular toxoplasmosis (6.6%), in contrast with five (62.5%) of the eight patients who did not receive treatment. These results suggest that pregnancy treatment reduces the relative risk of ocular toxoplasmosis in the newborn by 96% (95% CI: 33 - 100%). Only two (14%) of the patients who were evaluated, had nervous system involvement related to toxoplasmosis in CT scan or cerebral ultrasound. These two patients also developed ocular pathology and were diagnosed at the time of birth, so they did not received antenatal treatment. CONCLUSIONS: A protective effect was found against the ocular involvement in patients whose mother received treatment with spiramycin (OR=0.04;95% CI: 0.00-0.67), p<0.01 (Fisher's Exact Test).

Efecto del tratamiento prenatal con espiramicina en la frecuencia de retinocoroiditis por toxoplasmosis congénita en una cohorte colombiana / Effect of antenatal spiramycin treatment on the frequency of retinochoroiditis due to congenital toxoplasmosis in a Colombian cohort

Resumen Introducción. La toxoplasmosis de la gestación es frecuente y grave. Hasta ahora no hay consenso sobre la utilidad del tratamiento para prevenir complicaciones oculares en el neonato. En la actualidad, uno de los medicamentos utilizados en las madres diagnosticadas es la espiramicina oral. Infortunadamente, en algunas mujeres gestantes no se hace el diagnóstico prenatal y, por esta u otras razones, no reciben el tratamiento. Objetivo. Describir la relación entre el tratamiento con espiramicina durante el embarazo en madres con toxoplasmosis de la gestación y la presentación de toxoplasmosis ocular en los recién nacidos. Materiales y métodos. Se llevó a cabo un estudio observacional descriptivo de serie de casos. Se evaluó una serie prospectiva de pacientes con toxoplasmosis de la gestación durante tres años de seguimiento en el Servicio de Retinología de la Clínica Universitaria Bolivariana de Medellín. Resultados. Se registraron 23 madres con diagnóstico de toxoplasmosis de la gestación. Quince de ellas (65 %) recibieron durante la gestación tratamiento con espiramicina en dosis de 3 g al día; uno de los neonatos (6,6 %) presentó toxoplasmosis ocular. De las ocho (35 %) pacientes que no recibieron tratamiento, cinco (62,5 %) tuvieron hijos con compromiso ocular por toxoplasma. La razón de momios (odds ratio, OR) del efecto protector contra dicho compromiso en los pacientes cuyas madres recibieron tratamiento fue de 0,04 (IC95% 0,00-0,67), con valor de p menor de 0,01 en la prueba exacta de Fisher. Solo se evidenció compromiso del sistema nervioso central por toxoplasmosis mediante las imágenes de tomografía o ecografía cerebral en dos (14 %) pacientes de las 14 en quienes se hicieron estos estudios. Los dos pacientes presentaron, además, compromiso ocular; ambos fueron diagnosticados en el momento del nacimiento y sus madres no habían recibido tratamiento prenatal. Conclusiones. Estos resultados evidencian que el tratamiento con espiramicina durante el embarazo en la toxoplasmosis de la gestación redujo en 96 % (IC95% 33-100 %) el riesgo relativo de presentar la enfermedad en el recién nacido.

Abstrat Introduction: Gestational toxoplasmosis is frequent and severe. There is still debate about the benefits of treatment against ocular manifestations in the newborn. Spiramycin treatment is used for this purpose, unfortunately prenatal diagnosis is sometimes delayed and pregnant women are not treated. Objective: To describe the relationship between treatment with spiramycin during pregnancy in mothers with gestational toxoplasmosis and development of ocular toxoplasmosis in newborns. Materials and methods: We conducted a descriptive study of a case series. We evaluated a prospective cohort of patients diagnosed with gestational toxoplasmosis during three years at the Retinology Service at the Clínica Universitaria Bolivariana in Medellín. Results: Gestational toxoplasmosis was found in 23 mothers; 15 (65%) were treated during pregnancy with 3 g per day of spiramycin, eight (35%) patients were untreated. In the treated group just one newborn developed ocular toxoplasmosis (6.6%), in contrast with five (62.5%) of the eight patients who did not receive treatment. These results suggest that pregnancy treatment reduces the relative risk of ocular toxoplasmosis in the newborn by 96% (95% CI: 33 - 100%). Only two (14%) of the patients who were evaluated, had nervous system involvement related to toxoplasmosis in CT scan or cerebral ultrasound. These two patients also developed ocular pathology and were diagnosed at the time of birth, so they did not received antenatal treatment. Conclusions: A protective effect was found against the ocular involvement in patients whose mother received treatment with spiramycin (OR=0.04;95% CI: 0.00-0.67), p<0.01 (Fisher's Exact Test).

Clinical features of Hispanic thyroid cancer cases and the role of known genetic variants on disease risk.

Thyroid cancer (TC) is the second most common cancer among Hispanic women. Recent genome-wide association (GWA) and candidate studies identified 6 single nucleotide polymorphisms (SNPs; rs966423, rs2439302, rs965513, rs6983267, rs944289, and rs116909374), associated with increased TC risk in Europeans but their effects on disease risk have not been comprehensively tested in Hispanics. In this study, we aimed to describe the main clinicopathological manifestations and to evaluate the effects of known SNPs on TC risk and on clinicopathological manifestations in a Hispanic population.We analyzed 281 nonmedullary TC cases and 1146 cancer-free controls recruited in a multicenter population-based study in Colombia. SNPs were genotyped by Kompetitive allele specific polymerase chain reaction (KASP) technique. Association between genetic variants and TC risk was assessed by computing odds ratios (OR) and confidence intervals (CIs).Consistent with published data in U.S. Hispanics, our cases had a high prevalence of large tumors (>2 cm, 43%) and a high female/male ratio (5:1). We detected significant associations between TC risk and rs965513A (OR = 1.41), rs944289T (OR = 1.26), rs116909374A (OR = 1.96), rs2439302G (OR = 1.19), and rs6983267G (OR = 1.18). Cases carried more risk alleles than controls (5.16 vs. 4.78, P = 4.8 × 10). Individuals with ≥6 risk alleles had >6-fold increased TC risk (OR = 6.33, P = 4.0 × 10) compared to individuals with ≤2 risk alleles. rs944289T and rs116909374A were strongly associated with follicular histology (ORs = 1.61 and 3.33, respectively); rs2439302G with large tumors (OR = 1.50); and rs965513A with regional disease (OR = 1.92).To our knowledge, this is the first study of known TC risk variants in South American Hispanics and suggests that they increase TC susceptibility in this population and can identify patients at higher risk of severe disease.

The HABP2 G534E polymorphism does not increase nonmedullary thyroid cancer risk in Hispanics.

Familial nonmedullary thyroid cancer (NMTC) has not been clearly linked to causal germline variants, despite the large role that genetic factors play in risk. Recently, HABP2 G534E (rs7080536A) has been implicated as a causal variant in NMTC. We have previously shown that the HABP2 G534E variant is not associated with TC risk in patients from the British Isles. Hispanics are the largest and the youngest minority in the United States and NMTC is now the second most common malignancy in women from this population. In order to determine if the HABP2 G534E variant played a role in NMTC risk among Hispanic populations, we analyzed 281 cases and 1105 population-matched controls from a multicenter study in Colombia, evaluating the association through logistic regression. We found that the HABP2 G534E variant was not significantly associated with NMTC risk (P=0.843) in this Hispanic group. We also stratified available clinical data by multiple available clinicopathological variables and further analyzed the effect of HABP2 on NMTC presentation. However, we failed to detect associations between HABP2 G534E and NMTC risk, regardless of disease presentation (P≥0.273 for all cases). Therefore, without any significant associations between the HABP2 G534E variant and NMTC risk, we conclude that the variant is not causal of NMTC in this Hispanic population.

Sobrecarga en cuidadores primarios de pacientes con glaucoma avanzado / Overload in primary caregivers of patients with advanced glaucoma

Las personas dedicadas al cuidado de los pacientes con enfermedades avanzadas como el glaucoma pueden presentar sobrecarga física o emocional, esta es a menudo menospreciada por el paciente, el sistema de salud, la familia y el propio cuidador. El glaucoma avanzado es una patología que puede conducir a la ceguera y que generan dependencia del paciente frente a su cuidador primario. Consideramos relevante cuantificar el nivel de esta sobrecarga en personas dedicadas al cuidado de pacientes con glaucoma avanzado. Materiales y Métodos: para el estudio se utilizó una escala de sobrecarga internacional, validada en la ciudad de Medellín: la escala de Bedard de Cribado (abreviada de la escala de Zarit). Se aplicó vía telefónica - previo consentimiento informado - acompañada de un cuestionario corto en el cual se incluyeron datos sociodemográficos, a los cuidadores de pacientes con daño glaucomatoso avanzado. Resultados: se evaluaron en total 30 cuidadores, de estos 24 (80%) eran mujeres. El promedio± (DE) de la edad del cuidador fue 57.63 ± 12.48 años (R=33 - 93) años. El estado civil más frecuente fue casado 17 (56,7%). Diecisiete (56,7%) de los evaluados eran hijos, 9 (30%) cónyuge y 4 (13%) madre del paciente con glaucoma. El promedio ± (DE) del tiempo que llevaban a cargo del paciente era 10.37 ± (9.87) años (R=2 - 36) años. Además 17 (56,7%) tenían estudios de básica primaria, 10 (33,3%) de bachillerato, 2 (6,7%) técnica o tecnología y 1 (3,3%) universitarios. La mitad de los cuidadores 15 (50%) pertenecían al estrato socioeconómico 3 y solo cuatro (13,3%) al estrato 5 o 6. Asumiendo como punto de corte 8 puntos en la Escala de Bedard de Cribado encontramos sobrecarga en 5 de los 30 cuidadores (16,7%). Conclusiones: se puede concluir que el cuidador del paciente con glaucoma avanzado suele ser una mujer mayor, casada e hija del paciente. En su mayoría se trata de personas con estudios de primaria y que pertenece al estrato socioeconómico 3. Menos de una quinta parte de los encuestados mostraron sobrecarga en la escala actual, lo cual puede ser explicado por la edad, el sexo y el parentesco del cuidador.

The patient, family, system or the caregiver often underestimates the physic or emotional caregiver burden associated with chronic illnesses. Advanced glaucoma could lead to blindness and generate a great caregiver dependence. We tried to quantify the burden level in the primary caregivers of patients with advanced glaucoma. Methods. We performed a short standardized telephonic survey on the caregivers of advanced glaucoma patients, after verbal explanation and informed consent. We utilized a validated international Scale (Short or screening version of the Zarit Burden Scale). Results. We enrolled 30 caregivers, 24 (80%) were women. The Mean ± (SD) of the caregiver age was 57.63± 12.48 years (R=33-93). The majority of the evaluated were married 17 (56,7%). Seventeen (56,7%) were the patient's daughter, 9 (30%) wife or husband and 4 (13%) mother of the glaucoma patient. The mean ± (SD) of the time taking care of the patient was 10,37 ± (9.87) years range (R=2 -36). Additionally, 17 (56,7%) had elementary school, 10 (33,3%) high school, 2 (6,7%) technic or technology and 1 (3,3%) college degrees. Half the caregivers 15 (50%) were in the 3rd socioeconomic level and only four (13,3%) in the 5th or 6th level. Assuming an 8 point cut off level in the screening scale, we found burden in 5 of the 30 caregivers (16,7%) Conclusions We conclude that the caregiver of the glaucoma patient in our city is usually a married older woman, frequently the daughter of the patient. Mostly they have elementary school degrees and belong to the 3rd socioeconomic level. Less than a half of the caregivers showed burden using this scale. The authors' hypothesis is that these results could be explained by the age, the sex and the relationship of the caregiver.

Influenza-like illness sentinel surveillance in one hospital in Medellin, Colombia. 2007-2012.

BACKGROUND: The city of Medellin in Colombia has almost no documentation of the causes of acute respiratory infections (ARIs). As part of an ongoing collaboration, we conducted an epidemiologic surveillance for influenza and other respiratory viruses. It described the influenza strains that were circulating in the region along with their distribution over time, and performing molecular characterization to some of those strains. This will contribute to the knowledge of local and national epidemiology. OBJECTIVES: To analyze viral etiologic agents associated with influenza like illness (ILI) in participants reporting to one General hospital in Medelllin, Colombia. RESULTS: From January 2007 to December 2012, a total of 2039 participants were enrolled. Among them, 1120 (54.9%) were male and 1364 (69%) were under the age of five. Only 124 (6%) were older than the age of 15. From all 2039 participants, 1040 samples were diagnosed by either isolation or RT-PCR. One or more respiratory viruses were found in 737 (36%) participants. Of those, 426 (57.8%) got influenza A or B. Adenoviral and parainfluenza infections represented 19.1% and 14.9% of viral infections, respectively. Influenza A was detected almost throughout the whole year except for the first quarter of 2010, right after the 2009 influenza A pandemic. Influenza B was detected in 2008, 2010, and 2012 with no pattern detected. During 2008 and 2010, both types circulated in about the same proportion. Unusually, in many months of 2012, the proportion of influenza B infections was higher than influenza A (ranging between 30% and 42%). The higher proportion of adenovirus was mainly detected in the last quarter of years 2007 and 2010. Adenoviral cases are more frequent in participants under the age of four. CONCLUSIONS: The phylogenetic analysis of influenza viruses shows that only in the case of influenza A/H1N1, the circulating strains totally coincide with the vaccine strains each year.

Ocular trauma from land mines among soldiers treated at a University Hospital in Medellin, Colombia / Caracterización del trauma ocular por minas antipersonales en soldados atendidos en un hospital Universitario en Medellín, Colombia

Introduction: Currently ocular combat injuries are complex and associated with poor visual outcomes. Our objective is to characterize the military population that suffer land mine combat ocular trauma in Colombia and identify the type of wound, treatment and visual outcomes. Methods: Retrospectively review of medical history of soldiers evaluated in Pablo Tobon Uribe Hospital, whom had land mine trauma during January of 2004 and December 2012. Results: 635 soldiers had land mine trauma, 153 of them had ocular trauma (226 eyes). Open ocular trauma was observed in 29.6%. The Ocular Trauma Score was calculated in 183 eyes, the initial visual acuity was not possible to be reported in the rest of them; the 45% of the eyes were classified in category 3. Three patients had no light perception in both eyes. 97.3% of the eyes received medical treatment and 49.1% had surgery also. Primary evisceration was made in 5.8% and enucleation in 1.8%. Intraocular foreign body was observed by ultrasonography in 11.1% and in 5.8% by orbital tomography. Eleven patients were legally blind at discharge. Conclusions: The ocular trauma related to a land mine is highly destructive at an ocular level. The treatments associated with better visual outcomes are primary closure of globe and systemic antibiotics; although the characteristics of the wound itself are the main prognostic factor. The Ocular trauma score is a useful tool for determining visual outcome in combat ocular trauma.

Introducción: Los combates armados generan heridas oculares complejas con mal pronóstico visual. Nuestro objetivo es caracterizar la población militar que sufre trauma ocular de combate en Colombia asociado a minas antipersona, así como las características de las lesiones, el tratamiento recibido y desenlace visual final. Métodos: Se evaluó retrospectivamente las historias clínicas de soldados atendidos en el Hospital Pablo Tobon Uribe, que sufrieron accidente por mina antipersona durante el período entre enero de 2004 y diciembre de 2012. Resultados: 635 soldados, sufrieron trauma por mina antipersona; de estos, 153 (226 ojos) tuvieron trauma ocular. El 29.6% tuvieron trauma abierto. Se calculó el Ocular Trauma Score en 183 ojos. El 45% de los ojos se clasificaron como categoría 3. Tres pacientes tuvieron una visión final de no percepción de luz por ambos ojos. El 97.3% de los ojos tuvieron tratamiento farmacológico y 49.1% recibieron cirugía además. Se realizó evisceración primaria en el 5.8% y enucleación en 1.8%. Se logró comprobar cuerpo extraño intraocular por ecografía en el 11.1% y por tomografía de órbitas en el 5.8%. Once pacientes fueron legalmente ciegos, al momento de abandonar el hospital. Conclusiones: Las principales medidas terapéuticas asociadas con mejoría del pronóstico visual son el cierre primario de herida y la administración de antibióticos; aunque las características de las heridas oculares son el principal factor pronóstico. El Ocular Trauma Score es una herramienta útil para determinar el pronóstico visual en trauma ocular de combate.

Microvessel density and VEGF expression in pituitaries of pregnant women.

OBJECTIVE: In pregnant women, the pituitary is enlarged and the prolactin (PRL) secreting cells increase in size and number. This PRL cell hyperplasia is associated with hyperprolactinemia. The aim of the present work was to investigate adenohypophysial vascularization and immunoexpression of vascular endothelial growth factor (VEGF) in pituitaries of pregnant and post-partum women and compare the results with age-matched adenohypophyses of nonpregnant women who had no endocrine diseases. DESIGN: Pituitaries (n=18) obtained by autopsy from female patients of reproductive age who had died during pregnancy, after abortion or during post-partum were immunostained for CD-34 and VEGF using the streptavidinbiotin- peroxidase complex method. RESULTS: The results showed that microvessel densities and VEGF immunoexpression in the adenohypophyses of pregnant and post-partum women were similar to those found in the control pituitaries. CONCLUSION: It can be concluded that pituitary enlargement and PRL cell hyperplasia in pregnant women may occur without neovascularization and increased VEGF immunoexpression.