A randomized clinical trial of lipid metabolism modulation with fenofibrate for acute coronavirus disease 2019.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) cytotoxicity may involve inhibition of peroxisome proliferator-activated receptor alpha. Fenofibrate activates peroxisome proliferator-activated receptor alpha and inhibits SARS-CoV-2 replication in vitro. Whether fenofibrate can be used to treat coronavirus disease 2019 (COVID-19) infection in humans remains unknown. Here, we randomly assigned inpatients and outpatients with COVID-19 within 14 d of symptom onset to 145 mg of oral fenofibrate nanocrystal formulation versus placebo for 10 d, in a double-blinded fashion. The primary endpoint was a severity score whereby participants were ranked across hierarchical tiers incorporating time to death, mechanical ventilation duration, oxygenation, hospitalization and symptom severity and duration. In total, 701 participants were randomized to fenofibrate (n = 351) or placebo (n = 350). The mean age of participants was 49 ± 16 years, 330 (47%) were female, mean body mass index was 28 ± 6 kg/m2 and 102 (15%) had diabetes. Death occurred in 41 participants. Compared with placebo, fenofibrate had no effect on the primary endpoint. The median (interquartile range) rank in the placebo arm was 347 (172, 453) versus 345 (175, 453) in the fenofibrate arm (P = 0.819). There was no difference in secondary and exploratory endpoints, including all-cause death, across arms. There were 61 (17%) adverse events in the placebo arm compared with 46 (13%) in the fenofibrate arm, with slightly higher incidence of gastrointestinal side effects in the fenofibrate group. Overall, among patients with COVID-19, fenofibrate has no significant effect on various clinically relevant outcomes ( NCT04517396 ).

A Randomized Trial of Lipid Metabolism Modulation with Fenofibrate for Acute Coronavirus Disease 2019.

Background Abnormal cellular lipid metabolism appears to underlie SARS-CoV-2 cytotoxicity and may involve inhibition of peroxisome proliferator activated receptor alpha (PPARα). Fenofibrate, a PPAR-α activator, modulates cellular lipid metabolism. Fenofibric acid has also been shown to affect the dimerization of angiotensin-converting enzyme 2, the cellular receptor for SARS-CoV-2. Fenofibrate and fenofibric acid have been shown to inhibit SARS-CoV-2 replication in cell culture systems in vitro . Methods We randomly assigned 701 participants with COVID-19 within 14 days of symptom onset to 145 mg of fenofibrate (nanocrystal formulation with dose adjustment for renal function or dose-equivalent preparations of micronized fenofibrate or fenofibric acid) vs. placebo for 10 days, in a double-blinded fashion. The primary endpoint was a ranked severity score in which participants were ranked across hierarchical tiers incorporating time to death, duration of mechanical ventilation, oxygenation parameters, subsequent hospitalizations and symptom severity and duration. ClinicalTrials.gov registration: NCT04517396. Findings: Mean age of participants was 49 ± 16 years, 330 (47%) were female, mean BMI was 28 ± 6 kg/m 2 , and 102 (15%) had diabetes mellitus. A total of 41 deaths occurred. Compared with placebo, fenofibrate administration had no effect on the primary endpoint. The median (interquartile range [IQR]) rank in the placebo arm was 347 (172, 453) vs. 345 (175, 453) in the fenofibrate arm (P = 0.819). There was no difference in various secondary and exploratory endpoints, including all-cause death, across randomization arms. These results were highly consistent across pre-specified sensitivity and subgroup analyses. Conclusion Among patients with COVID-19, fenofibrate has no significant effect on various clinically relevant outcomes.

Parity and diabetes risk among hispanic women from Colombia: cross-sectional evidence.

OBJECTIVE: The association between parity and type 2 diabetes has been studied in developed countries and in Singapore and Chinese women but not in Hispanics. Herein we evaluated the association between parity (number of live births) with diabetes in a group of Hispanic postmenopausal women from Colombia. RESEARCH DESIGN AND METHODS: Herein we evaluated the association between parity and diabetes in a population of 1,795 women from Colombia. Women were divided in birth categories (0 [referent], 1 or 2, 3-5, 6 or > births). Medical history of diabetes and anthropometric characteristics were recorded. Logistic regressions were performed in order to find the association between parity and diabetes in bivariable and multivariable models after controlling for age, body mass index (BMI), waist hip ratio (WHR) and diabetes family history, among other variables. RESULTS: In our study, there was an association between parity and diabetes after adjusting for age, BMI and diabetes family history in the multiparous women groups when compared to the women with no births (Referent group) [1-2 births vs. referent OR 5.2 (95 CI 1.2-22.9), 3-5 births vs. referent OR 5.5 (1.3-23.0) and ≥6 births vs. referent OR 7.5 (1.8-31.8), respectively]. The association was maintained in two of the groups in the multivariable analysis [OR 5.0 (1.1-22.9) and 5.3 (1.2-23.5)], for 1 or 2 births and 6 or > births versus 0 births, respectively. Positive diabetes family history and WHR were also associated with an increased risk of diabetes [OR 4.6 (3.0-7.0) and 4.1 (2.0-8.1), respectively]. CONCLUSIONS: In postmenopausal Hispanic women, multiparity, as well as a positive family history of diabetes and a high waist-hip ratio were associated with higher diabetes risk.

Association between low lean body mass and osteoporotic fractures after menopause.

OBJECTIVE: This study evaluated dual-energy x-ray absorptiometry-assessed whole-body bone-muscle relationship (bone mineral content/lean mass [BMC/LM]) as an indicator of its nonmechanical perturbations (ie, systemic) in pre- and postmenopausal women. A total of 3,205 women were studied, either healthy (no fracture [No Fx] groups, 1,035 premenopausal, 1,556 postmenopausal) or with recent fractures (Fx groups, 139 premenopausal, 475 postmenopausal) located at osteoporotic sites (hip, spine, long-bone metaphyses; Type II Fx, n = 386) or at other skeletal sites (Type I Fx, n = 228) to evaluate the impact of decreased muscle mass on fracture incidence before and after menopause. DESIGN: SD-scored graphs of BMC/LM proportionality were obtained from the No Fx groups as normal references. Based on the reference BMC versus LM curves obtained from their respective No Fx pre- and postmenopausal controls, BMC-LM SD scores were calculated for all women with fractures. RESULTS: BMC-LM SD scores in all premenopausal women with fractures and in Type I Fx postmenopausal women were similar to the reference. In contrast, SD scores in Type II Fx postmenopausal women were lower than the reference, especially in those with hip fractures. Except for Type II Fx postmenopausal women, all groups showed linear and similar BMC versus LM curves. Type II Fx postmenopausal women showed nonlinear relationships, with progressively decreasing BMC and BMC-LM SD scores as their LM decreased. CONCLUSIONS: Results suggest that both LM and BMC-LM SD scores can help to differentiate between systemic and mechanical (disuse-related) osteopenia/osteoporosis after menopause. Low LM values or BMC-LM SD scores seem to constitute additional fracture risk factors beyond those usually detected in premenopausal women or in women with other types of fractures. This application of dual-energy x-ray absorptiometry technology may lead to more effective diagnosis and treatment at low cost.

A propósito del consenso para el manejo de las disfunciones tiroideas mínimas / About the consensus for the management of thyroid minimal dysfunctions

Subclinical hypothyroidism and its clinical consequences have been debated during several decades. With the publication of the Consensus Declaration about subclinical thyroid dysfunction by the Endocrine Society, the American Association of Clinical Endocrinologists (AACE), and the American Thyroid Association (ATA), a new field was open for endocrinologist in the management of some long ignored thyroid dysfunctions that did not have any therapeuticsolution. The authors describe the paradigm shift and the changes in the diagnostic and therapeutic approaches. Later they recount some experiences developed in Colombia, S.A. Finally, they suggest some guidelines from their own experience and from other sources obtained in different fields of modern endocrinology.

Hipotiroidismo subclínico y sus consecuencias clínicas ha sido objeto de debate científico por espacio de varias décadas. A raíz de la publicación de la declaración de consenso acerca de la disfunción tiroidea subclínica en el año 2005, realizada por la Sociedad Americana de Endocrinologìa (The Endocrine Society), la Asociación Americana de Endocrinólogos Clínicos (AACE) y la AsociaciónAmericana de la Tiroides (ATA) se abrió un nuevo espacio para los endocrinólogos en el manejo de algunas disfunciones tiroideas que no habían sido tenidas en cuenta dentro del campo de accion terapéutico. Los autores hacen un recuento de cómo se produce el cambio en los paradigmas y en el enfoque diagnostico y terapéutico. Luego hacen un recuento de algunas de las experiencias desarrolladas en Colombia. Finalmente sugieren algunos derroteros a partir de su propia experiencia y también basados en logros científicos de otras fuentes obtenidos en otros campos de la Endocrinologìa moderna.

Olive, soybean and palm oils intake have a similar acute detrimental effect over the endothelial function in healthy young subjects.

BACKGROUND AND AIM: Currently, more than 30% of the caloric intake in the Colombian population comes from vegetable oil consumption mainly by the ingestion of deep-fried foods. Recently, it has been reported that unsaturated fatty acid rich oils have a beneficial effect on the endothelial function. Nevertheless, it is well know that the deep-frying process alters the chemical composition of vegetable oils and can produce adverse effects in the endothelial function. OBJECTIVE: To evaluate the acute effect of the ingestion of large amounts of olive, soybean and palm oils, fresh and at two different deep-fry levels, on the glucose and lipid profiles and the endothelial function. METHODS AND RESULTS: Ten healthy young volunteers were included in the study. After performing a baseline evaluation of cardiovascular risk factors and drawing a fasting blood sample, subjects were exposed to a randomly assigned potato soup meal containing 60 mL of one of three different vegetable oils (olive, soybean and palm), either fresh or at one of two different deep-fry levels (10 and 20 fries, respectively). Flow-mediated vasodilation (FMD) was performed in fasting conditions and 3h after the intake of the oil rich meal. Furthermore, blood samples were taken at these stages for the lipid profiles and plasma glucose determinations. All the meals resulted in a similar acute endothelial impairment (FMD decrease of 32.1%, confidence interval [CI] 95%, 28.0-36.2) and postprandial increase in triglycerides (27.03%, CI 95%, 20.5-33.3), independently of the type of oil ingested (p=0.44) and regardless of its deep-fry level (p=0.62). No correlation was found between endothelial impairment and postprandial triglyceride increment (r=-0.22, p=0.09). CONCLUSIONS: No difference was found in the acute adverse effect of the ingestion of different vegetable oils on the endothelial function. All the vegetable oils, fresh and deep-fried, produced an increase in the triglyceride plasma levels in healthy subjects.

Reference charts for the relationships between dual-energy X-ray absorptiometry-assessed bone mineral content and lean mass in 3,063 healthy men and premenopausal and postmenopausal women.

Correlations between dual-energy X-ray absorptiometry (DXA)-assessed bone mineral content and lean mass (BMC-LM curves), and between BMC/LM ratio and age ([BMC/LM]-age curves), were analyzed in the whole body (WB), the upper limbs (ULs) and the lower limbs (LLs) of 3,063 healthy Hispanic adults. Groups of 472 men aged 25-87 years, 1,035 premenopausal (pre-MP) women aged 27-54 years, and 1,556 post-menopausal (post-MP) women aged 48-93 years were studied with a GE-Lunar DPX-Plus device. BMC-LM curves confirmed previous observations that BMC and LM masses always correlate linearly, with similar slopes within each region, but differing in intercepts according to gender and hormonal status. Multiple regression tests showed little or no independent interaction of body weight or height with those relationships. [BMC/LM]-age curves were flat in men but showed the positive influence of estrogens throughout the age range in women. Z-scored graphs of all the corresponding relationships were compiled, showing the confidence intervals for means +/-1, +/-2, and +/-3 SDs of the data (+/-1, +/-2, +/-3 z-scores) along BMC-LM and [BMC/LM]-age curves. These charts are proposed as references for assessing how well bone mass (as assessed by BMC) and muscle mass (assumed proportional to LM) follow the natural anthropometric/biomechanical proportionality in Hispanic men and women within the age range studied, employing similar devices. Charts for LLs, showing the lowest variance amongst the studied correlations and approaching the origin as an exclusive feature, could provide the most accurate reference curves. Differences between data from ULs and LLs may provide information about any eventual interaction of body-weight bearing with the general results. The proposed analysis may provide useful information for approaching a differential diagnosis between disuse-related and other types of osteopenias employing only DXA.

Absorptiometric assessment of muscle-bone relationships in humans: reference, validation, and application studies.

This report summarizes some preliminary absorptiometric (DXA, QCT/pQCT) studies from our laboratory, supporting the following assumptions. 1. In Homo sapiens at all ages, natural proportionality between DXA-assessed bone mineral mass (bone mineral content, BMC) and muscle mass (lean mass, LM) of the whole body or limbs is specific for ethnicity, gender, and reproductive status, but not for body weight, height, or body mass index. 2. This proportionality is sensitive to many kinds of endocrine-metabolic perturbations. 3. Percentilized or Z-scored charts of the BMC/LM correlations as determined in large samples of healthy individuals can provide a diagnostic reference for evaluating proportionality in different conditions. 4. Employing exclusively DXA, this methodology can be applied to discriminate between "disuse-related" and "metabolic" osteopenias based on the finding of normal or low BMC/LM percentiles or Z-scores respectively, with important therapeutic and monitoring implications.

Diabetes y embarazo / Diabetes and pregnancy

En la actualidad las altas tasas de mortalidad tanto materna como fetal de la diabetica embarazada se han reducido hasta casi igualarlas con la embarazada no diabetica gracias a los avances logrados en los metodos de control de la diabetes y la monitorizacion fetal. Sin embargo para lograr estos resultados es requisito indispensable el manejo estricto de la diabetes durante todo el embarazo de acuerndo a ls normas establecidas en la actualidad y ojala en unidades especializadas organizadas pra tal fin. De lo contrario la mortalidad especialmente perinatal seguira tan alta como siempre dependiendo de la severidad de la diabetes y el grado de control durante el embarazo. Ademas es importante la motivacion e informacion de la paciente quien debera asumir un papel activo en su control

Disfuncion tiroidea minima en ninos con talla baja / Minimal thyroid insufficiency in children with short stature

Se estudiaron 123 ninos aparentemente sanos que consultaron por talla baja y 30 controles sanos previamente seleccionados a quienes se les practico T3, T4 y TSH basal y post-THR, HGH post-ejercicio y carpograma. De acuerdo con la respuesta de TSH al TRH en relacion a los controles normales los clasificamos: en grupo I, respuestas normales, no hubo diferencia estadistica; grupo II, hipotiroidismos latentes, con diferencia en el pico de respuesta (P<0,01) y grupo III, hipotiroidismos subclinicos, con diferencia en las cifras basales (P<0.001) y en el pico (p<0.001). Encontramos 44 pacientes (35.8%) en el grupo I; 51 ptes. (41.5%) en el grupo II y 28 ptes. (22,8% en el III con un total de 79 pacientes (64.2%) hipotiroideos. Los porcentajes de retraso en edad osea fueron mayores en el grupo III, y en todos los grupos, este fue mayor en etapas prepuberales, pero practicamente desaparecio al completarse el desarrollo sexual. Del grupo original, se escogieron 43 pacientes que habian recibido hormonas tiroideas por mas de 4 meses: 14 del grupo I'; 10 del grupo II' y 12 del grupo III' y 7 pacientes a quienes se les dejo en obserbacion por igual periodo como grupo de control. La velocidad de crecimiento mensual fue mayor en cada uno de los grupos al ser comparada con el grupo de control asi: grupo I' P<0,005; grupo II' P<0,025 y III' P<0,05. Se concluye que un alto porcentaje de disfuncion tiroidea minima es causa de talla baja en nuestro medio

Cetoacidosis diabetica / Diabetic ketoacidosis

La cetoacidosis diabetica es una entidad que mal manejada ofrece una alta morbi-mortalidad.En este articulo de revision se presenta un analisis de los eventos fisiopatologicos que se desarrollan durante su ocurrencia, y se esboza un esquema de tratamiento que comprende el calculo de las perdidas y de los requerimientos basales de liquidos y electrolitos de acuerdo al grado de dshidratacion; reposicion de liquidos y electrolitos en las primeras ocho horas y en las restantes dieciseis horas del dia; manejo de la insulinoterapia durante la fase de hiperglicemia, cuando la glicemia es menor de 250 mg/dl, cuando se inicia la via oral y el cambio de insulina corriente a la insulina NPH. El manejo de interpretacion de los examenes de laboratorio y finalmente se hace un recuento de los errores mas frecuentes en le tratamiento de la cetoacidosis

Gamagrafía y captaciones a nivel del mar y su relación con función tiroidea / Gammagraphy and sea level uptake and its relation to thyroid

Revisamos 1.485 gamagrafías de tiroides y sus captaciones a las 4 y 24 horas, practicadas en el Hospital Universitario de Barranquilla entre los años de 1.980 a 1.983 descartando los hipertiroidismos diagnosticados y las tiroides subagudas. De acuerdo a su tamaño las dividimos en 3 grupos. I de menos de 4x2 cms; II de 4.5 a 7 cms y III más de 7.5 cms y en captaciones altas, normales y bajas. Encontramos 799 pacientes 53.8% con tiroides de tamaño normal, 661 (44.5%) con bocio moderado y 24 (1.3%) con bocio grande. El promedio de captaciones a las 24 horas en el grupo I fué de 24.6 + ou - 6.93% los cuales pueden considerarse como valores normales en nuestro medio. Las captaciones estuvieron altas en el 31.3%, normales en el 52.4% y bajas en el 16.3%. En 198 pacientes 13.3% se correlacionan los valores de T3, T4 y 113 con TSH con los valores de captación en cada grupo

Avances en el diagnóstico del hipotiroidismo / Advances in the diagnosis of hypothyroidism

Si bien el hipotiroidismo clínico clásico es sin particular dificultad diagnosticable, no es fácil la identificación de alteraciones mínimas en la función tiroidea en pacientes en quienes las pruebas convencionales no rastrean ningún tipo de alteración. Después de los desarrollos operados en endocrinología con el descubrimiento del Radioinmunoanálisis y, sobre todo, con el descubrimiento y síntesis de las hormonas hipotalámicas por Shally y Guilleman en 1.969, las condiciones diagnósticas gozan una significativa mutación

Uso de la calcitonina en el tratamiento multifactorial de la osteoporosis / Use of calcitonin in the multifactorial treatment of osteoporosis

Estudiamos 12 pacientes con osteoporosis, con edades promedio de 75,42 + ou - 6,79 años. Les evaluamos capacidad funcional en escala de 0 a 3 y dolor osteoarticular en escala de 0 a 5 repitiéndolos semanalmente durante el período experimental de 13 semanas. Al inicio y final de éste se les practicó laboratorio de rutina y radiografías con misma técnica para calcáneo, fémur proximal y manos, para evaluar patrón travecular (compresión y tensión) y la cortical como índices de osteoporosis y calcificación. El estado radiográfico del hueso se clasificó en escala de 0 a 3. Previa información y consentimiento, a 10 pacientes se les sometió a tratamiento con 100 unidades internacionales (UI) subcutáneas de calcitonina (CT) 4 veces por semana por 90 días, 1800 mgr. diarios de carbonato de calcio y 2 sesiones diarias de sol y ejercícios estandarizados. Otras 2 pacientes recibieron igual tratamiento sin incluir CT. Cinco pacientes de 6 con limitaciones funcionales y 7 de 8 con dolores osteoarticulares mejoraron con tratamiento de CT. La respuesta radiográfica al tratamiento con calcitonina se mostró favorable en el 70% de las pacientes al evaluar calcáneo, 78% en fémur proximal y 50% en manos. La evaluación ósea antes y después de tratamiento mostró radiográficamente marcada mejoría en 6 de las 10 pacientes, ligera en 3 y sin respuesta en una. Hubo una diferencia estadística en los patrones pre y post-CT de P<0,0005. Una de las 2 pacientes sin CT tuvo una mejoría en algunos de los parámetros radiológicos que nosotros atribuimos a su mayor actividad física cotidiana. Los resultados obtenidos nos sugieren que el tratamiento de la osteoporosis con Ct asociado con medidas generales de higiene, ejercicio, aporte adecuado de sol y calcio puede ser beneficioso para el manejo de la osteoporosis senil. Por otra parte la evaluación radiográfica de fémur proximal y calcáneo constituyen una ayuda diagnóstica en el seguimiento de la osteoporosis en nuestro medio