Therapeutic plasmapheresis for the treatment of thyrotoxicosis: A retrospective multi-center study.

BACKGROUND AND AIMS: Thyroid storm and severe thyrotoxicosis remain among the most frequent endocrine emergencies, and first-line hyperthyroidism treatment is not always an option. Since the first report in 1970, plasmapheresis is a second-line treatment for severe or otherwise untreatable thyrotoxicosis when rapid euthyroidism is desired. METHODS: We present a retrospective study of the experience in treating thyrotoxicosis with plasmapheresis between 2012 and 2020 in two specialized centers in Colombia. We register the demographic and clinical characteristic and compare the thyroid hormones and other biochemical measurements before and after treatment. RESULTS: Data from 19 patients was obtained, 58% female with a median age of 35 years (IQR 23.5), and most of them with Graves' disease. The most frequent indication for plasmapheresis was thyroid storm. A median of 4 (IQR 2) sessions lead to a significant reduction in FT4 (P .0001) and TT3 (P < .0003) with a nonsignificant decrease in beta-blocker (P .7353) dose, no change in hepatic enzymes, and no adverse events. After plasmapheresis, thyroidectomy was performed in 10 patients. CONCLUSIONS: Plasmapheresis is an effective and safe treatment option for reducing circulating thyroid hormones in severe thyrotoxicosis when other forms of treatment are contraindicated or in case of urgent thyroid and non-thyroid surgery. It is limited by its cost and the need for highly specialized resources.

Metabolomic Analysis of The Chemical Diversity of South Africa Leaf Litter Fungal Species Using an Epigenetic Culture-Based Approach.

Microbial natural products are an invaluable resource for the biotechnological industry. Genome mining studies have highlighted the huge biosynthetic potential of fungi, which is underexploited by standard fermentation conditions. Epigenetic effectors and/or cultivation-based approaches have successfully been applied to activate cryptic biosynthetic pathways in order to produce the chemical diversity suggested in available fungal genomes. The addition of Suberoylanilide Hydroxamic Acid to fermentation processes was evaluated to assess its effect on the metabolomic diversity of a taxonomically diverse fungal population. Here, metabolomic methodologies were implemented to identify changes in secondary metabolite profiles to determine the best fermentation conditions. The results confirmed previously described effects of the epigenetic modifier on the metabolism of a population of 232 wide diverse South Africa fungal strains cultured in different fermentation media where the induction of differential metabolites was observed. Furthermore, one solid-state fermentation (BRFT medium), two classic successful liquid fermentation media (LSFM and YES) and two new liquid media formulations (MCKX and SMK-II) were compared to identify the most productive conditions for the different populations of taxonomic subgroups.

[Complications associated with hyperglycemia in liver transplant patients]. / Complicaciones asociadas a la hiperglucemia en pacientes trasplantados de hígado.

BACKGROUND: Hyperglycemia is a frequent phenomenon in hospitalized patients that is associated with negative outcomes. It is common in liver transplant patients as a result of stress and is related to immunosuppressant drugs. Although studies are few, a history of diabetes and the presentation of hyperglycemia during liver transplantation have been associated with a higher risk for rejection. AIMS: To analyze whether hyperglycemia during the first 48hours after liver transplantation was associated with a higher risk for infection, rejection, or longer hospital stay. METHODS: A retrospective cohort study was conducted on patients above the age of 15years that received a liver transplant. Hyperglycemia was defined as a value above 140mg/dl and it was measured in three different manners (as an isolated value, as a mean value, and as a weighted value over time). The relation of hyperglycemia to a risk for acute rejection, infection, or longer hospital stay was evaluated. RESULTS: Some form of hyperglycemia was present in 94% of the patients during the first 48 post-transplantation hours, regardless of its definition. There was no increased risk for rejection (OR: 1.49; 95%CI: 0.55-4.05), infection (OR: 0.62; 95%CI: 0.16-2.25), or longer hospital stay between the patients that presented with hyperglycemia and those that did not. CONCLUSIONS: Hyperglycemia during the first 48hours after transplantation appeared to be an expected phenomenon in the majority of patients and was not associated with a greater risk for rejection or infection and it had no impact on the duration of hospital stay.

Insulinoma-related Endogenous Hypoglycaemia with a Negative Fasting Test: A Case Report and Literature Review.

We present the case of a patient with a history of symptomatic hypoglycaemic episodes and a negative 72-hour fasting test with histological confirmation of insulinoma. A literature review of hyperinsulinaemic hypoglycaemia with a negative fasting test was performed. LEARNING POINTS: The 72-hour fasting test is the gold standard for insulinoma diagnosis.Few cases of insulinoma with a negative fasting test have been reported.New strategies for insulinoma diagnosis are being investigated.

Pipecolisporin, a Novel Cyclic Peptide with Antimalarial and Antitrypanosome Activities from a Wheat Endophytic Nigrospora oryzae.

A novel cyclic antimalarial and antitrypanosome hexapeptide, pipecolisporin (1), was isolated from cultures of Nigrospora oryzae CF-298113, a fungal endophyte isolated from roots of Triticum sp. collected in a traditional agricultural land of Montefrío, Granada, Spain. The structure of this compound, including its absolute configuration, was elucidated by HRMS, 1-D and 2-D NMR spectroscopy, and Marfey's analysis. This metabolite displayed interesting activity against Plasmodium falciparum and Trypanosoma cruzi, with IC50 values in the micromolar range, and no significant cytotoxicity against the human cancer cell lines A549, A2058, MCF7, MIA PaCa-2, and HepG2.

Extending the Metabolite Diversity of the Endophyte Dimorphosporicola tragani.

Fungi are one of the most prolific sources of microbial secondary metabolites. The production of new metabolites can be achieved using multiple fermentation conditions and by adding small-molecule effectors, including epigenetic modifiers. In the framework of our Natural Product screening programme targeting the discovery of new antimicrobial compounds, we applied multiple fermentation conditions and adsorptive polymeric resins on a large collection of fungal endophytes, to increase and stimulate their fungal secondary metabolite production. During this work the endophytic fungus Dimorphosporicola tragani CF-090383 showed antimicrobial activity only when grown in presence of adsorptive polymeric resins. In addition, seven epigenetic modifiers were added to fermentations of this endophytic fungus, in an attempt to activate its cryptic pathways as well as to analyse the metabolites produced under these conditions. D. tragani was seen to produce three different mycotoxin dendrodolides when the epigenetic modifiers 5-azacytidine and valproic acid were added to the fermentations, and these compounds were further characterized. However, the fungus produced the fatty acid synthesis inhibitor cerulenin, a molecule not previously described to be produced by this fungal species, only when cultivated in presence of the XAD-16 resin. We have found that the addition of XAD-16 resin resulted in four-fold higher titers in the production of cerulenin when compared to the best production conditions described in literature for the original fungal producer strain, Cephalosporium caerulens KF-140 (=Sarocladium oryzae), in a zeolite-based fermentation, used as an ammonium ion-trapping agent. The production of cerulenin by this strain of D. tragani, represents an alternative source for the improved production of cerulenin with better yields.

Diabetes mellitus y COVID-19: fisiopatología y propuesta de tratamiento para el control glucémico en el tiempo de la pandemia / Diabetes mellitus and COVID-19: pathophysiology and treatment proposal for glycemic control at the time of the pandemic

RESUMEN El coronavirus 2 del síndrome respiratorio agudo grave es el tercer betacoronavirus desde el año 2003 capaz de ocasionar una infección del tracto respiratorio inferior, llevando, en casos críticos, al síndrome de dificultad respiratoria aguda y la muerte. La edad avanzada, la hipertensión arterial y la diabetes mellitus son, entre otros, tres factores determinantes en los peores desenlaces clínicos. Múltiples mecanismos pueden explicar la mayor susceptibilidad de las personas diabéticas a las infecciones respiratorias. La hiperglucemia crónica altera tanto a la inmunidad humoral como al celular. Esta enfermedad predispone a la sobreexpresión de la proteína de la membrana celular que sirve como receptora del virus y a una respuesta inflamatoria exacerbada, aumentando el riesgo de una descompensación y de la aparición de crisis hiperglicémicas. Ante la ausencia de un tratamiento efectivo o de una vacuna, todos los esfuerzos deben hacerse para procurar un buen control metabólico de los pacientes con diabetes mellitus con y sin COVID-19. Por lo anterior, se plantean en este artículo de reflexión, diferentes propuestas para el tratamiento de la diabetes mellitus en la unidad de cuidados intensivos, sin descartar la forma ambulatoria, en donde la telemedicina y otras tecnologías permitirán acortar la distancia y mantener las medidas de aislamiento preventivo.

SUMMARY Severe acute respiratory syndrome coronavirus 2 is the third beta-coronavirus since 2003 capable of causing lower respiratory tract infection, leading to severe cases of acute respiratory distress syndrome and death. Advanced age, high blood pressure and diabetes mellitus are three predictors of worse clinical outcomes. Multiple mechanisms could explain the greater susceptibility of diabetic people to respiratory infections. Chronic hyperglycemia alters both humoral and cellular immunity. This disease predisposes to virus receptor overexpression and an exaggerated inflammatory response, increasing the risk of decompensation and hyperglycemic crises. In the absence of an effective vaccine or treatment for the virus, this vicious circle should be stopped with an emphasis on controlling glucose. This paper presents different proposals for the treatment of diabetes mellitus both on an outpatient basis where telemedicine and other technologies will make it possible to continue adequate ambulatory care to maintain preventive isolation measures up to care in the intensive care unit.

Guía colombiana de práctica clínica para el tratamiento de la diabetes mellitus tipo 2: falla al tratamiento inicial / Colombian Clinical Practice Guideline for Treatment of Type 2 Diabetes Mellitus: First Line Treatment Failure

Introducción: Existen diferentes opciones de manejo para pacientes con diabetes mellitus tipo 2 (DMT2) que ya iniciaron tratamiento farmacológico con metformina y no han alcanzado metas de control glucémico. Resulta prioritario definir pautas para escoger la mejor opción en estos pacientes, así como en aquellos que no han tenido un control óptimo con la combinación de dos medicamentos. Objetivo: Definir cuál es antidiabético de elección, entre sulfonilureas, tiazolidinedionas, inhibidores de DPP-4, agonista del receptor de GLP-1 o insulina basal, como segunda y tercera líneas de manejo en pacientes con DMT2. Métodos: Se elaboró la guía de práctica clínica, siguiendo los lineamientos de la guía metodológica del Ministerio de Salud y Protección Social colombiano. Se revisó la evidencia disponible de forma sistemática y se formularon las recomendaciones utilizando la metodología GRADE. Conclusiones: En pacientes con DMT2 y falla terapéutica al manejo con metformina como monoterapia (HbA1C > 7 %) se recomienda como primera opción adicionar un inhibidor DPP-4, como segunda opción adicionar inhibidor SGLT2 o sulfonilureas con bajo riesgo de hipoglucemia y como tercera opción agregar insulina basal a los pacientes que con la combinación de dos fármacos fallen en alcanzar su meta de HbA1C. Si la falla terapéutica se asocia con un IMC persistentemente ≥ 30, se sugiere la adición de un agonista de GLP-1 por el potencial beneficio sobre la reducción de peso.

Introduction: There are different options to treat type 2 diabetes (DMT2) patients who began treatment with metformin and have not reached therapeutic golds. It is imperative to define rules to choose the best option, in these patients, as in those who have not achieved an optimal control under combined therapy. Aim: To define the best option between sulfonylureas, thiazolidinediones, DPP4 inhibitors, GLP-1 agonist or basal insulin, as second or third line treatment, in patients with DMT2 who have not reached therapeutic golds with metformin or combined therapy. Methods: A clinical practice guide has been developed following the broad outline of the methodological guide from the Colombian Ministry of Health and Social Welfare, with the aim of systematically gathering scientific evidence and formulating recommendations using the GRADE (Grading of Recommendations Assessment, Development and Evaluation) methodology. Conclusions: In patients with DMT2 who did not reach their therapeutic goal with metformin as a monotherapy (Hb1Ac <7%), addition of a second oral antidiabetic medication is recommended. it is recommended as a first step to add a DPP-4 inhibitor. It is suggested to add a SGLT2 inhibitor or a sulfonylurea having low risk of hypoglycemia as acceptable options. It is suggested to add basal insulin as a third antidiabetic medication if the combination of two pharmacological treatments does not enable the patient to reach and maintain the HbA1c goal. It is suggested to add a GLP-1 agonist if therapeutic failure appears in patients who remain obese (BMI ≥30 kg/m²), considering its potential to reduce weight.

Consumo de estatinas y asociación con la elevación en los niveles de creatina fosfoquinasa / Statin use and association with elevated levels of creatine phosphokinase

Introducción: las estatinas son medicamentos hipolipemiantes asociados con miotoxicidad como efecto adverso. Objetivo: determinar la asociación entre el uso de estatinas y la elevación de la creatinafosfoquinasa. Materiales y métodos: se realizó un estudio transversal en pacientes consecutivos que asistieron al Laboratorio Clínico Hematológico (Medellín, Colombia) para la determinación del perfil lipídico. Se incluyeron 661 pacientes, 329 en el grupo de estatinas y 332 en el de no estatinas.A todos se les midieron los niveles séricos de creatina fosfoquinasa y se consideraron como elevados los niveles superiores a 170 mg/dL. Se estableció un nivel de significancia menor de 0,05. Resultados: se registró mayor proporción de pacientes con creatina fosfoquinasa elevada en el grupo con consumo de estatinas (64,9% frente a 47% en el grupo de no estatinas; razón de disparidad: 2,01; intervalo de confianza del 95%: 1,21-3,32; p= 0,0085). No se encontró asociación entre la elevación de la creatina fosfoquinasa y la presencia de dolor (razón de disparidad: 0,78; intervalo de confianza del 95%: 0,40-1,50; p= 0,5615), fatiga (razón de disparidad: 0,85; intervalo de confianza del 95%: 0,45-1,61; p= 0,7385) y debilidad muscular (razón de disparidad: 1,46; intervalo de confianzadel 95%: 0,68-3,12; p= 0,4333); aunque el grupo de estatinas presentó mayor frecuencia de dolor (razón de disparidad: 2,96), fatiga (razón de disparidad: 1,98) y debilidad muscular (razón de disparidad: 4,19). Conclusiones: el consumo de estatinas se relaciona con síntomas musculares y elevación de creatina fosfoquinasa, sin relación entre la elevación de creatina fosfoquinasa y la presencia de síntomas musculares.

Introduction: statins are a class of lipid-lowering medications associated with the adverse effect of myotoxicity. Objetive: To determine the association between statin use and creatine phosphokinase elevation. Materials and methods: A cross-sectional study, involving consecutive patients attending in the clinical laboratory Laboratorio Clinico Hematologico (Medellin, Colombia) for a serum lipid profile test was performance. A total of 661 patients were included, 329 belonged to the statin group and 332 to the non-statin group. All patients were tested for serum creatine phosphokinase and were considered elevated the serum levels higher than 170 mg/dL. The threshold for significance was set as p-value less than 0.05. Results: Creatine phosphokinase levels were more elevated in the statin group (64.9% versus 47% in non-statin group; odds ratio: 2.01; 95% confidence interval: 1.21-3.32, p= 0.0085). No association was found between the degree of creatine phosphokinase elevation and the presence of muscular pain (odds ratio: 0.78; 95% confidence interval: 95%, 0.40-1.50, p= 0.5615), fatigue (odds ratio: 0.85; 95% confidence interval: 0.45-1.61, p= 0.7385) or muscle weakness (odds ratio: 1.46; 95% confidence interval: 0.68-3.12, p= 0.4333). However, the statin group exhibited greater frequency of muscle pain (odds ratio: 2.96), fatigue (odds ratio: 1.98) and muscle weakness (odds ratio: 4.19). Conclusions: statin use is associated with a higher frequency of muscular symptoms and higher creatine phosphokinase levels, with no relationship between creatine phosphokinase elevation and the presence of muscle symptoms.

Pancreatitis aguda inducida por hipertrigliceridemia y tratamiento con plasmaféresis: reporte de un caso / Acute pancreatitis induced by hypertriglyceridemia and treatment with plasmapheresis: case report

La hipertrigliceridemia (HTG) es una causa potencial de pancreatitis aguda (PA), especialmente cuando su valor es mayor de 1.000 mg/dL. Se han propuesto diferentes medidas para el tratamiento de pacientes con PA secundaria a HTG, entre ellas la que parece ser más efectiva: la plasmaféresis. Se reporta el caso de un paciente con HTG grave (triglicéridos de 6.480 mg/dL) que presentó una PA y cuya evolución fue favorable con la plasmaféresis.

Hypertriglyceridemia (HTG) is a potential cause of acute pancreatitis (AP), especially when its value is higher than 1.000 mg/dL. Different therapeutic measures have been proposed for patients with AP secondary to HTG, including the one that seems to be more effective: plasmapheresis. We report the case of a patient with severe HTG (triglycerides 6.480 mg/dL) that suffered from AP, and had favorable evolution with plasmapheresis.

Prevalencia de alteraciones de la creatina-fosfoquinasa (CPK) sérica en pacientes que toman estatinas / Prevalence of abnormalities of creatine phosphokinase (CPK) levels in patients taking statins

El uso de estatinas para combatir la dislipidemia se asocia con un espectro de síntomas musculares que van desde mialgias con o sin aumento de la creatina-fosfoquinasa (CPK), hasta rabdomiólisis fatal. Objetivo: determinar la prevalencia de la elevación de la CPK en pacientes que toman estatinas y determinar los posibles factores de riesgo asociados al aumento de la CPK en estos pacientes. Métodos: estudio observacional de corte transversal en el que se evaluaron las alteraciones de la CPK en una población de 503 pacientes con tratamiento con estatinas para el control de la dislipidemia, y que asisten al Laboratorio Clínico Hematológico en Medellín, Colombia por razones diferentes a la medición de la CPK. Mediante un cuestionario aplicado a los pacientes se obtuvieron los datos demográficos, los antecedentes personales y el tipo de estatina utilizada. Resultados: 56 (11,1 por ciento) pacientes presentaron aumento de la CPK por encima del rango de referencia normal; 7 pacientes (1,4 por ciento) tenían un aumento dos veces por encima del valor superior normal, y de ellos 3 (0,6 por ciento) tenían un aumento tres veces por encima del valor superior normal. Se encontró asociación significativa entre niveles altos de la CPK con el sexo masculino y con el uso de inhibidores selectivos de la recaptación de serotonina (ISRS). No se encontró asociación con otros factores de riesgo previamente descritos en otros estudios como son el ejercicio, el consumo de alcohol, el hipotiroidismo y la dosis de estatinas, entre otros. En cuanto a síntomas musculares, el 28,4 por ciento relató dolor muscular con el uso de estatinas, 26 por ciento cansancio y 15,9 por ciento debilidad muscular. Conclusión: los hallazgos de este estudio demuestran que el aumento asintomático de la CPK en pacientes que toman estatinas para la reducción por ciento del colesterol, es mayor al previamente reportado y confirma que el sexo masculino y el uso de fármacos tipo ISRS se relacionan con un aumento de la CPK. También se encontró que el porcentaje de pacientes con síntomas musculares, especialmente dolor y cansancio, es mucho mayor a lo reportado en la literatura mundial. Desde el punto de vista clínico se desconocen las repercusiones que pueda tener el aumento asintomático de la CPK, lo que requeriría estudios de seguimiento a largo plazo.

Pruebas dinómicas en endocrinologia: insuficiencia adrenal: [revisión] / Dynamic testing in endocrinology: adrenal insufficien: [review]

El diagnóstico de insuficiencia adrenal se sospecha con los hallazgos clínicos inespecíficos y no considere la posibilidad de un diagnóstico de insuficiencia adrenal. Una prueba de tamizacin ideal debe ser de bajo costo, fócil y segura; infortunadamente, hasta el momento, no se dispone de una prueba ideal para la insuficiencia adrenal...