Effect of Bifidobacterium Intake on Body Weight and Body Fat in Overweight and Obese Adult Subjects: A Systematic Review and Meta-Analysis.

This systematic review aimed to assess the impact of Bifidobacterium genus probiotics on body weight and body composition parameters in overweight and obese individuals.A systematic search for randomized controlled trials was conducted in MEDLINE, EMBASE, LILACS, and Google Scholar databases until April 17, 2023. The inclusion criteria required the trials to involve Bifidobacterium genus probiotics interventions and the evaluation of obesity-related anthropometric and body composition outcomes in overweight or obese subjects. Studies were excluded when involving obese individuals with genetic syndromes or pregnant women, as well as probiotic mixture interventions. The revised Cochrane risk-of-bias tool for randomized trials was utilized to assess the quality of the included studies. A random-effects meta-analysis was performed using the mean difference between endpoint measurements and change from baseline for body mass index, body weight, body fat mass, body fat percentage, waist circumference, waist-to-hip ratio, and visceral fat area.From 1,527 retrieved reports, 11 studies (911 subjects) were included in this review. Bifidobacterium probiotics administration resulted in significant reductions in body fat mass (MD = -0.64 kg, 95% CI: -1.09, -0.18, p = 0.006), body fat percentage (MD = -0.64%, 95% CI: -1.18, -0.11, p = 0.02), waist circumference (MD = -1.39 cm, 95% CI: -1.99, -0.79, p < 0.00001), and visceral fat area (MD = -4.38 cm2, 95% CI: -7.24, -1.52, p = 0.003). No significant differences were observed for body mass index, body weight, or waist-to-hip ratio.This systematic review suggests that Bifidobacterium genus probiotics may contribute to managing overweight and obesity by reducing body fat mass, body fat percentage, waist circumference, and visceral fat area. Further research is required to understand strain and species interactions, optimal dosages, and effective delivery methods for probiotics in obesity management. This review was pre-registered under the PROSPERO record CRD42022370057.

Probiotics from the Bifidobacterium genus show promise in reducing body fat mass, body fat percentage, waist circumference, and visceral fat area in overweight and obese adults.Further research is needed to identify the most effective species and strains within the Bifidobacterium genus for achieving these outcomes.There is an urgent need to determine the best probiotic delivery vehicle among enriched foods, capsules, or powders.More randomized controlled trials are necessary to determine optimal probiotic doses and intervention durations.

Metastatic differentiated thyroid cancer: worst prognosis in patients with metachronous metastases.

PURPOSE: To describe the overall survival and progression-free survival in patients diagnosed with differentiated thyroid carcinoma with synchronous and metachronous metastatic involvement. MATERIALS AND METHODS: A retrospective cohort study was conducted with 101 patients with differentiated thyroid cancer (DTC) who had metastatic involvement at diagnosis or during follow-up, who were treated at the National Cancer Institute between January 1, 2010 and December 31 of 2015. RESULTS: 81 patients (80.2%) were women and the mean age at diagnosis was 49 years (12-80). Synchronous metastases were detected in 54.5% of patients and metachronous metastasis was diagnosed in 45.5% of patients, in whom the mean time between initial diagnosis and the finding of distant metastases was 5 years. Pulmonary involvement occurred in almost all patients, with 131I uptake in 58% of synchronous metastases and in 21% of metachronous. There were 10 events in the patients with 131I-avid metastases with a median time to progression that was not reached, and there were 23 events in patients with 131I-refractory metastases with a median time to progression of 96 months; The median time to progression was significantly longer in patients with synchronous metastases compared to those with metachronous metastases (Not reached vs 95 months, P = 0.017) The 5-year overall survival rate was 95% to the entire cohort. CONCLUSIONS: The present study contributes to the expansion of the knowledge about this clinical course of DTC with the finding of a worst prognosis in patients with metachronous metastases.

Fast Skeletal Muscle Troponin and Tropomyosin as a Dietary Source of Antidiabetic and Antihypertensive Bioactive Peptides: An In Silico Study / Troponina y Tropomiosina de Músculo Esquelético como Fuente Alimentaria de Péptidos Bioactivos Antidiabéticos y Antihipertensivos: Estudio In Silico

Background: The nutraceutical properties of food hydrolysates rely on multiple biochemical interactions involving the modulation of enzymes and cellular receptors. Numerous bioactive peptides released from troponin and tropomyosin digestion have been identified. Their characterization has mostly been performed by hydrolysis catalyzed by proteases unrelated to the human digestive system. Objective: This study aimed to determine the bioactive profile of beef, pork, and chicken meat by analyzing the frequency and pharmacokinetics of biopeptides released from troponin and tropomyosin. Methods:In silico digestion and biopeptide release frequency were studied by three parameters; bioactive fragments release frequency (AE), frequency percentage (W), and mean occurrence (AS), all stated on the BIOPEP-UWM platform. Further on, hydrolysis end-products were screened based on gastrointestinal-absorption probability and pharmacokinetic profiling performed on SwissADME, SwissTargetPrediction, and ADME/Tlab bioinformatics web tools. Statistical analyses were performed using a one-way ANOVA test. Results: Dipeptidyl peptidase-IV (DPP-IV) and angiotensin-converting enzyme (ACE) inhibiting biopeptides exhibited the highest release frequency. Moreover, W and ASparameters showed no significant difference (p>0.05) between the myofibrillar isoforms assessed. Seven biopeptides were classified as highly absorbable and reported optimal drug-likeness compliance. Although biopeptides hold good pharmacokinetic properties, the therapeutic potency of biopeptides showed to be lower than those of DPP-IV and ACE-inhibiting drugs. Conclusions: Troponin and tropomyosin are rich dietary sources of bioactive peptides, mainly DPP-IV and ACE inhibitors. Digestion end-products are mainly dipeptides with optimal pharmacokinetic and drug-like properties, suggesting a potential therapeutic application in hypertensive and hyperglycemic disorders

Antecedentes: Las propiedades nutracéuticas de los hidrolizados de alimentos dependen de múltiples interacciones bioquímicos que involucran la modulación de enzimas y receptores celulares. Se han identificado numerosos péptidos bioactivos liberados de la digestión de troponina y tropomiosina, pero su caracterización se ha llevado a cabo principalmente por hidrólisis catalizada por proteasas ajenas al sistema digestivo humano. Objetivo: Este estudio tuvo como objetivo determinar el perfil bioactivo de la carne de res, cerdo y pollo mediante el análisis de la frecuencia y farmacocinética de los biopéptidos liberados de la troponina y la tropomiosina. Métodos: Se estudió la digestión in silico y la frecuencia de liberación de biopéptidos mediante dos parámetros; frecuencia de liberación de fragmentos bioactivos (AE), frecuencia porcentual (W) y ocurrencia media (AS), ambos indicados en la plataforma BIOPEP-UWM. Más adelante, los productos finales de la hidrólisis se examinaron en función de la probabilidad de absorción gastrointestinal y el perfil farmacocinético realizado en las herramientas bioinformáticas SwissADME, SwissTargetPrediction y ADME/Tlab. El análisis estadístico se llevó a cabo mediante una prueba ANOVA de una vía. Resultados: Los biopéptidos inhibidores de la dipeptidil peptidasa IV (DPP-IV) y la enzima convertidora de angiotensina (ECA) exhibieron la mayor frecuencia de liberación. Además, los parámetros W y ASno mostraron diferencias significativas (p> 0.05) entre las isoformas miofibrilares evaluadas. Siete biopéptidos se clasificaron como altamente absorbibles e informaron un cumplimiento óptimo de similitud con el fármaco. Aunque los biopéptidos tienen propiedades farmacocinéticas adecuadas, su potencia terapéutica demostró ser menor que la de los fármacos inhibidores de la DPP-IV y la ACE. Conclusiones: La troponina y la tropomiosina son una fuente dietética rica en péptidos bioactivos, principalmente DPP-IV e inhibidores de la ACE. Los productos finales de la digestión son principalmente dipéptidos con propiedades farmacocinéticas óptimas y similares a la de los fármacos, lo que sugiere una aplicación terapéutica factible en trastornos hipertensivos e hiperglicémicos

Neurotrauma Registries in Low- and Middle-Income Countries for Building Organized Neurotrauma Care: The LATINO Registry Experience Comment on "Neurotrauma Surveillance in National Registries of Low- and Middle-Income Countries: A Scoping Review and Comparative Analysis of Data Dictionaries".

Trauma registries play an important role in building capacity for trauma systems. Regularly, trauma registries exist in high-income countries (HICs) but not in low- and middle-income countries (LMICs). Neurotrauma includes common conditions, like traumatic brain injuries (TBIs) and spinal cord injuries. The development of organized neurotrauma care is crucial for improving the quality of care in less-resourced areas. The recent article published in International Journal of Health Policy and Management by Barthélemy et al entitled "Neurotrauma Surveillance in National Registries of Low- and Middle-Income Countries: A Scoping Review and Comparative Analysis of Data Dictionaries" adds an important body of literature to improve understanding of the importance of these types of efforts by promoting organized neurotrauma care systems in LMICs. Here, we provide a short commentary based on our experience with the Latin America and the Caribbean Neurotrauma Registry (LATINO-TBI) in the Latin America (LATAM) region.

Efectos deletéreos en el desarrollo de los niños a causa de la exposición temprana a pantallas: revisión de la literatura

Desde la década de los 90 debido al aumento en el consumo de material audiovisual y particularmente desde el inicio del confinamiento por la pandemia de COVID-19, la humanidad ha estado más expuesta al uso de pantallas, siendo los niños una población vulnerable al estímulo ambiental debido a que están atravesando períodos críticos importantes en su desarrollo. Se realizó una búsqueda de la literatura en PubMed, Google Scholar y Lilacs. Aplicando los criterios de exclusión e inclusión se obtuvieron 53 referencias de las cuales se desarrolló la revisión. Se encontró que la excesiva exposición a pantallas es perjudicial para los niños al producir alteraciones del lenguaje, la sociabilidad, ciclo sueño-vigilia, el sistema límbico, la conducta y el sistema mesolímbico dopaminérgico; los cuales pueden afectar su desarrollo normal, dependiendo principalmente de la edad al momento de la exposición, del tiempo y si hay acompañamiento o no.

Since the 1990s, due to the increase in the consumption of audiovisual material and particularly since the onset of the COVID-19 pandemic confinement, the population has been more exposed to development. A literature search was conducted in PubMed, Google Scholar and Lilacs. Applying the exclusion and inclusion criteria, 53 references were obtained, from which the review was developed. It was found that excessive exposure to screens is harmful to children as it produces alterations in language, sociability, sleep-wake cycle, limbic system, behavior and mesolimbic dopaminergic system; which can affect the normal development of a child, depending mainly on the age at the time of exposure, the time and whether there is accompaniment or not.

Implementing a Neurotrauma Registry in Latin America and the Caribbean.

Background Traumatic brain injury (TBI) has a disproportionately greater impact in low- and middle-income countries (LMICs). One strategy to reduce the burden of disease in LMICs is through the implementation of a trauma registry that standardizes the assessment of each patient's management of care. Objective This study aims to ascertain the interest of Latin America and the Caribbean (LAC) nations in establishing a shared neurotrauma registry in the regional block, based on an existing framework for collaboration. Methods A descriptive review was performed regarding the interests of LAC nations in implementing a shared neurotrauma registry in their region. We convened a meeting with seven Caribbean and five Latin American nations. Results One hundred percent ( n = 12) of the LAC representatives including neurosurgeons, neurointensivists, ministers of health, and chief medical officers/emergency medical technicians (EMTs) agreed to adopt the registry for tracking the burden of TBI and associated pathologies within the region. Conclusion The implementation of a neurotrauma registry can benefit the region through a shared database to track disease, improve outcomes, build research, and ultimately influence policy.

Tachykinin/neurokinin 3 receptor antagonists: In silico ADME/T analysis of novel compounds for menopause hot flashes therapy

SUMMARY Introduction: Neurokinin-B receptor (NK3R) activation is tightly involved in the onset of vasomotor symptoms during menopause, yet there are still no NK3R antagonistic drugs approved for hot flashes therapy. Determining the pharmacokinetic properties of current drug candidates is crucial for scaffold identification and prediction of feasible outcomes in future clinical trials. Aim: To develop a pharmacokinetic profile of new NK3R blockers with hot flashes reducing activity and by comparing them with trial-suspended NK3R antagonists (Osanetant & Talnetant), it is expected to identify enhanced properties in novel compounds. Methodology: For in silico evaluation, Smiles were retrieved from PubChem and DrugBank, and further analysis was carried out through ADMETlab and SwissADME to calculate compounds drug-likeness and pharmacokinetics. Results: Pavinetant & Fezoline-tant and SB-222.200 & SB-218.795 exhibited higher compliance with drug-likeness rules and more suitable physicochemical properties when compared to Osanetant & Talnetant. ADME/T evaluation showed considerable disparities between groups, yet no significant difference was reported. Pharmacokinetic properties varied irregularly among studied compounds. Conclusion: Novel NK3R antagonists exhibit enhanced properties when compared to formerly suspended ones. Fezolinetant is predicted to have more favorable outcomes based on in silico evaluation.

Introducción: la activación del receptor de neuroquinina-B (NK3R) está estrechamente relacionada con la aparición de síntomas vasomotores durante la menopausia, no obstante, a la fecha no se reportan fármacos antagonistas de NK3R aprobados para el manejo de sofocos. La evaluación de las propiedades farmacocinéticas de los compuestos inhibidores de NK3R resulta indispensable para la identificación de potenciales farmacóforos y para la estimación de posibles resultados en ensayos clínicos. Objetivo: determinar las características farmacocinéticas de los nuevos compuestos inhibidores de NK3R con propiedades reductoras de los fogajes asociados a la menopausia, y por medio de un análisis comparativo con los antagonistas de NK3R cuyo ensayo clínico fue suspendido (Osanetant & Talnetant), se espera identificar propiedades superiores en los nuevos compuestos desarrollados. Metodología: se obtuvieron los códigos Smiles a partir de PubChem y DrugBank, posteriormente, el análisis se basó en el cálculo de las propiedades farmacocinéticas y drug-like mediante las plataformas ADMETlab y SwissADME. Resultados: Pavi-netant & Fezolinetant y SB-222.200 & SB-218.795 exhiben mejores propiedades fisicoquímicas y cumplen a mayor cabalidad las reglas drug-likeness al compararse con Osanetant & Talnetant. La evaluación ADMET reveló variaciones entre los grupos, pero ninguna fue significativa. Las propiedades farmacocinéticas varían de forma irregular entre los distintos compuestos. Conclusiones: los antagonistas de NK3R recientemente desarrollados exhibieron propiedades superiores frente a los compuestos de ensayos suspendidos. Los resultados del estudio in silico permiten deducir que el Fezolinetant podría tener mejores resultados en futuros ensayos clínicos.

Introdução: a ativação do receptor de neuroquinina-B (NK3R) está intimamente relacionada ao aparecimento de sintomas vasomotores durante a menopausa, entretanto, até o momento não há relatos de drogas antagonistas de NK3R aprovadas para o manejo das ondas de calor. A avaliação das propriedades farmacocinéticas de compostos inibidores de NK3R é essencial para a identificação de potenciais farmaco-foros e para a estimativa de possíveis resultados em ensaios clínicos. Objetivo: determinar as características farmacocinéticas dos novos compostos inibidores de NK3R com propriedades redutoras de ondas de calor associadas à menopausa, e através de uma análise comparativa com os antagonistas de NK3R cujo ensaio clínico foi suspenso (Osanetant & Talnetant), espera-se identificar propriedades superiores nos compostos recém-desenvolvidos. Metodologia: os códigos Smiles foram obtidos do PubChem e DrugBank, posteriormente, a análise foi baseada no cálculo das propriedades farmacocinéticas e farmacocinéticas utilizando as plataformas ADMETlab e SwissADME. Resultados: Pavinetant & Fezolinetant e SB-222.200 & SB-218.795 apresentam melhores propriedades físico-químicas e atendem mais plenamente às regras de ""drug-likeness" quando comparados ao Osanetant & Talnetant. A avaliação ADMET revelou variações entre os grupos, mas nenhuma foi significativa. As propriedades farmacocinéticas variam irregularmente entre os diferentes compostos. Conclusões: os antagonistas de NK3R recém-desenvolvidos exibiram propriedades superiores em relação aos compostos de teste suspensos. Os resultados do estudo in silico permitem-nos deduzir que o Fezolinetant poderá ter melhores resultados em futuros ensaios clínicos.

A Multinational Pilot Study on Patients' Perceptions of Advanced Neuroendocrine Neoplasms on the EORTC QLQ-C30 and EORTC QLQ-GINET21 Questionnaires.

Among the available neuroendocrine neoplasm (NEN)-specific HR-QoL scales, only the EORTC QLQ-C30 and EORTC QLQ-G.I.NET21 questionnaires have been validated in several languages. We aim to assess patients' perceptions of these questionnaires. A cross-sectional qualitative pilot study was conducted among 65 adults from four countries with well-differentiated advanced gastro-entero-pancreatic (GEP) or unknown primary NENs. Patients completed the EORTC QLQ-C30 and EORTC QLQ-G.I.NET21 questionnaires and then a survey containing statements concerning the questionnaires. The majority of patients had a small intestine NET (52%). Most tumors were functioning (55%) and grade 2 NET (52%). Almost half of the patients identified limitations in the questionnaires, with nine (14%) patients scoring the questionnaires as poor and 16 (25%) patients as moderate. Overall, 37 (57%) patients were positive towards the questionnaires. Approximately a quarter of patients considered the questionnaires not suitable for all ages, missing some of their complaints, not representative of their overall HR-QoL regarding the treatment of their NET and too superficial. The current validated EORTC QLQ-C30 and EORTC QLQ-G.I.NET21 questionnaires may show some limitations in the design of questions and the patients' final satisfaction reporting of the questionnaire. Large-scale, high-quality prospective studies are required in HR-QoL assessment regarding NETs.

SDHB exon 1 deletion: A recurrent germline mutation in Colombian patients with pheochromocytomas and paragangliomas.

Pheochromocytomas (PCCs) and paragangliomas (PGLs) (known as PPGL in combination) are rare neuroendocrine tumors of the adrenal medulla and extra-adrenal ganglia. About 40% of the patients with PPGL have a hereditary predisposition. Here we present a case-series of 19 unrelated Colombian patients with a clinical diagnosis of PPGL tumors that underwent germline genetic testing as part of the Hereditary Cancer Program developed at the Instituto Nacional de Cancerología, Colombia (INC-C), the largest reference cancer center in the country. Ten of 19 patients (52.63%) were identified as carriers of a pathogenic/likely pathogenic (P/LP) germline variant in a known susceptibility gene. The majority of the P/LP variants were in the SDHB gene (9/10): one corresponded to a nonsense variant c.268C>T (p.Arg90*) and eight cases were found to be carriers of a recurrent CNV consisting of a large deletion of one copy of exon 1, explaining 42% (8/19) of all the affected cases. Only one additional case was found to be a carrier of a missense mutation in the VHL gene: c.355T>C (p.Phe119Leu). Our study highlights the major role of SDHB in Colombian patients with a clinical diagnosis of PGL/PCC tumors and supports the recommendation of including the analysis of large deletions/duplications of the SDHB gene as part of the genetic counselling to improve the detection rate of hereditary cases and their clinical care.

Carcinoma adrenocortical: Presentación y desenlaces en una institución oncológica / Adrenocortical carcinoma: Presentation and outcomes at an oncological institute

Resumen Introducción: El carcinoma adrenocortical es una neoplasia endocrina infrecuente pero con un comportamiento altamente agresivo y pobre pronóstico. Dado su baja prevalencia, la experiencia de los centros de referencia es fundamental para aumentar el conocimiento de esta entidad. Métodos: Se elaboró una serie de casos de pacientes con carcinoma adrenocortical, tratados en una institución oncológica de referencia entre enero de 2007 y diciembre de 2017. Se describieron las características clínicas e histopatológicas de los pacientes. Se estimó el tiempo de supervivencia libre de progresión y el tiempo de supervivencia global (SG) de forma gráfica y con funciones de tiempo al evento mediante la función de Kaplan-Meier. Resultados: Se identificaron 19 pacientes, 14 de los cuales fueron mujeres con edad media al diagnóstico de 43.4 años (rango 20 - 65). El 58% de los pacientes tuvo secreción hormonal, siendo el síndrome de Cushing el predominante. 7 pacientes tuvieron compromiso metastásico al momento del diagnóstico. Todos los pacientes fueron llevados a adrenalectomía y el estado postquirúrgico en 10 pacientes fue R0. Al final del periodo de estudio, 11 pacientes estaban vivos. La mediana de supervivencia libre de progresión fue de 18 meses +/- 7.86 y la mediana de supervivencia global fue de 30 meses +/-19.80. Conclusión: En la población de pacientes analizada, se encontraron desenlaces de supervivencia libre de progresión y supervivencia global similares a lo reportado en centros de alta experiencia en patología adrenal.

Abstract Introduction: Adrenocortical carcinoma is a rare endocrine neoplasm, but with highly aggressive behavior and a poor prognosis. Given its low prevalence, the experience of reference centers is essential to characterize the factors associated with this disease. Methods: It is a case series of patients with adrenocortical carcinoma, treated at a reference oncology institute between January 2007 and December 2017. The clinical and histopathological characteristics of patients are described. Progression-free survival and overall survival (OS) were estimated graphically and with time-to-event data using the Kaplan-Meier function. Results: 19 patients were identified; 14 of them were women with a mean age at diagnosis of 43.4 years (range 20-65). 58% of the patients had hormone secretion, with Cushing's syndrome being the predominant one. 7 patients had metastatic compromise at the time of diagnosis. All patients underwent adrenalectomy, and R0 was the post-surgical status in 10 of them. At the end of the study period, 11 patients were alive. The median progression-free survival was 18 months +/- 7.86, and the median overall survival was 30 months +/- 19.8. Conclusion: In the analyzed patient population, outcomes of progression-free survival and overall survival were similar to that reported at centers with extensive experience in adrenal disease.

Salivary alpha amylase and cortisol levels as stress biomarkers in children with cerebral palsy and their association with a physical therapy program.

INTRODUCTION: Cerebral palsy (CP) is one of the main causes of physical disabilities in childhood. There is evidence that CP children display high levels of stress, which could interfere with learning processes and interpretation of relevant sensory information during motor skills acquisition and socialization. OBJECTIVE: This study aims to compare basal levels of stress biomarkers (cortisol and alpha-amylase) of healthy children (HC) and children with CP, and to investigate whether a physical therapy session using the neurodevelopmental technique (NDT) interferes with these levels. METHODS: A cross-sectional design was used. A total of 86 children (HC: n = 45 and CP: n = 41) with matching age, sex, socioeconomic status, and sampling time. Salivary cortisol and alpha-amylase levels were measured by means of electrochemiluminescence and spectrophotometry methods. A single saliva sample was collected in the HC group to determine basal levels. For CP group three samples were collected: a first sample was taken 20-30 min prior to the intervention, while two post-intervention samples were collected (5 and 20 min) to evaluate individual changes in salivary stress biomarkers. RESULTS: Higher basal cortisol concentration was found in CP children when compared to HC group. Moreover, CP children showed a significant reduction in cortisol levels 20 min after NDT intervention. No significant differences were observed in alpha-amylase values. CONCLUSION: Present results show that CP causes alteration in basal cortisol values at childhood and suggest that CP children respond to environmental regulatory factors such as NDT, in attempt to reduce stress.

Pheochromocytoma presenting as fever of unknown origin, a case report

ABSTRACT Introduction: Pheochromocytoma is a generally benign neoplasm derived from chromaffin cells of the adrenal medulla. It is characterized by the production of large amounts of catecholamines and also by the capacity to secrete bioactive peptides such as cytokines, mainly interleukin-1 IL-1, interleukin-6 IL-6 and TNF alpha. Case presentation: 24-year-old man, who consulted for fever, myalgia, and choluria. His laboratory tests were compatible with a systemic inflammatory response without infectious or autoimmune causes. However, a fluorodeoxy-glucose positron emission tomography (FDG-PET) revealed a left adrenal mass, without extra-adrenal lesions. On admission, increased levels of differentiated urine methanephrines, elevated baseline cortisol, non-suppressed adrenocorticotrophic hormone (ACTH), and positive low dose dexamethasone suppression test for cortisol were found. With suspicion of catecholamine and ACTH-producing pheochromocytoma, a tumor resection was performed, which conspicuously resolved all alterations of the inflammatory response. The histologic findings confirmed a pheochromocytoma, but the immunostaining for ACTH was negative. A literature review and the comparison of the findings with other reported cases allowed inferring that this was a case of interleukin-producing pheochromocytoma. Conclusion: Pheochromocytoma may be a cause of febrile syndrome, with IL-6 being the main mediator, which explains the manifestations of systemic inflammation and ACTH-mediated hypercortisolism.

RESUMEN Introducción. Un feocromocitoma es una neoplasia generalmente benigna de las células cromafines de la médula suprarrenal que se caracteriza por producir grandes cantidades de catecolaminas y que tiene la capacidad de secretar citoquinas como interleucina-1 IL-1, interleucina-6 IL-6 y factor de necrosis tumoral (TNF) alfa. Presentación del caso. Paciente masculino de 24 años de edad, quien consultó por fiebre, mialgias y coluria. El sujeto presentó laboratorios compatibles con respuesta inflamatoria sistémica sin causa infecciosa o autoinmune y estudio de tomografía por emisión de positrones con fluoro-desoxiglucosa que evidenció masa suprarrenal izquierda sin lesiones extra-adrenales. Al ingreso, los niveles de metanefrinas diferenciadas en orina y de cortisol basal se encontraban elevados; la hormona adrenocorticotropa (ACTH) no estaba suprimida, y el test de supresión de cortisol con dexametasona registró rango de hipercortisolis-mo. Se sospechó diagnóstico de feocromocitoma productor de catecolaminas y ACTH, por lo que se llevó a resección tumoral, con lo cual, llamativamente, se resolvieron todas las anomalías de respuesta inflamatoria. El reporte de patología confirmó un feocromocitoma, pero la inmunotinción para ACTH fue negativa. La revisión de la literatura y la comparación de los hallazgos con otros casos reportados permitieron inferir que se trató de un feocromocitoma productor de interleucinas. Conclusión. El feocromocitoma puede ser una causa de síndrome febril, siendo la IL-6 el mediador principal que explicaría las manifestaciones de inflamación sistémica y el hipercortisolismo mediado por ACTH.

Uso de metformina y un inhibidor de SGLT2 en el manejo de lipodistrofia congénita generalizada. Reporte de caso / Use of metformin and an SGLT2 inhibitor to treat congenital generalized lipodystrophy. Case report

Resumen Introducción. La lipodistrofia congénita generalizada (LCG) es un síndrome genético autosómico recesivo extremadamente raro que se caracteriza por ausencia generalizada de tejido adiposo, deficiencia en la producción de hormonas como la leptina y complicaciones metabólicas potencialmente serias como diabetes mellitus tipo 2 (DM2), esteatohepatitis e hipertrigliceridemia. Presentación del caso. Paciente femenina de 17 años con un diagnóstico tardío de LCG y con diabetes mellitus (erróneamente clasificada como tipo I), hipertrigliceridemia severa e infecciones a repetición. Luego de introducir metformina y un inhibidor del SGLT2 en el manejo de la paciente, se logró un adecuado control metabólico. Conclusión. Con frecuencia, el desconocimiento de algunas enfermedades huérfanas lleva a diagnósticos erróneos y, por tanto, a tratamientos inadecuados que en algunos casos pueden empeorar la condición clínica de los pacientes. Por lo anterior, en el caso de la LCG, es necesario que la comunidad médica tenga una mejor comprensión de sus aspectos diagnósticos y terapéuticos para brindar un diagnóstico y tratamiento oportunos.

Abstract Introduction: Generalized congenital lipodystrophy (GDL) is an extremely rare autosomal recessive genetic syndrome characterized by generalized absence of adipose tissue, deficient production of hormones such as leptin, and potentially serious metabolic complications such as type 2 diabetes mellitus (DM2), steatohepatitis and hypertriglyceridemia. Case presentation: This is the case of a 17-year-old female patient with a late diagnosis of GDL and with diabetes mellitus (erroneously classified as type 1), severe hypertriglyceridemia and recurrent infections. Adequate metabolic control was achieved after the introduction of metformin and an SGLT2 inhibitor. Conclusion: Lack of knowledge about some orphan diseases usually leads to misdiagnosis and, therefore, to inadequate treatments that may worsen the clinical condition of patients. Therefore, in the case of GDL, the medical community should have a better understanding of its diagnostic and therapeutic aspects in order to provide timely diagnosis and treatment.

Síndrome de Cushing exógeno de difícil diagnóstico / Exogenous Cushings syndrome with a difficult diagnosis

Resumen Introducción: el síndrome de Cushing (SC) es un grupo de signos y síntomas causados por la exposición crónica al exceso de glucocorticoides. El uso de fármacos con glucocorticoides es la causa más frecuente, pero algunos productos vendidos como suplementos nutricionales o medicamentos naturistas para el control de los dolores articulares pueden contenerlos de forma oculta, lo cual dificulta el enfoque diagnóstico Presentación del caso: paciente de 40 años con signos clínico típicos de síndrome de Cushing con resultados discordantes en las pruebas diagnósticas para identificar su origen. Finalmente se logra establecer que el paciente consumía de forma crónica un producto "naturista" conocido como artrin®, el cual fue analizado en el laboratorio de la institución con resultados positivos para cortisol. Conclusión: la exposición crónica a glucocorticoides exógenos, ya sea subrepticia, desconocida o prescrita, causa SC y debe distinguirse tempranamente de las formas endógenas para evitar la realización de pruebas diagnósticas y tratamientos inadecuados.(Acta Med Colomb 2020; 45. DOI:https://doi.org/10.36104/amc.2020.1500).

Abstract Introduction: Cushing's syndrome (CS) is a group of signs and symptoms caused by chronic exposure to excessive glucocorticoids. The use of medications containing glucocorticoids is the most common cause, but they may be hidden in some products sold as nutritional supplements or naturopathic medications, which makes the diagnostic approach more difficult. Case presentation: this was a 40-year-old patient with typical clinical signs of Cushing's syndrome and discordant results of diagnostic tests to identify its origin. It was ultimately determined that the patient had been chronically taking a "naturopathic" product known as artrin®, which was analyzed in the institution's lab and found to contain cortisol. Conclusion: chronic exposure to exogenous glucocorticoids, whether surreptitious, unknown or prescribed, causes CS and should be promptly distinguished from endogenous forms to avoid inappropriate diagnostic tests and treatments.(Acta Med Colomb 2020; 45. DOI:https://doi.org/10.36104/amc.2020.1500).

Recommendations of the Colombian Consensus Committee for the Management of Traumatic Brain Injury in Prehospital, Emergency Department, Surgery, and Intensive Care (Beyond One Option for Treatment of Traumatic Brain Injury: A Stratified Protocol [BOOTStraP]).

Background Traumatic brain injury (TBI) is a global public health problem. In Colombia, it is estimated that 70% of deaths from violence and 90% of deaths from road traffic accidents are TBI related. In the year 2014, the Ministry of Health of Colombia funded the development of a clinical practice guideline (CPG) for the diagnosis and treatment of adult patients with severe TBI. A critical barrier to the widespread implementation was identified-that is, the lack of a specific protocol that spans various levels of resources and complexity across the four treatment phases. The objective of this article is to present the process and recommendations for the management of patients with TBI in various resource environments, across the treatment phases of prehospital care, emergency department (ED), surgery, and intensive care unit. Methods Using the Delphi methodology, a consensus of 20 experts in emergency medicine, neurosurgery, prehospital care, and intensive care nationwide developed recommendations based on 13 questions for the management of patients with TBI in Colombia. Discussion It is estimated that 80% of the global population live in developing economies where access to resources required for optimum treatment is limited. There is limitation for applications of CPGs recommendations in areas where there is low availability or absence of resources for integral care. Development of mixed methods consensus, including evidence review and expertise points of good clinical practices can fill gaps in application of CPGs. BOOTStraP (Beyond One Option for Treatment of Traumatic Brain Injury: A Stratified Protocol) is intended to be a practical handbook for care providers to use to treat TBI patients with whatever resources are available. Results Stratification of recommendations for interventions according to the availability of the resources on different stages of integral care is a proposed method for filling gaps in actual evidence, to organize a better strategy for interventions in different real-life scenarios. We develop 10 algorithms of management for building TBI protocols based on expert consensus to articulate treatment options in prehospital care, EDs, neurological surgery, and intensive care, independent of the level of availability of resources for care.

The Role of Decompressive Craniectomy in Limited Resource Environments.

Decompressive craniectomy (DC) is a neurosurgical procedure useful to prevent and manage the impact of high intracranial pressure (ICP) that leads to brain herniation and brain's tissue ischemia. In well-resourced environment this procedure has been proposed as a last tier therapy when ICP is not controlled by medical therapies in the management of different neurosurgical emergencies like traumatic brain injury (TBI), stroke, infectious diseases, hydrocephalus, tumors, etc. The purpose of this narrative review is to discuss the role of DC in areas of low neurosurgical and neurocritical care resources. We performed a literature review with a specific search strategy in web repositories and some local and regional journals from Low and Middle-Income Countries (LMICs). The most common publications include case reports, case series and observational studies describing the benefits of the procedure on different pathologies but with several types of biases due to the absence of robust studies or clinical registries analysis in these kinds of environments.

Combination of drug and stem cells neurotherapy: Potential interventions in neurotrauma and traumatic brain injury.

Traumatic brain injury (TBI) has been recognized as one of the major public health issues that leads to devastating neurological disability. As a consequence of primary and secondary injury phases, neuronal loss following brain trauma leads to pathophysiological alterations on the molecular and cellular levels that severely impact the neuropsycho-behavioral and motor outcomes. Thus, to mitigate the neuropathological sequelae post-TBI such as cerebral edema, inflammation and neural degeneration, several neurotherapeutic options have been investigated including drug intervention, stem cell use and combinational therapies. These treatments aim to ameliorate cellular degeneration, motor decline, cognitive and behavioral deficits. Recently, the use of neural stem cells (NSCs) coupled with selective drug therapy has emerged as an alternative treatment option for neural regeneration and behavioral rehabilitation post-neural injury. Given their neuroprotective abilities, NSC-based neurotherapy has been widely investigated and well-reported in numerous disease models, notably in trauma studies. In this review, we will elaborate on current updates in cell replacement therapy in the area of neurotrauma. In addition, we will discuss novel combination drug therapy treatments that have been investigated in conjunction with stem cells to overcome the limitations associated with stem cell transplantation. Understanding the regenerative capacities of stem cell and drug combination therapy will help improve functional recovery and brain repair post-TBI. This article is part of the Special Issue entitled "Novel Treatments for Traumatic Brain Injury".

Enduring Neuroprotective Effect of Subacute Neural Stem Cell Transplantation After Penetrating TBI.

Traumatic brain injury (TBI) is the largest cause of death and disability of persons under 45 years old, worldwide. Independent of the distribution, outcomes such as disability are associated with huge societal costs. The heterogeneity of TBI and its complicated biological response have helped clarify the limitations of current pharmacological approaches to TBI management. Five decades of effort have made some strides in reducing TBI mortality but little progress has been made to mitigate TBI-induced disability. Lessons learned from the failure of numerous randomized clinical trials and the inability to scale up results from single center clinical trials with neuroprotective agents led to the formation of organizations such as the Neurological Emergencies Treatment Trials (NETT) Network, and international collaborative comparative effectiveness research (CER) to re-orient TBI clinical research. With initiatives such as TRACK-TBI, generating rich and comprehensive human datasets with demographic, clinical, genomic, proteomic, imaging, and detailed outcome data across multiple time points has become the focus of the field in the United States (US). In addition, government institutions such as the US Department of Defense are investing in groups such as Operation Brain Trauma Therapy (OBTT), a multicenter, pre-clinical drug-screening consortium to address the barriers in translation. The consensus from such efforts including "The Lancet Neurology Commission" and current literature is that unmitigated cell death processes, incomplete debris clearance, aberrant neurotoxic immune, and glia cell response induce progressive tissue loss and spatiotemporal magnification of primary TBI. Our analysis suggests that the focus of neuroprotection research needs to shift from protecting dying and injured neurons at acute time points to modulating the aberrant glial response in sub-acute and chronic time points. One unexpected agent with neuroprotective properties that shows promise is transplantation of neural stem cells. In this review we present (i) a short survey of TBI epidemiology and summary of current care, (ii) findings of past neuroprotective clinical trials and possible reasons for failure based upon insights from human and preclinical TBI pathophysiology studies, including our group's inflammation-centered approach, (iii) the unmet need of TBI and unproven treatments and lastly, (iv) present evidence to support the rationale for sub-acute neural stem cell therapy to mediate enduring neuroprotection.

Embolización de metástasis hepáticas en insulinoma maligno: de la hipoglicemia a la hiperglicemia / Embolisation of liver metastasis in malignant insulinoma: from hyperglycaemia to hypoglycaemia

Resumen Se describe el caso de un paciente de 75 años sin antecedentes de relevancia, que fue diagnosticado con insulinoma maligno en estado avanzado, con metástasis hepáticas, con síntomas por hipoglucemia hiperinsulinémica refractaria al tratamiento, y con diazóxido y octreotide de acción corta. El paciente presentó una respuesta clínica poco esperada a la embolización transarterial de metástasis hepáticas, pues a pesar de que persisten las lesiones tumorales, desarrolló hiperglucemia persistente y requirió manejo con insulina. Adicionalmente, se hace una breve revisión de la literatura sobre las opciones terapéuticas disponibles para el tratamiento sintomático de la hipoglucemia hiperinsulinémica.

Abstract The case is presented of a 75 year-old man who was diagnosed with malignant insulinoma in an advanced stage with diffuse liver metastases and symptoms due to hyperinsulinaemic hypoglycaemia refractory to treatment with diazoxide and short-acting octreotide. The patient had an unexpected clinical response to trans-arterial embolisation of liver metastases, since, despite still having the tumour, he developed persistent hyperglycaemia that required insulin treatment. A brief review of the literature is also presented on the treatment options for hyperinsulinaemic hypoglycaemia.

Hepatic metastasis of a parathyroid carcinoma treated with intra-arterial embolization / Metástasis hepática de un carcinoma de paratiroides tratada con embolización intraarterial

Abstract This paper reports the case of a patient with parathyroid carcinoma and metastatic parathyroid carcinoma in the liver, as well as persistent hypercalcemia resistant to the management with zoledronic acid and cinacalcet. The patient was treated with intra-arterial embolization using polyvinyl alcohol microspheres in the right hepatic artery, achieving an excellent biochemical control after the intervention.

Resumen Se reporta el caso de una paciente con carcinoma de paratiroides metastásico al hígado con hipercalcemia de muy difícil control pese a manejo con ácido Zoledrónico y Cinacalcet. La paciente fue llevada a embolización intraarterial con microesferas de alcohol polivinílico de la arteria hepática derecha, con lo que se obtuvo un excelente control bioquímico después de la intervención.