Introduction and objectives: Subclinical systolic dysfunction is one of the proposed mechanisms for increased cardiovascular risk associated with metabolic syndrome (MS). This study investigated the association between MS and impaired left ventricular global longitudinal strain (GLS) and the role of each MS criteria in this association. Methods: We analyzed a random sample of the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil) after excluding participants with prevalent heart disease. Results: Among the 1055 participants fulfilling the inclusion criteria (53% women; 52 ± 9 years), 444 (42%) had MS. Those with MS had worse GLS (–18.0% ± 2.5%) than those without (–19.0% ± 2.4%; P < .0001). In multiple linear regression models, MS was associated with worse GLS after adjustment for various risk factors (GLS difference = 0.86%; P < .0001), even after inclusion of body mass index. Adjusted PR for impaired GLS as assessed by 3 cutoffs (1, 1.5, and 2 standard deviations) were higher among participants with than without MS: GLS –16.1% (PR, 1.76; 95%CI, 1.30-2.39); GLS –14.8% (PR, 2.35; 95%CI, 1.45-3.81); and GLS –13.5% (PR, 2.07; 95%CI, 0.97-4.41). After inclusion of body mass index in the models, these associations were attenuated, suggesting that they may, at least in part, be mediated by obesity. In quantile regression analyses, elevated waist circumference was the only MS component found to be independently associated with GLS across the whole range of values. Conclusions: Metabolic syndrome is independently associated with impaired GLS. Among the MS criteria, central obesity best depicted the link between metabolic derangement and cardiac function. Introducción y objetivos: La disfunción sistólica subclínica es uno de los mecanismos propuestos para el aumento del riesgo cardiovascular asociado con el síndrome metabólico (SM). Este estudio investigó la asociación entre SM y deterioro del strain longitudinal global (SLG) del ventrículo izquierdo y el papel de cada criterio de SM en esta asociación. Métodos: Se analizó una muestra aleatoria del Estudo Longitudinal da Saúde do Adulto (ELSA-Brasil) después de excluir a aquellos con cardiopatía prevalente. Resultados: De los 1.055 participantes que cumplían los criterios de inclusión (el 53% mujeres; edad, 52 ± 9 años), 444 (42%) reunían criterios de SM. Aquellos con SM presentaron un SLG más reducido (–18,0 ± 2,5%) que aquellos sin SM (–19,0 ± 2,4%; p < 0,0001). En los modelos de regresión lineal múltiple, el SM se asoció con SLG más reducido después de ajustar por varios factores de riesgo (diferencia de SLG, 0,86%; p < 0,0001), incluso después de incluir el índice de masa corporal. Las TP ajustadas para los participantes con SLG reducido evaluados con 3 puntos de corte (1, 1,5 y 2 desviaciones estándar) fueron más altas entre aquellos con SM que sin este: SLG –16,1% (TP = 1,76; IC95%, 1,30-2,39); SLG –14,8% (TP = 2,35; IC95%, 1,45-3,81), y SLG –13,5% (TP = 2,07; IC95%, 0,97-4,41). Después de incluir el índice de masa corporal en los modelos, estas asociaciones se atenuaron; lo que indica que la obesidad puede mediar, al menos en parte, estas asociaciones. En los análisis de regresión cuantílica, la circunferencia de cintura aumentada fue el único componente del SM que se halló independientemente asociado con el SLG a lo largo de todo el rango de valores. Conclusiones: El SM se asocia de manera independiente con alteración del SLG. Entre los criterios de SM, la obesidad central describe mejor la relación entre el trastorno metabólico y la función cardiaca.

Objective: To evaluate the effectiveness of the chemically assisted dissection with sodium 2-mercaptoethanesulfonate (MESNA), in the reduction of residual and recurrent cholesteatoma after mastoidectomy in children with chronic cholesteatomatous otitis media (CCOM). Study Design: Retrospective case–control study. Setting: Tertiary referral center. Population: One hundred forty mastoidectomies performed in patients under 18 years of age for the treatment of CCOM. Interventions: Chemically assisted dissection (CAD) with MESNA compared with surgical dissection without MESNA. Main Outcome Measures: Recidivism of cholesteatoma (recurrence and residual disease), variations in the average of bone conduction threshold after treatment, and complications. Results: Recidivism of cholesteatoma was significantly lower when CAD with MESNA was used (p<0.0001). No difference was found in the mean variation of the average of bone conduction thresholds between the groups, confirming its safety profile regarding auditory function. Meatoplasty stenosis after surgery was more prevalent within CAD with MESNA group (p: 0.049). Conclusion: Recurrent and residual cholesteatoma remains a problem, especially in children and despite surgical techniques such as canal wall down mastoidectomy and endoscopic ear surgery. CAD with MESNA can be safe and effective to reduce recurrence rates. Resumen. Objetivo: Evaluar la efectividad de la disección químicamente asistida con 2-mercaptoetanosulfonato de sodio (MESNA), en la reducción de colesteatoma residual y recurrente después de mastoidectomía en niños con otitis media colesteatomatosa crónica (OMCC). Diseño del estudio: Estudio retrospectivo de casos y controles. Lugar: Centro de referencia terciario pediatrico. Población: Ciento cuarenta mastoidectomías realizadas en pacientes menores de 18 años para el tratamiento de OMCC. Intervenciones: Disección químicamente asistida (DQA) con MESNA en comparación con disección quirúrgica sin MESNA. Principales medidas de resultado: Reincidencia de colesteatoma (recurrencia y enfermedad residual), variaciones en el promedio del umbral de conducción ósea después del tratamiento y complicaciones. Resultados: La reincidencia del colesteatoma fue significativamente menor cuando se utilizó DQA con MESNA (p <0,0001). No se encontraron diferencias en la variación media del promedio de los umbrales de conducción ósea entre los grupos, lo que confirma su perfil de seguridad con respecto a la función auditiva. La estenosis de la meatoplastia después de la cirugía fue más frecuente dentro del grupo de DQA con MESNA (p: 0.049). Conclusión: El colesteatoma recurrente y residual sigue siendo un problema, especialmente en niños y a pesar de las técnicas quirúrgicas, como la mastoidectomía radical y la cirugía endoscópica del oído. La DQA con MESNA puede ser segura y efectiva para reducir las tasas de recurrencia.

Background: Current scores do not adequately predict cardiovascular risk in patients with chronic kidney disease who are at a very high CV risk in short and medium term. Aim: The aim of our analysis was to create a Bayesian network to predict the 2-year occurrence of a cardiovascular event in patients with chronic kidney disease. Methods and results: The data originated from the observational and prospective Photo-Graphe V3 cohort. Sixty-two nephrologists in 20 French regions included 1144 non-dialysed patients with chronic kidney disease. Seven hundred and thirty patients with known medical status at 2 years were analysed. An initial Bayesian model was first built using 26 variables related to the characteristics of the patients, their medical background, and treatments. A cardiovascular event (heart failure, acute coronary syndrome, transient ischemic attack, stroke or cardiovascular death) occurred in 20.0% of the patients after two years of follow-up. The model was first optimized using synthetic data (created from the original database) to increase its reliability. The number of variables was then reduced using the 13 most informative variables to increase its clinical applicability. The10-fold cross validation showed that the optimized clinical model with 13 variables had an area under the ROC curve of 0.90+0.02, a sensitivity of 82.5+5.9%, a specificity of 80.6+5.1%, a predictive positive value of 81.2+3.4% and a negative predictive value of 82.5+4.4%. The percentage of misclassified subjects was 18.4+2.6%. Conclusion: Using artificial intelligence methods, a new clinical tool to predict cardiovascular events in patients with chronic kidney disease is proposed.

This thesis examines the concept of medical futility and its importance for the practice of medicine nowadays. It presents an overview of the development of the concept throughout history and it discusses the main arguments in favor and against a determination of futile treatment in the clinical setting. The notion of futility, in broad terms, describes the situation in which certain medical interventions no longer benefit the patient and therefore, it follows that there must be a derived moral obligation to stop said intervention. Such an idea brings forward numerous problematic pitfalls that are discussed in this thesis, among which are the debate about the limits of medicine, the tension between the notions of patient autonomy and physician authority and the practice of medical rationing in hospitals. This thesis aims to provide a new perspective on the subject in hopes that it will help to keep the ongoing debate running so in the near future, more experts will decide to contribute themselves with their expertise. Situations where a medical intervention ceases to benefit the patient will continue to occur at the bedside; what is more, these ethical conundrums will become more and more problematic as the technological imperative intensifies and the possibilities of biotechnology increase. The leading question that directed the development of the thesis was “when enough it’s enough?” in other words, what are the ethical considerations on the limits of medicine? The paper concludes that the concept of medical futility has a heuristic value, and thus it has helped yield more clarity about relevant matters such as the differentiation between futility and rationing, the fact that more research is needed to test what works and what does not and it has brought to the spotlight the importance of more robust standards of practice that, for example, prevent physicians from practicing defensive medicine. Resumen: Esta tesis examina el concepto de futilidad médica y su importancia para la práctica de la medicina en la actualidad. Presenta una visión general del desarrollo del concepto a lo largo de la historia y discute los principales argumentos a favor y en contra de la determinación de un tratamiento fútil en el ámbito clínico. La noción de futilidad, en términos generales, describe la situación en la que ciertas intervenciones médicas ya no benefician al paciente y, por lo tanto, se deduce que debe existir una obligación moral derivada de detener dicha intervención. Esta idea plantea numerosos asuntos problemáticos que se discuten en esta tesis, entre los que se encuentran el debate sobre los límites de la medicina, la tensión entre las nociones de autonomía del paciente y autoridad del médico, y la práctica del racionamiento médico en los hospitales. Esta tesis pretende aportar una nueva perspectiva sobre el tema con la esperanza de que esta ayude a mantener el debate vigente, de manera que, en un futuro próximo, más expertos decidan aportar su experiencia. Las situaciones en las que una intervención médica deja de beneficiar al paciente seguirán; más aún, estos debates éticos se volverán cada vez más problemáticos a medida que se intensifique el imperativo tecnológico y aumenten las posibilidades de la biotecnología. La pregunta principal que dirigió el desarrollo de la tesis fue ""¿cuándo es momento de parar?"", es decir, ¿cuáles son las consideraciones éticas sobre los límites de la medicina? El documento concluye que el concepto de futilidad médica tiene un valor heurístico y, por lo tanto, ha contribuido a aclarar cuestiones pertinentes como la diferenciación entre futilidad y racionamiento, el hecho de que se necesita más investigación para probar lo que funciona y lo que no, y ha puesto de relieve la importancia de contar con normas de práctica más sólidas que, por ejemplo, impidan a los médicos practicar la medicina defensiva.

Mutations in PCDH19 gene are associated with Early Infantile Epileptic Encephalopathy type 9 (EIEE-9), a very rare disorder characterized by early onset of seizures, intellectual disability and psychiatric comorbidities with an unusual form of X-linked inheritance in which only females and mosaic male patients are affected. Materials and Methods: We report three patients, one male and two females carrying PCDH19 variants (D233G, V589Cfs*8 and N1103K) found by Whole exome sequencing (WES). One is a novel missense mutation (N1103K) while the others had been previously reported in female affected patients. Although, there is the first time that variant V589Cfs*8 is reported in a male patient. We performed a complete phenotype evaluation of our cases and establish the pathogenicity of each variant by in silico and functional analysis accessing many aspects of Protocadherin-19 including subcellular localization and protein expression. Results: Two of the three variants are predicted to be deleterious to protein function. The variant D233G is predicted to affect the calcium binding site and avoids cadherin strands swapping compromising the cell adhesion activity and the structural stability of the protein. While, the variant V589Cfs*8 introduced a premature stop codon which led to the loss of the transmembrane domain of the protein as well as to the cytoplasmic domain, including all predicted nuclear localization signals, suggesting the variant might affect the subcellular localization of Pcdh-19. The last findings were corroborated by western blotting and immunolabelling comparing the protein localization in patient and control fibroblasts. Conclusions: Our findings enhance understanding of molecular functions of Protocadherin-19, as well as highlighting the importance of functional testing of variants that emerge from NGS studies. Resumen: Las mutaciones en el gen PCDH19 están asociadas con la encefalopatía epiléptica infantil temprana tipo 9 (EIEE-9), un trastorno muy raro caracterizado por la aparición temprana de convulsiones, discapacidad intelectual y comorbilidades psiquiátricas con una forma inusual de herencia ligada al cromosoma X en la que solo las mujeres y mosaico pacientes masculinos se ven afectados. Materiales y métodos: Reportamos tres pacientes, un hombre y dos mujeres con variantes en el gen PCDH19 (D233G, V589Cfs*8 y N1103K) encontrados por secuenciación de exoma completo (WES). Una es una nueva mutación sin sentido (N1103K) mientras que las otras habían sido reportadas previamente en pacientes femeninas afectadas. Aunque, es la primera vez que se informa la variante V589Cfs*8 en un paciente masculino. Realizamos una evaluación completa del fenotipo de nuestros casos y establecimos la patogenicidad de cada variante mediante análisis in silico y funcional accediendo a muchos aspectos de la Protocadherin-19, incluida la localización subcelular y la expresión de proteínas. Resultados: se predice que dos de las tres variantes son perjudiciales para la función de la proteína. La variante D233G afecta el sitio de unión al calcio y evita el intercambio de hebras de caderina que comprometen la actividad de adhesión celular y la estabilidad estructural de la proteína. Mientras que la variante V589Cfs*8 introdujo un codón de parada prematuro que condujo a la pérdida del dominio transmembrana de la proteína, así como al dominio citoplasmático, incluidas todas las señales de localización nuclear esperadas, lo que sugiere que la variante podría afectar la localización subcelular de la proteína. Los últimos hallazgos fueron corroborados por Western blot e inmunomarcaje comparando la localización de la proteína en fibroblastos de pacientes y controles. Conclusiones: Nuestros hallazgos mejoran la comprensión de las funciones moleculares de Protocadherin-19, así como resaltan la importancia de las pruebas funcionales de las variantes que surgen de los estudios de secuenciación de siguiente generación (NGS).

El ambiente escolar es uno de los entornos más relevantes y significativos de nuestra vida, pues allí se tejen comportamientos, relaciones y hábitos que suelen modelar patrones de alimentación que impactan en nuestras preferencias de consumo. En este sentido, si bien es cierto que existe una combinación de factores individuales, como cuestiones psicológicas y culturales, que impactan en nuestros hábitos alimentarios, diversos estudios han demostrado el carácter determinante de los existen factores ambientales, entre ellos la disponibilidad, la accesibilidad y la invasiva publicidad de alimentos en los entornos donde nos relacionamos. Según UNICEF, en Colombia 3 de cada 10 niños y niñas entre 6 y 12 años padecen de sobrepeso. Esto lo confirman los datos recolectados por la ENSIN, reflejando que en 2005. El 4,3% de la población escolar (niños y niñas entre 5 y 12 años) tenía exceso de peso. Ya para el 2010 esta cifra habría aumentado a 18,8% y para el 2015 este porcentaje alcanzó el 24,4%. Este panorama es altamente preocupante, pues según la Organización Mundial de la Salud, la obesidad infantil se asocia con una mayor probabilidad de muerte prematura y discapacidad en la edad adulta. Esta cartilla resume los argumentos legales y de salud pública, por los cuales la regulación de venta y publicidad de ultraprocesados en entornos escolares es una política necesaria para favorecer la salud y la alimentación de los niños y niñas en Colombia. Descripción tomada de: https://www.dejusticia.org/publication/promoviendo-ambientes-escolares-libres-de-comida-chatarra-en-colombia/

Sala de cirugía de un hospital, al parecer se trata de una sala de partos. Posiblemente sea de algún hospital de Bogotá.

Abstract: Background: Multidrug resistant TB cases have been on the rise, risking advances in TB prevalence and control. Early diagnosis and targeted initial treatment are paramount for effective management and control of spreading of MDR/XDR-TB cases Methods: 161 isolates from patients with L-J culture confirmed TB in Lima, Peru, were tested with MODS+ assay, the diagnostic test and Sensititre, the reference standard. Analysis of growth patterns of bacteria in both methods were used to determine susceptibility/resistance of each isolate to three first line and six second line anti-TB agents, using two different critical concentrations (CC) for each antibiotic. Results: Agreement between susceptibility profiles and operational characteristics of diagnostic test yielded high performance and strong agreement with rifampicin 1μg/ml (agreement percent 90%, Kappa value 0.80) and amikacin 1μg/ml (agreement percent 96%, Kappa value 0.81), moderate for isoniazid 0.4μg/ml (agreement percent 89.4%, Kappa value 0.78), moxifloxacin at both CC’s 0.5μg/ml and 0.25μg/ml (agreement percent 93 and kappa values 0.73 for both), levofloxacin 2μg/ml (agreement 93%, kappa 0.69) and amikacin 2μg/ml (agreement 96%, Kappa 0.81), minimal for levofloxacin at CC 1.5μg/ml (agreement 90%, kappa 0.57) kanamycin at both CC’s 10μg/ml and 5μg/ml (agreement 87%, kappa 0.52) and ethionamide 5μg/ml (agreement 89%, kappa 0.46), weak for PAS 10μg/ml (agreement percent 93.9, kappa value 0.29), and none for ethambutol (Kappa value 0.02 for CC 10μg/ml, 0.07 for CC 5μg/ml). Conclusions: MODS+ assay is a cost-effective option for the diagnosis of TB and MDR/XDRTB, specially, in low resource settings with high TB incidence. Further operational research using lower CC’s, results read on different days and placed in settings with high and low TB and MDR/XDRTB burden could offer better sensitivities and wider applicability of results.

Background: Data are rare about the incidence of severe Fontan-associated liver disease (FALD) and its association with mortality. We sought to: (1) estimate the probability of developing severe FALD in patients who undergo the Fontan procedure (Fontan patients), compared with severe liver complications in patients with a ventricular septal defect; (2) assess the severe FALD-mortality association; and (3) identify risk factors for developing severe FALD. Methods and Results: Using the Quebec Congenital Heart Disease database, a total of 512 Fontan patients and 10232 patients with a ventricular septal defect were identified. Kaplan-Meier curves demonstrated significantly higher cumulative risk of severe FALD in Fontan patients (11.95% and 52.24% at 10 and 35years, respectively), than the risk of severe liver complica- tions in patients with a ventricular septal defect (0.50% and 2.75%, respectively). At 5years, the cumulative risk of death was 12.60% in patients with severe FALD versus 3.70% in Fontan patients without FALD (log-rank P=0.0171). Cox proportional hazard models identified significant associations between the development of severe FALD and congestive heart failure and supraventricular tachycardia, with hazard ratios (HRs) of 2.36 (95% CI, 1.38–4.02) and 2.45 (95% CI, 1.37–4.39), respectively. More recent Fontan completion was related to reduced risks of severe FALD, with an HR of 0.95 (95% CI, 0.93–0.97) for each more recent year. Conclusions: This large-scale population-based study documents that severe FALD in Fontan patients was associated with a >3-fold increase in mortality. The risk of FALD is time-dependent and can reach >50% by 35years after the Fontan operation. Conditions promoting poor Fontan hemodynamics were associated with severe FALD development.

Background: Post-stroke fatigue (PSF) is one of the most challenging clinical consequences to manage after stroke as no effective treatment has been developed. However, the mechanisms of PSF remain unclear. Aims: This study aimed to replicate Vecchio et al (2017) using resting-state EEG in stroke patients suffering from varying degrees of fatigue to describe the functional organisation within sensory and motor networks. Methods: Resting-state eyes-open EEG was recorded in 22 strokesurvivors. Upper limb functional tests (grip strength, Nine Hole Peg Test), symbol digit modalities test (SDTM), anxiety and depression scale (HADS), Fatigue Severity Scale (FSS-7), state fatigue, and Neurological Fatigue Index (NFI-stroke) were measured. Graph theory was used to calculate the small-world (SW) index. SW was calculated in four separate networks, motor and sensory within the left and right hemispheres. Exact low-resolution brain electromagnetic tomography (eLORETA) was applied using seven frequency bands (delta, theta, alpha1, alpha2, beta1, beta2, and gamma). Results: Correlation analysis demonstrated a positive association between SW in the right motor network in beta2 band and higher FSS-7 score and a negative correlation between SW in the left sensory network in alpha1 and higher state fatigue. Conclusion: Beta oscillations have been associated with top-down processes which are crucial for perceptual inference and alpha oscillations are involved in sensorimotor information processing. The interaction between the top-down and bottom-up processes, and perceived error explains the sensory attenuation model of fatigue. Our results were consistent this model of fatigue as stroke survivors had difficulty in attenuating the sensory input leading to higher perceived effort.