Low-to-moderate alcohol consumption is associated with increased fibrosis in individuals with metabolic dysfunction-associated steatotic liver disease.

BACKGROUND & AIMS: Both metabolic dysfunction and alcohol consumption cause steatotic liver disease (SLD). New nomenclature and distinction of metabolic dysfunction-associated SLD (MASLD) and MetALD categories is based on arbitrary thresholds of alcohol intake. We assessed the impact of different levels of alcohol consumption on SLD severity and its interaction with metabolic comorbidities. METHODS: Population-based study with transient elastography (FibroScan®) data from participants in Spain (derivation) and U.S. (validation) cohorts. Controlled attenuation parameter (CAP≥275 dB/m) identified SLD. At least one cardiometabolic risk factor was required to define MASLD. Among MASLD patients, low alcohol consumption was defined as an average of 5-9 drinks/week, moderate consumption as 10-13 drinks/week for females and 10-20 drinks/week for males, and increased alcohol intake (MetALD) as 14-35 drinks/week for females and 21-42 drinks/week for males. Significant fibrosis was defined as LSM≥8 kPa and at-risk MASH as FAST score≥0.35. RESULTS: The derivation cohort included 2,227 subjects with MASLD (9% reported low, 14% moderate alcohol consumption), and 76 cases with MetALD. Overall prevalence of significant fibrosis and at-risk MASH were 7.6% and 14.8%, respectively. In the multivariable analysis, alcohol consumption was independently associated with significant fibrosis and at-risk MASH. A dose-dependent increase in the prevalence of significant fibrosis and at-risk MASH was observed between the number of drinks/week and the number of cardiometabolic factors. The validation cohort included 1,732 participants with MASLD, of whom 17% had significant fibrosis and 13% at-risk MASH. This cohort validated the association between moderate intake and MASLD at risk of progression (OR=1.69 [95%CI 1.06-2.71]). CONCLUSIONS: Moderate alcohol intake is commonly seen in MASLD and increases the risk of advanced disease, in a similar magnitude to MetALD spectrum. IMPACT AND IMPLICATIONS: Metabolic risk factors such as overweight, diabetes or dyslipidemia, and alcohol consumption can cause liver disease. These factors frequently co-exist, but their joint effects on liver fibrosis remain uncertain. This study analyzes subjects form the general population with metabolic dysfunction-associated steatotic liver disease (MASLD) enrolled in Spain and U.S. We show that moderate alcohol consumption has a supra-additive effect with metabolic risk factors, exponentially increasing the risk of liver fibrosis. These results suggest that patients with unhealthy metabolic status and MASLD have no safe limits of daily alcohol intake.

Hepatic venous pressure gradient predicts risk of hepatic decompensation and liver-related mortality in patients with MASLD.

BACKGROUND & AIMS: Metabolic dysfunction-associated steatotic liver disease (MASLD) is a leading cause of advanced chronic liver disease (ACLD). Portal hypertension drives hepatic decompensation and is best diagnosed by hepatic venous pressure gradient (HVPG) measurement. Here, we investigate the prognostic value of HVPG in MASLD-related compensated ACLD (MASLD-cACLD). METHODS: This European multicentre study included patients with MASLD-cACLD characterised by HVPG at baseline. Hepatic decompensation (variceal bleeding/ascites/hepatic encephalopathy) and liver-related mortality were considered the primary events of interest. RESULTS: A total of 340 patients with MASLD-cACLD (56.2% male; median age 62 [55-68] years, median MELD 8 [7-9], 71.2% with diabetes) were included. Clinically significant portal hypertension (CSPH: i.e., HVPG ≥10 mmHg) was found in 209 patients (61.5%). During a median follow-up of 41.5 (27.5-65.8) months, 65 patients developed hepatic decompensation with a cumulative incidence of 10.0% after 2 years (2Y) and 30.7% after 5 years (5Y) in those with MASLD-cACLD with CSPH, compared to 2.4% after 2Y and 9.4% after 5Y in patients without CSPH. Variceal bleeding did not occur without CSPH. CSPH (subdistribution hazard ratio [SHR] 5.13; p <0.001) was associated with an increased decompensation risk and a higher HVPG remained an independent risk factor in the multivariable model (adjusted SHR per mmHg: 1.12, p <0.001). Liver-related mortality occurred in 37 patients at a cumulative incidence of 3.3% after 2Y and 21.4% after 5Y in CSPH. Without CSPH, the incidence after 5Y was 0.8%. Accordingly, a higher HVPG was also independently associated with a higher risk of liver-related death (adjusted SHR per mmHg: 1.20, p <0.001). CONCLUSION: HVPG measurement is of high prognostic value in MASLD-cACLD. In patients with MASLD-cACLD without CSPH, the short-term risk of decompensation is very low and liver-related mortality is rare, while the presence of CSPH substantially increases the risk of both. IMPACT AND IMPLICATIONS: While the incidence of compensated advanced chronic liver disease (cACLD) due to metabolic dysfunction-associated steatotic liver disease (MASLD) is increasing worldwide, insights into the impact of clinically significant portal hypertension (CSPH) on the risk of liver-related events in MASLD-cACLD remain limited. Based on the findings of this European multicentre study including 340 MASLD-cACLD patients, we could show that increasing HVPG values and the presence of CSPH in particular were associated with a significantly higher risk of first hepatic decompensation and liver-related mortality. In contrast, the short-term incidence of decompensation in patients with MASLD-cACLD without CSPH was low and the risk of liver-mortality remained negligible. Thus, HVPG measurements can provide important prognostic information for individualised risk stratification in MASLD-cACLD and may help facilitate the study of novel and promising treatment possibilities for MASLD.

Phenotypes of Metabolic Dysfunction-Associated Steatotic Liver Disease-Associated Hepatocellular Carcinoma.

Hepatocellular carcinoma (HCC) typically develops as a consequence of liver cirrhosis, but HCC epidemiology has evolved drastically in recent years. Metabolic dysfunction-associated steatotic liver disease (MASLD), including metabolic dysfunction-associated steatohepatitis, has emerged as the most common chronic liver disease worldwide and a leading cause of HCC. A substantial proportion of MASLD-associated HCC (MASLD-HCC) also can develop in patients without cirrhosis. The specific pathways that trigger carcinogenesis in this context are not elucidated completely, and recommendations for HCC surveillance in MASLD patients are challenging. In the era of precision medicine, it is critical to understand the processes that define the profiles of patients at increased risk of HCC in the MASLD setting, including cardiometabolic risk factors and the molecular targets that could be tackled effectively. Ideally, defining categories that encompass key pathophysiological features, associated with tailored diagnostic and treatment strategies, should facilitate the identification of specific MASLD-HCC phenotypes. In this review, we discuss MASLD-HCC, including its epidemiology and health care burden, the mechanistic data promoting MASLD, metabolic dysfunction-associated steatohepatitis, and MASLD-HCC. Its natural history, prognosis, and treatment are addressed specifically, as the role of metabolic phenotypes of MASLD-HCC as a potential strategy for risk stratification. The challenges in identifying high-risk patients and screening strategies also are discussed, as well as the potential approaches for MASLD-HCC prevention and treatment.

Extraction of 5-Hydroxymethylfurfural and Furfural in Aqueous Biphasic Systems: A COSMO-RS Guided Approach to Greener Solvent Selection.

5-Hydroxymethylfurfural (HMF) and furfural (Fur) are promising biobased platform chemicals, derived from the dehydration of carbohydrate feedstocks, normally conducted in an aqueous phase. Plagued by side-reactions in such phase, such as the rehydration to levulinic acid (LA) and formic acid (FA) or self-condensation to humins, HMF and Fur necessitates diversification from monophasic aqueous reaction systems toward biphasic systems to mitigate undesired side-reactions. Here, a methodology based on the COnductor-like Screening MOdel for Real Solvents (COSMO-RS) method was used to screen solvent candidates based on the predicted partition coefficients (Ki). Hansen solubility parameters in conjunction with excess thermodynamic quantities determined by COSMO-RS were employed to assess solvent compatibility. Experimental validation of the COSMO-RS values highlighted only minor deviations from the predictions with root-mean-square-error (RMSE) values of HMF and Fur at 0.76 and 5.32, respectively, at 298 K. The combined effort suggested cyclohexanone, isophorone, and methyl isobutyl ketone (MIBK) as the best candidates. Finally, extraction solvent reuse demonstrated cyclohexanone suitability for HMF extraction with KHMF of 3.66 and MIBK for Fur with KFur 7.80 with consistent partitioning across four total runs. Both solvents are classified as recommended by the CHEM21 solvent selection guide, hence adding to the sustainability of the process.

Mapping the Slow Stabilization of End States with Length along a Laterally Extended Graphene Nanoribbon.

With a lateral bisnaphtho-extended chemical structure, finite 7-13 carbon atom wide armchair graphene nanoribbons (7-13-aGNRs) were on-surface synthesized. For all lengths up to N = 7 monomer units, low-temperature ultrahigh vacuum scanning tunneling spectroscopy and spatial dI/dV maps were recorded at each captured tunneling resonance. The degeneracy of the two central electronic end states (ESs) occurs in a slowly decaying regime with N converging toward zero for N = 6 long 7-13-aGNR (12 bonded anthracenes), while it is N = 2 (4 bonded anthracenes) for seven carbon atoms wide armchair GNRs (7-aGNRs). The two end dI/dV conductance maxima of ESs are also shifted away from strictly two ends of the 7-13-aGNR compared to the 7-aGNR. Using the quantum topology graph filiation between finite length polyacetylene and 7-13-aGNRs wires, we show that this slow decay of 7-13-aGNR ESs is coming from the property of the topological Hückel band matrix that expels the ESs into its eigenvalue spectrum gaps to keep harmony in the core spectrum.

Needs assessment for creation of a platform trial network in metabolic-dysfunction associated steatohepatitis.

BACKGROUND: The EU Patient-cEntric clinicAl tRial pLatforms (EU-PEARL) project (IMI2-853966) aimed to develop tools to establish integrated research platforms (IRP) for conducting adaptive-design trials in various diseases, including metabolic-dysfunction associated steatohepatitis (MASH). One essential component of a successful MASH IRP is a robust and reliable Clinical Research Network (CRN). Herein, we outline the required elements and anticipated steps to set-up such a CRN. METHODS: We identified European clinical research sites that could potentially serve as the foundation for MASH IRP and a CRN. A survey was sent to sites to assess their interest in joining a CRN, their familiarity with platform trials, and their capacity to participate in a future MASH IRP. RESULTS: A total of 141 investigators were invited to participate in the survey, and 40% responded. More than half of the answers (52%) identify MASH with advanced fibrosis (F3-4) as the subpopulation with the greatest unmet need. Regarding the difficulty in identifying candidates for trials, 65% find it is moderately difficult and 30% very difficult. Most respondents (94%) believe that a platform trial could offer substantial benefits to patients. Nearly all researchers express interest in participating in a platform trial (78%), with 22% indicating their interest would be contingent on initial industry funding. CONCLUSION: While preliminary, our findings on responding sites are encouraging for the potential establishment of a CRN for a MASH IRP. However, funding schemes and sustainability strategies to provide proof-of-platform in MASH seem key in the short-term scenario.

Metabolic dysfunction-associated steatohepatitis (MASH) occurs when the liver becomes damaged due to the build up of fat, which is often related to obesity and diabetes. There is a lack of effective drug treatments for MASH, so strategies to strengthen clinical research in this area are needed. Here, we survey key European experts on MASH to assess their interest in joining a network of MASH researchers and their interest in participating in a new type of clinical trial called a platform trial, where multiple drugs can be tested simultaneously. Researchers largely agree that these are promising approaches to boost drug development in the field, although have concerns regarding funding and sustainability strategies. Our findings may inform the creation of a network of MASH researchers capable of running a platform trial, which in turn may speed up research into treatments for MASH.

Metabolic-associated fatty liver voxel-based quantification on CT images using a contrast adapted automatic tool.

BACKGROUND & AIMS: Metabolic-dysfunction associated fatty liver disease (MAFLD) is highly prevalent and can lead to liver complications and comorbidities, with non-invasive tests such as vibration-controlled transient elastography (VCTE) and invasive liver biopsies being used for diagnosis The aim of the present study was to develop a new fully automatized method for quantifying the percentage of fat in the liver based on a voxel analysis on computed tomography (CT) images to solve previously unconcluded diagnostic deficiencies either in contrast (CE) or non-contrast enhanced (NCE) assessments. METHODS: Liver and spleen were segmented using nn-UNet on CE- and NCE-CT images. Radiodensity values were obtained for both organs for defining the key benchmarks for fatty liver assessment: liver mean, liver-to-spleen ratio, liver-spleen difference, and their average. VCTE was used for validation. A classification task method was developed for detection of suitable patients to fulfill maximum reproducibility across cohorts and highlight subjects with other potential radiodensity-related diseases. RESULTS: Best accuracy was attained using the average of all proposed benchmarks being the liver-to-spleen ratio highly useful for CE and the liver-to-spleen difference for NCE. The proposed whole-organ automatic segmentation displayed superior potential when compared to the typically used manual region-of-interest drawing as it allows to accurately obtain the percent of fat in liver, among other improvements. Atypical patients were successfully stratified through a function based on biochemical data. CONCLUSIONS: The developed method tackles the current drawbacks including biopsy invasiveness, and CT-related weaknesses such as lack of automaticity, dependency on contrast agent, no quantification of the percentage of fat in liver, and limited information on region-to-organ affectation. We propose this tool as an alternative for individualized MAFLD evaluation by an early detection of abnormal CT patterns based in radiodensity whilst abording detection of non-suitable patients to avoid unnecessary exposure to CT radiation. Furthermore, this work presents a surrogate aid for assessing fatty liver at a primary assessment of MAFLD using elastography data.

Fibroblast growth factor 21 is a hepatokine involved in MASLD progression.

AIM: We aimed to assess the role of FGF21 in metabolic dysfunction-associated steatotic liver disease (MASLD) at a multi-scale level. METHODS: We used human MASLD pathology samples for FGF21 gene expression analyses (qPCR and RNAseq), serum to measure circulating FGF21 levels and DNA for genotyping the FGF21 rs838133 variant in both estimation and validation cohorts. A hepatocyte-derived cell line was exposed to free fatty acids at different timepoints. Finally, C57BL/6J mice were fed a high-fat and choline-deficient diet (CDA-HFD) for 16 weeks to assess hepatic FGF21 protein expression and FGF21 levels by ELISA. RESULTS: A significant upregulation in FGF21 mRNA expression was observed in the liver analysed by both qPCR (fold change 5.32 ± 5.25 vs. 0.59 ± 0.66; p = 0.017) and RNA-Seq (3.5 fold; FDR: 0.006; p < 0.0001) in MASLD patients vs. controls. Circulating levels of FGF21 were increased in patients with steatohepatitis vs. bland steatosis (386.6 ± 328.9 vs. 297.9 ± 231.5 pg/mL; p = 0.009). Besides, sex, age, A-allele from FGF21, GG genotype from PNPLA3, ALT, type 2 diabetes mellitus and BMI were independently associated with MASH and significant fibrosis in both estimation and validation cohorts. In vitro exposure of Huh7.5 cells to high concentrations of free fatty acids (FFAs) resulted in overexpression of FGF21 (p < 0.001). Finally, Circulating FGF21 levels and hepatic FGF21 expression were found to be significantly increased (p < 0.001) in animals under CDA-HFD. CONCLUSIONS: Hepatic and circulating FGF21 expression was increased in MASH patients, in Huh7.5 cells under FFAs and in CDA-HFD animals. The A-allele from the rs838133 variant was also associated with an increased risk of steatohepatitis and significant and advanced fibrosis in MASLD patients.

Morbilidad metabólica en la población penitenciaria de Cataluña / Metabolic morbidity in the prison population of Catalonia, Spain

Objetivo: Investigar la prevalencia de la morbilidad metabólica (MM) en población penitenciaria. Diseño: Estudio observacional, transversal y multicéntrico. Emplazamiento: Los 9 centros penitenciarios de Cataluña. Participantes: Reclusos que no están en «régimen abierto» y, por consiguiente, dependen sanitariamente de los equipos de atención primaria penitenciaria (EAPP). Intervenciones: Se consideraron internos con MM los que presentaban al menos un componente del síndrome metabólico: obesidad, hipertensión arterial, diabetes tipo2 y/o dislipidemia. Se estudiaron variables antropométricas, antecedentes clínicos y parámetros analíticos asociados a la MM. Fuente de información: Sistema de Información de los Servicios de Atención Primaria de Cataluña (SISAP). Mediciones principales: Cálculo de prevalencia de la MM, total y por categorías. Para estudiar variables asociadas se realizó un análisis de regresión logística multivariante, calculándose la odds ratio ajustada (ORA) con intervalo de confianza del 95%. Resultados: Un total de 4.338 internos estudiados: el 93,9% hombres, edad media 38,4años, 51,7% de la Unión Europea y 6,7% (8,2% de los analizados) infectados por VIH. Presentaron más MM los de más edad y las personas infectadas por VIH y menos los europeos de países no miembros de la Unión Europea, los del Magreb y los del África subsahariana. Conclusiones: La prevalencia de MM es alta en presos, aun siendo una población joven, especialmente en reclusos de mayor edad y en infectados por VIH. La prevalencia varía mucho según el origen geográfico. Es conveniente que la MM sea detectada precozmente para evitar complicaciones. La prevención, la detección y el manejo terapéutico deben ser actividades prioritarias de la atención primaria penitenciaria.(AU)

Objective: To investigate the prevalence of metabolic morbidity (MM) amongst prison inmates. Design: Multicentric, cross-sectional observational study. Setting: All (nine) prisons in Catalonia. Participants: Convicted inmates that are not in an «open regime», whose healthcare relies on the Prison Primary Care Teams. Interventions: MM was defined as the presence of at least one component of the metabolic syndrome, i.e., obesity, arterial hypertension, type2 diabetes, and/or dyslipidemia. The variables collected included anthropometric measurements, medical history and laboratory values related to MM. The source of information was the Catalan Primary Healthcare Services Information System (SISAP). Main measurements: The prevalence of MM, overall and by several participant subcategories, was calculated. To investigate the risk factors associated to a higher prevalence of MM, a multivariable logistic regression analysis was carried out and expressed as adjusted odds ratios and 95% confidence intervals. Results: 4338 inmates were studied, of whom 93.9% were male. Mean age was 38.4years, 51.7% were born in European Union countries, and 6.7% were infected by HIV. The variables associated with a significantly increased risk of presenting MM were older age and HIV infection, whereas certain geographical origins (i.e., non-UE European countries, Maghreb and Sub-Saharan Africa) were associated with lower risk of MM. Conclusions: In spite of being an overall young population, prison inmates present high rates of MM. Older age, HIV infection and geographic origin appear as the most strongly associated factors with MM in the prison population. MM should be detected early in order to prevent complications. Prevention, screening and treatment of MM ought to be considered a priority in the clinical routine of prison healthcare professionals.(AU)

Guía de observación para el examen práctico parcial de los Sistemas Respiratorio y Cardiovascular en Introducción a la Clínica / Observation guide for the partial practical exam of the Respiratory and Cardiovascular Systems in Introduction to the Clinic

RESUMEN Fundamento: el examen práctico constituye el momento en que se comprueba la adquisición de habilidades para la comunicación, realización del examen físico a los individuos sanos, así como la transcripción de los hallazgos. Las dificultades que han existido en el desarrollo de esta actividad y la ausencia de homogeneidad en su aplicación, unido al elevado número de evaluaciones excelentes al aplicarlo, hace necesario establecer una guía para su ejecución. Objetivo: diseñar una guía de observación para el examen práctico parcial de los Sistemas Respiratorio y Cardiovascular en Introducción a la Clínica. Métodos: se realizó trabajo investigativo de tipo exploratorio, descriptivo y transversal utilizando el método de análisis documental partiendo de la revisión de los siguientes documentos: Resolución 02/2018, Programa de la asignatura Introducción a la Clínica, el Programa de la Disciplina Principal integradora y el método de observación científica participativa. Resultados: la guía de observación consta de tres bloques, el primero de comunicación, el segundo ejecución del examen físico y el tercero de transcripción, que se evalúan y califican de forma independiente. Se propone y explica la forma de evaluar cada bloque y la metodología a seguir. Conclusiones: la guía propuesta permitirá elevar la calidad y el rigor, así como una mayor preparación de los estudiantes para efectuar el examen físico de los Sistemas Respiratorio y Cardiovascular. Su utilización constituye un elemento clave en la evaluación parcial de la asignatura.

ABSTRACT Background: the practical examination constitutes the moment in which the acquisition of communication skills, the physical examination of healthy individuals, as well as the transcription of the findings is verified. The difficulties that have existed in the development of this activity and the lack of homogeneity in its application, together with the high number of excellent evaluations when applying it, make it necessary to establish a guide for its execution. Objective: to design an observation guide for the partial practical exam of the Respiratory and Cardiovascular Systems in Introduction to the Clinic. Methods: exploratory, descriptive and cross-sectional research work was carried out using the method of documentary analysis based on the following documents review: Resolution 02/2018, Program of the subject Introduction to the Clinic, the Integrative Main Discipline Program and the method of participatory scientific observation. Results: the observation guide consists of three blocks, the first of communication, the second execution of the physical examination and the third transcription, which are evaluated and scored independently. The way to evaluate each block and the methodology to be followed is proposed and explained. Conclusions: the proposed guide will allow raising the quality and rigor, as well as a greater preparation of the students to carry out the physical examination of the Respiratory and Cardiovascular Systems. Its use constitutes a key element in the partial evaluation of the subject.

Comorbilidad metabólica, el nuevo enemigo. Síndrome y esteatohepatitis metabólica / Metabolic comorbidity, the new enemy. Metabolic syndrome and steatohepatitis

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Consideraciones actuales sobre la tutoría en el posgrado de Medicina Familiar / Considerations about tutoring in the postgraduate course of Family Medicine

RESUMEN La función tutorial es parte integrante de la práctica docente y factor de calidad de la educación en el posgrado. Esta revisión se propone caracterizar la labor del tutor y la tutoría como elementos claves para la formación de un especialista competente en el posgrado de Medicina Familiar y Comunitaria. Para ello, se revisaron los aspectos más actuales de la tutoría en servicio, así como las funciones del tutor, lo que permitió constatar que aún es largo el trecho a recorrer para lograr una correcta tutoría en servicio que permita una formación integral de los posgradistas. Se pudo concluir que los tutores de medicina familiar no han sido suficientemente preparados para ejercer su profesión como docentes, por lo que se precisa una formación específica en esta área que, además, es una necesidad sentida por los tutores y expresada en multitud de reuniones en que han participado.

ABSTRACT The tutorial function is an integrating part of the teaching practice and quality factor of postgraduate education. This review aims at characterizing the tutor´s and mentoring work as key elements for training competent specialists in the postgraduate course in Family and Community Medicine. For this, the most current aspects of in-service tutoring were reviewed, as well as the tutor's functions, which allowed authors to confirm that the distance to be followed is still long to achieve a correct in-service tutoring that allows a comprehensive training of postgraduates. It was concluded that family medicine tutors have not been sufficiently prepared to practice their profession as professors, so specific training is needed in this area, which is also a need felt by tutors and expressed in many meetings they have participated in.

Prediction of clinical events by liver stiffness and chronic kidney disease by NAFLD in patients with type-2 diabetes / Predicción de eventos clínicos por elasticidad hepática y enfermedad renal crónica por EHMet en pacientes con diabetes tipo 2

Background & Aims: Non-alcoholic fatty liver disease (NAFLD) is associated with poorer glycemic control and a higher risk of type-2 diabetes (T2D) complications, extrahepatic and cardiovascular disease (CVD). Our study aim was to evaluate the association between NAFLD, T2D complications, and the development of overall clinical events (OCE) (CV, liver-related, and mortality) in patients with T2D. Methods: Prospective single-center study comprising T2D subjects with no history of CVD and non-T2D matched controls. Patients were selected from the Outpatient Diabetes Clinic of Vall d’Hebron Hospital and related primary care centers. Results: 186 diabetics and 57 controls were included. Amongst T2D, 124/186 subjects had NAFLD (66.6%). T2D-NAFLD subjects showed a heavier metabolic burden and higher median liver stiffness (5.6kPa [4.5–7.3] vs 4.8 [4.2–5.8]; p=0.004) compared to non-NAFLD diabetics. During a median follow-up of 5.6 years, 33 (17.7%) T2D patients developed OCE vs 4 (7.0%) controls (p=0.049). No differences were found for OCE between NAFLD and non-NAFLD diabetics (16.9% vs 19.4%; p=0.68). CV was the most reported outcome and only one liver event occurred. NAFLD diabetics showed more often chronic kidney disease (CKD), whereas T2D complications and subclinical CVD rates were similar. A higher liver stiffness, older age, and male gender were independently associated with OCE amongst the entire T2D population and NAFLD diabetics. Conclusions: NAFLD and liver stiffness were associated with CKD and clinical outcomes in diabetics, respectively. A hepatic evaluation is recommended to identify high-risk T2D patients that would benefit from early referral to specialized care. (AU)

Antecedentes y objetivos: La esteatosis hepática metabólica (EHMet) se asocia con un peor control glucémico y un mayor riesgo de complicaciones de la diabetes tipo 2 (DM2), enfermedad extrahepática y cardiovascular (CV). El objetivo fue evaluar la asociación entre EHMet, complicaciones microvasculares y el desarrollo de eventos clínicos globales (ECG) (CV, hepáticos y mortalidad) en diabéticos. Métodos: Estudio unicéntrico prospectivo que incluye diabéticos sin historia de CV y controles sin DM2. Se seleccionaron pacientes de la consulta de Diabetes del Hospital Vall d’Hebron y centros de atención primaria asociados. Resultados: Se incluyeron 186 diabéticos y 57 controles. Entre los diabéticos, 124/186 presentaron EHMet (66,6%). Los pacientes DM2 con EHMet presentaron mayor carga metabólica y una elasticidad hepática superior (5,6kPa [4,5-7,3] vs. 4,8 [4,2-5,8]; p=0,004) a los diabéticos sin EHMet. Durante una mediana de seguimiento de 5,6 años, 33 (17,7%) diabéticos desarrollaron ECG vs. 4 (7,0%) controles (p=0,049). No hubo diferencias en ECG entre diabéticos con y sin EHMet (16,9% vs. 19,4%; p=0,68). El evento más reportado fue CV y solamente se produjo un evento hepático. La enfermedad renal crónica (ERC) fue más frecuente en diabéticos con EHMet, mientras que los ratios de complicaciones microvasculares y enfermedad CV silente fueron similares. El género masculino, una mayor edad y elasticidad hepática se asociaron de forma independiente a ECG para el total de diabéticos y para aquellos con EHMet. Conclusiones: La EHMet y la elasticidad hepática se asociaron a ERC y eventos clínicos en diabéticos. Se recomienda una evaluación hepática para identificar pacientes diabéticos de riesgo que se beneficiarían de una derivación precoz al especialista. (AU)

Anemia microcítica secundaria a úlcera anastomótica ileocólica / Microcytic anemia due to ileocolic anastomotic ulcer

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Poliomielitis paralítica. Nuevos problemas: el síndrome postpolio / Polio paralytic. New Problems: postpolio syndrome

En 1875 M Raymond describió la aparición de una atrofia y debilidad muscular progresiva en 3 individuos supervivientes de una poliomielitis aguda en la infancia. Jean-Martin Charcot, sugirió que la lesión inicial debía dejar a las neuronas de estos individuos más sensibles para desarrollar enfermedades medulares posteriores y que la nueva debilidad era consecuencia del sobreuso de los músculos afectos. En 1979, tras la publicación de la descripción realizada por un paciente de 57 años de las dificultades motoras que desarrolló tras el padecimiento de una poliomielitis en la infancia, se produjo un incremento muy importante de comentarios de otros individuos con síntomas similares, llegando a acuñarse en los años 80 el término de síndrome post-polio (SPP). El término se reserva para describir el desarrollo de nuevos síntomas neurológicos, en especial para el desarrollo de una debilidad muscular, atrofia muscular y fatiga muscular nueva que no son explicables por otra causa médica, y que aparecen después de más de 15 años de la infección aguda. Se estima que afecta del 20 al 85% de individuos con antecedentes de poliomielitis en la infancia. En el año 2000 se describieron los primeros criterios diagnósticos. El SPP condiciona una alteración de la capacidad funcional del individuo. Su etiopatogenia es desconocida, pudiendo estar relacionada con el envejecimiento. También podría deberse a un cuadro inflamatorio persistente o estar influenciado por factores genéticos. No existe tratamiento farmacológico eficaz, por lo que sólo se puede recomendar tratamiento sintomático y de entrenamiento muscular moderado (AU)

In 1875 M Raymond described a progressive muscle wasting and weakness in 3 individuals survivors of childhood acute poliomyelitis. Jean-Martin Charcot suggested that the initial injury should let these guys neurons more sensitive to develop posterior spinal diseases and new weakness was the result of overuse of the affected muscles. In 1979, after the publication of the description given by a 57 year old patien on motor difficulties that developed after suffering of polio in childhood, there was a very significant increase of comments of other individuals with similar symptoms, reaching wedged in the 80s the term of post-polio syndrome. The term is reserved for describing the development of new neurological symptoms, especially for the development of muscle weakness, muscle atrophy and new muscle fatigue not explained by other medical causes, and appear after more than 15 years of infection acute. Is estimated to affect 20 to 85% of individuals with a history of polio in childhood. In 2000 first described the diagnostic criteria. This syndrome determines a change in the functional abilities. Its pathogenesis is unknown, may be associated with aging. It could also be due to an inflammatory persistent or be influenced by genetic factors. There is no effective drug treatment, so I can only recommend symptomatic and moderate muscle training (AU)

Folato sérico en población adolescente de la Comunidad de Madrid / Serum folate levels in adolescent population in Madrid, Spain

FUNDAMENTO Y OBJETIVO: Conocer los valores séricos de folato en niños es imprescindible para establecerunos percentiles que permitan realizar comparaciones entre regiones o países, asícomo para plantear la suplementación de la dieta con vitaminas del grupo B y ácido fólicocomo prevención secundaria frente a las enfermedades cardiovasculares. El objetivo de este estudioha sido analizar las concentraciones de folatos en adolescentes de la Comunidad de Madrid.SUJETOS Y MÉTODO: Se ha realizado un estudio epidemiológico descriptivo de tipo transversal conel fin de estimar los valores séricos de folato en la población escolar de 13 a 15 años de la Comunidadde Madrid. Se determinaron las concentraciones de folato y vitamina B12 en las muestrasde sangre de 311 adolescentes (141 niños y 170 niñas) obtenidas en ayunas. Se determinóel genotipo C677T de la enzima metilentetrahidrofolato reductasa (MTHFR) por reacción encadena de la polimerasa.RESULTADOS: Los valores medios de folato obtenidos en nuestro estudio fueron de 7,83 nmol/l(intervalo de confianza del 95%, 7,42-8,23 nmol/l) y la mediana fue de 6,89 nmol/l (recorridointercuartílico: 5,30-9,30 nmol/l).No se encontraron diferencias estadísticamente significativas por sexo, edad o presencia o ausenciade menstruación. La concentración sérica de folato disminuyó significativamente con lamutación del genotipo C677T de la enzima MTHFR. La prevalencia de valores deficitarios defolato (< 5,3 nmol/l) fue del 23,8% y aumentó significativamente con el genotipo C677TMTHFR mutado en homocigosis: un 18,8% para CC; un 20,4% para CT, y un 46,7% para TT.Este aumento se produjo en mayor medida en las mujeres a partir de la primera menstruación.CONCLUSIONES: El genotipo mutado C677T en homocigosis de la enzima MTHFR produce déficitde folato, especialmente en mujeres a partir de la pubertad. Se propone el valor de 5,3 nmol/lcomo posible punto de corte para definir el déficit de folato sérico en la población adolescentede nuestro país

BACKGROUND AND OBJECTIVE: Serum folate concentrations in children are essential to establish valueswhich allow to compare different regions or countries, and raise the possibility of fortifyingdiet with group B vitamins and folic acid as a secondary prevention against cardiovascular diseases.SUBJECTS AND METHOD: A cross-sectional epidemiological study was performed to assess serum folatelevels in school children, aged 13-15 years, in Madrid. Folate and vitamin B12 determinationswere determined in blood samples of fasting children. Genotype C677T of methylentetrahydrofolatereductase (MTHFR) enzyme was determined by polimerase chain reaction.RESULTS: Average folate levels obtained in our study were 7.83 nmol/l (95% confidence interval,7.42 to 8.23 nmol/l). Median was 6.89 nmol/l (interquartilic range: 5.30 to –9.30 nmol/l).No statistically significant differences were found by gender, age or presence of menstruation.Serum folate concentration decreased significantly with the mutation of the C677T genotypefor MTHFR. Prevalence of deficits of folate (< 5.3 nmol/l) was 23.8% and raised significantlywith the mutation of the C677T genotype for MTHFR: 18.8% for CC, 20.4% for CT, and46.7% for TT. This effect was mainly observed in girls after menstruation.CONCLUSIONS: Homozygosis mutation in C677T genotype of the enzyme MTHFR induces lowerfolate levels, mainly in girls after menstruation. 5.3 nmol/l is proposed as a threshold to definedeficient serum folate levels in the Spanish adolescent population

Hospitalización por paludismo en España durante el período 1999-2002 / Burden of hospitalizations attributable to malaria in Spain during 1999-2002

Fundamento y objetivo: Describir las hospitalizaciones atribuibles a paludismo y calcular su tasa de incidencia y los costes directos que generó durante 1999-2002 en España. Material y método: Estudio retrospectivo sobre hospitalizaciones con diagnóstico principal al alta de malaria (códigos 084.0 a 084.9 de la novena edición de la Clasificación Internacional de Enfermedades-Modificación Clínica) recogidas del Conjunto Mínimo Básico de Datos durante 1999-2002. Resultados: Se registraron 2.044 hospitalizaciones por malaria (tasa de incidencia de 1,3 casos por 100.000 habitantes/año). El 20,6% fueron niños menores de 15 años. Además, se encontró una tendencia lineal ascendente significativa en la incidencia en los niños de 0-4 años (p<0,001). El 57,3% de los casos se debieron a Plasmodium falciparum, el 11,5% a P. vivax, el 2,4% a P. malariae y el 3,3% a P. ovale. El 64% de los ingresos tuvo lugar entre verano y otoño, patrón estacional atribuido a la especie P. falciparum. El coste anual fue de 1,2 millones de euros. Conclusiones: El paludismo ocasiona un número creciente de hospitalizaciones en España, situación que puede incrementarse debido al aumento de viajes a zonas endémicas

Background and objective: To calculate the incidence rates and direct costs, and to describe hospital admissions for malaria in Spain between 1999 and 2002. Material and method: Retrospective study of hospital admissions whose fundamental discharge diagnosis was malaria (codes CIE-9 from 084.0 to 084.9), using the national surveillance system for hospital data (CMBD) between 1999 and 2002. Results: 2,044 hospitalizations for malaria were recorded in Spain (incidence rate 1.3 cases per 100,000 inhabitants/year). 20.6% were children under the age of 15. We found an increasing linear trend in the incidence rate of malaria in the 0-4 age group (p < 0.001). 57.3% of malaria cases were due to Plasmodium falciparum, 11.5% to P. vivax, 2.4% to P. malariae and 3.3% to P. ovale. On the other hand, 64% of admissions occurred between summer and autumn, a seasonal pattern attributable to P. falciparum. The annual cost of the hospitalizations was e 1.2 million. Conclusions: There is an increasing number of hospitalizations in Spain due to malaria, which might be higher in coming years. This fact mainly owes to the population movements we are currently experiencing