Expression of miR-let7b and miR-19b in progressive familial intrahepatic cholestasis (PFIC) children / Expresión de miR-let7b y miR-19b en niños con colestasis intrahepática familiar progresiva (PFIC)

Background MicroRNAs (miRNAs) are a group of small non-coding RNAs that bind to the target mRNA and regulate gene expression. Recently circulating microRNAs were investigated as markers of diseases and therapeutic targets. Although various studies analyze the miRNA expression in liver disease, these studies on PFIC are few. Progressive familial intrahepatic cholestasis (PFIC) is a rare liver disease with autosomal recessive inheritance. Most children with PFIC progress to cirrhosis and liver failure and consequently need to have a liver transplant. The aim of this study is the investigation of the miR-19b and miR-let7b expression levels in Iranian PFIC children. Methods 25 PFIC patients, 25 healthy children and 25 Biliary Atresia patients were considered as case and two control groups respectively. Blood samples were obtained and Liver function tests (LFTs) were measured. After RNA extraction and cDNA synthesis, quantitative PCR was performed using specific primers for miR-19b and miR-let7b. The U6 gene is used as an internal control. Results qPCR on PFIC patients’ samples demonstrated that the miR-19b and the miR-let7b expression were significantly decreased in patients compared to the control groups, with a p-value<0.0001 and p-value=0.0006 receptively. Conclusion In conclusion, circulating micro-RNA like miR-19b and miR-let7b have a potential opportunity to be a non-invasive diagnostic marker or therapeutic target for PFIC in the future (AU)

Antecedentes Los microRNA (miRNA) son un grupo de pequeños RNA no codificantes que se unen al ARNm diana y regulan la expresión génica. Recientemente se han investigado los microRNA circulantes como marcadores de enfermedades y dianas terapéuticas. Aunque varios estudios analizan la expresión de miRNA en enfermedades hepáticas, estos estudios sobre PFIC son escasos. La colestasis intrahepática familiar progresiva (PFIC) es una enfermedad hepática rara con herencia autosómica recesiva. La mayoría de los niños con PFIC progresan a cirrosis e insuficiencia hepática y, en consecuencia, requieren de un trasplante de hígado. El objetivo de este trabajo es la investigación de los niveles de expresión de miR-19b y miR-17b en niños iraníes con PFIC. Métodos Se consideraron 25 pacientes con PFIC, 25 niños sanos y 25 pacientes con atresia biliar como grupos de casos y controles. Se obtuvieron muestras de sangre y se midieron las pruebas de función hepática (LFT). Después de la extracción de RNA y la síntesis de cDNA, se realizó PCR cuantitativa usando cebadores específicos para miR-19b y miR-17b. El gen U6 se utiliza como control interno. Resultados La qPCR en muestras de pacientes con PFIC demostró que la expresión de miR-19b y miR-17b disminuyó significativamente en los pacientes en comparación con dos grupos de control, con un valor de p<0,0001 y un valor de p=0,0006, receptivamente. Conclusión En conclusión, los micro-RNA circulantes, como miR-19b y miR-let7b, tienen una oportunidad potencial de ser un marcador de diagnóstico no invasivo o un objetivo terapéutico para PFIC en el futuro (AU)

Uso de la resonancia magnetica con primovist® (gadotrexate disodio) para diagnóstico de lesiones renales benignas y malignas / Use of magnetic resonance imaging with primovist® (gadoterate disodium) for the diagnosis of benign and malignant renal lesions

Objetiv: Evaluar la calidad de lasimágenes contrastadas del tracto urinario que permitandiagnosticar patologías benignas, malignas y malformaciones con el uso de una resonancia magnética contrastada con Primovist® (gadoxetato disodio).Material y métodos: Se realizó una revisión de lasimágenes y diagnósticos del servicio de radiología demanera retrospectiva de pacientes con una resonanciamagnética contrastada con Primovist® por padecerinsuficiencia hepática sin aparente patología urinaria,con el objeto de buscar diagnósticos incidentales en eltracto urinario superior e inferior. Resultados: Se revisaron durante el periodo de juliodel 2014 a noviembre del 2018, 117 estudios, se excluyeron 5 por no contar con el estudio completo parasu revaloración. La edad promedio fue de 59,6±16,6años. Se encontraron 48 anormalidades urinarias sinprevia sospecha diagnóstica por lo que fueron considerados como incidentales. A continuación se enumeranlos hallazgos renales diagnosticados: 36 quistes simples, 6 cambios perirenales compatibles con secuelasde pielonefritis, 1 cáncer renal, 1 hipotrofia renal, 1angulación funcional del uréter proximal sin cruce vascular con pelvis extrarenal contralateral, 1 hidronefrosisbilateral secundaria a obstrucción vesical por hiperplasia prostática y 1 quiste complejo. Ningún estudio se indicó por sospecha de anormalidades del tracto urinarioConclusiones: Aun cuando no era la indicacióndel estudio de resonancia, fue posible encontrar algunas patologías renales como hallazgos que incluyeronpatología benigna, maligna y malformaciones, demostrando que la resonancia magnética con Primovist® sepodría realizar como estudio contrastado para patologías renales.(AU)

Objetive: To evaluate the quality of thecontrast images obtained with a Primovist® (gadoxetatedisodium) Magnetic Resonance Image in order to diagnose benign, malignant and malformations in the urinarytract. Material and methods: A retrospective image anddiagnosis review of Primovist® MRI studies performed inliver insufficient patients without apparent renal abnormalities was done, in order to evaluate the urinary tractfor irregularities.Results: A total of 117 Primovist® MRI studies performed between july 2014 and November 2018 werereviewed, 5 were excluded because they were incomplete. The average age was 59.6 ± 16.6 years old.The following diagnosis were encountered: 36 simplecysts, 6 perirenal fibrosis after pyelonephritis, 1 renalcancer, 1 renal atrophy, 1 proximal uretheric flexure, 1bilateral hydronephrosis due to lower urinary obstructionbecause of benign prostatic hyperplasia and 1 complexcyst. No MRI study was indicated with suspicions ofrenal abnormalities. Relevant images are included thatdemonstrate the capability of Primovist® MRI to diagnose renal abnormalities.Conclusion: Even though none of the Primovist®MRI studies was done with suspicious of renal abnormalities it was possible to diagnose incidental benign,malignant and malformations of the urinary tract. Thisstudy shows how Primovist® MRI can be useful contraststudy for urinary tract irregularities.(AU)

Insuficiencia hepática secundaria a amiloidosis primaria de cadenas ligeras Kappa: un caso poco frecuente de presentación de mieloma múltiple / No disponible

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Algoritmo de reversión para los pacientes anticoagulados con dabigatrán en cirugía urgente / Reversion algorithm for patients anticoagulated with dabigatran in urgent surgery

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ALPPS torniquete complicado con giro de la vena suprahepática izquierda. Nuevas complicaciones en nuevas hepatectomías / ALPPS tourniquet complicated with twisting of the left hepatic vein. New complications in new hepatectomies

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Hipertensión portal secundaria a hemangiomatosis hepática múltiple / Portal hypertension secondary to multiple hepatic hemangiomatosis

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Trasplante hepatorrenal simultáneo en pacientes adultos con hiperoxaluria primaria. Experiencia del Hospital Universitario 12 de Octubre / Liver-kidney simultaneous transplantation in adult patients with primary hyperoxaluria. Experience at Hospital Universitario 12 de Octubre

La hiperoxaluria primaria es un trastorno del metabolismo autosómico recesivo que origina una hiperproducción hepática de oxalato, que no puede ser metabolizado por el hígado y se elimina por vía renal formando litiasis, nefrocalcinosis y ocasionando un deterioro progresivo y precoz de la función renal que, generalmente, a pesar del tratamiento médico precisará de una terapia renal sustitutiva. La hiperoxaluria primaria (HOP) tipo 1 es el trastorno más frecuente, se debe a un déficit de la enzima alanina-glicolato aminotransferasa que se encuentra en los peroxisomas hepáticos. Por tanto, el trasplante hepatorrenal simultáneo (THRS) es el tratamiento definitivo para los pacientes con enfermedad renal crónica terminal. Sin embargo, algunos resultados sugieren que la morbimortalidad es mayor al realizar este procedimiento frente al trasplante renal aislado. Se presentan cinco pacientes adultos con hiperoxaluria primaria y un filtrado glomerular medio de 20,2 ± 1,3 ml/min/1,73 m2 a los que se les realizó un THRS entre 1999 y 2015 en el Hospital Universitario 12 de Octubre. No se observó recurrencia de la enfermedad ni pérdida del injerto hepático o renal durante el postoperatorio y únicamente un episodio de rechazo agudo tardío sin pérdida del injerto renal. La supervivencia de los receptores fue del 100% con una mediana de seguimiento de 84 meses. Debido a que el THRS permite la curación de la enfermedad y constituye una técnica segura, con una baja morbimortalidad y elevada supervivencia, debe considerarse como el tratamiento de elección en la hiperoxaluria primaria con enfermedad renal terminal (AU)

Primary hyperoxaluria (PH) is a metabolic liver disease with an autosomal recessive inheritance that results in oxalate overproduction that cannot be metabolized by the liver. Urinary excretion of oxalate results in lithiasis and nephrocalcinosis leading to a progressive loss of renal function that often requires renal replacement therapy despite medical treatment. Type 1 PH is the most common form and is due to a deficiency in the alanine-glycolate aminotransferase enzyme found in hepatic peroxisomes. Therefore, a liver-kidney simultaneous transplant (LKST) is the definitive treatment for end-stage renal disease (ESRD) patients. However, some studies suggest that the morbidity and mortality rates are greater when this procedure is performed instead of only a kidney transplant (IKT). Herein, we report five patients with PH and a mean glomerular filtration rate of 20.2 ± 1.3 ml/min/1.73 m2 who received a LKST between 1999 and 2015 at the Hospital Universitario 12 de Octubre. Recurrence and liver or kidney graft loss was not observed during the postoperative period and only one case of late acute rejection without graft loss was diagnosed. The recipient survival rate was 100% with a median follow up of 84 months. As LKST is a curative and safe procedure with a low mortality and high survival rate, it must be considered as the treatment of choice in adults with HP and ESRD (AU)

Methylation status of the estrogen receptor 1 promoter predicts poor prognosis of acute-on-chronic hepatitis B liver failure

Background: Acute-on-chronic hepatitis B liver failure (ACHBLF) is an acute deteriorating liver disease and rapidly progresses to multiple organ failure. There is currently no adequate accurate predictive models of ACHBLF prognosis. Aims: To identify the methylation frequency of the estrogen receptor 1 (ESR1) promoter in ACHBLF and analyze the associated prognostic significance. Methods: Methylation-specific PCR (MSP) was used to determine the methylation frequency of the ESR1 promoter in peripheral blood mononuclear cells from a training and validation cohort of patients. The training cohort included 113 patients with ACHBLF, 73 with chronic hepatitis B (CHB) and 40 healthy controls (HCs). The validation cohort consisted of 37 patients with ACHBLF. Another 18 patients with pre-ACHBLF who progressed to ACHBLF were used to dynamically evaluate ESR1 promoter methylation changes associated with a severe clinical condition. Results: Death from ACHBLF was associated with hyperbilirubinemia, a higher score in the model for end-stage liver disease (MELD), a higher incidence of hepatic encephalopathy (HE) and an increased frequency of ESR1 promoter methylation during the 28 day follow-up. HE, MELD score and ESR1 promoter methylation were the independent risk factors associated with 28-day mortality from ACHBLF. The frequency of ESR1 promoter methylation was significantly higher than in patients with CHB and HCs. Albumin and the MELD score were significantly associated with ESR1 promoter methylation. Moreover, ESR1 promoter methylation frequency increased with ACHBLF progression. More importantly, ESR1 promoter methylation was an independent risk factor and had a high value to predict 28-day mortality from ACHBLF. Conclusions: Abnormal ESR1 methylation could be a prognostic biomarker for ACHBLF (AU)

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Importancia de la biopsia hepática transyugular en el fallo hepático agudo en ancianos / Relevance of transjugular liver biopsy in acute liver failure in the elderly

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Acute-on-chronic liver failure: a time to step forward

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CLIF-C ACLF score is a better mortality predictor than MELD, MELD-Na and CTP in patients with acute on chronic liver failure admitted to the ward

Background and aims: Acute-on-chronic liver failure (ACLF) is a frequent syndrome associated with high mortality. The aims of the present study are: a) comparing the Chronic Liver Failure Consortium (CLIF-C) ACLF Model for End-Stage Liver Disease (MELD), MELD Sodium (MELD-Na) and Child-Turcotte- Pugh (CTP) scores for prediction of short/medium term mortality; b) identifying ACLF prevalence in patients admitted to the ward; and c) comparing mortality between non-ACLF/ACLF. Methods: Retrospective cohort study of 177 patients admitted to the Gastroenterology ward for acute decompensation of cirrhosis. Results: We included 132 males. Alcohol was the cirrhosis cause/co-factor in 79.7% of cases. Infection was present in 40.7%. At admission, 19.8% of patients presented ACLF and 7.9% developed it during hospitalization (overall prevalence was 27.7%). ACLF grade 1 was diagnosed in 55.1% of the ACLF patients; grade 2, in 42.8%, and grade 3, in 2.0%. Infection (p < 0.001) and hepatic encephalopathy (p = 0.004) were more prevalent and C-reactive protein and leukocyte counts were higher in ACLF patients. ACLF 28 and 90-day mortality was 45.8% and 60.4%, respectively. The CLIF-C ACLF score was significantly superior to CTP, MELD, MELD-Na in predicting 28-day (AUROC 0.799 ± 0.078, 95% CI 0.637-0.891) and 90-day mortality (AUROC 0.828 ± 0.063, 95% CI 0.705-0.952). Conclusion: ACLF is highly prevalent in the ward. The new CLIF scores identify high mortality cirrhotic patients admitted to the ward and are better than their predecessors to predict ACLF patients’ short/medium term mortality (AU)

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Contribution of inducible and neuronal nitric oxide synthases to mitochondrial damage and melatonin rescue in LPS-treated mice

NOS isoform activation is related to liver failure during sepsis, but the mechanisms driving mitochondrial impairment remain unclear. We induced sepsis by LPS administration to inducible nitric oxide synthase (iNOS-/-) and neuronal nitric oxide synthase (nNOS-/-) mice and their respective wild-type controls to examine the contribution of iNOS to mitochondrial failure in the absence of nNOS. To achieve this goal, the determination of messenger RNA (mRNA) expression and protein content of iNOS in cytosol and mitochondria, the mitochondrial respiratory complex content, and the levels of nitrosative and oxidative stress (by measuring 3-nitrotyrosine residues and carbonyl groups, respectively) were examined in the liver of control and septic mice. We detected strongly elevated iNOS mRNA expression and protein levels in liver cytosol and mitochondria of septic mice, which were related to enhanced oxidative and nitrosative stress, and with fewer changes in respiratory complexes. The absence of the iNOS, but not nNOS, gene absolutely prevented mitochondrial impairment during sepsis. Moreover, the nNOS gene did not modify the expression and the effects of iNOS here shown. Melatonin administration counteracted iNOS activation and mitochondrial damage and enhanced the expression of the respiratory complexes above the control values. These effects were unrelated to the presence or absence of nNOS. iNOS is a main target to prevent liver mitochondrial impairment during sepsis, and melatonin represents an efficient antagonist of these iNOS-dependent effects whereas it may boost mitochondrial respiration to enhance liver survival (AU)

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Comparison of the prognostic value of Chronic Liver Failure Consortium scores and traditional models for predicting mortality in patients with cirrhosis / Comparación del valor pronóstico de los modelos del Chronic Liver Failure Consortium y modelos tradicionales para predecir la mortalidad en pacientes con cirrosis

BACKGROUND AND AIM: Recently, the European Association for the Study of the Liver - Chronic Liver Failure (CLIF) Consortium defined two new prognostic scores, according to the presence or absence of acute-on-chronic liver failure (ACLF): the CLIF Consortium ACLF score (CLIF-C ACLFs) and the CLIF-C Acute Decompensation score (CLIF-C ADs). We sought to compare their accuracy in predicting 30- and 90-day mortality with some of the existing models: Child-Turcotte-Pugh (CTP), Model for End-Stage Liver Disease (MELD), MELD-Na, integrated MELD (iMELD), MELD to serum sodium ratio index (MESO), Refit MELD and Refit MELD-Na. METHODS: Retrospective cohort study that evaluated all admissions due to decompensated cirrhosis in 2 centers between 2011 and 2014. At admission each score was assessed, and the discrimination ability was compared by measuring the area under the ROC curve (AUROC). RESULTS: A total of 779 hospitalizations were evaluated. Two hundred and twenty-two patients met criteria for ACLF (25.9%). The 30- and 90-day mortality were respectively 17.7 and 37.3%. CLIF-C ACLFs presented an AUROC for predicting 30- and 90-day mortality of 0.684 (95% CI: 0.599-0.770) and 0.666 (95% CI: 0.588-0.744) respectively. No statistically significant differences were found when compared to traditional models. For patients without ACLF, CLIF-C ADs had an AUROC for predicting 30- and 90-day mortality of 0.689 (95% CI: 0.614-0.763) and 0.672 (95% CI: 0.624-0.720) respectively. When compared to other scores, it was only statistically superior to MELD for predicting 30-day mortality (p = 0.0296). CONCLUSIONS: The new CLIF-C scores were not statistically superior to the traditional models, with the exception of CLIF-C ADs for predicting 30-day mortality

ANTECEDENTES Y OBJETIVOS: Recientemente The European Association for the Study of the Liver-Chronic Liver Failure Consortium estableció 2 nuevos sistemas pronósticos considerando la existencia o no de Acute-on-chronic liver failure (ACLF): el score CLIF Consortium ACLF (CLIF-C ACLF) y el CLIF-C Acute Descompensation score (CLIF-C ADs). Pretendimos comparar su fiabilidad para predecir la mortalidad a los 30 y 90 días con la de algunos de los sistemas de puntuación existentes: Child-Turcotte-Pugh, Model for End-Stage Liver Disease (MELD), MELD-Na, integrated MELD, MELD to serum sodium ratio index, Refit MELD y Refit MELD-Na. MÉTODOS: Estudio retrospectivo de cohortes incluyendo todos los pacientes con cirrosis ingresados en 2 centros entre 2011 y 2014 por descompensación de su enfermedad. En el momento de la admisión cada puntación fue calculada y fueron comparadas las áreas bajo la curva ROC (AUROC) para evaluar su capacidad de discriminación respecto a la mortalidad a los 30 y 90 días. RESULTADOS: Fueron analizadas un total de 779 hospitalizaciones. Doscientos y veintidós pacientes cumplían criterios para ACLF (25,9%). La mortalidad a los 30 y 90 días fue de 17,7% y 37,3% respectivamente. En los pacientes con ACLF el AUROC del CLIF-C ACLF para predecir la mortalidad a los 30 y 90 días fue 0,684 (IC 95%: 0,599-0,770) y 0,666 (IC 95%: 0,588-0,744) respectivamente. No se encontraron diferencias significativas con los modelos tradicionales. En los pacientes sin ACLF, el AUROC del CLIF-C ADs para predecir la mortalidad a los 30 y 90 días fue 0,689 (IC 95%: 0,614-0,763) y 0,672 (IC 95%: 0,624-0,720) respectivamente. Únicamente fue estadísticamente superior al MELD para predecir la mortalidad a los 30 días (p = 0,0296). CONCLUSIONES: Los nuevos modelos CLIF-C no fueron superiores estadísticamente a los modelos tradicionales, con la excepción del CLIF-C ADs en la predicción de la mortalidad a los 30 días

Déficit de vitamina D en la enfermedad hepática crónica, análisis clínico epidemiológico y tras aporte vitamínico / Vitamin D deficiency in chronic liver disease, clinical-epidemiological analysis and report after vitamin d supplementation

INTRODUCCIÓN: La vitamina D (VD) participa en multitud de funciones extraesqueléticas en el organismo y cada vez es más importante su relación con las enfermedades hepáticas crónicas (EHC). OBJETIVOS: Analizar la prevalencia de déficit o insuficiencia de VD en los pacientes con EHC de nuestra área. Evaluar si el aporte de VD influye en la concentración sérica y se asocia a mejoría de la función hepática. MATERIAL Y MÉTODOS: Realizamos un estudio en 2 fases. En el primer tiempo se analizaron características clínico-epidemiológicas de 94 pacientes con EHC; en un segundo tiempo, se administraron diferentes dosis de calcifediol (25-OH-VD) a aquellos pacientes con déficit (<20ng/mL) e insuficiencia (20-30ng/mL) de VD. Se determinaron concentraciones plasmáticas, variables analíticas y de función hepática (Child-Pugh y MELD) al finalizar el tratamiento y se compararon con los datos basales. RESULTADOS: El 87% de los pacientes tenían concentraciones deficitarias o insuficientes de VD, con una media de 18,8ng/mL, siendo menor en los cirróticos (15,9ng/mL) (p = 0,002) y en la etiología por alcohol. Igualmente la concentración sérica de VD era inversamente proporcionales al grado de función hepática: Child A (16,52ng/mL) vs. C (7,75ng/mL). Tras el aporte con VD, se consiguió normalizar los niveles en el 94% de los pacientes, mejorar significativamente la cifra de plaquetas, de albúmina (p < 0,05) y el grado funcional valorado por la escala de Child-Pugh (p < 0,05). CONCLUSIÓN: Dada la alta prevalencia de déficit o insuficiencia de VD debería plantearse la necesidad de cribado en la población con EHC. El aporte de VD podría ser seguro y eficaz

INTRODUCTION: Vitamin D (VD) is known to have multiple extra-skeletal health functions. There is emerging interest in exploring the relationship between vitamin D and chronic liver disease (CLD). OBJECTIVES: To determine the prevalence of VD deficiency in patients with CLD in our setting and to assess whether VD supplementation influences plasma levels and is associated with improved liver function. MATERIAL AND METHODS: We conducted a study in 2 phases. First, we analysed clinical and epidemiological characteristics in 94 patients with CLD; second, different doses of calcifediol (25-OH-VD) were administered to patients with VD deficiency (<20ng/mL) and insufficiency (20-30ng/mL). Plasma concentrations and liver function (Child-Pugh and MELD) at the end of treatment were compared with baseline data. RESULTS: Deficient or insufficient VD levels were found in 87% of the patients, with an average concentration of 18.8ng/mL. Levels were lower in patients with cirrhosis (15.9ng/mL) (P=.002) and in alcoholic liver disease. VD levels were inversely proportional to the degree of liver function: Child A (16.52ng/mL) vs C (7.75ng/mL). After VD supplementation, optimal serum levels were achieved in 94% of patients and significant improvements were observed in platelet count, albumin levels (P<.05) and functional status assessed by the Child-Pugh scale (P<.05). CONCLUSION: Given the high prevalence of VD deficiency or insufficiency, the need for screening should be considered in the population with CLD. VD supplementation could be safe and effective

Papel de la rifaximina en el tratamiento de la encefalopatía hepática / Role of rifaximin in the treatment of hepatic encephalopathy

La encefalopatía hepática (EH) es una complicación grave y frecuente de la cirrosis hepática. Además de corregir los factores precipitantes, los tratamientos más utilizados y con los que existe mayor experiencia son los disacáridos no absorbibles y la rifaximina. Muchas de las recomendaciones se basan en la práctica clínica con escasos estudios controlados y aleatorizados. Actualmente, la rifaximina se debería iniciar durante un episodio de EH, si tras 24-48 horas con tratamiento con disacáridos no absorbibles no presenta mejoría clínica. En la EH recurrente es aconsejable añadir rifaximina si, el paciente estando en tratamiento con disacáridos no absorbibles, presenta clínica. Por el momento, no se recomienda el tratamiento habitual de la EH mínima con rifaximina. La rifaximina ha demostrado que es eficaz en el tratamiento agudo de la EH así como en la prevención de recidivas

Hepatic encephalopathy (HE) is a frequent and serious complication of liver cirrhosis. In addition to correction of the precipitating factors, the most commonly used treatments are non-absorbable disaccharides and rifaximin. Many of the recommendations are based on current clinical practice and there are few randomized controlled trials. Currently, rifaximin should be initiated during an episode of EH if, after 24-48 hours of non-absorbable disaccharide therapy, there is no clinical improvement. In recurrent EH, it is advisable to add rifaximin in patients under non-absorbable disaccharide therapy who develop a new episode. Currently, standard treatment with rifaximin for minimal EH is not recommended. Rifaximin is effective in the acute treatment of overt encephalopathy and in preventing recurrence

Treatment of invasive fungal disease using anidulafungin alone or in combination for hematologic patients with concomitant hepatic or renal impairment / / Tratamiento de infecciones fúngicas invasivas con anidulafungina sola o combinada en pacientes hematológicos con insuficiencia hepática o renal concomitante

Background. Invasive fungal disease (IFD) treatment is challenging in hematologic patients due to drug interactions and toxicities that limit the use of the antifungal agents. Aims. To analyze retrospectively in terms of safety and potential efficacy anidulafungin therapy, alone or in combination. Methods. Our institutional guidelines recommended anidulafungin treatment in hematologic patients with suspected IFD and concomitant renal or liver impairment (to avoid drug interactions and preserve organ function). Results. From 2008 to 2013, 24 episodes of IFD occurring in 21 patients were classified as proven (4 cases), probable (15 cases) and possible (5 cases). Anidulafungin was administered alone (13%) or in combination (88%). Eight (33%) episodes were resolved, using monotherapy (1 out of 3, 33%) or a combined therapy (7 out of 21, 33%). Twelve cases (50%) were registered as failure (death due to IFD progression in 4 patients, and treatment change due to lack of efficacy in 8), and 4 cases (17%) were not evaluable (death unrelated to the IFD). Anidulafungin was not withdrawn in any case due to toxicity. Conclusions. Anidulafungin therapy, alone or in combination, could be considered in hematologic patients with IFD and concomitant liver or renal impairment. Due to the low number of patients, we cannot draw any conclusion about efficacy (AU)

Antecedentes. El tratamiento de una infección fúngica invasiva (IFI) supone un importante desafío en los pacientes hematológicos debido a las interacciones farmacológicas y a la toxicidad de los agentes antifúngicos, que restringen su uso. Objetivos. Analizar de forma retrospectiva el tratamiento con anidulafungina, sola o combinada, en términos de su seguridad y posible eficacia. Métodos. En los pacientes hematológicos con sospecha de IFI e insuficiencia renal o hepática concomitante, las guías clínicas de nuestro entorno recomendaban el tratamiento con anidulafungina (para evitar las interacciones farmacológicas y preservar la función orgánica). Resultados. De 2008 a 2013 se documentaron 24 episodios de IFI en 21 pacientes, que se clasificaron como IFI demostrada (4 casos), IFI probable (15 casos) e IFI posible (5 casos). Se administró anidulafungina como monoterapia (13%) y en combinación (88%). Se resolvieron 8 episodios (33%), 1 caso de 3 tratados con monoterapia (33%) y 7 casos de 21 tratados con terapia combinada, (33%). En 12 casos (50%), el tratamiento fracasó (muerte por progresión de la IFI en 4 pacientes y cambio de tratamiento por falta de eficacia en 8). Por último, 4 casos (17%) no se pudieron evaluar (muerte no relacionada con IFI). En ningún caso se retiró el tratamiento con anidulafungina por toxicidad. Conclusiones. El tratamiento con anidulafungina, sola o combinada, podría considerarse apropiado para pacientes hematológicos con IFI e insuficiencia hepática o renal concomitante. Debido al reducido número de pacientes incluidos, no es posible extraer conclusiones respecto a la eficacia(AU)

FTO-dependent function of N6-methyladenosine is involved in the hepatoprotective effects of betaine on adolescent mice

Nonalcoholic fatty liver disease (NAFLD) is now the most common cause of chronic liver disease among children and adolescents in the developed world. Betaine, as a methyl donor, recently has been demonstrated to exert its hepatoprotective effects through rectifying the genomic DNA hypomethylation state. However, whether betaine supplementation affects N6-methyladenosine (m6A) mRNA methylation in NAFLD is still unknown. We conducted the current study to investigate the effects of betaine supplementation during adolescence on high-fat diet-induced pathological changes in liver of mice, and we further identified the effects of betaine supplementation on expression of the fat mass and obesity-associated gene (FTO) and hepatic m6A mRNA methylation. Our results showed that betaine supplementation across adolescence significantly alleviated high-fat-induced impairment of liver function and morphology as well as ectopic fat accumulation. Surprisingly, no significant effects on serum TG and NEFA level, as well as fat mass, were observed in mice supplemented with betaine. We also found that high-fat diet upregulated ACC1 and FAS gene expression and downregulated HSL and ATGL gene expression. However, these alterations were rectified by betaine supplementation. Moreover, an m6A hypomethylation state and increased FTO expression were detected in mice fed with high-fat diet, while betaine supplementation prevented these changes. Our results suggested that betaine supplementation during adolescence could protect mice from high-fat-induced NAFLD by decreasing de novo lipogenesis and increasing lipolysis. Furthermore, a novel FTO-dependent function of m6A may involve in the hepatoprotective effects of betaine

ALPPS monosegmento: una nueva variante de las técnicas de regeneración hepática rápida. Revisión crítica de los resultados iniciales de nuestra serie / Monosegment ALPPS: A new variant of the techniques for rapid hepatic regeneration. Critical review of the initial results of our series

La hepatectomía secuencial, descrita en la literatura anglosajona con el acrónimo ALPPS (Associating Liver Partition and Portal vein ligation for Staged hepatectomy) es una técnica novedosa que ofrece un crecimiento rápido y efectivo del volumen remanente hepático, y que permite la resección quirúrgica de lesiones hepáticas consideradas inicialmente irresecables. Los resultados a corto y largo plazo y la conveniencia de realizar esta técnica son cuestiones que permanecen en discusión a la espera de los resultados finales de los registros multicéntricos. El objetivo del presente trabajo es la revisión crítica de los resultados de la serie de casos realizados en nuestro centro (n = 8). Por otra parte, es posible con esta técnica dejar un único segmento hepático como remanente y realizamos una descripción de esta variante técnica novedosa (ALPPS monosegmento), llevada a cabo en uno de los casos

Associating Liver Partition and Portal vein ligation for Staged hepatectomy (ALPPS) is a novel surgical technique that provides fast and effective growth of liver remnant volume, allowing surgical resection of hepatic lesions initially considered unresectable. Short and long-term results and the convenience of carrying out this technique are issues that still remain under debate while waiting for the final outcomes of the multicenter registries with larger number of cases. The aim of this paper is to describe, from a critical point of view, the outcomes of the cases performed at our center (n = 8). On the other hand, it is possible to leave only one hepatic segment as a liver remnant and we illustrate this new surgical procedure (ALPPS monosegment) performed in one patient