Ecto-nucleotidase triphosphate diphosphohydrolase-2 (NTPDase2) is an ecto-enzyme that is expressed on portal fibroblasts in the liver that modulates P2 receptor signaling by regulating local concentrations of extracellular ATP and ADP. NTPDase2 has protective properties in liver fibrosis and may impact bile duct epithelial turnover. Here, we study the role of NTPDase2 in acute liver injury using an experimental model of acetaminophen (APAP) intoxication in mice with global deletion of NTPDase2. Acute liver toxicity was caused by administration of acetaminophen in wild type (WT) and NTPDase2-deficient (Entpd2 null) mice. The extent of liver injury was compared by histology and serum alanine transaminase (ALT). Markers of inflammation, regeneration and fibrosis were determined by qPCR). We found that Entpd2 expression is significantly upregulated after acetaminophen-induced hepatotoxicity. Entpd2 null mice showed significantly more necrosis and higher serum ALT compared to WT. Hepatic expression of IL-6 and PDGF-B are higher in Entpd2 null mice. Our data suggest inducible and protective roles of portal fibroblast-expressed NTPDase2 in acute necrotizing liver injury. Further studies should investigate the relevance of these purinergic pathways in hepatic periportal and sinusoidal biology as such advances in understanding might provide possible therapeutic targets.

Infections caused by multidrug- (MDROs) or extensively drug- (XDROs) resistant organisms are an increasing global concern in cirrhosis. While MDRO colonization is a recognized risk factor for infection in critical care settings, evidence in ward-based patients with decompensated cirrhosis is limited. This study aimed to determine the prevalence, dynamics, and clinical impact of MDRO colonization outside the intensive care unit (ICU) and to identify predictors of colonization and infection. We conducted a single-center prospective study (2017–2020) enrolling 408 patients with decompensated cirrhosis consecutively admitted to the ward (n = 272) or ICU (n = 136). Rectal and nasal swabs were obtained at admission and weekly for up to 12 months. Colonization dynamics, resistance profiles, infection rates, and outcomes were analyzed in ward patients, with the ICU cohort serving as a comparator. Baseline rectal MDRO colonization was common in both the ward and ICU (23% vs. 17%; p = 0.38) and increased over time, reaching similar rates at 1 year (39% vs. 43%; p = 0.13). XDROs emerged during follow-up in both settings. In ward patients, baseline (52% vs. 19%; p <0.0001) or follow-up (55% vs. 11%; p <0.0001) colonization was associated with MDRO infection by the colonizing strain and with higher mortality (60% vs. 22%; p <0.0001). Baseline (hazard ratio [HR] 9.6; p <0.0001) and follow-up colonization (HR 4.4; p <0.0001) independently predicted infection, and colonization at either time point predicted mortality (HR 2.07; p <0.0001). Recent acute-on-chronic liver failure predicted colonization (HR 2.5; p <0.0001) and infection (HR 2.8; p = 0.0003). MDRO colonization is frequent and clinically significant outside the ICU in patients with cirrhosis, predicting both infection and mortality. Extending targeted surveillance and antibiotic stewardship beyond critical care may help reduce infection-related morbidity and mortality. This study demonstrates that rectal colonization with multidrug-resistant organisms is both common and clinically significant in patients with decompensated cirrhosis outside the intensive care unit. These findings are highly relevant for hepatologists, infectious disease clinicians, and epidemiologists, as colonized ward patients faced a substantially increased risk of developing infections from their colonizing strain and experienced worse outcomes, particularly those with recent acute-on-chronic liver failure. Practically, incorporating colonization status into empirical antibiotic decision-making and evaluating targeted multidrug-resistant organism surveillance strategies beyond the intensive care unit could enhance early management and improve risk stratification. While further work is needed to assess feasibility and cost-effectiveness, our results provide a strong evidence base to inform the development of surveillance-driven approaches in routine cirrhosis care.

Minimal-invasive techniques are increasingly applied in clinical practice and have contributed towards improving postoperative outcomes. While comparing favorably with open surgery in terms of safety, the occurrence of severe complications remains a grave concern. To date, no objective predictive system has been established to guide clinicians in estimating complication risks as the relative contribution of general patient health, liver function and surgical parameters remain unclear. Here, we perform a single-center analysis of all consecutive patients undergoing laparoscopic liver resection for primary hepatic malignancies since 2010. Among the 210 patients identified, 32 developed major complications. Several independent predictors were identified through a multivariate analysis, defining a preoperative model: diabetes, history of previous hepatectomy, surgical approach, alanine aminotransferase levels and lesion entity. The addition of operative time and whether conversion was required significantly improved predictions and were thus incorporated into the postoperative model. Both models were able to identify patients with major complications with acceptable performance (area under the receiver-operating characteristic curve (AUC) for a preoperative model = 0.77 vs. postoperative model = 0.80). Internal validation was performed and confirmed the discriminatory ability of the models. An easily accessible online tool was deployed in order to estimate probabilities of severe complication without the need for manual calculation.

ResumenObjetivoDefinir la prevalencia del infarto de origen criptogénico en pacientes con diagnóstico de infarto cerebral isquémico entre los años 2007 a 2014.MétodosSe realizó un estudio de tipo corte transversal. Se incluyeron todos los pacientes mayores de 18 años con ataque cerebrovascular isquémico agudo. Se evaluó cada caso mediante una lista de chequeo para la etiología y los estudios de cardiología. Se hizo una descripción de la población y de los factores de riesgo con análisis univariado. La asociación de los criptogénicos y no criptogénicos con las diferentes exposiciones se evaluó con el uso de Chi2 o T de Student de acuerdo con el tipo de variable. Se calcularon las razones de disparidad para los factores de riesgo. Se hizo un análisis multivariado para las variables independientes con p<0,1.Resultadosen 340 pacientes se encontró una prevalencia de evento cerebrovascular criptogénico del 19,71% (n=67). Al dicotomizar la edad se observó que la prevalencia de ataque cerebrovascular criptogénico fue mayor en el grupo de <45 años 42,31% vs. 17,83% ≥45 años (p=0,003), con una razón de prevalencias de 2,37. Solo la enfermedad coronaria (p=0,04) y la fibrilación auricular (p<0,0001), se relacionaron con los casos no criptogénicos en el modelo multivariado.Conclusionesse halló una prevalencia de infarto criptogénico ligeramente inferior a la encontrada en la literatura reciente, que pudiera explicarse por un estudio más profundo en nuestra población o un subregistro de la enfermedad.AbstractObjectiveTo define the prevalence of cryptogenic stroke in patients with a diagnosis of ischemic cerebral infarction between 2007 and 2014.MethodsA cross-sectional study was performed that included all patients over the age of 18 who had suffered an acute ischemic stroke. Each case was evaluated using a checklist for aetiology and cardiology studies. A description was made of the population and the risk factors with univariate analysis. The association with different exposures of cryptogenic and non-cryptogenic stroke was evaluated using the Chi2 or Student's t-test according to the type of variable. The disparity ratios were calculated for the risk factors. A multivariate analysis was undertaken for the independent variables with p<0.1.Resultsa prevalence of 19.71% (n=67) of cryptogenic stroke was found in 340 patients. When dichotomising age it was observed that the prevalence of cryptogenic stroke was greater in the <45 age group, 42.31% vs 17.83% in the ≥45 age group (p=0.003), with a prevalence ratio of 2.37. Only coronary heart disease (p=0.04) and atrial fibrillation (p<0.0001), were associated with the non-cryptogenic cases in the multivariate model.Conclusionsa slightly lower prevalence of cryptogenic stroke was found than that described in the recent literature. This could be explained by a more in-depth study in our population or under-reporting of the disease