11 research outputs found
Alterations in Intestinal Mucosal Barrier Visualized by Confocal Laser Endomicroscopy in Liver Cirrhosis: A Pilot Trial (AMBIC)
No full textBackground: Chronic liver disease occurs throughout the world irrespective of region, age,
sex, or race, and it is caused by a variety of liver conditions. One of the most frequent infectious
complications in liver cirrhosis that severely reduces the median survival is spontaneous bacterial
peritonitis. Current guidelines recommend a paracentesis before starting an antibiotic prophylaxis
for this complication. Methods: Selective intestinal decontamination significantly lowers the rate of
first or recurrent SBP in cirrhotic patients, so in this study we aimed to investigate and quantify the
intestinal integrity of patients with liver cirrhosis and correlate a pathologically increased permeability
with the incidence of SPB. We included 14 patients who met the inclusion criteria. No patient was
excluded. For the CLE investigation, we use probe based confocal laser endomicroscopy techniques
from Mauna Kea (Cellvizio), enabling in vivo surface imaging. The images (optical biopsies) were
analyzed for functional and structural barrier defects after the procedure using Mauna Kea software
(version 2.2.6). Results: Because of the small number of included patients and healthy controls, most
results are lacking statistical relevance. We found that the CLE investigation showed an increased
intestinal permeability in patients with liver cirrhosis, in concordance with previous published data,
based on other assessment methods. Conclusions: This study confirms that previously published
permeability scores can be applied for patients with liver cirrhosis and is, to our knowledge, the
first to investigate the intestinal permeability in vivo in patients with liver cirrhosis. Further data
are needed to identify patients at risk and help develop new and less invasive diagnostic criteria for
cirrhotic patients who may profit from a prophylactic antibiotic treatment
Alterations in Intestinal Mucosal Barrier Visualized by Confocal Laser Endomicroscopy in Liver Cirrhosis: A Pilot Trial (AMBIC)
No full textBackground: Chronic liver disease occurs throughout the world irrespective of region, age, sex, or race, and it is caused by a variety of liver conditions. One of the most frequent infectious complications in liver cirrhosis that severely reduces the median survival is spontaneous bacterial peritonitis. Current guidelines recommend a paracentesis before starting an antibiotic prophylaxis for this complication. Methods: Selective intestinal decontamination significantly lowers the rate of first or recurrent SBP in cirrhotic patients, so in this study we aimed to investigate and quantify the intestinal integrity of patients with liver cirrhosis and correlate a pathologically increased permeability with the incidence of SPB. We included 14 patients who met the inclusion criteria. No patient was excluded. For the CLE investigation, we use probe based confocal laser endomicroscopy techniques from Mauna Kea (Cellvizio), enabling in vivo surface imaging. The images (optical biopsies) were analyzed for functional and structural barrier defects after the procedure using Mauna Kea software (version 1.0.09). Results: Because of the small number of included patients and healthy controls, most results are lacking statistical relevance. We found that the CLE investigation showed an increased intestinal permeability in patients with liver cirrhosis, in concordance with previous published data, based on other assessment methods. Conclusions: This study confirms that previously published permeability scores can be applied for patients with liver cirrhosis and is, to our knowledge, the first to investigate the intestinal permeability in vivo in patients with liver cirrhosis. Further data are needed to identify patients at risk and help develop new and less invasive diagnostic criteria for cirrhotic patients who may profit from a prophylactic antibiotic treatment
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Author Correction: Somatic mosaicism and common genetic variation contribute to the risk of very-early-onset inflammatory bowel disease (Nature Communications, (2020), 11, 1, (995), 10.1038/s41467-019-14275-y)
No full textAuthor Correction: Somatic mosaicism and common genetic variation contribute to the risk of very-early-onset inflammatory bowel disease (Nature Communications, (2020), 11, 1, (995), 10.1038/s41467-019-14275-y)
No full textSomatic mosaicism and common genetic variation contribute to the risk of very-early-onset inflammatory bowel disease
No full textVery-early-onset inflammatory bowel disease (VEO-IBD) is a heterogeneous phenotype associated with a spectrum of rare Mendelian disorders. Here, we perform whole-exome-sequencing and genome-wide genotyping in 145 patients (median age-at-diagnosis of 3.5 years), in whom no Mendelian disorders were clinically suspected. In five patients we detect a primary immunodeficiency or enteropathy, with clinical consequences (XIAP, CYBA, SH2D1A, PCSK1). We also present a case study of a VEO-IBD patient with a mosaic de novo, pathogenic allele in CYBB. The mutation is present in ~70% of phagocytes and sufficient to result in defective bacterial handling but not life-threatening infections. Finally, we show that VEO-IBD patients have, on average, higher IBD polygenic risk scores than population controls (99 patients and 18,780 controls; P < 4 × 10-10), and replicate this finding in an independent cohort of VEO-IBD cases and controls (117 patients and 2,603 controls; P < 5 × 10-10). This discovery indicates that a polygenic component operates in VEO-IBD pathogenesis
Loss of the branched-chain amino acid transporter CD98hc alters the development of colonic macrophages in mice
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