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Background: Hepatitis E virus (HEV) infection especially in immunocompromised individuals can lead to chronic hepatitis. Aggressive courses of chronic hepatitis E leading to liver cirrhosis in a short period of time have been described, but evidence on the degree of liver involvement in chronic hepatitis E is rare. We therefore aimed to quantify liver fibrosis in patients with chronic active hepatitis E compared to patients with sustained virological response after ribavirin (RBV) treatment using 2D-shear wave elastography (2D-SWE) to measure liver stiffness. Methods: Patients with chronic hepatitis E underwent 2D-SWE, B-mode and Doppler ultrasound and laboratory testing in order to assess severity of liver involvement. Results: In this cross-sectional study, we included 14 patients of whom 8 had ongoing chronic hepatitis E and 6 patients had been successfully treated for chronic hepatitis E. The most frequent cause for immunosuppression was prior kidney transplantation (n=12), one patient was a multivisceral transplant recipient, one had been treated for lymphoma. Five patients cleared HEV after RBV therapy, one patient reached viral clearance after reduction of his immunosuppressive medication. Using 2D-SWE measurement, 71.4% displayed increased stiffness indicative of liver fibrosis: 57.1% classified as significant fibrosis and 14.3% as severe fibrosis. Liver stiffness did not differ between patients with active chronic hepatitis E and in patients who had cleared HEV (1.59 and 1.54 m/s respectively). Compared with a control group of kidney transplant recipients without hepatitis E (1.44 m/s), the patients with a history of hepatitis E displayed a significantly higher liver stiffness (P=0.04). Conclusions: In our cohort of chronic hepatitis E patients, elevated liver stiffness indicating liver fibrosis was common and significantly higher than in controls. This is consistent with prior sparse reports of the presence of liver fibrosis or cirrhosis in chronic hepatitis E and emphasizes the need for HEV testing, therapy and research on new therapeutic options. As elevated liver stiffness was also present in patients after HEV treatment, continuous liver surveillance including elastography and ultrasound should be considered.
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OBJECTIVE: Patients infected with Helicobacter pylori develop chronic gastritis with a subgroup progressing to further complications. The role of microbiota from the oral cavity swallowed with saliva and either transiting the stomach or persisting in the gastric mucosa is uncertain. It is also not known whether the bacterial community differs in luminal and mucosal niches. A key question is whether H. pylori influences the bacterial communities of gastroduodenal niches. DESIGN: Saliva, gastric and duodenal aspirates as well as gastric and duodenal biopsies were collected during oesophagogastroduodenoscopy from 24 patients (m:9, f:15, mean age 52.2±SD 14.5â years). RNA was extracted and the V1-V2 region of the retrotranscribed bacterial 16S rRNA amplified and sequenced on the Illumina MiSeq platform. RESULTS: Overall, 687 bacterial phylotypes that belonged to 95 genera and 11 phyla were observed. Each individual comprised a unique microbiota composition that was consistent across the different niches. However, the stomach fluid enriched for specific microbiota components. Helicobacter spp were shown to dominate the mucosa-associated community in the stomach, and to significantly influence duodenal and oral communities. CONCLUSIONS: The detailed analysis of the active global bacterial communities from the five distinct sites of the upper GI tract allowed for the first time the differentiation between host effects and the influence of sampling region on the bacterial community. The influence of Helicobacter spp on the global community structures is striking.
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Duodeno/microbiologia , Mucosa Gástrica/microbiologia , Infecções por Helicobacter/microbiologia , Helicobacter pylori , Mucosa Intestinal/microbiologia , Saliva/microbiologia , Adulto , Idoso , Biópsia , Doença Crônica , Duodeno/patologia , Endoscopia Gastrointestinal , Feminino , Suco Gástrico/microbiologia , Mucosa Gástrica/patologia , Gastrite/microbiologia , Gastrite/patologia , Microbioma Gastrointestinal , Infecções por Helicobacter/patologia , Humanos , Mucosa Intestinal/patologia , Masculino , Pessoa de Meia-Idade , Boca/microbiologia , RNA Ribossômico 16S/análiseRESUMO
The discovery of Helicobacter pylori (H. pylori) changed the dogma of the stomach as a sterile organ. H. pylori is an obligate pathogen in the human stomach and recognized as a definite carcinogen. Extensive research on the interaction of this bacterium with the gastric mucosa has been performed over the past three decades. The development of new nucleotide sequencing techniques and new biocomputational tools has opened the field for studying the diversity and complexity of the microbiome in the gastrointestinal tract independently of cultural methods. These techniques allow to better characterize further gastric bacteria. However, the differentiation of alive resident and transient microbes requires an analysis beyond the pure detection of bacterial genomic material applying a combination with metabolomic analyses. Currently, the interaction of gastric microbiota with each other, with H. pylori and with the host is addressed by extensive research. This review gives a concise overview on current knowledge on this topic.
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Microbioma Gastrointestinal/fisiologia , Infecções por Helicobacter/microbiologia , Helicobacter pylori/fisiologia , Bactérias/isolamento & purificação , Pesquisa Biomédica/métodos , Ácido Gástrico/fisiologia , Gastroenteropatias/microbiologia , Trato Gastrointestinal/microbiologia , Infecções por Helicobacter/tratamento farmacológico , Interações Hospedeiro-Patógeno , Humanos , Probióticos/uso terapêuticoRESUMO
BACKGROUND: An electronic portal imaging device (EPID) is used to control for patient setup and positioning during fractionated radiotherapy. Due to the rising complexity and conformity of irradiation techniques, the demand for an accurate verification of the dose delivered to the patient has also increased. The purpose of this study was to investigate a simple guidance for dosimetry with an Elekta iViewGT™ EPID using commercial software modules. MATERIAL AND METHODS: EPID measurements were performed using an Elekta iViewGT™ EPID on a linear accelerator with 6 MV x-ray beam. The EPID signal was studied for reproducibility, as well as characteristics as a function of dose, dose rate, and field size. A series of experiments, comparing the response of the flat panel imager and ionization chamber measurements of dose, determine the parameters for the calibration model. EPID measurements were also compared with calculations of the treatment planning system. RESULTS: We found a stable response of the EPID signal over a period of 14 months. It showed nonlinearity depending on dose up to 6.8%. There were low oscillations up to 1.2% depending on dose rate. For all fields, the calibrated flat panel profiles match the measured and calculated dose profiles with maximum deviation of 2-3% for the in-field region. In the high gradient areas, higher differences up to 6% were found. CONCLUSIONS: The gamma evaluation indicates good correlation between predicted and acquired EPID images. The EPID-based pretreatment IMRT verification method will help to improve the quality assurance procedure.
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Radiometria/métodos , Software , Calibragem , Fracionamento da Dose de Radiação , Humanos , Radiometria/normas , Planejamento da Radioterapia Assistida por Computador/métodosRESUMO
Phagocytes, such as monocytes and macrophages, are important cells of the innate immunity in the defense against microbes. So far, it is unclear how these cells survive at the site of combat against microbes, where a hostile inflammatory environment prevails with strong complement activity. We hypothesized that IL-10, a key cytokine involved in the resolution of inflammation, induces resistance to complement attack. Here, we demonstrate for the first time such a cell-protective effect of IL-10 on human monocytes and macrophages. IL-10 is indeed able to protect these cell types in an in vitro model of complement lysis triggered by an anti-MHCI antibody or by binding of zymosan. Investigating potential underlying mechanisms, we found that IL-10 up-regulated the expression of complement regulatory membrane protein CD59 and the general cell-protective stress protein HO-1 in human monocytes. However, further functional analysis failed to link these individual IL-10-mediated effects with the increased protection from complement lysis. Blocking the protective effect of CD59 with an antibody increased complement lysis but did not abrogate the IL-10-protective effect. Interestingly, chemical interference with HO-1 activity did abrogate the protective effect of IL-10, but siRNA-mediated knockdown of HO-1 did not confirm this observation. Our results suggest that IL-10 generates pathogen-clearing phagocytes, which are resistant to complement lysis and thereby, enabled to survive longer in a hostile inflammatory environment.