Discovery and validation of mucosal TNF expression combined with histological score - a biomarker for personalized treatment in ulcerative colitis.

BACKGROUND: There are no accurate markers that can predict clinical outcome in ulcerative colitis at time of diagnosis. The aim of this study was to explore a comprehensive data set to identify and validate predictors of clinical outcome in the first year following diagnosis. METHODS: Treatment naive-patients with ulcerative colitis were included at time of initial diagnosis from 2004 to 2014, followed by a validation study from 2014 to 2018. Patients were treated according to clinical guidelines following a standard step-up regime. Patients were categorized according to the treatment level necessary to achieve clinical remission: mild, moderate and severe. The biopsies were assessed by Robarts histopathology index (RHI) and TNF gene transcripts. RESULTS: We included 66 patients in the calibration cohort and 89 patients in the validation. Mucosal TNF transcripts showed high test reliability for predicting severe outcome in UC. When combined with histological activity (RHI) scores the test improved its diagnostic reliability. Based on the cut-off values of mucosal TNF and RHI scores from the calibration cohort, the combined test had still high reliability in the validation cohort (specificity 0.99, sensitivity 0.44, PPV 0.89, NPV 0.87) and a diagnostic odds-ratio (DOR) of 54. CONCLUSIONS: The combined test using TNF transcript and histological score at debut of UC can predict severe outcome and the need for anti-TNF therapy with a high level of precision. These validated data may be of great clinical utility and contribute to a personalized medical approach with the possibility of top-down treatment for selected patients.

Development and external validation of a clinical prediction model for MRSA carriage at hospital admission in Southeast Lower Saxony, Germany.

In countries with low endemic Methicillin-resistant Staphylococcus aureus (MRSA) prevalence, identification of risk groups at hospital admission is considered more cost-effective than universal MRSA screening. Predictive statistical models support the selection of suitable stratification factors for effective screening programs. Currently, there are no universal guidelines in Germany for MRSA screening. Instead, a list of criteria is available from the Commission for Hospital Hygiene and Infection Prevention (KRINKO) based on which local strategies should be adopted. We developed and externally validated a model for individual prediction of MRSA carriage at hospital admission in the region of Southeast Lower Saxony based on two prospective studies with universal screening in Braunschweig (n = 2065) and Wolfsburg (n = 461). Logistic regression was used for model development. The final model (simplified to an unweighted score) included history of MRSA carriage, care dependency and cancer treatment. In the external validation dataset, the score showed a sensitivity of 78.4% (95% CI: 64.7-88.7%), and a specificity of 70.3% (95% CI: 65.0-75.2%). Of all admitted patients, 25.4% had to be screened if the score was applied. A model based on KRINKO criteria showed similar sensitivity but lower specificity, leading to a considerably higher proportion of patients to be screened (49.5%).

Knowledge on Antibiotic Use, Self-Reported Adherence to Antibiotic Intake, and Knowledge on Multi-Drug Resistant Pathogens - Results of a Population-Based Survey in Lower Saxony, Germany.

INTRODUCTION: Assessment of public awareness on antibiotic use and resistance can identify key issues for campaigns addressing these problems. Our aim was to assess the knowledge, attitudes, and practice (KAP) related to antibiotic use and multi-drug resistant (MDR) pathogens in a general population in Germany. METHODS: We conducted a KAP survey on antibiotics and on MDR pathogens using an online panel recruited from the general population, which was established using stratified random sampling from the population registry in four districts in Lower Saxony, Germany. RESULTS: In the 12 months preceding the survey, 32.3% of the participants had received at least one prescription for antibiotics, 95.7% reported to follow the recommendations of prescribers, and 10.3% reported to stop taking antibiotics as soon as they feel better. Up to 94.9% of the participants had heard of MDR pathogens, 42.7% reported to know somebody who had been tested positive for it, 0.8% had an infection with it, and 37.2% were worried of contracting it. In case of contact with a carrier of MDR pathogens, over 90% would increase hand hygiene and 0.8% would avoid the carrier completely. Participants considered health care workers (75.1%) and everybody in society (87.8%) to be responsible for combating the spread of MDR pathogens. CONCLUSION: There is a high reported exposure to antibiotics and awareness of the problem of MDR pathogens. Despite personal worries, most of the participants indicated a reasonable, non-stigmatizing behavior toward carriers of MDR pathogens, and that every individual was responsible to avoid their spread.

Metformin in patients with non-alcoholic fatty liver disease: a randomized, controlled trial.

OBJECTIVE: The antidiabetic agent metformin is regularly discussed as a promising treatment for non-alcoholic fatty liver disease (NAFLD), which is characterized by insulin resistance. However, the evidence for its beneficial effects is limited, and conflicting reports have been published. The purpose of this study was to conduct a randomized, double-blind, placebo-controlled trial to test whether metformin improves liver histology in patients with non-alcoholic fatty liver disease. MATERIAL AND METHODS: Forty-eight patients with biopsy-proven NAFLD were randomized to treatment with metformin (n=24) or placebo (n=24) for 6 months. A second liver biopsy was obtained in all subjects who completed the trial (n=44). Data analyses are restricted to this group (per-protocol analyses). The primary outcome was changes in histologically assessed liver steatosis. Secondary outcomes were changes in NAFLD activity (NAS)-score, liver steatosis assessed by computed tomography (CT), liver transaminases, body-weight, metabolic variables and inflammatory markers. RESULTS: No significant differences between treatment with metformin or placebo were observed for changes in liver steatosis, assessed either histologically or by CT, NAS-score, liver transaminases or on markers of insulin resistance or inflammation. In contrast, beneficial effects of metformin were observed on changes in body-weight (p<0.001), serum levels of cholesterol (p=0.004), LDL-cholesterol (p<0.001), glucose (p=0.032) and on HbA1c (p=0.020). CONCLUSIONS: Treatment with metformin for 6 months was no better than placebo in terms of improvement in liver histology in patients with NAFLD. Nevertheless, the use of metformin could still be beneficial in this group as it is associated with a reduction in serum levels of lipids and glucose. (ClinicalTrials.gov number, NCT00303537).

Helicobacter pylori stimulates a mixed adaptive immune response with a strong T-regulatory component in human gastric mucosa.

BACKGROUND: Host factors play an important role in the pathophysiology of Helicobacter pylori infection and development of gastritis and related disease. The established opinion is that the T-cell-mediated immune response to H. pylori infection is of Th1 type. Our earlier immune cell phenotype studies indicate a mixed Th1-Th2 profile of the effector cells. Therefore, an extensive adaptive and regulatory cytokine gene expression profile was conducted by quantitative real-time polymerase chain reaction (qPCR). MATERIALS AND METHODS: Biopsies from gastric mucosa of 91 patients diagnosed as H. pylori negative, H. pylori positive with gastritis, or H. pylori positive with peptic ulcer were obtained by endoscopy. Gene expressions of nine cytokines and CagA status were measured by qPCR. RESULTS: All cytokine genes showed higher expression levels in the presence of H. pylori when compared to H. pylori-negative samples (fold increase: IL8: x 11.2; IL12A: x 2.4; TNF-alpha: x 5.2; IFN-gamma: x 4.3; IL4: x 3.6; IL6: x 14.7; and IL10: x 6.7). Patients infected with CagA-positive strains had higher expression of IL1-beta and IL18 compared to patients infected with CagA-negative strains (x 1.6 for IL1-beta and x 2.0 for IL18). Patients with duodenal ulcer had a lower antral Th1/Th2 ratio than other H. pylori-positive patients. CONCLUSIONS: The cytokine profile of H. pylori-infected gastric mucosa shows a mixed Th1-Th2 profile. Furthermore, a high IL10 expression may indicate that also regulatory T cells play a role in the chronic phase of H. pylori infection.