Nonalcoholic fatty liver disease as a risk factor for Clostridium difficile-associated diarrhea.

AIMS: Clostridium difficile is the most common cause of infectious nosocomial diarrhea among adults in developed countries. Nonalcoholic fatty liver disease (NAFLD) is considered the most common chronic liver disease and it is associated with bacterial infections. Our goal was to assess whether NAFLD considered a risk factor for C. difficile-associated diarrhea (CDAD). METHODS: We conducted a retrospective study of patients admitted with CDAD at Baruch Padeh Medical Center, Poria, Israel during a period of four years. Data on demographic characteristics, clinical signs, underlying conditions, presence of fatty liver based on computed tomography/ultrasonography imaging and several risk factors for CDI were collected. The control group included patients with diarrhea who were negative for CDT and had been hospitalized during the same period. The controls were matched for age (±5 years) and gender. RESULTS: Totally, 115/164 patients with CDAD met the inclusion criteria. The control group was consisted of 115 hospitalized patients with non-CDAD. The mean age of all the participants (230) was 69.57 ± 18 years. NAFLD was found in 76/115 (66%) patients with CDAD vs. 35/115 (30.4%) in the control group, P < 0.001. Moreover, we found significant associations between CDAD group and metabolic syndrome, prior use of antibiotic in the last 3 months, NAFLD and high serum levels of C-reactive protein. Multivariate analysis showed that NAFLD, odds ratio 1.51, 95% confidence interval 1.2-1.95, P = 0.05 was significantly associated with CDAD. CONCLUSIONS: This retrospective study showed that NAFLD is a risk factor for CDAD. Moreover, metabolic syndrome and high serum levels of C-reactive protein were significantly associated with the risk of CDAD.

Non-alcoholic fatty liver disease and 30-day all-cause mortality in adult patients with community-acquired pneumonia.

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) is a common and serious form of chronic liver disease. Risk factors of NAFLD include obesity and type 2 diabetes which are associated with infections. AIM: We aimed to determine the association of NAFLD with 30-day all-cause mortality in adult patients with community-acquired pneumonia (CAP). METHODS: A retrospective cohort study on hospitalized patients with CAP that was conducted during a period of 4 years. We included patients aged ≥18 years with CAP who underwent abdominal ultrasonography. We compared between patients with and without NAFLD in term of age, gender, body mass index (BMI), comorbidities, CURB-65, pneumonia severity index (PSI), liver enzymes, C-reactive protein (CRP) and 30-day all-cause mortality. We used fibrosis score to distinguish between patients with NAFLD who have advanced fibrosis (F3-F4) and do not have (F0-F2). RESULTS: A total of 561 patients were included in this study. The overall prevalence of NAFLD was 200/561 (35.6%). Significant differences were found between the groups with and without NAFLD in term of BMI, CURB-65, ALT, GGT and CRP. The 30-day all-cause mortality rate was 9.8% (55/561). Among the NAFLD group 34/200 (17%) subjects died vs. 21/361 (5.82%) among patients without NAFLD, P < 0.001. Multi-variate logistic regression analysis after adjusting for other multiple covariates showed that NAFLD with fibrosis score 0-2 [odds ratio (OR) 1.38, 95% confidence interval (CI) 1.12-1.51, P = 0.04], NAFLD with fibrosis score> 2 (1.52; 1.25-1.70, P = 0.03) were associated with 30-day all-cause mortality among patients with CAP. CONCLUSIONS: NAFLD was associated with 30-day all-cause mortality in patients with CAP. This association was more significant in patients with advanced hepatic fibrosis.

Monitoring public interest toward pertussis outbreaks: an extensive Google Trends-based analysis.

OBJECTIVES: Pertussis is a vaccine-preventable disease. Despite this, it remains a major health problem among children in developing countries and in recent years, has re-emerged and has led to considerable outbreaks. Pertussis surveillance is of paramount importance; however, classical monitoring approaches are plagued by some shortcomings, such as considerable time delay and potential underestimation/underreporting of cases. STUDY DESIGN: This study aims at investigating the possibility of using Google Trends (GT) as an instrument for tracking pertussis outbreaks to see if infodemiology and infoveillance approaches could overcome the previously mentioned issues because they are based on real-time monitoring and tracking of web-related activities. METHODS: In the present study, GT was mined from inception (01 January 2004) to 31 December 2015 in the different European countries. Pertussis was searched using the 'search topic' strategy. Pertussis-related GT figures were correlated with the number of pertussis cases and deaths retrieved from the European Centre for Disease prevention and Control database. RESULTS: At the European countries level, correlation between pertussis cases and GT-based search volumes was very large (ranging from 0.94 to 0.97) from 2004 to 2015. When examining each country, however, only a few reached the threshold of statistical significance. CONCLUSIONS: GT could be particularly useful in pertussis surveillance and control, provided that the algorithm is better adjusted and refined at the country level.

Oral administration of non-absorbable delayed release 6-mercaptopurine is locally active in the gut, exerts a systemic immune effect and alleviates Crohn's disease with low rate of side effects: results of double blind Phase II clinical trial.

Therapy for Crohn's disease (CD) with thiopurines is limited by systemic side effects. A novel formulation of fixed-dose, delayed-release 6-mercaptopurine (DR-6MP) was developed, with local effect on the gut immune system and minimal absorption. The aim of this study was to evaluate the safety and efficacy of DR-6MP in patients with moderately severe CD compared to systemically delivered 6-mercaptopurine (Purinethol). Seventy CD patients were enrolled into a 12-week, double-blind controlled trial. The primary end-point was the percentage of subjects with clinical remission [Crohn's Disease Activity Index (CDAI) < 150] or clinical response (100-point CDAI reduction). Twenty-six (56·5%) and 13 (54·2%) subjects from the DR-6MP and Purinethol cohorts, respectively, completed the study. DR-6MP had similar efficacy to Purinethol following 12 weeks of treatment. However, the time to maximal clinical response was 8 weeks for DR-6MP versus 12 weeks for Purinethol. A higher proportion of patients on DR-6MP showed clinical remission at week 8. A greater improvement in Inflammatory Bowel Disease Questionnaire (IBDQ) score was noted in the DR-6MP group. DR-6MP led to a decrease of CD62(+) expression on T cells, implying a reduction of lymphocyte adhesion to site of inflammation. DR-6MP was safer than Purinethol, with significantly fewer adverse events (AEs). There was no evidence of drug-induced leucopenia in the DR-6MP group; the proportion of subjects who developed hepatotoxicity was lower for the DR-6MP. Non-absorbable DR-6MP is safe and biologically active in the gut. It is clinically effective, exerting a systemic immune response with low systemic bioavailability and a low incidence of side effects.

Randomised clinical trial: simvastatin as adjuvant therapy improves significantly the Helicobacter pylori eradication rate--a placebo-controlled study.

BACKGROUND: The eradication rate of Helicobacter pylori with standard treatments are decreasing worldwide. AIM: To determine whether adding simvastatin as adjuvant to triple regimen in patients with H. pylori infection will improve the eradication rate. METHODS: We conducted a double-blind, placebo-controlled, randomised clinical trial comparing a 7-day, triple eradication regimen consisting of two antibiotics (clarithromycin 500 mg and amoxicillin 1 g, all twice per day) plus a proton pump inhibitor (omeprazole 20 mg twice daily) supplemented with simvastatin 20 mg (CAO + S) or a comparable placebo (CAO + P). Both the simvastatin and the placebo were taken orally twice daily for 1 week in 113 patients with H. pylori infection. The presence of H. pylori was determined by positive rapid urease test and histology. Eradication was confirmed by ¹³C-urea breath test at least 1 month after treatment. Adverse effects were assessed by questionnaire. RESULTS: A total of 113 patients underwent randomisation. Intention-to-treat analysis (ITT; n = 113) eradication rates were: CAO + S (86%; 95% CI: 78-92%), CAO + P (69%; 95% CI: 64-74%). Per protocol analysis (PP; n = 108) eradication rates were: CAO + S (91%; 95% CI: 84-94%), CAO + P (72%; 95% CI: 65-78%). Eradication rates were higher with CAO + S than CAO + P in PP and ITT (P = 0.03, P = 0.04 respectively). No differences were demonstrated between the two groups concerning compliance or adverse effects. CONCLUSION: In this randomised clinical trial simvastatin as adjuvant to standard therapy improves significantly the H. pylori eradication rate.

Amelioration of hepatic fibrosis via Padma Hepaten is associated with altered natural killer T lymphocytes.

Hepatic fibrosis is the end-stage consequence of chronic liver disease, affecting many people worldwide. Unlike the anti-fibrotic effect of natural killer (NK) cells, CD8 and NK T subsets are considered as profibrogenic subsets. Padma Hepaten is a multi-compound herbal preparation derived from Tibetan medicine and has proven efficacy in some clinical trials and tests at the cellular level. In this study, we evaluate the immune efficacy of Padma Hepaten administered intraperitoneally (i.p.) and/or orally in a mice model of hepatic fibrosis. Hepatic fibrosis was induced by 6 weeks of biweekly i.p. carbon tetrachloride (CCl4) injections in male C57Bl6 mice. There were four groups, including naive mice, non-treated fibrotic mice and fibrotic mice treated by Padma Hepaten at weeks 5-6 of fibrosis induction either orally or by i.p. injections. Padma Hepaten was prepared at 10 mg/ml in saline and 250 microl (2.5 mg) were administered four times per week. After week 6, animals were killed. To isolate a Padma Hepaten-associated effect on lymphocytes, splenocytes were harvested from either naive or Padma Hepaten-treated non-fibrotic donors. Isolated splenocytes were therefore reconstituted into two groups of irradiated recipients. Recipients were then administered the same CCl4 regimen. Hepatic fibrosis was determined by sirius red staining of liver sections and by assessment of alpha smooth muscle actin expression compared with beta-actin (both by mRNA as well as the protein liver extract western blotting). Hepatic fibrosis and alanine aminotransferase serum levels were decreased significantly in both Padma Hepaten-treated groups compared with the non-treated fibrotic group. Padma Hepaten treatment was associated with attenuation of lymphocyte subsets in both treated groups. Using a chemiluminescence technique to assess total anti-oxidant capacities (TAC), it was found that both the plasmas and livers of mice treated by CCl4 had significantly higher TAC compared with controls. However, the levels of TAC in animals treated either by CCl4 alone or CCl4 with Padma Hepaten were similar. Adoptive transfer of Padma Hepaten-treated lymphocytes was associated with fibrosis amelioration compared with recipients with naive lymphocytes. CCl4 generates higher levels of anti-oxidant capacities, probably as a response to oxidative stress. Padma Hepaten administration attenuated hepatic fibrogenesis significantly, accompanied by attenuation of lymphocyte but not anti-oxidant capacities.