Selective improvement by rifaximin of changes in the immunophenotype in patients who improve minimal hepatic encephalopathy.

BACKGROUND: Minimal hepatic encephalopathy (MHE) in cirrhotic patients is associated with specific changes in parameters of the immune system reflecting a more pro-inflammatory environment than in patients without MHE. The aims of this work were to assess the effects of rifaximin treatment of cirrhotic patients with MHE on: (1) MHE; (2) intermediate (CD14++CD16+) pro-inflammatory monocytes; (3) expression of early activation marker CD69 in T lymphocytes; (4) autoreactive CD4+CD28- T lymphocytes; (5) differentiation of CD4+ T lymphocytes to Th follicular and Th22; (6) serum IgG levels; and (7) levels of some pro-inflammatory cytokines. METHODS: These parameters were measured by immunophenotyping and cytokine profile analysis in 30 controls without liver disease, 30 cirrhotic patients without MHE and 22 patients with MHE. Patients with MHE were treated with rifaximin and the same parameters were measured at 3 and 6 months of treatment. We assessed if changes in these parameters are different in patients who improve MHE (responders) and those who remain in MHE (non-responders). RESULTS: Rifaximin improved MHE in 59% of patients with MHE. In these responder patients rifaximin normalized all alterations in the immune system measured while in non-responders it normalizes only IL-6, CCL20, and differentiation of T lymphocytes to Th22. Non-responder patients do not show increased expression of CD69 before treatment. CONCLUSIONS: Rifaximin normalizes changes in the immune system in patients who improve MHE but not in non-responders. Some alterations before treatment are different in responders and non-responders. Understanding these differences may identify predictors of the response of MHE to rifaximin.

Prevalence of complications of open tibial shaft fractures stratified as per the Gustilo-Anderson classification.

The aim of the present study was to comparatively analyse certain outcome measures of open tibial fractures, stratified per grade of open injury and method of treatment. For this purpose, a systematic review of the English literature from 1990 until 2010 was undertaken, comprising 32 eligible articles reporting on 3060 open tibial fractures. Outcome measures included rates of union progress (early union, delayed union, late union and non-union rates) and certain complication rates (deep infection, compartment syndrome and amputation rates). Statistical heterogeneity across component studies was detected with the use of Cochran chi-square and I(2) tests. In the absence of significant statistical heterogeneity a pooled estimate of effect size for each outcome/complication of interest was produced. All component studies were assigned on average a moderate quality score. Reamed tibial nails (RTNs) were associated with significantly higher odds of early union compared with unreamed tibial nails (UTNs) in IIIB open fractures (odds ratio: 12, 95% CI: 2.4-61). Comparing RTN and UTN modes of treatment, no significant differences were documented per grade of open fractures with respect to both delayed and late union rates. Surprisingly, nonunion rates in IIIB open fractures treated with either RTNs or UTNs were lower than IIIA or II open fractures, although the differences were not statistically significant. Significantly increased deep infection rates of IIIB open fractures compared with all other grades were documented for both modes of treatment (RTN, UTN). However, lower deep infection rates for IIIA open fractures treated with RTNs were recorded compared with grades I and II. Interestingly, grade II open tibial fractures, treated with UTN, presented significantly greater odds for developing compartment syndrome than when treated with RTNs. Our cumulative analysis, providing for each grade of open injury and each particular method of treatment a summarised estimate of effect size for the most important outcome measures of open tibial fractures, constitutes a useful tool of the practicing surgeon for optimal decision making when operative treatment of such fractures is contemplated.

Prophylactic treatment with escitalopram of pegylated interferon alfa-2a-induced depression in hepatitis C: a 12-week, randomized, double-blind, placebo-controlled trial.

BACKGROUND: Depression is one of the main reasons for treatment withdrawal and failure in chronic hepatitis C patients treated with interferon. Antidepressants are useful for its treatment, but whether they can also be used for prevention has yet to be established. METHOD: To evaluate the efficacy and safety of escitalopram for preventing interferon alfa-2a-induced depression, we conducted an investigator-initiated multicenter, randomized, double-blind, placebo-controlled trial in 133 chronic hepatitis C patients without baseline mental disorders who were randomly assigned to receive escitalopram or placebo during the first 12 weeks of treatment. Primary efficacy outcomes were the development of DSM-IV major depression and scores on the Montgomery-Asberg Depression Rating Scale (MADRS) and the Hospital Anxiety and Depression Scale (HADS). Primary safety end points were biochemical and virological responses. Patients were recruited between March 2005 and July 2006. RESULTS: Rates of major depression were low (5.4%) and did not differ between placebo (3.2%) and escitalopram (7.6%). MADRS and HADS scores significantly increased during treatment (P < .001 and P = .028, respectively), but there were no differences between treatment groups. Sustained virological response was achieved by 69.2% of patients, 70.4% in the placebo group and 67.9% in the escitalopram group. CONCLUSIONS: Findings do not support the use of an antidepressant to prevent interferon-induced depression during the first 12 weeks of treatment in chronic hepatitis C patients at low psychiatric risk. Future studies should be directed to subpopulations of patients at high psychiatric risk. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00166296.