Contextual determinants of alcohol consumption changes and preventive alcohol policies: a 12-country European study in progress.

Beginning with France in the 1950s, alcohol consumption has decreased in Southern European countries with few or no preventive alcohol policy measures being implemented, while alcohol consumption has been increasing in Northern European countries where historically more restrictive alcohol control policies were in place, even though more recently they were loosened. At the same time, Central and Eastern Europe have shown an intermediate behavior. We propose that country-specific changes in alcohol consumption between 1960 and 2008 are explained by a combination of a number of factors: (1) preventive alcohol policies and (2) social, cultural, economic, and demographic determinants. This article describes the methodology of a research study designed to understand the complex interactions that have occurred throughout Europe over the past five decades. These include changes in alcohol consumption, drinking patterns and alcohol-related harm, and the actual determinants of such changes.

Algies après cure de hernie inguinale: que faire [Pain after inguinal hernia repair: what to do?]

Hernia repair one of the most frequently performed operations in general surgery. With the introduction of tension-free mesh repair, recurrence rates dropped well below 5% for open and laparoscopic procedures. However, chronic postoperative pain remains a widely neglected complication with a high socio-economic impact. It occurs in about 10-20% of patients after hernia repair. We review the different types of post-herniorrhaphy pain with the typical diagnostic features and we conclude with a pragmatic algorithm based on our clinical experience.

Preoperative hyperfractionated accelerated radiotherapy (HART) and concomitant CPT-11 in locally advanced rectal carcinoma: a phase I study.

PURPOSE: Patients with locally advanced rectal carcinoma are at risk for both local recurrence and distant metastases. We demonstrated the efficacy of preoperative hyperfractionated accelerated radiotherapy (HART). In this Phase I trial, we aimed at introducing chemotherapy early in the treatment course with both intrinsic antitumor activity and a radiosensitizer effect. METHODS AND MATERIALS: Twenty-eight patients (19 males; median age 63, range 28-75) with advanced rectal carcinoma (cT3: 24; cT4: 4; cN+: 12; M1: 5) were enrolled, including 8 patients treated at the maximally tolerated dose. Escalating doses of CPT-11 (30-105 mg/m(2)/week) were given on Days 1, 8, and 15, and concomitant HART (41.6 Gy, 1.6 Gy bid x 13 days) started on Day 8. Surgery was to be performed within 1 week after the end of radiochemotherapy. RESULTS: Twenty-six patients completed all preoperative radiochemotherapy as scheduled; all patients underwent surgery. Dose-limiting toxicity was diarrhea Grade 3 occurring at dose level 6 (105 mg/m(2)). Hematotoxicity was mild, with only 1 patient experiencing Grade 3 neutropenia. Postoperative complications (30 days) occurred in 7 patients, with an anastomotic leak rate of 22%. CONCLUSIONS: The recommended Phase II dose of CPT-11 in this setting is 90 mg/m(2)/week. Further Phase II exploration at this dose is warranted.

Functional plasticity of the LACK-reactive Vbeta4-Valpha8 CD4(+) T cells normally producing the early IL-4 instructing Th2 cell development and susceptibility to Leishmania major in BALB / c mice.

Early production of IL-4 by LACK-reactive Vbeta4-Valpha8 CD4(+) T cells instructs aberrant Th2 cell development and susceptibility to Leishmania major in BALB / c mice. This was demonstrated using Vbeta4(+)-deficient BALB / c mice as a result of chronic infection with MMTV (SIM), a mouse mammary tumor virus expressing a Vbeta4-specific superantigen. The early IL-4 response was absent in these mice which develop a Th1 response to L. major. Here, we studied the functional plasticity of LACK-reactive Vbeta4-Valpha8 CD4(+) T cells using BALB/ c mice inoculated with L. major shortly after infection with MMTV (SIM), i. e. before deletion of Vbeta4(+) cells. These mice fail to produce the early IL-4 response to L. major and instead exhibit an IFN-gamma response that occurs within LACK-reactive Vbeta4-Valpha8 CD4(+) T cells. Neutralization of IFN-gamma restores the production of IL-4 by these cells. These data suggest that the functional properties of LACK-reactive Vbeta4-Valpha8 CD4(+) T cells are not irreversibly fixed.

Identification of a Poor-Prognosis BRAF-Mutant-Like Population of Patients With Colon Cancer.

PURPOSE Our purpose was development and assessment of a BRAF-mutant gene expression signature for colon cancer (CC) and the study of its prognostic implications. Materials and METHODS A set of 668 stage II and III CC samples from the PETACC-3 (Pan-European Trails in Alimentary Tract Cancers) clinical trial were used to assess differential gene expression between c.1799T>A (p.V600E) BRAF mutant and non-BRAF, non-KRAS mutant cancers (double wild type) and to construct a gene expression-based classifier for detecting BRAF mutant samples with high sensitivity. The classifier was validated in independent data sets, and survival rates were compared between classifier positive and negative tumors. Results A 64 gene-based classifier was developed with 96% sensitivity and 86% specificity for detecting BRAF mutant tumors in PETACC-3 and independent samples. A subpopulation of BRAF wild-type patients (30% of KRAS mutants, 13% of double wild type) showed a gene expression pattern and had poor overall survival and survival after relapse, similar to those observed in BRAF-mutant patients. Thus they form a distinct prognostic subgroup within their mutation class. CONCLUSION A characteristic pattern of gene expression is associated with and accurately predicts BRAF mutation status and, in addition, identifies a population of BRAF mutated-like KRAS mutants and double wild-type patients with similarly poor prognosis. This suggests a common biology between these tumors and provides a novel classification tool for cancers, adding prognostic and biologic information that is not captured by the mutation status alone. These results may guide therapeutic strategies for this patient segment and may help in population stratification for clinical trials.

Impact of extracardiac findings during cardiac MR on patient management and outcome.

BACKGROUND: Cardiac magnetic resonance (CMR) is increasingly used to assess heart diseases. Relevant non-cardiac diseases may also be incidentally found on CMR images. The aim of this study was to determine the prevalence and nature of incidental extra-cardiac findings (IEF) and their clinical impact in non-selected patients referred for CMR. MATERIAL/METHODS: MR images of 762 consecutive patients (515 men, age: 56±18 years) referred for CMR were prospectively interpreted by 2 radiologists blinded for any previous imaging study. IEFs were classified as major when requiring treatment, follow-up, or further investigation. Clinical follow-up was performed by checking hospital information records and by calling referring physicians. The 2 endpoints were: 1) non-cardiac death and new treatment related to major IEFs, and 2) hospitalization related to major IEFs during follow-up. RESULTS: Major IEFs were proven in 129 patients (18.6% of the study population), 14% of those being unknown before CMR. During 15±6 month follow-up, treatment of confirmed major IEFs was initiated in 1.4%, and no non-cardiac deaths occurred. Hospitalization occurred in 8 patients (1.0% of the study population) with confirmed major IEFs and none occurred in the remaining 110 patients with unconfirmed/unexplored major IEFs (p<0.001). CONCLUSIONS: Screening for major IEFs in a population referred for routine CMR changed management in 1.4% of patients. Major IEFs unknown before CMR but without further exploration, however, carried a favorable prognosis over a follow-up period of 15 months.