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International audience; Objective: The primary endpoint of this meta-analysis was the PSH rate at 1 year of follow-up with or without the use of a mesh.Summary of background data: European guidelines currently recommend the use of a mesh at the time of a stoma formation for the prevention of PSH. These recommendations are based on the RCT and meta-analyses published before 2017. More recently 2 large RCT found no benefit in the mesh group. We investigated whether these latest results could change the conclusion of a meta-analysis.Methods: We conducted a comprehensive literature search and analyzed RCT investigating the use of a mesh to prevent PSH formation. All studies including end colostomies were included in the qualitative analysis no matter the surgical technique or the type of mesh. All studies with a limited risk of bias and presenting with usable data were used in the quantitative analysis.Results: There is a large heterogeneity among the studies, in terms of position of the mesh, surgical technique, and diagnostic method for the PSH. No statistically significant difference was found on the PSH rate at 1 or 2 years between the mesh and non-mesh groups.Conclusions: Based on this meta-analysis including the latest RCT on the prevention of PSH, the use of a mesh should not be recommended.

International audience; To evaluate whether systematic mesh implantation upon primary colostomy creation was effective to prevent PSH.Summary of background data: Previous randomized trials on prevention of PSH by mesh placement have shown contradictory results.Methods: This was a prospective, randomized controlled trial in 18 hospitals in France on patients aged ≥18 receiving a first colostomy for an indication other than infection. Participants were randomized by blocks of random size, stratified by center in a 1:1 ratio to colostomy with or without a synthetic, lightweight monofilament mesh. Patients and outcome assessors were blinded to patient group. The primary endpoint was clinically diagnosed PSH rate at 24 months of the intention-to-treat population. This trial was registered at ClinicalTrials.gov, number NCT01380860.Results: From November 2012 to October 2016, 200 patients were enrolled. Finally, 65 patients remained in the no mesh group (Group A) and 70 in the mesh group (Group B) at 24 months with the most common reason for drop-out being death (n = 41). At 24 months, PSH was clinically detected in 28 patients (28%) in Group A and 30 (31%) in Group B [P = 0.77, odds ratio = 1.15 95% confidence interval = (0.62;2.13)]. Stoma-related complications were reported in 32 Group A patients and 37 Group B patients, but no mesh infections. There were no deaths related to mesh insertion.Conclusion: We failed to show efficiency of a prophylactic mesh on PSH rate. Placement of a mesh in a retro-muscular position with a central incision to allow colon passage cannot be recommended to prevent PSH. Optimization of mesh location and reinforcement material should be performed.

International audience; Malignancies can be associated with positive antiphospholipid antibodies but the incidence of cancer among women with the purely obstetric form of antiphospholipid syndrome (APS) is currently unknown. Our aim was to investigate the comparative incidence of cancers in women with a history of obstetric APS within a referral university hospital-based cohort (NOH-APS cohort). We performed a 17-year observational study of 1,592 non-thrombotic women with three consecutive spontaneous abortions before the 10th week of gestation or one fetal death at or beyond the 10th week of gestation. We compared the incidence of cancer diagnosis during follow-up among the cohort of women positive for antiphospholipid antibodies (n=517), the cohort of women carrying the F5 rs6025 or F2 rs1799963 polymorphism (n=279) and a cohort of women with negative thrombophilia screening results (n=796). The annualized rate of cancer was 0.300% (0.20%-0.44%) for women with obstetric APS and their cancer risk was substantially higher than that of women with negative thrombophilia screening [adjusted hazard ratio (aHR) 2.483; 95% confidence interval (CI) 1.27-4.85]. The computed standardized incidence ratio for women with obstetric APS was 2.89; 95% CI: 1.89-4.23. Among antiphospholipid antibodies, lupus anticoagulant was associated with incident cancers (aHR 2.608; 95% CI: 1.091-6.236). Our cohort study shows that the risk of cancer is substantially higher in women with a history of obstetric APS than in the general population, and in women with a similar initial clinical history but negative for antiphospholipid antibodies.

International audience; Background. Glioblastomas (GB) are the most common and lethal primary brain tumors. Significant progress has been made toward identifying potential risk factors for GB and diagnostic and prognostic biomarkers. However, the current standard of care for newly diagnosed GB, the Stupp protocol, has remained unchanged for over a decade. Large-scale translational programs based on a large clinicobiological database are required to improve our understanding of GB biology, potentially facilitating the development of personalized and specifically targeted therapies. With this goal in mind, a well-annotated clinicobiological database housing data and samples from GB patients has been set up in France: the French GB biobank (FGB).Methods. The biobank contains data and samples from adult GB patients from 24 centers in France providing written informed consent. Clinical and biomaterial data are stored in anonymized certified electronic case report forms. Biological samples (including frozen and formalin-fixed paraffin-embedded tumor tissues, blood samples, and hair) are conserved in certified biological resource centers or tumor tissue banks at each participating center.Results. Clinical data and biological materials have been collected for 1087 GB patients. A complete set of samples (tumor, blood and hair) is available for 66%, and at least one frozen tumor sample is available for 88% of the GB patients.ConclusionsThis large biobank is unique in Europe and can support the large-scale translational projects required to improve GB care. Additional biological materials, such as peritumoral brain zone and fecal samples, will be collected in the future, to respond to research needs.

Key Points Question Is the occurrence of preeclampsia or eclampsia during a first pregnancy associated with a future risk of cancer? Findings In this cohort study of 4 322 970 female individuals with and without preeclampsia or eclampsia during their first pregnancy, myelodysplastic syndromes or myeloproliferative diseases and kidney cancer were more common among those who experienced preeclampsia or eclampsia, whereas breast cancer was less common. Meaning The study’s findings suggest that there may be a pathophysiological association between preeclampsia or eclampsia during a first pregnancy and the incidence of some myelodysplastic syndromes or myeloproliferative diseases, kidney cancer, and breast cancer., Importance Preeclampsia or eclampsia (preeclampsia/eclampsia) during pregnancy induces major physiological changes and may be associated with specific cancer occurrences in later life. The current data regarding the association between preeclampsia/eclampsia and cancer are heterogeneous, and cancer risk after preeclampsia/eclampsia could be different depending on the organ. These uncertainties warrant reexamination of the association between preeclampsia/eclampsia and the risk of cancer overall and by specific cancer type. Objective To evaluate the risk of cancer, overall and by type, after preeclampsia/eclampsia during a first pregnancy. Design, Setting, and Participants This retrospective cohort study used data from the French hospital discharge database to identify all female individuals who had a pregnancy-associated hospitalization between January 1, 2010, and December 31, 2019. To allow a minimum of 2 years for the detection of medical history, individuals with a first detected pregnancy before January 1, 2012, were excluded, as were those with a cancer-associated hospitalization before or during their first detected pregnancy. Exposures, comorbidities, and occurrences of cancer were evaluated using data from the medico-administrative registers of hospitalizations in private and public French hospitals. Cox proportional hazards models were used to analyze cancer risk according to the occurrence of preeclampsia/eclampsia during first pregnancy. Exposures Preeclampsia/eclampsia-associated hospitalization during the first detected pregnancy. Main Outcomes and Measures The primary outcome was the incidence of cancer, including myelodysplastic or myeloproliferative diseases, after a first pregnancy with and without preeclampsia/eclampsia. Results After exclusions, a total of 4 322 970 female individuals (mean [SD] age at first detected pregnancy, 29.6 [6.2] years) with and without preeclampsia/eclampsia during their first pregnancy were included. Of those, 45 523 individuals (1.1%) were diagnosed with preeclampsia/eclampsia during their first detected pregnancy. The maximum follow-up was 8 years, during which 29 173 individuals (0.7%) were diagnosed with cancer. No significant difference in overall cancer incidence was found between those with and without preeclampsia/eclampsia during their first pregnancy (adjusted hazard ratio [AHR], 0.94; 95% CI, 0.84-1.05). Preeclampsia/eclampsia was associated with an increase in the risk of myelodysplastic syndromes or myeloproliferative diseases (AHR, 2.43; 95% CI, 1.46-4.06) and kidney cancer (AHR, 2.19; 95% CI, 1.09-4.42) and a decrease in the risk of breast cancer (AHR, 0.79; 95% CI, 0.62-0.99) and cervical cancer (AHR, 0.75; 95% CI, 0.58-0.96). Conclusions and Relevance In this study, a history of preeclampsia/eclampsia during first pregnancy was associated with an increase in the incidence of myelodysplastic or myeloproliferative diseases and kidney cancer and a decrease in the incidence of cervical and breast cancers. These associations might reflect an underlying common factor among preeclampsia/eclampsia and these pathologies and/or an association between preeclampsia/eclampsia and the development of these cancers., This cohort study uses data from the French hospital discharge database to assess the association between preeclampsia or eclampsia during first pregnancy and the risk of future cancer and some cancer-associated blood diseases among female participants with a first pregnancy between 2012 and 2019.

BackgroundThis study aims to compare improvements in Attention Deficit and Hyperactivity Disorder (ADHD) symptom severity between a group of ADHD children and parents undergoing a new therapeutic program based on third generation cognitive-behavioural therapy (Hyper-mCBT) and a similar group undergoing treatment-as-usual with the Barkley program.Methods248 children diagnosed with ADHD will be randomly assigned to either a Hyper-mCBT program or a Barkley program. This is a randomized (1:1), 2 parallel-group, superiority trial with evaluator blinding and stratification according to center and methylphenidate treatment. Hyper-mCBT program consists in a series of 16 simultaneous-but-separate therapies sessions for parents and for children.DiscussionMore effective psychotherapeutic approaches are needed for ADHD children. Pharmacotherapy seems to be more effective in reducing ADHD symptoms but it is not always helpful, carries side effects and it is rejected by many parents/professionals. Results for psychotherapy programs for ADHD are inconsistent although several studies have shown clinical improvements. This trial will substantiate encouraging preliminary results of an innovative psychotherapy program for both parents and children.Trial registration: Sponsor Number: PHRC-N/2016/JLC-01RCB Identification: 2017-A01349-44 Clinicaltrials.gov registration: NCT03437772 (first posted: February 19, 2018)

Background: The etiology of the central nervous system (CNS) tumors remains largely unknown. The role of pesticide exposure has been suggested by several epidemiological studies, but with no definitive conclusion. Objective: To analyze associations between occupational pesticide exposure and primary CNS tumors in adults in the CERENAT study. Methods: CERENAT is a multicenter case-control study conducted in France in 2004-2006. Data about occupational pesticide uses - in and outside agriculture - were collected during detailed face-to-face interviews and reviewed by experts for consistency and exposure assignment. Odds ratios (ORs) and 95% confidence intervals (95%CI) were estimated with conditional logistic regression. Results: A total of 596 cases (273 gliomas, 218 meningiomas, 105 others) and 1 192 age- and sex-matched controls selected in the general population were analyzed. Direct and indirect exposures to pesticides in agriculture were respectively assigned to 125 (7.0%) and 629 (35.2%) individuals and exposure outside agriculture to 146 (8.2%) individuals. For overall agricultural exposure, we observed no increase in risk for all brain tumors (OR=1.04, 0.69-1.57) and a slight increase for gliomas (OR=1.37, 0.79-2.39). Risks for gliomas were higher when considering agricultural exposure for more than 10 years (OR=2.22, 0.94-2.24) and significantly trebled in open field agriculture (OR=3.58, 1.20-0.70). Increases in risk were also observed in non-agricultural exposures, especially in green space workers who were directly exposed (OR=1.89, 0.82-4.39), and these were statistically significant for those exposed for over 10 years (OR=2.84, 1.15-6.99). Discussion: These data support some previous findings regarding the potential role of occupational exposures to pesticides in CNS tumors, both inside and outside agriculture.

Introduction Lung cancer (LC) has the highest cancer mortality worldwide with poor prognosis. Screening with low-dose computed tomography (LDCT) in populations highly exposed to tobacco has been proposed to improve LC prognosis. Our objective was to perform a systematic review and meta-analysis to evaluate the efficacy of screening by LDCT compared with any other intervention in populations who reported tobacco consumption for more than 15 years on LC and overall mortality. Methods We searched randomised controlled trials (RCTs) studying screening by LDCT compared with any other intervention in a population who reported an average smoking history greater than 15 pack-years from inception until the 19th February 2018 using Medline and Cochrane Library databases. Publication selection and data extraction were made independently by two double-blind reviewers. Results Seven RCTs were included in the meta-analysis which corresponds to 84,558 participants. A significant relative reduction of LC-specific mortality of 17% (risk ratio [RR] = 0.83, 95% confidence interval [CI]: 0.76–0.91) and a relative reduction of overall mortality of 4% (RR = 0.96, 95% CI: 0.92–1.00) was observed in the screening group compared with the control group. Conclusion In populations highly exposed to tobacco, screening by LDCT reduces lung cancer mortality.

Background Glioblastomas (GB) are the most common and lethal primary brain tumors. Significant progress has been made toward identifying potential risk factors for GB and diagnostic and prognostic biomarkers. However, the current standard of care for newly diagnosed GB, the Stupp protocol, has remained unchanged for over a decade. Large-scale translational programs based on a large clinicobiological database are required to improve our understanding of GB biology, potentially facilitating the development of personalized and specifically targeted therapies. With this goal in mind, a well-annotated clinicobiological database housing data and samples from GB patients has been set up in France: the French GB biobank (FGB). Methods The biobank contains data and samples from adult GB patients from 24 centers in France providing written informed consent. Clinical and biomaterial data are stored in anonymized certified electronic case report forms. Biological samples (including frozen and formalin-fixed paraffin-embedded tumor tissues, blood samples, and hair) are conserved in certified biological resource centers or tumor tissue banks at each participating center. Results Clinical data and biological materials have been collected for 1087 GB patients. A complete set of samples (tumor, blood and hair) is available for 66%, and at least one frozen tumor sample is available for 88% of the GB patients. Conclusions This large biobank is unique in Europe and can support the large-scale translational projects required to improve GB care. Additional biological materials, such as peritumoral brain zone and fecal samples, will be collected in the future, to respond to research needs.

Background Prostate cancer patients are known to suffer from poor sexual and urinary long-term side-effects following treatment, potentially impacting quality of life. The purpose of our study was to compare health-related quality of life at 3 years between prostate cancer patients and healthy controls according to key life-style characteristics. Secondary objectives were to compare urological dysfunction, sexual function, anxiety and depression.Methods Multicentric, case-control, observational prospective, open, follow-up study including 819 prostate cancer patients Results In total, 564 participants were included (mean age 67.9 years): 376 patients and 188 controls. Treatment breakdown was: 258 underwent RP, 90 received EBRT, 52 brachytherapy or HIFU, 15 CT, 26 ADT and 61 AS. There was no difference in median global quality of life between patients and controls (94.87 vs 94.15, p = 0.71). Multivariate analysis showed poorer social functioning in patients (24.3% vs. 16.3%, p = 0.0209), more dyspnea (22% vs. 12.4%, p = 0.0078), and yet less current pain (23% vs 33%, p = 0.0151).Conclusions Global health status score at 3 years after diagnosis was similar between patients and controls, though patients showed a significantly worse social functioning. Prostate cancer diagnosis per se does not impact the quality of life of patients. However, the therapeutic option that will be chosen following diagnosis should be carefully discussed with the medical staff in terms of benefit-risk ratios as it could have a long-term impact on urinary or erectile dysfunction.Trial registration: clinicaltrials.gov, NCT02854982. Registered 4 August 2016 – retrospectively registered, https://clinicaltrials.gov/ct2/show/NCT02854982

Background Prostate cancer patients are known to suffer from poor sexual and urinary long-term side-effects following treatment, potentially impacting quality of life. The purpose of our study was to compare health-related quality of life at 3 years between prostate cancer patients and healthy controls according to key life-style characteristics. Secondary objectives were to compare urological dysfunction, sexual function, anxiety and depression. Methods Multicentric, case-control, observational prospective, open, follow-up study including 819 prostate cancer patients Results In total, 564 participants were included (mean age 67.9 years): 376 patients and 188 controls. Treatment breakdown was: 258 underwent RP, 90 received EBRT, 52 brachytherapy or HIFU, 15 CT, 26 ADT and 61 AS. There was no difference in median global quality of life between patients and controls (94.87 vs 94.15, p = 0.71). Multivariate analysis showed poorer social functioning in patients (24.3% vs. 16.3%, p = 0.0209), more dyspnea (22% vs. 12.4%, p = 0.0078), and yet less current pain (23% vs 33%, p = 0.0151). Conclusions Global health status score at 3 years after diagnosis was similar between patients and controls, though patients showed a significantly worse social functioning. Prostate cancer diagnosis per se does not seem to impact the quality of life of patients Trial registration clinicaltrials.gov, NCT02854982. Registered 4 August 2016, retrospectively registered.

Background Glioblastoma is the most frequent primary malignant brain tumor. In daily practice and at whole country level, oncological care management for glioblastoma patients is not completely known. Objectives To describe oncological patterns of care, prognostic factors, and survival for all patients in France with newly-diagnosed and histologically confirmed glioblastoma, and evaluate the impact of extended temozolomide use at the population level. Methods Nationwide population-based cohort study including all patients with newly-diagnosed and histologically confirmed glioblastoma in France in 2008 and followed until 2015. Results Data from 2053 glioblastoma patients were analyzed (male/female ratio 1.5, median age 64 years). Median overall survival (OS) was 11.2 [95% confidence interval (CI) 10.7–11.9] months. The first-line therapy and corresponding median survival (MS, in months) were: 13% did not receive any oncological treatment (biopsy only) (MS = 1.8, 95% CI 1.6–2.1), 27% received treatment without the combination of radiotherapy (RT)–temozolomide (MS = 5.9, 95% CI 5.5–6.6), 60% received treatment including the initiation of the concomitant phase of RT–temozolomide (MS = 16.4, 95% CI 15.2–17.4) whom 44% of patients initiated the temozolomide adjuvant phase (MS = 18.9, 95% CI 18.0–19.8). Only 22% patients received 6 cycles or more of adjuvant temozolomide (MS = 25.5, 95% CI 24.0–28.3). The multivariate analysis showed that the risk of mortality was significantly higher for the non-progressive patients who stopped at 6 cycles (standard protocol) than those who continued the treatment, hazard ratio = 1.5 (95% CI 1.2–1.9). Conclusion In non-progressive patients, prolonging the adjuvant temozolomide beyond 6 cycles may improve OS. Electronic supplementary material The online version of this article (10.1007/s11060-018-03065-z) contains supplementary material, which is available to authorized users.

International audience; Occupational exposure to pesticides concerns a wide population of workers not only in agriculture. The reliability of self-reported information on pesticide use is questionable because of the diversity of use. The PESTIPOP job-exposure matrix has been designed to assess pesticide occupational exposure in the general population. The matrix is composed of two axes: the first axis corresponding to jobs (combinations of occupations and industries) and the second one to pesticide exposure. The estimated exposure metric is the probability of exposure coupled with a reliability assessment (low, medium or high). These metrics were defined by combining different sources: (1) an a priori expert assessment (Agricultural industry experts); (2) data from a multicenter case-control study on brain tumors in the general population (occupational history, specific questionnaires); and (3) an a posteriori expert assessment based on the data of a case-control study. So far, 2559 jobs have been identified and 209 (8%) were found to be exposed to pesticides. Jobs with agricultural exposure had a higher exposure probability than jobs with non-agricultural exposure (wood preservation, park maintenance, pest control). Indirect exposure was more frequent than direct exposure. The PESTIPOP matrix will be transcoded into international classifications for use in epidemiological studies.

International audience; Vitamin K antagonists are widely used, yet have a slim therapeutic margin and high iatrogenicity. Patients are monitored through international normalised ratio (INR) by venipuncture, but coagulometers could measure INR by capillary puncture. This prospective study evaluated the clinical concordance of capillary INR versus venous INR in 31 nursing home patients. Concordance was good and mean time in therapeutic range (TTR) markedly increased. Capillary INR is thus reliable, could improve TTR and decrease iatrogenicity.

International audience; Aims: To evaluate the safety and efficacy of the Uphold LITE mesh in the treatment of pelvic organ prolapse at 12-month follow-up.Methods: Women undergoing a mesh surgery due to an anterior prolapse plus a symptomatic anterior prolapse (classed as pelvic organ prolapse quantification stage ≥2) were included in this prospective, multicentre, observational study. The primary endpoint was a composite outcome including a good anatomical correction, no prolapse symptoms, and no reintervention for an anterior or apical recurrent prolapse within 12 months of surgery. Secondary outcomes included safety, improvements in quality of life (QoL), and risk factor for recurrence. This study was registered with ClinicalTrials.gov, number NCT01559168.Results: A total of 121 patients were included. Symptomatic and anatomic cure rates were 94% (95 of 101) and 76.8% (76 of 99), respectively. The composite success rate was 72.4% (71 of 98). The rate of reoperation for apical or anterior recurrent prolapse was 3.9% (4 of 103). Anatomical anterior or apical recurrence occurred in 18.2% (18 of 97) and 7.2% (7 of 97) of patients, respectively. The composite success rate was significantly higher in centres where more than 30 patients had been treated (80% vs 50%; P = .045). The rate of serious complication was 5.4% (6 of 111). Improvements were recorded in QoL including sexual function.Conclusions: The Uphold LITE mesh procedure provides satisfactory outcomes in the treatment of anterior and apical prolapse, particularly in high-volume centres. The rates of adverse effects and reintervention for recurrent prolapse were acceptable.

International audience; Importance: Professional use of pesticides is a risk factor for non-Hodgkin lymphoma. The main biological mechanisms of pesticides and chemotherapy are genotoxicity and reactive oxygen species generation. Cellular adaptation among patients exposed to low doses of genotoxic and oxidative compounds might hinder chemotherapy efficiency in patients with lymphoma. Objective: To examine the association of occupational exposure to pesticides with immunochemotherapy response and survival among patients treated for diffuse large B-cell lymphoma. Design, setting, and participants: This retrospective cohort study assessed patients treated from July 1, 2010, to May 31, 2015, for diffuse large B-cell lymphoma, with a 2-year follow-up. The study took place at 6 university and nonuniversity hospitals in Languedoc-Roussillon, France. A total of 404 patients with newly diagnosed diffuse large B-cell lymphoma treated with anthracycline-based immunochemotherapy were included before the study began. Occupational history was reconstructed for 244 patients and analyzed with the PESTIPOP French job-exposure matrix to determine likelihood of occupational exposure to pesticides. Analysis of the data was performed from July 15, 2017, to July 15, 2018. Main outcomes and measures: Treatment failure (ie, partial response, stable disease, disease progression, or interruption for toxic effects) rate, 2-year event-free survival, and overall survival between exposed and nonexposed patients after adjustment for confounding factors. Results: A total of 244 patients (mean [SD] age, 61.3 [15.2] years; 153 [62.7%] male) had complete occupational data. Of these patients, 67 (27.4%) had occupational exposure to pesticides, with 38 exposed through agricultural occupations. Occupational exposure was not associated with clinical and biological characteristics at diagnosis. Occupationally exposed patients had a significantly higher treatment failure rate (22.4% vs 11.3%; P = .03; adjusted odds ratio [AOR] for confounding factors, 3.0; 95% CI, 1.3-6.9); this difference was higher among patients with exposing agricultural occupations compared with other patients (29.0% vs 11.7%; AOR, 5.1; 95% CI, 2.0-12.8). Two-year event-free survival was 70% in the occupationally exposed group vs 82% in the unexposed group (adjusted hazard ratio [AHR] for confounding factors, 2.2; 95% CI, 1.3-3.9). Among patients with exposing agricultural occupations compared with other patients, the difference was more pronounced (2-year event-free survival, 56% vs 83%; AHR, 3.5; 95% CI, 1.9-6.5). Similarly, 2-year overall survival was lower in the group of patients with exposing agricultural occupations compared with other patients (81% vs 92%; AHR, 3.9; 95% CI, 1.5-10.0). Conclusions and relevance: This retrospective study showed that agricultural occupational exposure to pesticides was associated with treatment failure, event-free survival, and overall survival among patients with diffuse large B-cell lymphoma.

International audience; Objective To assess morbidity and mortality following pelvic organ prolapse surgery in France, irrespective of the surgical technique, using a broad national database. Materials and methods: This descriptive multicenter retrospective study was conducted using a database populated via an application run by a professional association. Results 286 gynecologists contributed data to the database. Of the 4322 surgeries analyzed, an abdominal approach was used in 975 of cases (22.5%), a vaginal approach in 3277 (75.9%), and a combined approach in 68 (1.6%). After one year, abdominal surgery was associated with higher rates of de novo urinary incontinence, constipation, and intestinal obstruction, whereas vaginal surgery was associated with higher rates of urinary retention, hematoma, de novo chronic pain, and vaginal mesh extrusion. There was no significant difference between the groups in the incidence of severe complications. After one year, vaginal mesh-augmented cystocele repair was associated with higher rates of de novo urinary incontinence, de novo chronic pain, and reoperation than native tissue repair. Mesh repair was also associated with higher rates of severe complications at one year. Conclusion After pelvic organ prolapse surgery, the perioperative morbidity and mortality associated with transabdominal and transvaginal approaches are similar. However, transvaginal mesh repair is associated with greater perioperative morbidity than transvaginal native tissue repair.

Summary Background Little information is available on the long-term incidence of bleeding events after ST-segment elevation myocardial infarction (STEMI) with the current antithrombotic strategy. Aims To evaluate the effect of bleedings for up to 12 months on clinical events and therapeutic compliance in unselected STEMI patients treated with prasugrel or clopidogrel. Methods Patients were treated with clopidogrel or prasugrel according to guidelines. The primary endpoint was first occurrence of a bleeding event from hospital discharge to 12 months, assessed by the Bleeding Academic Research Consortium (BARC) classification using a dedicated questionnaire. Topography of bleedings, causes of premature cessation and ischaemic events were compared between clopidogrel- and prasugrel-treated patients. Results A total of 390 patients were enrolled (211 in the prasugrel group, 179 in the clopidogrel group). Elderly, female and low-body weight patients were more likely to receive clopidogrel. At 12 months, the incidence of major bleedings (BARC 3) was lower with prasugrel (1% vs 6%; P = 0.02), mainly due to fewer transfusions. Elderly age was a risk factor for severe bleeding. Premature treatment cessation was related to ischaemic complications (P = 0.03), and occurred more frequently with prasugrel (P = 0.001). One-year mortality was very low (1.9 per 100 person-years, 95% confidence interval 0.9–4.0), and was higher in the clopidogrel group (P = 0.03). Conclusions In this unselected STEMI population, the rate of major bleedings with prasugrel at 12 months was low, but nuisance bleedings were frequent and led to more premature cessations than with clopidogrel. Prevention of bleeding complications, even minor, is necessary to prevent disruption of antithrombotic medication.

We assessed prognostic factors in relation to OS from progression in recurrent glioblastomas. Retrospective multicentric study enrolling 407 (training set) and 370 (external validation set) adult patients with a recurrent supratentorial glioblastoma treated by surgical resection and standard combined chemoradiotherapy as first-line treatment. Four complementary multivariate prognostic models were evaluated: Cox proportional hazards regression modeling, single-tree recursive partitioning, random survival forest, conditional random forest. Median overall survival from progression was 7.6 months (mean, 10.1; range, 0-86) and 8.0 months (mean, 8.5; range, 0-56) in the training and validation sets, respectively (p = 0.900). Using the Cox model in the training set, independent predictors of poorer overall survival from progression included increasing age at histopathological diagnosis (aHR, 1.47; 95% CI [1.03-2.08]; p = 0.032), RTOG-RPA V-VI classes (aHR, 1.38; 95% CI [1.11-1.73]; p = 0.004), decreasing KPS at progression (aHR, 3.46; 95% CI [2.10-5.72]; p

The incidence of glioblastoma (GBM) has increased in patients aged 70 years or older, and will continue to grow. Elderly GBM patients have been excluded from most clinical trials; furthermore, optimal care management as well as benefit/risk ratio of GBM treatments are still being debated. This study describes oncological patterns of care, prognostic factors, and survival for patients ≥70 years in France. We identified patients over 70 with newly diagnosed and histologically confirmed GBM on data previously published by the French Brain Tumor DataBase. We included 265 patients. Neurological deficits and mental status disorders were the most frequent symptoms. The surgery consisted of resection (RS n = 95) or biopsy (B n = 170); 98 patients did not have subsequent oncological treatment. After surgery, first-line treatment consisted of radiotherapy (RT n = 76), chemotherapy (CT n = 52), and concomitant radiochemotherapy (CRC n = 39). The median age at diagnosis was 76, 74, and 73 years, respectively, for the untreated, B + RT and/or CT, RS ± RT and/or CT groups. Median survival (in days, 95 % CI) with these main strategies, when analyzed according to surgical groups, was: B-CT n = 41, 199[155–280]; B-CRC n = 21, 318[166–480]; B-RT n = 37, 149[130–214]; RS-CT n = 11, 245[211–na]; RS-CRC n = 18, 372[349–593]; RS-RT n = 39, 269[218–343]. This population study for elderly GBM patients is one of the most important in Europe, and could be considered as a historical cohort to compare future treatments. Moreover, we can hypothesize that elderly patients (versus patients

Introduction: Lymphoma incidence continues to rise in France since early 80', although differently among subtypes. Recent improvements in patient survival in major lymphoma subtypes at populational level raise new questions about patient outcome (in specific subgroups) and survivorship (i.e. quality of life, long term sequelae). Numerous epidemiological studies have investigated factors related to lymphoma risk, but far fewer have addressed the extent to which socioeconomic status, social institutional context (i.e. healthcare system), social relationships, environmental context (exposures), individual behaviours (lifestyle) or genetic determinants influence lymphoma outcomes, especially in the general population. Moreover, the knowledge of the disease behaviour achieved from clinical trials data is partly biased because of patient selection. Study Design and Methods: The REALYSA ("REal world dAta in LYmphoma and Survival in Adults") study is a real-life multicentric cohort set in France areas mostly covered by population-based cancer registries to study the prognostic value of epidemiological, clinical and biological factors with a prospective 9-year follow up. ClinicalTrials.gov identifier is NCT03869619. We aim to include 6000 patients over 4 years. Adult patients without lymphoma history and newly diagnosed of one of the following 7 lymphoma subtypes (diffuse large B cell (DLBCL), follicular (FL), marginal zone (MZL), mantle cell (MCL), Burkitt, Hodgkin (HL), T-cell (T-NHL)) are offered to participate during a medical consultation with their hematologist. Exclusion criteria are: having already received anti-lymphoma treatment (except pre-phase) and having a documented HIV infection. After having given signed informed consent, participants fill in three auto-questionnaires regarding lifelong history of residences and occupations, quality of life (QoL / QLQ-C30 questionnaire) and social support (SS / SSQ6 questionnaire). Patients are then interviewed to collect their sociodemographic characteristics, medical and familial history, professional and domestic exposures to major chemicals and pesticides, lifestyle and women health. Clinical data are obtained using patients medical records, including care pathway, medical history, concomitant treatments, initial diagnosis characteristics, nodal/extra-nodal involvement, exams performed, staging, laboratory data, serologic tests, geriatric screening (G8 questionnaire), treatments received (including pre-phase, detailed treatment phases and molecules, reasons for treatment discontinuation), progressions, and treatment response evaluation. Biological samples at baseline and during treatment are collected including plasma and peripheral mononuclear cells. Additionally, a virtual tumor biobank is constituted for baseline tumor samples. The diagnosis will be ensured thanks to the review of French Lymphopath network. Follow-up, including clinical outcomes, new morbidities, lifestyle, professional situation, QoL, SS, fertility, health behavior, are collected every 6 months in the first 3 years and every year thereafter. Results: A pilot phase was implemented between November 2018 and June 2019 in 7 French hospitals/clinics. By June 30, 328 patients were recruited. Biological samples at baseline were obtained for 81% of included patients (n=265). 52% were male and 48% were female. The median age was 62 years (range: 18-95). The histological subtypes were the following (n=308 patients with complete data): 132 DLBCL (42.8%); 59 FL (19.5%); 52 HL (16.9%); 29 MCL (9.4%); 22 MZL (7.1%); 13 T-NHL (4.2%); 1 other (0.3%). We observed a good adherence to clinical research process despite the complexity of data collection. An extension phase with 10 additional centres will be launched during the last 2019 trimester. Discussion: The pilot phase of REALYSA study showed a good compliance to study guidelines and a good quality of data collected at baseline. Consequently, the study design is prospectively feasible in real-life setting. This cohort will constitute an innovative platform for clinical, biological, epidemiological and socio-economical research projects. Disclosures Oberic: Takeda: Membership on an entity's Board of Directors or advisory committees; Janssen: Honoraria; Roche: Membership on an entity's Board of Directors or advisory committees. Salles:Amgen: Honoraria, Other: Educational events; Novartis, Servier, AbbVie, Karyopharm, Kite, MorphoSys: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Educational events; BMS: Honoraria; Roche, Janssen, Gilead, Celgene: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Educational events; Takeda: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Educational events; Merck: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Autolus: Consultancy, Membership on an entity's Board of Directors or advisory committees; Epizyme: Consultancy, Honoraria.

Plasmatic proteasome (p-proteasome) has recently been described as a new marker for metastatic melanoma. The objective of this study was to compare the diagnostic and prognostic values of p-proteasome with three other melanoma serological markers: S100B protein, melanoma inhibitory activity protein (MIA) and lactate dehydrogenase (LDH) in the plasma of 121 stage I-IV melanoma patients. Laboratory analyses were performed by standardized ELISA (p-proteasome, MIA), immunoluminometric assay (S100B) and colorimetry (LDH). We found that all markers were relevant for discriminating metastatic from nonmetastatic patients but p-proteasome displayed the highest diagnostic accuracy. P-proteasome and S100B were the most sensitive (58.1%) and p-proteasome and MIA the most specific (98.7 and 100%) in detecting metastatic disease. P-proteasome and S100B had the highest area under receiver operating characteristics curve, 0.811 (95% CI: 0.725-0.897) and 0.822 (95% CI: 0.738-0.906), respectively. These two markers were the best in detecting patients with lymph node metastases. S100B, MIA and LDH diagnostic accuracy was increased when these markers were combined with p-proteasome. As shown with univariate analysis, shorter progression-free and overall survival rates were significantly associated with elevated plasma levels of each markers. The multivariate Cox regression analysis identified p-proteasome as the only independent predictor of a poorer progression-free survival (p = 0.030). In conclusion, this comparative study established that p-proteasome quantification in combination with other melanoma biomarkers is an attractive approach for the biological follow-up of melanoma patients.

Background: Little is known about the relationship between diet and central nervous system (CNS) tumors, especially in terms of their histological subtypes. This study investigated the overall associations between food groups, alcohol intake and CNS tumors, and in particular about the associations between neuroepithelial tumors and meningiomas. Methods: Data were collected through the CERENAT (CEREbral tumors: a NATional study) case-control study conducted in France during the period 2004-2010. Data were available for 1,479 subjects (494 cases, including 201 neuroepithelial tumors, 193 meningiomas, 100 other CNS tumors, and their 985 matched controls). Conditional logistic regressions for matched sets were adjusted based on the participants' educational level, occupation, smoking status and frequency of food group consumption. Results: A heavy consumption of grilled meat and poultry was associated with neuroepithelial tumors in a dose-related relationship (ORQ4vsQ1 = 3.72, 95% CI 1.62-8.52, p = 0.005). Higher fruit and vegetable intake was inversely associated with meningiomas (for fruits: ORQ4vsQ1 = 0.38, 95% CI 0.17-0.87, p = 0.06, for vegetables ORQ4vsQ1 = 0.26, 95% CI 0.11-0.62, p = 0.007). Consumption of alcohol on a daily basis was inversely associated with CNS tumors especially for meningiomas (ORQ4vsQ1 = 0.33, 95% CI 0.18-0.61, p = 0.001). Conclusions: Results obtained in terms of grilled meat, fruits and vegetables consumption were in line with those published in epidemiological literature. Contradictions in results between neuroepithelial tumors and meningiomas confirmed the need to analyze the effects of dietary factors on the basis of the histological subtypes of CNS tumors.

The assessment of a health technology is frequently accompanied by uncertainty about its impact, at short or long terms, on the health of the population. The Health Authorities may request additional « post-registration » data that will allow a relevant reassessment of these technologies. The responsibility to collect this information lies with the industry and the HAS evaluates the methodology. This guideline provides practical benchmarks on methodological aspects of these studies. It describes the different types of studies to consider depending on the objectives, including the use of databases and cohorts and European studies. It emphasizes the importance of establishing a scientific committee, clearly defining the objectives of the study, justifying the methodological choices, documenting the representativeness or completeness of centers, investigators and patients, limiting the number of lost of follow-up patients and missing data, describing the statistical analysis methods, the bias and their possible impact on results. The publication of the results of these studies is strongly encouraged.

The most-used prognostic scheme for malignant gliomas included only patients aged 18 to 70 years. The purpose of this study was to develop a prognostic model for patients ≥70 years of age with newly diagnosed glioblastoma.A total of 437 patients ≥70 years of age with newly diagnosed glioblastoma, pooled from 2 tertiary academic institutions, was identified for recursive partitioning analysis (RPA). The resulting prognostic model, based on the final pruned RPA tree, was validated using 265 glioblastoma patients ≥70 years of age from a data set independently compiled by a French consortium.RPA produced 9 terminal nodes, which were pruned to 4 prognostic subgroups with markedly different median survivals: subgroup I = patients75.5 years of age who underwent surgical resection (9.3 months); subgroup II = patients ≥75.5 years of age who underwent surgical resection (6.4 months); subgroup III = patients with Karnofsky performance status of 70 to 100 who underwent biopsy only (4.6 months); and subgroup IV = patients with Karnofsky performance status70 who underwent biopsy only (2.3 months). Application of this prognostic model to the French cohort also resulted in significantly different (P.0001) median survivals for subgroups I (8.5 months), II (7.7 months), III (4.3 months), and IV (3.1 months).This model divides elderly glioblastoma patients into prognostic subgroups that can be easily implemented in both the patient care and the clinical trial settings. This purely clinical prognostic model serves as a backbone for the future incorporation of the increasing number of potential molecular prognostic markers.

Background and purposeThis work aimed at prospectively record all primary central nervous system tumor (PCNST) cases in France, for which histological diagnosis was available. The objectives were to (i) create a national database and network to perform epidemiological studies, (ii) implement clinical and basic research protocols, and (iii) harmonize the health care of patients affected by PCNST.MethodsThe methodology is based on a multidisciplinary national network already established by the French Brain Tumor DataBase (FBTDB) (Recensement national histologique des tumeurs primitives du système nerveux central [RnhTPSNC]), and the active participation of the Scientific Societies involved in neuro-oncology in France.ResultsFrom 2004 to 2009, 43,929 cases of newly diagnosed and histologically confirmed PCNST have been recorded. Histological diagnoses included gliomas (42,4%), all other neuroepithelial tumors (4,4%), tumors of the meninges (32,3%), nerve sheath tumors (9,2%), lymphomas (3,4%) and others (8,3%). Cryopreservation was reported for 9603 PCNST specimens. Tumor resections were performed in 78% cases, while biopsies accounted for 22%. Median age at diagnosis, sex, percentage of resections and number of cryopreserved tumors were detailed for each histology, according to the WHO classification.Discussion/conclusionMany current applications and perspectives for the FBTDB are illustrated in the discussion. To our knowledge, this work is the first database in Europe, dedicated to PCNST, including clinical, surgical and histological data (with also cryopreservation of the specimens), and which may have major epidemiological, clinical and research implications.RésuméObjectifCe travail a pour objectif de recenser de manière prospective l’ensemble des cas de tumeurs primitives du système nerveux central (TPSNC), ayant un diagnostic histologique, en France. Les buts sont de créer une base de données et un réseau national pour favoriser la mise en place d’études épidémiologiques, biologiques et cliniques, et d’harmoniser la prise en charge des patients atteints de TPSNC.MéthodeLa méthodologie est basée sur l’existence d’un réseau national multidisciplinaire déjà établi par le Recensement national histologique des tumeurs primitives du système nerveux central (RnhTPSNC) (French Brain Tumor DataBase [FBTDB]), et la participation active des sociétés savantes impliquées en neuro-oncologie.RésultatsDe 2004 à 2009, 43 929 cas incidents de TPSNC ayant une confirmation histologique ont été recensés : gliomes (42,4 %), ensemble des autres tumeurs neuroépithéliales (4,4 %), tumeurs des méninges (32,3 %), tumeurs des nerfs intracrâniens et/ou intrarachidiens (9,2 %), lymphomes (3,4 %), et autres (8,3 %). La cryopréservation a été notée pour 9603 cas de TPSNC. Une intervention d’exérèse a été réalisée dans 78 % des cas, et une biopsie dans 22 %. L’âge médian au diagnostic, le sexe, le pourcentage de tumeurs réséquées, et le nombre de cas cryopréservés sont détaillés pour chaque histologie.Discussion/conclusionLes principales applications actuelles et futures du RnhTPSNC sont présentées dans la discussion. À notre connaissance, ce travail constitue la première base de données en Europe, dédiée aux TPSNC, qui recense des données cliniques, chirurgicales et histologiques (incluant la cryopréservation), et ses applications et perspectives sont très nombreuses.

This work aimed to prospectively record all primary central nervous system tumor (PCNST) cases in France, for which histological diagnosis is available. The objectives were to (i) create a national registry and a network to perform epidemiological studies; (ii) implement clinical and basic research protocols; and (iii) harmonize the health care of patients affected by PCNST. For 5 years, 25 756 cases of newly diagnosed and histologically confirmed PCNST have been recorded. Histological diagnoses included glioma (48.9%), all other neuroepithelial tumors (5%), meningioma (28.8%), nerve sheath tumors (8.4%), lymphoma (3.2%) and others (5.7%). Cryopreservation was reported for 6018 PCNST specimens. Tumor resections (R) were performed in 78% cases, while biopsies accounted for 22%. Median age (MA), sex, percentage R and number of cryopreserved tumors were detailed for each histology; for example, out of 6053 glioblastomas (MA 63 years, male 59.4%, R 62%, 1611 were cryopreserved), and out of 37 atypical teratoid/rhabdoid tumors (MA 2 years, male 56.8%, R 94%, 17 were cryopreserved). This database or databank dedicated to PCNST cases contains detailed data on clinical, histological and other characteristics, such as the inclusion of data on cryopreserved specimens that are not available in other European registries. Therefore, this is a valuable resource that can be used for planning future epidemiological and clinical research.

Arteriovenous fistula (AVF) is still in 2010 the gold standard of vascular(2) access in haemodialysis (HD) patients. Nevertheless it may be difficult to obtain and/or to use AVF in elderly. With this prospective randomised pilot study, we compare two strategies of vascular access in 70 years old or more new HD patients. AVF were compared to tunnelled jugular vein catheters (TIJC) with taurolidine as bacterial lock solution. Results were as follow: [table: see text] The responses with the visual analogic scale of comfort was 8/10 for TIJC and 5/10 with AVF * P

Plasmatic proteasome (p-proteasome) also called circulating proteasome has recently been described as a tumor marker. We investigated the diagnostic and prognostic accuracies of p-proteasome levels in a melanoma population classified according to the American Joint Committee on Cancer staging system. Using an ELISA test, we measured p-proteasome levels in 90 patients and 40 controls between March 2003 and March 2008. The subunit composition of p-proteasomes was determined in metastatic melanoma by proteomic analysis. The mean p-proteasome levels were correlated with stages (P 4300 ng/ml) were significantly correlated with an increased risk of progression [hazard ratio (HR) = 7.34; 95% CI 3.54-15.21, P < 0.0001] and a risk of death (HR = 5.92; 95% CI 2.84-12.33, P < 0.0001). In multivariate analysis, high p-proteasome levels were correlated with a poorer clinical outcome in the subgroup analysis limited to patients with disease stages I, II and III. Proteomic analysis confirmed the presence of all proteasome and immunoproteasome subunits. Taken together, these results indicate that p-proteasomes are a new marker for metastatic dissemination in patients with melanoma.

Summary Importance Professional use of pesticides is a risk factor for non-Hodgkin lymphoma. The main biological mechanisms of both pesticides and chemotherapy are genotoxicity and reactive oxygen species generation. Cellular adaptation among patients exposed to low doses of genotoxic and oxidative compounds may hinder chemotherapy efficiency in lymphoma patients. Objective We aim to determine the influence of occupational exposure to pesticides on response to immuno-chemotherapy and survival of patients treated for Diffuse Large B Cell Lymphoma (DLBCL). Design The ProLyPhy study is a retrospective cohort of patients treated between 2010 and mid-2015, for DLBCL, with a least 2-year follow-up. Setting The study took place in six hospitals of central southern France (Languedoc-Roussillon district): two university hospitals, three general hospitals, and one private hospital. Participants We pre-included 404 patients with newly-diagnosed DLBCL treated with anthracycline-based immuno-chemotherapy (R-CHOP like). Occupational history was reconstructed for 244 patients. Occupational data were analysed with the Pestipop French job-exposure matrix to determine probability of occupational exposure to pesticides, and with the Pestimat French crop exposure matrix for farming activities to characterise the probability of using specific compounds. Main outcome and measure We have compared complete response (CR), 2-year event-free survival (EFS) and overall survival (OS) of exposed and non-exposed patients, after adjustment on confounding factors. Results Average age was 61.3 years (range 19–90), 62.7% of patients were male, 67 had occupational exposure to pesticides, of which 38 from farming activities. Occupational exposure did not impact clinical and biological characteristics at diagnostic. We observed that exposed patients had significantly lower CR rate: 77.6% versus 88.7% (P = 0.027), OR = 0.31 (0.55–0.09, P = 0.007); this difference was higher among farmers: 68.6% CR versus 87.2%, P = 0.005, OR = 0.22 (0.56–0.09, P = 0.001). Two-year EFS was 70% in the occupationally-exposed group versus 82%, HR = 2.1 (95% CI: 1.2–3.6, P = 0.008). Among farmers, the difference was more pronounced: 2-year EFS was 56% versus 83%, HR = 3.1 (95% CI: 1.7–5.6, P Conclusion and relevance This retrospective study suggests that agricultural occupational exposure to pesticides is an independent risk factor for treatment failure, EFS and OS in DLBCL. Trial registration The study was registered in ClinicalTrials.gov ( NCT02898870 ).

1564Background: Professional use of pesticides is a risk factor for non-Hodgkin lymphoma. The main biological mechanisms of both pesticides and chemotherapy are genotoxicity and reactive oxygen spe...

This report, an audit requested by the French government, describes oncological patterns of care, prognostic factors, and survival for patients with newly diagnosed and histologically confirmed glioblastoma multiforme (GBM) in France. The French Brain Tumor DataBase, which is a national multidisciplinary (neurosurgeons, neuropathologists, radiotherapists, neurooncologists, epidemiologists, and biostatisticians) network, prospectively collected initial data for the cases of GBM in 2004, and a specific data card was used to retrospectively collect data on the management and follow-up care of these patients between January 1, 2004, and December 1, 2006. We recorded 952 cases of GBM (male/female ratio 1.6, median age 63.9 years, mean preoperative Karnofsky performance status [KPS] 79). Surgery consisted of resection (RS; n = 541) and biopsy (n = 411); 180 patients did not have subsequent oncological treatment. After surgery, first-line treatment (n = 772) consisted of radiotherapy (RT) and temozolomide (TMZ) concomitant +/- adjuvant in 314 patients, RT alone in 236 patients, chemotherapy (CT) alone in 157 patients, and other treatment modalities in 65 patients. Median overall survival was 286 days (95% CI, 266-314) and was significantly affected by age, KPS, and tumor location. Median survival (days, 95% CI) associated with these main strategies, when analyzed by a surgical group, were as follows: RS + RT-TMZ((n=224)): 476 (441-506), biopsy + RT-TMZ((n=90)): 329 (301-413), RS + RT((n=147)): 363 (331-431), biopsy + RT((n=89)): 178 (153-237), RS + CT((n=61)): 245 (190-361), biopsy + CT((n=96)): 244 (198-280), and biopsy only((n=118)): 55 (46-71). This study illustrates the usefulness of a national brain tumor database. To our knowledge, this work is the largest report of recent GBM management in Europe.

The Sapporo criteria-related definition commonly used for diagnosis of the antiphospholipid syndrome (APS) associates the occurrence of thrombotic and/or obstetrical events with persistently positive antiphospholipid antibodies (aPL-Ab), including lupus anticoagulant (LAC), anticardiolipin IgG (aCL-G) or IgM, and/or anti-b2-glycoprotein I IgG or IgM antibodies. Criteria used to define the purely obstetrical clinical subtype of the APS syndrome include the aPLs listed above plus a fetal loss later than 10-weeks gestation, 3 or more unexplained consecutive embryonic losses before the 10th week gestation, or eclampsia or features of placental insufficiency requiring the preterm birth before 34 weeks of a morphologically normal child. Some investigators have questioned the serological criteria associated with this form of APS and have suggested that the aCL-G, anticardiolipin IgM, and anti-b2-glycoprotein I IgM measurements should be excluded. To determine the effects of the various aPL-Ab subtypes on pregnancy outcome, the investigators prospectively monitored women who had had an unexplained embryonic loss during their first pregnancy and were undergoing their untreated second pregnancy. They selected women who did not have APS; any hormonal abnormalities; or inflammatory, infectious, or malignant diseases; and who had normal parental karyotypes; the pregnancy outcomes of 142 women who tested positive for at least 1 of the 5 classical aPL-Abs were compared with those of 142 control women who were confirmed to be aPL-Abs negative. Compared with the women without aPL-Abs, the aPL-Ab-positive women experienced more clinical complications during their second pregnancy, including pregnancy loss (of which the majority were embryonic losses), preeclampsia, placental abruption, and intrauterine fetal growth restriction. The presence of LAC alone (type IIa aPL-Ab positivity) was associated with the highest risk of recurrent embryonic loss and intrauterine growth restriction. Positive tests for combinations of aPL-Ab (type I aPL-Ab positivity) were associated with the highest risk of late complications, placental abruption, and preeclampsia. A finding of anti-b2-glycoprotein I IgM positivity had no apparent diagnostic clinical relevance. These findings demonstrate that among women with a first unexplained pregnancy loss before the 10th week of gestation, those who are aPL-Abs positive have a higher risk of complications in their next pregnancy, including embryonic loss, preeclampsia, placental abruption, and intrauterine growth restriction, than women who are aPL-Abs negative. These findings suggest that the aPL-Ab LAC, aCL-G or IgM, and anti-b2-glycoprotein I IgG are helpful in identifying patients at increased risk of an adverse outcome, whereas anti-b2-glycoprotein I IgM has questionable diagnostic value.

Background and purpose Glioblastoma, the most common malignant primary brain tumor in adults, is usually rapidly fatal. The current care standards for newly diagnosed glioblastoma consist, when feasible, in surgical resection, radiotherapy, and chemotherapy, as described in the Stupp protocol. Despite optimal treatment, nearly all malignant gliomas recur. If the tumor is symptomatic for mass effect, repeated surgery may be proposed. Methods We retrospectively analyzed the survival of patients with histologically confirmed primary glioblastoma (WHO grade 4) who were operated in two centers between January 2004 and December 2007. All patients who underwent a second resection for recurrent glioblastoma were included. Results During this period, 320 patients were operated in the two centers, with 240 surgical resections and 80 surgical biopsies. In the surgical resection group, 8.3% (20 patients) underwent a second surgical resection for glioblastoma. The mean age was 52 years. At the end of the study, seven patients were alive. The median survival was 24 months and progression-free survival was 7.5 months. Conclusions The effect of resection of recurrent glioblastoma on survival has not been extensively studied. No randomized trials have been conducted. Our data were globally identical to other retrospective studies. Selected patients with recurrent glioblastoma may be candidates for repeated surgery when the situation appears favorable based on assessment of the individual patient's factors. Factors such medical history, neurological status, location of the tumor, and progression-free survival have been proven in retrospective studies to give better results.

SummaryAdministration of heparin in the secondary prevention of placental vascular complications is still experimental. In women with a previous placental abruption, we investigated the effectiveness of enoxaparin, a low-molecular-weight heparin, in preventing these complications. Between January 2000 and January 2009, 160 women from the NOHA First cohort, with previous abruptio placentae but no foetal loss during their first pregnancy and negative for antiphospholipid antibodies, were randomised to either a prophylactic daily dose of enoxaparin starting from the positive pregnancy test (n=80), or no enoxaparin (n=80). The primary outcome was a composite of at least one of the following: abruptio placentae, preeclampsia, birthweight < 5th percentile, or foetal loss after 20 weeks. Enoxaparin was associated with a lower frequency of primary outcome: 12.5% (n=10/80) vs. 31.3 % (25/80), p=0.004, adjusted hazard ratio = 0.37, 95% confidence interval (0.18–0.77), p=0.011. Enoxaparin was safe, with no obvious side-effect, no thrombocytopenia nor major bleeding event excess. This pilot study shows that enoxaparin given early during the second pregnancy decreases the occurrence of placental vascular complications in women with a previous placental abruption during their first pregnancy.

We estimated the direct additional medical costs of nosocomial infections (NI) using a cohort study in acute and longer-term care at Nîmes University Hospital in France. Patients hospitalised between May 2001 and January 2003 with NI were considered as exposed; all others were eligible as non-exposed. Thirty patients were randomly chosen for each site of infection: respiratory tract, bloodstream, surgical site, urinary tract and other sites for a total of 150 exposed patients. Each exposed patient was matched with a non-exposed patient according to gender, age, severity of the underlying disease, diagnosis according to hospital discharge records, ward type and length of hospitalisation before inclusion. Additional direct medical costs for the exposed patients compared to the non-exposed and the difference between actual costs and the diagnosis-related group rate were measured. Costs resulting from laboratory tests, radiology, surgery and exploratory examinations, and antimicrobial agents were estimated to be Euro2421 for a respiratory tract infection, Euro1814 for a surgical site infection, Euro953 for a bloodstream infection and Euro574 for a urinary tract infection. Total additional costs of NI (direct medical costs and costs of extra length of stay) in acute care were estimated to be up to Euro3.2 million per year (95% confidence interval: 2,275,063-4,132,157). In conclusion, both prevention of avoidable NI and better estimation of the actual costs of NI should be priorities for all healthcare facilities.

SummaryBackground Case reports on recombinant human factor VIIa (rhuFVIIa) use in women with severe postpartum hemorrhage (PPH) showed encouraging results, but no randomized controlled trial (RCT) is available. Patients and methods Eighty-four women with severe PPH unresponsive to uterotonics were randomized to receive one early single rhuFVIIa infusion (n = 42) or standard care (no rhuFVIIa; n = 42). The primary efficacy outcome measure was the reduction of the need for specific second-line therapies, such as interventional hemostatic procedures, for blood loss and transfusions. The primary safety outcome measure was the number of deaths and thrombotic events during the 5 days following rhuFVIIa infusion. Results rhuFVIIa was associated with a reduction in the number of patients who needed second-line therapies compared with controls (standard care). Specifically, 39/42 (93%) patients in the standard care arm received second-line therapies and 22/42 (52%) patients in the rhuFVIIa arm (absolute difference, 41%; range, 18–63%; relative risk RR, 0.56 [0.42–0.76]). The delivery mode (vaginal or Cesarean section) did not affect the primary outcome. No death occurred. Two venous thrombotic events were recorded in the rhuFVIIa arm: one ovarian vein thrombosis and one deep vein thrombosis with a non-severe pulmonary embolism. Conclusion This open RCT in women with severe PPH refractory to uterotonics shows that rhuFVIIa reduces the need for specific second-line therapies in about one in three patients, with the occurrence of non-fatal venous thrombotic events in one in 20 patients.

Escherichia coli urinary tract isolates were collected in 1997–2003 from NîmesUniversity Hospital in order to investigate long-term trends in antibiotic resistance and to explore the relationship between antibiotic use and the emergence of resistance. Time-series analysis (ARIMA models) and dynamic regression models were used to investigate relationships between antibiotic use and resistance to ofloxacin and ciprofloxacin. Significant increases were seen in the frequency of ofloxacin (8.9 to 16.7%) and ciprofloxacin resistance (6.2 to 10.1%) (p < 0.001). Using multivariate dynamic regression analysis, it was found that an increased use of one defined daily dose (DDD)/1000 patient-days for ofloxacin, ciprofloxacin and norfloxacin induced average increases of 0.81%, 0.65%and 0.53%in E. coli ofloxacin resistance (p < 0.01), with average delays of 4, 4 and 6 months, respectively. An increase of 1 DDD/1000 patient-days of ciprofloxacin, ofloxacin and norfloxacin use induced increases of 0.73%, 0.82% and 0.63% in E. coli ciprofloxacin resistance (p < 0.01), with average delays of 4, 4 and 5 months, respectively. The use of nalidixic acid was not associated significantly with an increase in resistance to fluoroquinolones by multivariate analysis.

Background The prognostic value of cardiac troponin T (cTn-T) in a mixture of patients with both acute and chronic congestive heart failure (CHF), simultaneously assessed and compared with neurohormonal factors, has not yet been thoroughly evaluated. Thus, we focused on the prognostic value of cTn-T in comparison with atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP) and plasma norepinephrine (PNE) in this population. Methods Prognostic correlates of elevation of cTn-T, ANP, BNP, PNE were analyzed in 63 acute and chronic CHF patients followed up to record worsening CHF and cardiac death. Results cTn-T (≥0.03 μg/L) was found in 17.4% (11 of 63) of patients. cTn-T correlated with ANP, BNP, PNE. Acute CHF patients were more positive for cTn-T and BNP. In our cohort, neither cTn-T (≥0.03 μg/L) nor PNE were associated with increased mortality and worsening HF in CHF patients. After adjustment, BNP was the only independent predictor of cardiac events (RR, 3.23; p=0.01). Conclusions BNP emerged as the only independent predictor of cardiac events in a mixture of patients with both acute and chronic CHF, suggesting that it is the analyte that best reflects long-term prognosis in a diverse population enrolled to mirror the “real world” situation.

A case-control study was conducted in a university hospital to determine the risk factors for nosocomial infection with multidrug-resistant Pseudomonas aeruginosa (MDR-PA) among all hospitalized patients and among those with a nosocomial infection due to P. aeruginosa. Eighty patients infected with MDR-PA, 75 infected with a non-MDR phenotype and 240 random controls were included in the 12-month study. Among all hospitalized patients, age, severity index, having a bedridden condition, transfer from other units, nasogastric feeding, urinary catheterization and exposure to beta-lactams (OR=2.5) or fluoroquinolones (OR=4.1) in the seven days before infection were linked to nosocomial infection due to MDR-PA. Among patients infected by P. aeruginosa, exposure to fluoroquinolones (OR=4.7) or surgery (OR=0.5) were linked to the isolation of MDR-PA. This study showed that, in addition to urinary catheterization, nasogastric feeding is an important risk factor in MDR-PA infection. Indeed, an imbalance in gut flora, modifications to the mucous membranes due to the use of nasogastric feeding and the selection pressures exerted by antibiotics were implicated in the occurrence of this infection.

Maternal hypercoagulability is a possible cause of miscarriage during the eighth and ninth weeks of pregnancy, when the placenta replaces the yolk sac. We thus examined associations between putative markers of an acquired hypercoagulable state and the risk of first miscarriage. We conducted a case-control study comparing 743 women who miscarried in weeks 8 and 9 with 743 women who underwent a first provoked abortion, matched for age, number of pregnancies, and time elapsed since abortion. Levels of plasma homocysteine and of various antiphospholipid/antiprotein and hemostasis-related autoantibodies were categorized in 4 strata (percentiles 1-80, 81-95, 96-99, 100 among control patients) and analyzed in conditional logistic regression models. Pregnancy loss was independently associated with positive lupus anticoagulant (matched odds ratio [OR], 2.6; 95% confidence interval [CI], 1.1-6.0), high levels of immunoglobulin M (IgM) antibodies against cardiolipin (OR for percentile 100 versus 0-80, 3.5; CI, 1.2-10.1) and against phosphatidylethanolamine (OR, 4.7; CI, 1.9-12.1), high levels of IgG antibodies against annexin V (OR, 3.2; CI, 1.1-9.1) and against tissue-type plasminogen activator (OR, 19.5; CI, 7.9-48.0), and high homocystinemia (OR, 4.1; CI, 1.3-12.5). A first early pregnancy loss is associated with increased levels of several autoantibodies and of homocysteine. (Blood. 2003;102:3504-3513)

Background: Cardiac troponins I (cTnI) and T (cTnT) have been shown to be highly sensitive and specific markers of myocardial cell injury. We investigated the diagnostic value of cTnI and cTnT for the diagnosis of myocardial damage in a rat model of doxorubicin (DOX)-induced cardiomyopathy, and we examined the relationship between serial cTnI and cTnT with the development of cardiac disorders monitored by echocardiography and histological examinations in this model. Methods: Thirty-five Wistar rats were given 1.5 mg/kg DOX, i.v., weekly for up to 8 weeks for a total cumulative dose of 12 mg/kg BW. Ten rats received saline as a control group. cTnI was measured with Access® (ng/ml) and a research immunoassay (pg/ml), and compared with cTnT, CK-MB mass and CK. By using transthoracic echocardiography, anterior and posterior wall thickness, LV diameters and LV fractional shortening (FS) were measured in all rats before DOX or saline, and at weeks 6 and 9 after treatment in all surviving rats. Histology was performed in DOX-rats at 6 and 9 weeks after the last DOX dose and in all controls. Results: Eighteen of the DOX rats died prematurely of general toxicity during the 9-week period. End-diastolic (ED) and end-systolic (ES) LV diameters/BW significantly increased, whereas LV FS was decreased after 9 weeks in the DOX group (p

Numerous studies have demonstrated efficacy of imipenem-cilastatin, 50 mg/kg/day, as first line therapy in febrile patients with neutropenia of short duration consecutive to cytostatic chemotherapy. However, only two studies used low dosage of this antibiotic as 1.5 g/day, in prospective, double blind, randomized clinical trials, in this indication. Efficacy and tolerability of imipenem-cilastatin 0.5 g three times daily IV in 30-min infusions, as first-line empiric therapy, were retrospectively evaluated in our hematological unit. From January 1996 to September 2000, 30 neutropenic patients (12 females) with 45 febrile episodes were included. Median age was 57.5 years (31-75). Twenty-four of them had lymphomas, 4 solid tumors and 2 myelomas. There were 13 clinically documented infections, (CD, 28.8%), 16 microbiologically documented infections, (MD, 35.6%) and 16 febrile episodes corresponding to fever of unknown origin, (FUO, 35.6%). The median neutrophils count on nadir (n = 44), was 67/mm3 (8-369). The median duration of neutropenia was 5 days (3-15). Bacteremia was observed in 10 patients, urinary tract infection in 3 patients. The most frequently isolated microorganism was Escherichia coli. The overall success rate of the first line therapy was 66.7%. Adverse events were observed in 11.1% of the patients without necessity to stop treatment. The MD infections showed a lower rate of success compared with CD infections and FUO. These data were in accordance with the previous studies. The importance of number of microorganisms (p = 0.007) and of infected sites (p = 0.01) appeared as prognostic factors (univariate analysis). Although imipenem-cilastatin has been used in numerous studies as empiric broad-spectrum antibiotic therapy in the treatment of febrile neutropenic cancer patients, the exact dosage of this antibiotic is still not standardized. However, utilization of this antibiotic in monotherapy at low dosage seems to us to be safe and effective as usual dosage in the antimicrobial treatment ofthe febrile patients with post chemotherapy neutropenia of short duration.

Background and Objectives The aim of this study was to establish a correlation between a thermal measurement and a magnetic resonance imaging (MRI) signal during laser-induced interstitial thermotherapy (LITT) in liver. Study Design/Materials and Methods Pig liver was irradiated for 15 minutes with a diode laser at two different powers, 0.5 W (450 J) and 1.5 W (1,350 J). Tissue temperature was monitored every 20 seconds using thermocouples. Thermosensitive MRI sequences (T1-weighted Turbo-Flash) were acquired with the same irradiation parameters. Correlation between MRI signals (SI) and temperature measures was defined at two different distances from the fiber (5 and 10 mm). Results At 0.5 W, temperatures rose progressively up to a maximum increase of 9.5°C at 5 mm and 4°C at 10 mm after 15 minutes. The corresponding MRI signal decreased progressively to −27.6 SI at 5 mm and −18.5 SI at 10 mm. At 1.5 W, temperatures rose dramatically at 5 mm, reaching a plateau. The temperature elevation measured at the end of the irradiation was of 30°C whereas at 10 mm it was only 14.5°C. The MRI signal varied accordingly, remaining inversely proportional to temperature (−76 SI at 5 mm and −35.5 SI at 10 mm). Conclusions An inversely proportional relationship was observed between MRI signal in sequential Turbo-Flash and temperature. MRI should allow to analyze heat diffusion in the liver, and thus to monitor real-time LITT treatments. Lasers Surg. Med. 32:54–60,2003. © 2003 Wiley-Liss, Inc.

Objectives: To evaluate antimicrobial therapy management of secondary peritonitis in a University Hospital. Patients and methods: All patients admitted to the intensive care unit of the University Hospital of Nimes from 1 January 1997 to 31 July 1999 with a diagnosis of secondary peritonitis were retrospectively included. Patients' medical records were collected from the data recordings of the Department of Critical Care and Emergency and the Departments of Surgery. Acute Physiology and Chronic Health Evaluation II (APACHE II) was calculated for each patient at the time of admission. Antimicrobial treatment management before and after the diagnosis of peritonitis was studied. Results: One hundred and twenty patients were included. Results concerning mortality, aetiology of peritonitis and microbiological data were in accordance with previous studies. APACHE II score (P = 0.005), age (P = 0.002), presence of Enterococcus in the peri-operative samples (P= 0.02) and period between diagnosis and surgery (P= 0.04) were predictive of death within 30 days after diagnosis of peritonitis. No significant difference was shown in the mortality rate in patients whose post-operative antibiotic treatment was changed following results of intra-operative peritoneal cultures versus patients having inappropriate treatment (P = 0.96). The same observations were noted for anti-enterococcal treatment. Conclusion: This study emphasizes the importance of prompt surgical treatment and shows the modest impact of adapting antibiotic treatment. The morbidity and mortality associated with the presence of Enterococcus, which was not influenced by antibiotic treatment, would seem to suggest the pro-inflammatory role of Enterococcus. However, prospective randomized studies are needed to evaluate the real contribution of enterococcal antibiotic coverage in this context.

Background The study was designed to compare the effects of equimolar concentrations of racemic bupivacaine, levobupivacaine, and ropivacaine on ventricular conduction, anisotropy, duration and homogeneity of refractoriness, and wavelengths, and to provide a potency ratio for effects on conduction velocity. Methods Isolated frozen rabbit hearts (which leave a thin layer of surviving epicardial muscle) were treated with 0.1, 1, and 10 mum racemic bupivacaine, levobupivacaine, or ropivacaine. Left ventricular longitudinal and transverse conduction velocities, anisotropic ratio, minimum pacing cycle length, use dependency, duration and dispersion of ventricular effective refractory period, and wavelengths were studied. A high-resolution mapping system was used for data acquisition. In addition to two-way analysis of variance for repeated measures, data for conduction velocities were fitted simultaneously using a nonlinear mixed-effect modeling program to allow intergroup comparison. Results Each agent induced a concentration- and use-dependent slowing of conduction velocities, with no change of the anisotropic ratio. The use-dependent effect of levobupivacaine is similar to that of racemic bupivacaine concerning longitudinal conduction velocity. Fitting of conduction velocities provided a racemic bupivacaine to levobupivacaine and to ropivacaine ratio of 1:1.38 for concentration effect at 1,000-ms pacing cycle length, and 1:0.74 for use-dependent effect at 600-ms pacing cycle length. Racemic bupivacaine and levobupivacaine prolonged the ventricular effective refractory period, whereas ropivacaine did not. No dispersion in ventricular effective refractory period values occurred. All three agents induced significant decreases in wavelengths. This effect was not different among groups. Conclusions Differences among racemic bupivacaine, levobupivacaine, and ropivacaine at equimolar concentrations are mainly caused by the use-dependent effects on conduction velocities and the concentration-dependent effects on ventricular effective refractory period. Therefore, one must take into account the corresponding pacing rates when comparing the potency ratios of local anesthetics.