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To determine a potential window of opportunity for retreatment with rituximab in patients with rheumatoid arthritis (RA) from a multicentre longitudinal real-life study based on tight monitoring with ultrasonography (US).Thirty RA patients treated with rituximab were included. US parameters were collected at each time (8 visits) of the 18-month follow-up, notably the global score of power Doppler (PD) activity. Clinical relapse was defined as a DAS28 ESR of3.2 after 6 months in responders while US relapse was defined as an increase of ≥20% of the global score of PD activity. The decision of retreatment was based exclusively on clinical findings.A total of 29 patients were analysed (mean (SD) age: 57.2 (12.2) years; female gender: 66%). The mean (SD) PD score decreased from 8.8 (5.2) at baseline to 4.9 (4.3) at 6 months (p0.0001). A clinical response was observed at Month 4 or Month 6 for 93% of patients. A total of 19 patients had a first clinical relapse (with or without US relapse) after Month 6 (18 of them were retreated with rituximab). Among 10 patients without clinical relapse, 3 had US relapse (only one was retreated) and 7 had no US relapse (but 4 were retreated).This study highlights a great heterogeneity in terms of sequence of clinical relapse, US relapse and retreatment in RA patients receiving rituximab. Therefore, US monitoring does not seem to be relevant to determine the best time for retreatment with rituximab.

Aim: The STARR (Stapled Trans-Anal Rectal Resection) procedure consists of a surgical correction of symptomatic rectocele refractory to medical treatment, involving anal dilatation. The aim of the ...

Summary Background Fructose malabsorption may trigger gastrointestinal symptoms in irritable bowel syndrome patients and a low fructose diet seems to improve digestive symptoms. Aim The aim of our study was to determine whether fructose malabsorption detected by a 25g fructose breath test could be a predictor of the efficacy of a low fructose diet. Methods 88 patients (73 women, median age, 45.5 years, range 18–69) with irritable bowel syndrome according to Rome III criteria were included in this prospective, controlled study. All 88 patients had a 25 g fructose breath test; 37 had a positive test result defining fructose malabsorption. All 88 patients followed a low fructose diet for 2 weeks, blinded to their test results. Patients filled self validated-questionnaires before and at the end of the dietary period. The main outcome measurement was the Irritable Bowel Syndrome-Symptom Severity Score. Results Irritable Bowel Syndrome-Symptom Severity Score significantly decreased in fructose absorbers and fructose malabsorbers after a low fructose diet (−68.0 [−137; 0] versus −73.5 [−173; −11.5]) with no difference according to fructose breath test result (adjusted P = 0.984). Conclusion A positive 25 g fructose breath test is not a predictor of the efficacy of a low fructose diet in irritable bowel syndrome. Registered clinical trial www.clinicaltrials.gov ( NCT02188680 ).

Migraine may be a factor of increased cerebral sensitivity to ischemia. Previous studies were conducted within 6 to 72 after stroke onset. We aimed to determine if an accelerated infarct growth exists in migraine patients within the first 4.5 h.A retrospective case-control study was conducted where all patients admitted for acute stroke started4.5 h before and who underwent perfusion CT were assessed. The hypoperfusion and necrosis volumes on initial CT perfusion were analyzed, as well as the final infarct volume on MRI performed within 72 h after admission. A no-mismatch pattern was defined as a ratio necrosis/hypoperfusion volume 83%.24 patients with personal history of migraine were identified, 8 of them with aura. The control cohort included 51 patients. No difference was found between groups in terms of demographics, initial severity or outcome or presumed cause of stroke. Mean time to CT scan was 125 min in migraine patients and 127 min in the control group. A no-mismatch pattern was equally found in migraine patients and controls, even after adjustment for age, sex and presence of proximal occlusion (p = .22). The final infarct volume was also similar in both groups.Migraine patients did not display more no-mismatch pattern than controls within the 4.5 h of stroke onset. This deviates from previous studies and may be due to our earlier time from stroke onset to CT scan. A history of migraine may lead to malignant progression of ischemia but occurring only after several hours.

International audience; Many pregnant women, in the world, drink caffeine-containing beverages. Maternal caffeine consumption during pregnancy may have adverse effects on foetus but results are conflicting. Our goals were to estimate the prevalence of caffeine use in a cohort of French pregnant women using maternal self-reports and to evaluate the association between caffeine consumption during pregnancy and delivery and newborn characteristics. All pregnant women who gave birth in a large French urban area during a limited period of time were included (in total 724 mothers were included). Coffee, tea or cola consumption as well as pregnancy and neonate characteristics were analysed. The mean consumption of caffeine per day slightly decreased from the first to the third trimester of pregnancy: 587 caffeine users, with a consumption of caffeine of 59.2 ± 61.5 mg/day during the first trimester as compared to 577 consumers (54.3 ± 55.4 mg/day) during the third trimester, respectively. A significant decrease of neonates' birth length was observed when mothers were using at least 100 mg/day (or two cups) of caffeine during the second and third trimesters but this difference was no longer significant after adjustment on potential confounding factors such as tobacco use. The potential existence of other confounders (e.g. poorer dietary habits or other lifestyle variables) that might also be associated with reduced birth length, may not be excluded. Caffeine use during pregnancy was associated with reduced birth length but this effect was no longer significant after adjustment on potential confounding variables.

Summary Background Corticosteroids (CS) with or without adjuvant immunosuppressant agents are standard treatment for pemphigus vulgaris (PV). The efficacy of adjuvant therapies in minimizing steroid‐related adverse events (AEs) is unproven. Objectives To utilize data collected in a French investigator‐initiated, phase III, open‐label, randomized controlled trial to demonstrate the efficacy and safety of rituximab and seek approval for its use in PV. Methods This was an independently conducted post hoc analysis of the moderate‐to‐severe PV subset enrolled in the Ritux 3 study. Patients were randomized to rituximab plus 0·5 or 1·0 mg kg−1 per day prednisone tapered over 3 or 6 months, or 1·0 or 1·5 mg kg−1 per day prednisone alone tapered over 12 or 18 months, respectively (according to disease severity). The primary end point was complete remission at month 24 without CS (CRoff) for ≥ 2 months, and 24‐month efficacy and safety results were also reported. Results At month 24, 34 of 38 patients (90%) on rituximab plus prednisone achieved CRoff ≥ 2 months vs. 10 of 36 patients (28%) on prednisone alone. Median total cumulative prednisone dose was 5800 mg in the rituximab plus prednisone arm vs. 20 520 mg for prednisone alone. Eight of 36 patients (22%) who received prednisone alone withdrew from treatment owing to AEs; one rituximab‐plus‐prednisone patient withdrew due to pregnancy. Overall, 24 of 36 patients (67%) on prednisone alone experienced a grade 3/4 CS‐related AE vs. 13 of 38 patients (34%) on rituximab plus prednisone. Conclusions In patients with moderate‐to‐severe PV, rituximab plus short‐term prednisone was more effective than prednisone alone. Patients treated with rituximab had less CS exposure and were less likely to experience severe or life‐threatening CS‐related AEs. What's already known about this topic? Pemphigus vulgaris (PV) is the most common type of pemphigus.Corticosteroids, a standard first‐line treatment for PV, have significant side‐effects.Although their effects are unproven, adjuvant corticosteroid‐sparing agents are routinely used to minimize steroid exposure and corticosteroid‐related side‐effects.There is evidence that the anti‐CD20 antibody rituximab is effective in the treatment of patients with severe recalcitrant pemphigus and in patients with newly diagnosed pemphigus. What does this study add? This study provides a more detailed analysis of patients with PV enrolled in an investigator‐initiated trial.Rituximab plus prednisone had a steroid‐sparing effect and more patients achieved complete remission off prednisone.Fewer patients experienced grade 3 or grade 4 steroid‐related adverse events than those on prednisone alone.This collaboration between academia and industry, utilizing independent post hoc analyses, led to regulatory authority approvals of rituximab in moderate‐to‐severe PV., Linked Comment: Scorer et al. Br J Dermatol 2020; 182:1078–1079.

Objective: The aim of this study was to evaluate the efficacy of intrasphincteric injections of autologous myoblasts (AMs) in fecal incontinence (FI) in a controlled study. Summary of Background Data: Adult stem cell therapy is expected to definitively cure FI by regenerating damaged sphincter. Preclinical data and results of open-label trials suggest that myoblast therapy may represent a noninvasive treatment option. Methods: We conducted a phase 2 randomized, double-blind, placebo-controlled study of intrasphincteric injections of AM in 24 patients. The study compared outcome after AM (n = 12) or placebo (n = 12) injection using Cleveland Clinic Incontinence (CCI), score at 6 and 12 months. Patients in the placebo group were eligible to receive frozen AM after 1 year. Results: At 6 months, the median CCI score significantly decreased from baseline in both the AM (9 vs 15, P = 0.02) and placebo (10 vs 15, P = 0.01) groups. Hence, no significant difference was found between the 2 groups (primary endpoint) at 6 months. At 12 months, the median CCI score continued to ameliorate in the AM group (6.5 vs 15, P = 0.006), while effect was lost in the placebo group (14 vs 15, P = 0.35). Consequently, there was a higher response rate at 12 months in the treated than the placebo arm (58% vs 8%, P = 0.03). After delayed frozen AM injection in the placebo group, the response rate was 60% (6/10) at 12 months. Conclusions: Intrasphincteric AM injections in FI patients have shown tolerance, safety, and clinical benefit at 12 months despite a transient placebo effect at 6 months.

Background About 25% of patients with acute diverticulitis require emergency intervention. Currently, most patients with diverticular peritonitis undergo a Hartmann's procedure. Our objective was to assess whether primary anastomosis (PA) with a diverting stoma results in lower mortality rates than Hartmann's procedure (HP) in patients with diverticular peritonitis. Study Design We conducted a multicenter randomized controlled trial conducted between June 2008 and May 2012: the DIVERTI (Primary vs Secondary Anastomosis for Hinchey Stage III-IV Diverticulitis) trial. Follow-up duration was up to 18 months. A random sample of 102 eligible participants with purulent or fecal diverticular peritonitis from tertiary care referral centers and associated centers in France were equally randomized to either a PA arm or to an HP arm. Data were analyzed on an intention-to-treat basis. The primary end point was mortality rate at 18 months. Secondary outcomes were postoperative complications, operative time, length of hospital stay, rate of definitive stoma, and morbidity. Results All 102 patients enrolled were comparable for age (p = 0.4453), sex (p = 0.2347), Hinchey stage III vs IV (p = 0.2347), and Mannheim Peritonitis Index (p = 0.0606). Overall mortality did not differ significantly between HP (7.7%) and PA (4%) (p = 0.4233). Morbidity for both resection and stoma reversal operations were comparable (39% in the HP arm vs 44% in the PA arm; p = 0.4233). At 18 months, 96% of PA patients and 65% of HP patients had a stoma reversal (p = 0.0001). Conclusions Although mortality was similar in both arms, the rate of stoma reversal was significantly higher in the PA arm. This trial provides additional evidence in favor of PA with diverting ileostomy over HP in patients with diverticular peritonitis. ClinicalTrials.gov Identifier: NCT 00692393.

Objectives The aim of this study was to investigate the clinical value of sVE and anti-vascular endothelial-cadherin antibodies (AAVE) in RA treated with etanercept or adalimumab combined with methotrexate. Methods This was an 18-month prospective multicenter study in which patients had active RA, requiring TNF antagonist. sVE rates and AAVE titers were measured respectively by dot blot and ELISA. The relationship of these biomarkers with parameters reflecting articular or systemic disease activity, progression of structural damage, and response or remission to treatment was analyzed. Results Forty-eight patients received TNF blocking agents. Variation of sVE rates were significantly correlated with that of C-reactive protein (CRP) levels at weeks 6, 12, 26 and 52. A significant decrease in sVE levels was observed in the group of patients exhibiting a decrease in CRP levels as compared to the patient group with unmodified CRP. AAVE at baseline were correlated with rheumatoid factor. Kinetics analysis of sVE levels and AAVE titers showed that their level were not associated with disease activity score and to methotrexate/adalimumab or etanercept response. Conclusions sVE is a biomarker associated with systemic RA activity under anti-TNF. AAVE are related to autoantibodies usually associated to RA.

We conducted a prospective study to assess the prognostic impact of selected copy number variations (CNVs) in stage II-III microsatellite stable (MSS) colon cancer. A total of 401 patients were included from 01/2004 to 01/2009. The CNVs in 8 selected target genes, DCC/18q, EGFR/7p, TP53/17p, BLK/8p, MYC/8q, APC/5q, ERBB2/17q, and STK6/20q, were detected using a quantitative multiplex polymerase chain reaction of short fluorescent fragment (QMPSF) method. The primary end-point was the impact of the CNVs on the 4-year disease-free survival (DFS). The recurrence rate at 4 years was 20.9%, corresponding to 14% stage II patients vs 31% stage III patients (p

AIM Faecal incontinence is frequent in the elderly. Little is currently known about the efficacy of sacral nerve modulation (SNM) in the elderly. The present study aimed to assess the impact of age on the outcome of SNM and on the surgical revision and explantation rates by comparing the results of a large data set of patients. METHOD Prospectively collected data from patients who underwent an implant procedure between January 2010 and December 2015 in seven French centres were retrospectively evaluated. In total, 352 patients [321 women; median age (range): 63 (24-86) years] were included. Clinically favourable and unfavourable outcomes, and surgical revision and explantation rates, were compared according to the age of the patients. RESULTS A similar outcome was observed when comparing patients

Tobacco and/or alcohol use during pregnancy is a major public health concern. The aim of our study was to identify risk factors associated to maternal alcohol and tobacco use assessed by maternal self-reports combined with biological measurements in meconium samples of cotinine and ethylglucuronide which reflect fetal exposure to tobacco and alcohol, respectively, during the 3rd trimester of pregnancy. We conducted a prospective study in three maternity hospitals in a large urban area during consecutive weeks (2010 and 2011). Maternal sociodemographic and clinical characteristics were assessed after delivery, using the French version of the Addiction Severity Index. Cotinine and ethylglucuronide were measured in meconium samples. Seven hundred and twenty-four women were included, and 645 meconium samples collected. Using multivariate analyses, we found that not being married or having a smoking partner predicts maternal tobacco use. In contrast, a decreased risk was associated with higher education level and wanted pregnancy. The risk for alcohol use increased when the mother had been in conflict with any relative or her partner for a long time throughout her life, as well as in case of previous treatment for any mental or emotional disorder. Using multivariate analyses and cotinine presence in meconium samples, the risks were similar except for marital status, which was not associated to cotinine presence. Community education and prevention programs should urgently be improved for all women of childbearing age with a special focus on those with past histories of mental or emotional disorders and addictive disorders. Smoking cessation should be recommended to both parents.

BACKGROUND Two pemphigus severity scores, Autoimmune Bullous Skin Disorder Intensity Score (ABSIS) and Pemphigus Disease Area Index (PDAI), have been proposed to provide an objective measure of disease activity. However, the use of these scores in clinical practice is limited by the absence of cut-off values that allow differentiation between moderate, significant and extensive types of pemphigus. OBJECTIVES To calculate cut-off values defining moderate, significant and extensive pemphigus based on the ABSIS and PDAI scores. METHODS In 31 dermatology departments in six countries, consecutive patients with newly diagnosed pemphigus were assessed for pemphigus severity, using ABSIS, PDAI, Physician's Global Assessment (PGA) and Dermatology Life Quality Index (DLQI) scores. Cut-off values defining moderate, significant and extensive subgroups were calculated based on the 25th and 75th percentiles of the ABSIS and PDAI scores. The median ABSIS, PDAI, PGA and DLQI scores of the three severity subgroups were compared in order to validate these subgroups. RESULTS Ninety-six patients with pemphigus vulgaris (n = 77) or pemphigus foliaceus (n = 19) were included. The median PDAI activity and ABSIS total scores were 27·5 (range 3-84) and 34·8 points (range 0·5-90·5), respectively. The respective cut-off values corresponding to the first and third quartiles of the scores were 15 and 45 for the PDAI, and 17 and 53 for ABSIS. The moderate, significant and extensive subgroups were thus defined, and had distinguishing median ABSIS (P < 0·001), PDAI (P < 0·001), PGA (P < 0·001) and DLQI (P = 0·03) scores. CONCLUSIONS This study suggests cut-off values of 15 and 45 for PDAI and 17 and 53 for ABSIS, to distinguish moderate, significant and extensive pemphigus forms. Identifying these pemphigus activity subgroups should help physicians to classify and manage patients with pemphigus.

Importance Rituximab and short-term corticosteroid therapy are the criterion standard treatments for patients with newly diagnosed moderate to severe pemphigus. Objective To examine factors associated with short-term relapse in patients with pemphigus treated with rituximab. Design, Setting, and Participants This post hoc analysis of a randomized clinical trial (Comparison Between Rituximab Treatment and Oral Corticosteroid Treatment in Patients With Pemphigus [RITUX 3]) conducted from January 1, 2010, to December 31, 2015, included patients from 20 dermatology departments of tertiary care centers in France from the RITUX 3 trial and 3 newly diagnosed patients treated according to the trial protocol. Data analysis was performed from February 1 to June 30, 2019. Exposure Patients randomly assigned to the rituximab group in the RITUX 3 trial and the 3 additional patients were treated with 1000 mg of intravenous rituximab on days 0 and 14 and 500 mg at months 12 and 18 combined with a short-term prednisone regimen. Main Outcomes and Measures Baseline (pretreatment) clinical and biological characteristics (Pemphigus Disease Area Index [PDAI] score, ranging from 0-250 points, with higher values indicating more severe disease) and changes in anti–desmoglein (DSG) 1 and anti-DSG3 values as measured by enzyme-linked immunosorbent assay during the 3 months after rituximab treatment were compared between patients with disease relapse and those who maintained clinical remission during the first 12 months after treatment. The positive and negative predictive values of these factors were calculated. Results Among 47 patients (mean [SD] age, 54.3 [17.0] years; 17 [36%] male and 30 [64%] female) included in the study, the mean (SD) baseline PDAI score for patients with relapsing disease was higher than that of the patients with nonrelapsing disease (54 [33] vs 28 [24];P = .03). At month 3, 7 of 11 patients with relapsing disease (64%) vs 7 of 36 patients with nonrelapsing disease (19%) had persistent anti-DSG1 antibody values of 20 IU/mL or higher and/or anti-DSG3 antibody values of 130 IU/mL or higher (P = .01). A PDAI score of 45 or higher defining severe pemphigus and/or persistent anti-DSG1 antibody values of 20 IU/mL or higher and/or anti-DSG3 antibody values of 130 IU/mL or higher at month 3 provided a positive predictive value of 50% (95% CI, 27%-73%) and a negative predictive value of 94% (95% CI, 73%-100%) for the occurrence of relapse after rituximab. Conclusions and Relevance The findings suggest that initial PDAI score and changes in anti-DSG antibody values after the initial cycle of rituximab might help differentiate a subgroup of patients with high risk of relapse who might benefit from maintenance rituximab infusion at month 6 from a subgroup of patients with low risk of relapse who do not need early maintenance therapy. Trial Registration NCT00784589

Key Points Question Is tocolysis associated with lower rates of death and intraventricular hemorrhage in preterm infants owing to an effect on the fetal blood-brain barrier? Findings In this cohort study of 1127 mothers who experienced preterm labor and delivered at gestational weeks 24 through 31, the estimated prevalence of death and/or grades III to IV intraventricular hemorrhage was significantly lower in preterm infants with vs without tocolytic exposure (25.3% vs 32.5%). Differences between atosiban and nifedipine exposure for death and/or intraventricular hemorrhage (44.9% vs 51.2%) and for intraventricular hemorrhage (39.1% vs 45.3%) were not significant. Meaning Results for tocolytics are reassuring regarding death and/or intraventricular hemorrhage in preterm infants, but other studies appear to be necessary to compare the effects of atosiban vs nifedipine., This population-based cohort study assesses the risks associated with tocolysis as measured by death and intraventricular hemorrhage in preterm infants and compares the risks between calcium channel blockers and atosiban., Importance No trials to date have demonstrated the benefits of tocolysis on death and/or neonatal morbidity in preterm infants; tocolytics may affect the fetal blood-brain barrier. Objectives To assess the risks associated with tocolysis in women delivering prematurely as measured by death and/or intraventricular hemorrhage (IVH) in preterm infants and to compare the association of calcium channel blockers (CCBs) nifedipine and nicardipine hydrochloride vs atosiban used for tocolysis with death and/or IVH. Design, Settings, and Participants The French 2011 EPIPAGE-2 (Enquête Épidémiologique sur les Petits Âges Gestationnels) cohort was limited to mothers admitted for preterm labor without fever, who delivered from 24 to 31 weeks of gestation from April 1 through December 31, 2011. Groups of preterm infants with vs without tocolytic exposure and groups with atosiban vs CCB exposure were compared. Data analysis was performed from June 7, 2014, through September 3, 2017. Exposures Tocolytics. Main Outcomes and Measures The primary outcome was a composite of death and/or IVH in preterm infants. Secondary outcomes included death, IVH, and a composite of death and/or grades III to IV IVH. Results A total of 1127 mothers (mean [SD] age, 25.5 [6.0] years) experienced preterm labor and gave birth to 1343 preterm infants with a male to female ratio of 1.23 and mean (SD) gestational age of 27 (2.5) weeks. Of these, 789 mothers (70.0%) received tocolytics; 314 (39.8%) received only atosiban, and 118 (15.0%) received only a CCB. In the first analysis, the primary outcome (death and/or IVH) was not significantly different in preterm infants with vs without tocolytic exposure (183 of 363 [50.4%] vs 207 of 363 [57.0%]; relative risk [RR], 0.88; 95% CI, 0.77-1.01; P = .07). The secondary outcome (death and/or grades III-IV IVH) was significantly lower in preterm infants with vs without tocolytic exposure (92 of 363 [25.3%] vs 118 of 363 [32.5%]; RR, 0.78; 95% CI, 0.62-0.98; P = .03). Other outcomes did not differ significantly. In the secondary analysis, death and/or IVH was not significantly different in preterm infants with atosiban vs CCB exposure (96 of 214 [44.9%] vs 62 of 121 [51.2%]; RR, 0.88; 95% CI, 0.70-1.10; P = .26), nor was IVH (77 of 197 [39.1%] vs 48 of 106 [45.3%]; RR, 0.86; 95% CI, 0.66-1.13; P = .29). Conclusions and Relevance In this population-based study, findings suggest that tocolytics were associated with a reduction of death and severe IVH. Other studies are necessary to compare perinatal outcomes after use of atosiban vs CCBs.

Introduction Une difference d’appreciation de la severite d’une dermatose et de l’efficacite du traitement peut etre responsable d’une alteration de la relation medecin-patient. L’objectif de cette etude etait de comparer l’evaluation de la severite du pemphigus et de l’efficacite du traitement par les medecins et les patients par un questionnaire en miroir. Materiel et methodes Une etude prospective a ete realisee entre 2015 et 2017 dans 11 centres francais. Deux questionnaires evaluant la severite du pemphigus et l’efficacite du traitement ont ete realises avec 2 versions en miroir, l’une remplie par les patients, l’autre par les medecins. Ces questionnaires ont ete realises a la suite d’entretiens semi-diriges. Les scores des questionnaires de severite medecin versus patient ont ete compares. La version patient du questionnaire de severite etait correlee a des scores psychologiques (anxiete, incertitude, strategies de coping et perception du soutien social) et de qualite de vie (ABQOL et TABQOL) par un coefficient de correlation de Spearman. De meme la version medecin du score de severite etait correlee au score de severite objectif PDAI. Resultats Quarante-six patients (6 presentant un pemphigus recemment diagnostique et 40 presentant un pemphigus ancien) ont ete inclus. La version medecin du questionnaire de severite etait bien correlee au PDAI (r = 0,45 ; p = 0,003) et la version patient etait correlee a l’ABQOL (r = 0,47 ; p = 0,0061) et au TABQOL (r = 0,59 ; p = 0,0002). La severite du pemphigus etait estimee deux fois plus importante par les patients que par les medecins (20,9 ± 13,7 vs 11,5 ± 8,6 ; p Conclusion Cette etude rapporte une importante difference d’evaluation de la severite du pemphigus entre patients et medecins, notamment chez les patients dont le pemphigus est ancien. En effet chez ces patients le PDAI et la version medecin du questionnaire de severite etaient en faveur d’une atteinte legere alors que l’evaluation de la severite par les patients restait elevee. Ces resultats etaient en accord avec l’absence d’amelioration du TABQOL au cours de l’evolution. Les medecins doivent rester attentifs aux repercussions du pemphigus telles que l’anxiete et le sentiment d’isolement lie a une baisse du soutien social tout au long de l’evolution du pemphigus afin de maintenir une bonne relation medecin-patient.

Introduction Depuis la publication princeps rapportant l’efficacite du methotrexate (MTX) seul ou associe a 20 mg/j de prednisone (1), 16 etudes ouvertes ont ete publiees. La meta analyse qui les a integrees (2) a estime un taux de repousse complete de 35 % (IC95 % = 25–48 %), (44 % chez les adultes) et un taux de repousse > 50 % de 63 % (IC95 % = 54 % > 71 %) (69 % chez les adultes). Materiel et methodes Etude multicentrique randomisee en double aveugle comportant 2 phases : Phase 1 (M0 a M6) : randomisation : MTX : 20 a 25/semaine po versus placebo. Phase 2 (M6 a M12) : les patients ayant obtenu une repousse > 25 % (evaluee par 3 experts independants) restaient dans leur groupe de randomisation jusqu’a M12. Les autres patients etaient a nouveau randomises MTX + prednisone 20 mg/j puis 15 mg/j versus MTX + placebo. Criteres d’inclusion pelade totale ou universelle evoluant sans repousse depuis au moins 6 mois malgre des traitements anterieurs. L’evaluation de la repousse a M12 etait realisee par les investigateurs, les patients et par 3 experts independants. Resultats Un total de 89 patients d’âge moyen 38,6 ± 14,3 ans ont ete inclus, dont 66 provenaient d’un centre specialise dans la pathologie du cuir chevelu. La duree mediane d’evolution de la pelade etait de 5,8 ans [1,7–12,5]. Le taux de repousse complete a M12 chez les patients ayant obtenu une repousse > 25 % a M6 et etant restes dans leur groupe de randomisation initial (critere de jugement principal) etait de 1/45 (MTX) versus 0/44 (placebo). Le taux de repousse complete (evaluee par 3 experts independants) chez les patients re-randomises a M6 variait de 12 % a 38 % (MTX + prednisone) versus 12 % (MTX + placebo) et le taux de repousse > 50 % etait de 50 % (MTX + prednisone) versus 12 % (MTX + placebo). Aucun effet secondaire (ES) grave n’a ete observe. Le taux d’ES a M6 etait de 45 % dans le bras MTX (nausees, fatigue) versus 16 % dans le bras placebo (fatigue). Le taux d’ES a M12 des patients re-randomises dans les bras MTX + prednisone etait de 38 % a 44 % (diabete, prise de poids). L’appreciation de la repousse par les patients, les investigateurs et les experts etaient tres concordante : R = 0,96, R = 0,81, R = 0,89. Conclusion Cette etude confirme l’efficacite du MTX dans les formes les plus severes de pelades (totales et universelles d’evolution chronique ayant resiste a des traitements anterieurs), surtout lorsqu’il est associe a de faibles doses de prednisone. L’efficacite legerement moindre que celle rapportee dans la meta-analyse recente est vraisemblablement liee a un biais de selection puisque 70 % des malades ont ete inclus par un centre tertiaire. La combinaison avec une corticotherapie a faible dose ne semble pas augmenter la frequence des ES de maniere importante.

Introduction L’essai Ritux3 a montre la superiorite du rituximab (RTX) associe a une corticotherapie orale (CO) courte en termes d’efficacite et de tolerance dans le traitement de 1re intention du pemphigus par rapport a la CO longue. Malgre ces resultats, le cout eleve du RTX peut etre un frein a son remboursement par les differents systemes de sante. Notre objectif etait de comparer les couts directs d’un traitement par RTX + CO courte par rapport a la CO standard de reference dans le traitement de 1re ligne du pemphigus. Patients et methodes Dans l’essai randomise Ritux3, les patients du bras RTX recevaient 1 g de RTX a j0 et j14 et deux perfusions d’entretien de 500 mg a M12 et M18 associe a une CO faible pendant 3 a 6 mois. Les patients du bras corticotherapie recevaient une CO forte pendant 12 a 18 mois. Le calendrier des visites etait le meme pour les deux bras. Nous avons estime les couts directs (RTX, corticotherapie, consultations, hospitalisations) en relation avec le protocole, mais aussi les couts lies a une evolution defavorable (rechute, aggravation, addition d’un immunosuppresseur…) ou lies a la survenue d’effets indesirables (EI) dans les deux bras avec un suivi de 3 ans. Resultats Apres 3 ans, 40 des 46 patients (87 %) du bras RTX versus 15/44 (34 %) du bras CO etaient en remission complete. Treize patients du bras RTX ont eu au moins une rechute durant le suivi dont 11 traites par une perfusion anticipee de RTX et 2 par une perfusion additionnelle (1 g). Un patient sorti d’etude a recu des immunoglobulines intraveineuses (IGIV). Trente patients du bras CO ont eu une rechute dont 14 traites par RTX, 2 par IGIV et 7 par immunosuppresseurs. Cinquante-trois EI severes etaient reportes dans les bras CO et 27 dans le bras RTX. Les couts lies aux traitements etaient de 335 725 € dans le bras CO et 484 496 € dans le bras RTX. Ils etaient superieurs la 1re annee dans le bras RTX (+184 644 €) puis contre-balances par les couts lies au traitement des rechutes dans le bras CO la 3e annee (−70 485 € en faveur du bras RTX). Les couts lies a la prise en charge des EI etaient plus eleves dans le bras CO que dans le bras RTX : 294 183 € vs 112 356 €. Le cout moyen par patient cumule sur les 3 ans de l’etude etait de 11 8441 € dans le bras CO vs 12 975 € dans le bras RTX, soit un surcout de 1134 € par patient (+9,6 %). Discussion Cette etude montre que le RTX engendre un surcout initial qui est presque completement contrebalance apres 3 ans par la reduction des couts lies a la prise en charge des EI et des rechutes chez les patients traites par CO standard. Conclusion Le cout du RTX en traitement de 1ere intention du pemphigus ne semble pas etre une limite a sa prescription.

IF 44.002; International audience; Background High doses of corticosteroids are considered the standard treatment for pemphigus. Because long-term corticosteroid treatment can cause severe and even life-threatening side-effects in patients with this disease, we assessed whether first-line use of rituximab as adjuvant therapy could improve the proportion of patients achieving complete remission off-therapy, compared with corticosteroid treatment alone, while decreasing treatment side-effects of corticosteroids.Methods We did a prospective, multicentre, parallel-group, open-label, randomised trial in 25 dermatology hospital departments in France (Ritux 3). Eligible participants were patients with newly diagnosed pemphigus aged 18-80 years being treated for the first time (not at the time of a relapse). We randomly assigned participants (1: 1) to receive either oral prednisone alone, 1.0 or 1.5 mg/kg per day tapered over 12 or 18 months (prednisone alone group), or 1000 mg of intravenous rituximab on days 0 and 14, and 500 mg at months 12 and 18, combined with a short-term prednisone regimen, 0.5 or 1.0 mg/kg per day tapered over 3 or 6 months (rituximab plus short-term prednisone group). Follow-up was for 3 years (study visits were scheduled weekly during the first month of the study, then monthly until month 24, then an additional visit at month 36). Treatment was assigned through central computer-generated randomisation, with stratification according to disease-severity (severe or moderate, based on Harman's criteria). The primary endpoint was the proportion of patients who achieved complete remission off-therapy at month 24 (intention-to-treat analysis). This study is registered with ClinicalTrials.gov, number NCT00784589.Findings Between May 10, 2010, and Dec 7, 2012, we enrolled 91 patients and randomly assigned 90 to treatment (90 were analysed; 1 patient withdrew consent before the random assignment). At month 24, 41 (89%) of 46 patients assigned to rituximab plus short-term prednisone were in complete remission off-therapy versus 15 (34%) of 44 assigned to prednisone alone (absolute difference 55 percentage points, 95% CI 38.4-71.7; p

International audience; On fluorine-18 fludeoxyglucose ((18)F-FDG) positron emission tomography (PET) CT of pulmonary or hepatic lesions, standard uptake value (SUV) is often underestimated due to patient breathing. The aim of this study is to validate, on phantom and patient data, a motion correction algorithm [reconstruct, register and averaged (RRA)] implemented on a PET-CT system.

On fluorine-18 fludeoxyglucose (Three phantoms containing five spheres filled withPhantoms: 4 min was required to obtain a stable quantification with the RRA method. The reference phase and the number of phases used for RRA did not affect the quantification which was similar on static acquisitions but different on ungated images. The results showed that the maximum standard uptake value (SUVSUVAccording to the results obtained using phantoms, RRA method is promising, showing a real impact on the lesion quantification on phantom data. With regard to the patient study, our results showed a trend towards an increase in the SUVs and a decrease in the volume between the ungated and RRA data. We also noticed a statistically significant correlation between the quantitative restoration obtained with RRA compared with ungated data and lesion displacement, indicating that the RRA approach should be reserved to patients with small lesions or nodes moving with a displacement larger than 1.2 cm. Advances in knowledge: This article investigates the performances of motion correction software recently introduced in PET. The conclusion revealed that such respiratory motion correction approach shows a real impact on the lesion quantification but must be reserved to the patient for whom lesion displacement was confirmed and high enough to clearly impact lesion evaluation.

International audience; To determine if the at-risk single-nucleotide polymorphism (SNP) alleles for colorectal cancer (CRC) could contribute to clinical situations suggestive of an increased genetic risk for CRC, we performed a prospective national case-control study based on highly selected patients (CRC in two first-degree relatives, one before 61 years of age; or CRC diagnosed before 51 years of age; or multiple primary CRCs, the first before 61 years of age; exclusion of Lynch syndrome and polyposes) and controls without personal or familial history of CRC. SNPs were genotyped using SNaPshot, and statistical analyses were performed using Pearson's chi(2) test, Cochran-Armitage test of trend and logistic regression. We included 1029 patients and 350 controls. We confirmed the association of CRC risk with four SNPs, with odds ratio (OR) higher than previously reported: rs16892766 on 8q23.3 (OR: 1.88, 95% confidence interval (CI): 1.30-2.72; P=0.0007); rs4779584 on 15q13.3 (OR: 1.42, CI: 1.11-1.83; P=0.0061) and rs4939827 and rs58920878/Novel 1 on 18q21.1 (OR: 1.49, CI: 1.13-1.98; P=0.007 and OR: 1.49, CI: 1.14-1.95; P=0.0035). We found a significant (P

Several studies have reported that, in Lynch syndrome resulting from mutations of the mismatch repair (MMR) genes, a CA repeat ≤17 within the IGF1 promoter, SNPs within the xenobiotic metabolizing enzyme gene CYP1A1 and SNPs on 8q23.3 and 11q23.1 modify colorectal cancer (CRC) risk in MMR mutation carriers. We analysed the impact of these polymorphisms on CRC risk in 748 French MMR mutation carriers derived from 359 families. We also analysed the effect of the Novel 1 SNP (18q21), which has recently been shown to increase CRC risk in the general population. We observed a significant difference in the CRC-free survival time between males and females, between MSH2 and MSH6 mutation carriers and between MLH1 and MSH6, indicating that this series is representative of Lynch syndrome. In contrast, the univariate log-rank test, as well as multivariate Cox model analysis controlling for familial aggregation and mutated MMR gene, year of birth and gender showed that the polymorphic alleles tested were not associated with a significant CRC risk increase, neither on the entire sample nor among males and females. This discrepancy with previous reports might be explained both by the genetic heterogeneity between the different populations analysed and the allelic heterogeneity of the MMR mutations. We conclude that genotyping of these polymorphisms is not useful to evaluate CRC risk in MMR mutation carriers and to optimize their clinical follow-up.

International audience

Background Under-prescription of antidepressants (ADs) among people meeting the criteria for major depressive episodes and excessive prescription in less symptomatic patients have been reported. The reasons influencing general practitioners’ (GPs) prescription of ADs remain little explored. This study aimed at assessing the influence of GP and patient characteristics on AD prescription. Methods This cross-sectional study was based on a sample of 816 GPs working within the main health care insurance system in the Seine-Maritime district of France during 2010. Only GPs meeting the criteria for full-time GP practice were included. The ratio of AD prescription to overall prescription volume, a relative measure of AD prescription level, was calculated for each GP, using the defined daily dose (DDD) concept. Associations of this AD prescription ratio with GPs’ age, gender, practice location, number of years of practice, number of days of sickness certificates prescribed, number of home visits and consultations, number and mean age of registered patients, mean patient income, and number of patients with a chronic condition were assessed using univariate and multivariate analysis. Results The high prescribers were middle-aged (40–59) urban GPs, with a moderate number of consultations and fewer low-income and chronic patients. GPs’ workload (e.g., volume of prescribed drug reimbursement and number of consultations) had no influence on the AD prescription ratio. GPs with more patients with risk factors for depression prescribed fewer ADs, however, which could suggest the medications were under-prescribed among the at-risk population. Conclusions Our study described a profile of the typical higher AD prescriber that did not include heavy workload. In future work, a more detailed assessment of all biopsychosocial components of the consultation and other influences on GP behavior such as prior training would be useful to explain AD prescription in GP’s practice. Electronic supplementary material The online version of this article (doi:10.1186/s12991-015-0041-7) contains supplementary material, which is available to authorized users.

Introduction L’ABSIS et le PDAI ont ete proposes comme scores d’evaluation de la severite des lesions cutanees et muqueuses pemphigus. Leur interet depend de la reproductibilite entre differents observateurs, pour comparer des populations de malades entre differentes etudes. Notre objectif a ete d’etudier la concordance des scores ABSIS et PDAI entre deux observateurs lors du diagnostic et pendant le suivi sous traitement. Materiel et methodes Les scores de severite ABSIS, PDAI et le score de severite global PGA ont ete prospectivement recueillis lors d’une etude multicentrique europeenne ayant inclus des patients atteints de pemphigus nouvellement diagnostique, suivis pendant 2 ans. Les scores etaient realises a chaque visite (j0, m1, m3, m6, m12, m18, m24) par deux investigateurs en insu. La reproductibilite inter-observateur a ete analysee via coefficient de correlation intra-classe (ICC) : – sur les scores totaux ; – sur les sous-scores d’atteinte cutanee (PDAI skin, et ABSIS skin) et muqueuse (PDAI mucosa, ABSIS mucosa) ; – en fonction de la severite du pemphigus (legere, moderee, severe) definie selon les seuils precedemment calcules. Resultats Cent seize patients (68F/48H, âge median 53 ans) 32PS et 84PV ont ete inclus. A j0, une bonne concordance inter-observateur etait observee pour l’ABSIS total (0,90 ; IC95 % : 0,85–0,93), le PDAI total (0,91 ; IC95 % = : 0,87–0,94) et le PGA (0,80 ; IC95 % : 0,72–0,86). Lors du suivi jusqu’a M6, la concordance restait elevee au cours des differentes evaluations (ICC ABSIS : 0,86 a 0,94 et ICC PDAI : 0,70–0,98). La concordance inter-observateur des sous-scores cutanes et muqueux etait tres proche : ICC PDAI-skin = 0,97 (IC95 % : 0,96–0,98) ; ICC PDAI-m = 0,91 (IC95 % : 0,87–0,94) ; ICC ABSIS-skin = 0,96 (IC95 % : 0,94–0,97) ; ICC ABSIS-m = 0,96 (IC95 % : 0,94–0,97). En cas de discordance, le niveau de discordance etait plus elevee dans l’evaluation des lesions muqueuses que des lesions cutanees (ABSIS : 5,0 pts vs 2,0 pts ; PDAI : 4,0 vs 3,0pts). La concordance inter-observateur de l’ABSIS etait mediocre dans les pemphigus de severite legere (0,44 ; IC95 % : 0,4–0,74) et meilleure dans le pemphigus de severite moyenne (0,69 ; IC95 % : 0,51–0,81) ou severe (0,75 ; IC95 % : 0,51–0,88). La concordance inter-observateur du PDAI etait moyenne (ICC = 0,50 ; IC95 % : 0,27–0,68) dans les pemphigus de severite moderee et bonne dans les formes legeres (0,82 ; IC95 % : 0,63–0,92) ou severes (0,80 ; IC95 % : 0,62–0,90). Discussion La reproductibilite inter-observateur des scores ABSIS et PDAI est bonne et se maintient durant le suivi, ils sont donc des outils robustes d’evaluation de la severite du pemphigus. Le niveau de discordance est plus eleve dans l’evaluation des lesions muqueuses que des lesions cutanees. La concordance inter-observateur de l’ABSIS est plus faible dans les pemphigus peu severes et celle du PDAI plus faible dans les pemphigus moderes.

Introduction Deux scores de severite du pemphigus, l’ABSIS et le PDAI ont ete recemment proposes afin de grader la severite au moment du diagnostic et faciliter le suivi des patients. Le but de cette etude a ete d’etudier la correlation de ces scores entre eux et avec d’autres marqueurs de severite : score de severite global (PGA), DLQI et taux d’Ac anti-desmogleine (DSG), lors du diagnostic et pendant le traitement. Ces correlations ont egalement ete etudiees en prenant en compte les sous-scores d’atteinte cutanee (PDAI skin et ABSIS skin) et muqueuse (PDAI mucosa et ABSIS mucosa). Materiel et methodes Etude prospective multicentrique europeenne ayant inclus des patients atteints de pemphigus superficiel ou vulgaire (PS ou PV) nouvellement diagnostique puis suivis pendant deux ans avec evaluations regulieres des scores ABSIS, PDAI, PGA, DLQI et mesure centralisee des taux d’Ac anti-DSG1 et DSG3. Les correlations entre les differents scores cliniques et les taux d’AC anti-DSG1 et 3 ont ete analysees via le coefficient de correlation (CC) de Spearman a j0 puis entre jO et m6 (la majorite des malades n’ayant plus de lesions apres m6). Resultats Cent seize patients (68F/48H) d’âge median 53 ans, 32PS et 84PV ont ete inclus. A j0 : le PDAI total et l’ABSIS total etaient moderement correles avec le PGA (CC = 0,68 et CC = 0,57 ; p p p p p p p p p Discussion Les scores ABSIS et PDAI sont bien correles au PGA mais pas avec le DLQI qui est mal adapte a l’evaluation de la qualite de vie des pemphigus, ne prenant pas en compte l’atteinte muqueuse. Les sous-scores cutanes et muqueux decrivent plus precisement l’evolution des lesions sous traitement que les scores globaux (PGA et DLQI). Les Ac anti-DSG1 sont plus fortement correles a l’evolution des lesions cutanees que les Ac anti-DSG3 ne le sont aux lesions muqueuses.

SummaryBackground The incidence of myocardial events has been reported to be increased in patients with psoriasis. Objectives To investigate whether psoriasis is an independent risk factor for coronary artery disease (CAD). Methods We compared the prevalence of psoriasis between case patients with a diagnosis of CAD based on coronary angiography findings and control patients with no CAD referred to the emergency surgery department for an acute noncardiovascular condition. Case and control patients were examined for the presence of psoriasis by two dermatologists. The prevalence of psoriasis was compared among patients with CAD according to CAD severity. Five-hundred cases and 500 age- and sex-matched controls were included. Results Using matched univariate analysis, the prevalence of psoriasis was about twofold higher in CAD case patients than in control patients [8·0% vs. 3·4%, odds ratio (OR) 2·64; 95% confidence interval (CI) 1·42–4·88]. Using unconditional multivariate analysis, the association of psoriasis with CAD appeared to be borderline significant (OR 1·84; 95% CI 0·99–3·40). Psoriasis in patients with CAD was significantly associated with three-vessel involvement relative to one-or two-vessel involvement (13·1% vs. 6·1%; OR 3·07; 95% CI 1·50–6·25). Conclusions The prevalence of psoriasis is twofold higher in patients with CAD than in control patients without CAD. It is associated with a more severe coronary artery involvement.

Aim. The aim of the present retrospective study was to evaluate the efficacy of four bariatric surgical procedures to induce diabetes remission and lower cardiovascular risk factors in diabetic obese patients. Moreover, the influence of surgery on weight evolution in the diabetic population was compared with that observed in a nondiabetic matched population.Methods. Among 970 patients who were operated on in our center since 2001, 81 patients were identified as type 2 diabetes. Laparoscopic adjustable gastric banding (GB), intervention type Mason (MA), gastric bypass (RYGB), and sleeve gastrectomy (SG) were performed, respectively, in 25%, 17%, 28%, and 30% of this diabetic population.Results. The resolution rate of diabetes one year after surgery was significantly higher after SG than GB (62.5% versus 20%,P<0.01), but not significantly different between SG and RYGB. In terms of LDL-cholesterol reduction, RYGB was equivalent to SG and superior to CGMA or GB. Considering the other cardiovascular risk factors, there was no significant difference according to surgical procedures. The weight loss was not statistically different between diabetic and nondiabetic matched patients regardless of the surgical procedures used.Conclusion. Our data confirm that the efficacy of surgery to treat diabetes is variable among the diverse procedures and SG might be an interesting option in this context.

In a French randomized trial, children at school-age demonstrated no evidence of harm from fetal exposure to MgSO4 before very preterm birth. Motor dysfunction/death, qualitative behavioral disorders, cognitive difficulties, school grade repetition, and education services were decreased in the children exposed to MgSO4, although the differences were not significant.

Introduction La gale represente actuellement un veritable probleme de sante publique. Les echecs de traitement sont frequents et les raisons en sont mal connues. L’objectif de l’etude etait d’identifier les facteurs predictifs d’echec de traitement. Patients et methodes Il s’agit d’une etude cas-temoins multicentrique realisee entre 2011 et 2013 par des dermatologues hospitaliers et liberaux. Le diagnostic de gale etait fait sur des criteres standardises. Les cas correspondaient a des patients consultant pour une recidive de gale survenue dans les 3 mois precedents. Les temoins etaient des patients primo-traites dont on verifiait la guerison a 3 mois. Un questionnaire etait rempli par les medecins et les patients evaluant les modalites de realisation du traitement, le niveau de comprehension, les conditions socio-economiques et familiales. Une analyse univariee puis multivariee par regression logistique en pas a pas descendant ont ete realisees. Resultats Deux cent trente et un patients ont ete inclus et 210 analyses (112 cas et 98 temoins) ; 21 patients n’ayant pu etre recontactes a 3 mois ont ete exclus. Pour les groupes temoins et cas respectivement, 29 et 46 patients ont ete traites par traitement local seul, 5 et 12 par traitement local seul, 64 et 54 ont eu les 2 types de traitements. Un echec de traitement etait associe a une duree d’evolution > 30 jours lors du diagnostic (OR = 3,97 ; IC 95 % 2,10–7,50), l’absence de traitement local (OR = 2,41 ; IC 95 % 1,02–13,60), l’absence d’une seconde prise de stromectol (OR = 10,2 ; IC 95 % 4,49–23,17) ou sa prise non a jeun (OR = 4,3 ; IC 95 % 1,89–9,84), l’application de dermocorticoides (DC) apres traitement (OR = 2,05 ; IC 95 % 1,12–3,79), le traitement du seul cas index (OR = 2,59 ; IC 95 % 1,31–5,14), l’absence de consignes ecrites remises aux patients (OR = 5,82 ; IC 95 % 2,37–10,44), la presence d’enfants en bas âge gardes en creche, garderie, ou par une nourrice (OR = 2,55 ; IC 95 % 1,03–6,32), l’absence d’utilisation d’acaricide pour le linge (OR = 8,62 ; IC 95 % 3,46–21,48), l’absence de traitement du mobilier de salon (OR = 5,89 ; IC 95 % 2,34–14,88), des sieges de voiture (OR = 6,56 ; IC 95 % 3,27–13,19) et de la literie (OR = 4,16 ; IC 95 % 1,32–12,84). Aucun facteur socio-economique ou lie au statut familial n’etait lie a un echec therapeutique. L’analyse multivariee confirmait l’association entre l’echec du traitement et un long delai avant traitement (OR = 2,82 ; IC 95 % 1,15–6,89), l’utilisation de DC (OR = 3,00 ; IC 95 % 1,24–7,27), la non-utilisation d’acaricide (OR = 4,74 ; IC 95 % 1,30–17,24) et le non-traitement des sieges auto (OR = 6,02 ; IC 95 % 2,36–15,34). Discussion Les facteurs d’echec semblent lies au mode de realisation du traitement et non aux conditions familiales ou socio-economiques. L’importance d’une seconde prise de stromectol, de consignes ecrites, l’utilisation d’acaricides et le role deletere des DC sont suggeres. Conclusion Cette etude montre que le non-respect des regles complexes de traitement de la gale est le principal facteur d’echec de traitement.

International audience; The aim of the study was to analyze the impact of MenBvac, an outer membrane vesicle (OMV) vaccine against P1.7,16 strains, on meningococcal carriage. During a B:14:P1.7,16/ST-32 outbreak in Normandy (France), children aged 1-7 years were randomly selected to participate in the study. Among the 1082 volunteers, there were 17 Neisseria meningitidis carriers (carriage rate of 1.57%). MenBvac vaccination appeared associated with lower carriage rate, i.e., 0.31% among the vaccinated children versus 2.10% among the non-vaccinated (p=0.03). The beneficial effect on carriage was observed regardless of the strain serogroup. OMV-vaccinated mice also showed reduction of bacterial acquisition of OMV-homolog and hererolog strains in respiratory pathways after intranasal challenge. These results suggest that meningococcal OMV-based vaccines reduce meningococcal carriage and may hence confer herd immunity.

International audience; OBJECTIVE To identify the prognostic factors of overall survival in a series of patients with paraneoplastic pemphigus (PNP). DESIGN Multicenter retrospective cohort study. SETTING Twenty-seven dermatology departments in France. PATIENTS A total of 53 patients (31 men and 22 women; median age, 59 years; age range, 30-88 years) were diagnosed as having PNP between 1992 and 2010. MAIN OUTCOME MEASURES Overall Kaplan-Meier survival rates were estimated, and features associated with survival were assessed using univariate (log-rank test) and multivariate (Cox regression) analyses. RESULTS The study included 53 patients with PNP. Thirty-six patients (68%) died during the study. The 1-, 3-, and 5-year overall survival rates were 49%, 41%, and 38%, respectively. The main causes of death were infections (n = 21) and evolution of neoplasia (n = 6). In univariate analysis, the main detrimental prognostic factors identified were erythema multiforme-like skin lesions (P = .05) and histologic keratinocyte necrosis (P = .03). None of the 5 patients with Castleman disease died during the study. After adjustment for age and sex in multivariate analysis, erythema multiforme-like skin lesions remained predictive of fatal outcome, with a 2-fold increase in death rate (hazard ratio [HR], 2.3; 95% CI, 1.05-5.03; P = .04). The prognosis of patients with PNP was even poorer when erythema multiforme-like skin lesions were associated with severe skin or mucosal involvement at presentation (HR of death, 3.0; 95% CI, 1.01-8.92; P = .049). CONCLUSION Patients with PNP with erythema multiforme-like skin lesions and histologic keratinocyte necrosis, especially when associated with extensive lesions at presentation, are likely to have a more severe and rapid fatal outcome and should be managed very carefully.

International audience; A meningococcal B:14:P1.7,16 outbreak in Normandy (France) was recently controlled using MenBvac, an outer membrane vesicle vaccine previously designed against the B:15:P1.7,16 strain. The further emergence of a new B:14:P1.7,16 outbreak in another district in Normandy led us to explore immunity against B:14:P1.7,16 before and after the MenBvac campaign using a 2+1 (day 0, week 6, month 8) schedule. Children (1-5 years) were sampled before, during and up to one year after vaccination. Serum bactericidal activity against B:14:P1.7,16 was titrated using human complement (hSBA) and immune response was defined by hSBA titer ≥4 as a surrogate for protection. The percentage of hSBA titer ≥4 was 10.8% before vaccination, raised to 84.1% 6 weeks after the completion of the schedule, but declined to 39.7% one year later. This level is lower than the targeted 60% level and suggests only short-term persistence of response against B:14:P1.7,16 using this schedule.

Introduction L’utilisation du rituximab (R) en 2nde intention dans les formes severes de pemphigus est bien validee. Nous avons evalue l’interet du R comme traitement de 1re intention du pemphigus, dans le but d’augmenter l’efficacite du traitement tout en realisant une epargne de corticoides. Materiel et methodes Etude multicentrique prospective sans insu, dans laquelle les malades randomises dans le bras corticotherapie standard (CS) recevaient initialement 1 a 1,5 mg/kg/j de prednisone en fonction de la severite avec decroissance secondaire et arret au bout de 12 a 18 mois. Les malades randomises dans le bras « R » recevaient initialement 2 g de R IV associe a 0,5 ou 1 mg/kg/j de prednisone en fonction de la severite. La corticotherapie etait arretee apres 3 a 6 mois, Le critere du jugement principal etait le taux de malades en remission complete sans traitement (RCST) a 2 ans. Resultats Quatre-vingt-dix malades d’âge median 53 ans, 82 % PV, 18 % PS ont ete inclus. Soixante-dix-neuf malades (88 %) etaient severes et 11 moderes (12 %). 46 ont ete randomises dans le bras R et 44 dans le bras CS. En ITT, le taux de malades en RCST a 2 ans etait de 87 % dans le bras R vs 34 % dans le bras CS (p Conclusion Cette etude suggere d’utiliser du R en 1ere intention dans le traitement du pemphigus, pour ameliorer le taux de RCST et permettre un sevrage rapide de la corticotherapie.

Complications of bone marrow transplantation (BMT) are usually considered to be related to the secretion of inflammatory cytokines, which generate membrane microparticles rich in procoagulant phospholipids (PPL) from different cellular origins and release of endothelial proteins such as thrombomodulin (TM). The use of soluble TM quantified by ELISA (TM:Ag) as a marker of endothelial injury is complex in children since it is age-dependent.Using a functional assay which quantifies the activity of sTM activity (TMa), we performed a pilot study to analyze the ratio TMa/TM:Ag in a control group of 25 healthy children, 8 children with autologous and 16 children with allogeneic BMT. In this last group, 8 experienced BMT complications. In addition, we used a functional assay which quantifies PPL.In healthy children the ratio TMa/TM:Ag was independent of age and stable in children with a favorable outcome but significantly (p0.05) reduced by the use of antithymocyte globulin during the conditioning regimen, and regularly decreased in children with BMT complications. Surprisingly, low plasma PPL levels were associated with a poor outcome.The ratio TMa/TM:Ag could constitute a marker of endothelium injury, and its follow-up could be of interest for an early discrimination of children with high risk of complications during allogeneic BMT. The decrease of PPL could be also another marker of a poor evolution and deserves further investigations.

Aim: Genomic quantitative alteration is a backbone event during the carcinogenesis process in microsatellite stable colon cancer. However, the prognostic value of loss or gain of the main genomic regions is still controversial. We conducted a prospective study to assess the prognostic impact of the main genomic quantitative alterations in stage II-III MSS colon cancer (NCT02110329). Methods: Patients treated for stage II-III colon cancer from 01/2002 to 01/2009 with available frozen tissue were included. The Quantitative Multiplex PCR of Short Fluorescent Fragments (QMPSF) method was used for molecular screening (1). The QMPSF was based on the simultaneous amplification, from normal and tumoral tissues, of 8 selected target genomic sequences according to literature data: DCC (18q21); EGFR (7p12); TP53 (17p13.1); BLK (8p23-p22); MYC (8q24.12); APC (5q22.2); ERBB2 (17q12); STK6 (20q13.31); and two control: PCBD2 (5q31.1); HMBS (11q23.3). The primary end-point was to determine the association between molecular alterations and disease-free survival (DSF). Combinations of alterations were defined according to univariate results (p Results: A total of 401 patients were included with a median follow-up of 48 months. There were 236 stage II and 165 stage III and the recurrence rate was 30.2%. Loss of DCC/18q, TP53/17p, BLK/8p, and APC/5q were detected in respectively 33.2%, 26.7%, 22.7%, 9.7% and gain of EGFR/7p, MYC/8q, ERBB2/17q and STK6/20q were observed in 31.7%, 35.7%, 18.7% and 48.9% of cases, respectively. There was no significant interaction between alterations and disease stage. DFS was significantly associated with loss of DCC/18q (57.5 vs 70.6%, p = 0.02) with a trend for BLK/8p loss (59.8 vs 68.6%, p = 0.08) and ERBB2/17q gain (59.2 vs 68.5%, p = 0.14). In multivariate analysis, the combination of loss DCC/18q and/or loss BLK/8p and/or gain ERBB2/17q was significantly associated with DFS. The DFS significantly decreased from 74.2% to 61.7% (HR = 1.78, 95CI: 1.14-2.77) and to 57.2% (HR =2.06, 95CI: 1.26-3.37) in patients with respectively none, 1 and at least 2 of these 3 alterations. Conclusions: Combination of DCC/18q, BLK/8p and ERBB2/17q gene copy number alterations is associated with disease-free survival in stage II-III colon cancer. Disclosure: All authors have declared no conflicts of interest.

Following the publication of our article entitled ‘Evaluation of Lynch syndrome modifier genes in 748 MMR mutation carriers'1 in which we reported that in MMR mutation carriers 8q23.3 and 11q23.1 polymorphic alleles were not significantly associated with an increased colorectal cancer (CRC) risk, Talseth-Palmer et al2 indicated that we did not correctly report their results by indicating: ‘During the submission of this study Talseth-Palmer et al reported that in MLH1 carriers, but not in MSH2 carriers, the 11q23.1 CC and 8q23.3 AC genotypes were associated with an increased risk, but this significant association detected in 373 Australian mutation carriers was not found in 311 Polish mutation carriers analysed in the same study'. Their study was indeed performed in two distinct samples of MMR mutation carriers, originated from Australian and Polish families, respectively.2 As indicated in Figure 1C of their article, the variation in CRC risk according to the 11q23.1 CC genotype was not statistically significant in the Polish sample cohort, but only a trend was observed (log-rank P=0.1336; Wilcoxon P=0.1109, and tware P=0.117). Moreover, the variation in CRC risk according to the 8q23.1 genotype was significant only in the Australian sample whereas no results are reported for the combined sample or the Polish sample, likely pointing to non-significant results. Therefore, our comment is appropriate. Moreover, the combination of the Australian and Polish MMR mutation carrier performed in their study amounts to a meta-analysis using pooled data from two different populations. Finally, all significant differences reported were restricted to MLH1 mutation carriers and no results were reported for MSH2 mutation carriers or for all subjects, which also raises questions on the real impact of the 8q23.3 and 11q23.1 genotypes on the CRC risk in MMR mutation carriers. Therefore, the title of their article ‘Colorectal susceptibility loci on chromosome 8q23.3 and 11q23.1 as modifiers for disease expression in Lynch syndrome' appears too broad. We do not agree with their conclusion suggesting that 8q23.3 and 11q23.1 genotyping might have a clinical utility in MLH1 mutation carriers.

To assess the usefulness of enzyme-linked immunosorbent assay (ELISA) assessment of the combination of bullous pemphigoid antigen 1 (BPAG1) and BPAG2 in the diagnosis of bullous pemphigoid (BP).Retrospective study of serum samples from patients with BP.Tertiary care center.A total of 190 patients with newly diagnosed BP and 78 controls with other autoimmune bullous diseases.Serum samples were tested using commercialized BPAG1 and BPAG2 ELISA and indirect immunofluorescence (IIF).The sensitivity and specificity of ELISA for the combination of BPAG1 and BPAG2 in the diagnosis of BP were contrasted with ELISA for each of the antigens alone and with IIF.The sensitivity and specificity of ELISA for the combination of BPAG1 and BPAG2 were 87% and 88%, respectively, compared with 79% and 90% for BPAG2 ELISA, 61% and 96% for BPAG1 ELISA, and 81% and 63% for IIF. The combination of BPAG1 ELISA and BPAG2 ELISA permitted 8% and 16% gains in sensitivity compared with each of BPAG2 ELISA and BPAG1 ELISA alone, respectively. Anti-BPAG1 antibodies were detected in 15 of 40 BP serum samples with no anti-BPAG2 antibodies (38%) and in 8 of 13 serum samples from patients with BP and mucosal involvement (62%) compared with 2 of 22 samples of cicatricial pemphigoid (P = .002) and 0 of 16 epidermolysis bullosa acquisita serum samples (P.001). The BPAG2 ELISA values were more closely correlated with initial extent of BP lesions (r = 0.44, P.001) than BPAG1 ELISA values (r = 0.16, P = .03).Since the combination of BPAG1 and BPAG2 ELISA only slightly increases the sensitivity of BP diagnosis over BPAG2 ELISA alone, BPAG1 ELISA could be adequately proposed in a minority of BP cases with mucosal involvement and in those with no circulating anti-BPAG2 antibodies.

International audience; The aim of this study performed in Normandy, France, was to analyze the pharyngeal meningococcal carriage at the peak of a clonal meningococcal B outbreak, which was subsequently controlled using an outer membrane vesicle vaccination. This cross-sectional study included randomly selected subjects aged 1-25 years. Carriers and non carriers were compared using unconditional logistic regression. Among the 3,522 volunteers, there were 196 (standardized rate: 6.46 %) Neisseria meningitidis carriers, of which there were only five with the outbreak strain (B:14:P1.7,16/ST-32; standardized rate: 0.18 %). From the multivariate analysis, older age, smoking, higher degree of socialization, and social deprivation appear to favor the carriage of all the strains included. Prior antibiotic treatment up to 12 months before swabbing, even with β-lactam, was protective against carriage. Our data indicate a low overall meningococcal carriage rate with a surprising protective effect of prior antibiotic exposure. The observed low carriage rate of the epidemic strain (B:14:P1.7,16/ST-32) contrasts with the high incidence of invasive meningococcal diseases (IMD) due to this strain. Hence, our data underline the high virulence of the strain and suggest a low level of natural immunity of the population against this strain. Although highly resource-consuming, carriage studies are helpful in guiding the implementation of control measures of IMD, such as mass vaccination or chemoprophylaxis.