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Objective To report the 10-year outcome of an inception cohort of patients with early rheumatoid arthritis (RA), the ESPOIR cohort, and predictors of outcome. Methods From 2003 to 2005, 813 patients were included if they had early arthritis ( Results In total, 521 (64.1%) RA patients were followed up for 10 years; 35 (4.3%) died, which appears to be similar to the French general population. Overall, 480 (92.1%) patients received a DMARD; 174 (33.4%) received at least one biologic DMARD, 13.6% within 2 years. At year 10, 273 (52.4%) patients were in DAS28 remission, 40.1% in sustained remission, 14.1% in drug-free remission, 39.7% in CDAI remission. Half of the patients achieved a health assessment questionnaire-disability index (HAQ-DI) < 0.5. SF-36 physical component and pain were well controlled. Structural progression was weak, with a mean change from baseline in modified Sharp score of 11.0 (17.9). Only 34 (6.5%) patients required major joint surgery. A substantial number of patients showed new comorbidities over 10 years. Positivity for anti-citrullinated peptides antibodies (ACPA) was confirmed as a robust predictor of long-term outcome. Conclusions We report a very mild 10-year outcome of a large cohort of patients with early RA diagnosed in the early 2000s, which was much better than results for a previous cohort of patients who were recruited in 1993. This current favourable outcome may be related to more intensive care for real-life patients.

Resume Objectif L’objectif de cette etude est de presenter l’evolution des donnees d’incidence et de mortalite du cancer des organes genitaux externes de l’homme dans l’Herault a partir des donnees du Registre des tumeurs de l’Herault (RTH) sur une periode de 30 ans. Materiel et methodes A partir de la base de donnees du RTH, nous avons etudie l’evolution des tumeurs germinales du testicule (TGT) et du cancer du penis (CP) sur 30 ans (de 1987 a 2016). Nous avons analyse les donnees d’incidence et de mortalite de ces tumeurs. Nous avons compare ces resultats aux donnees francaises, europeennes et mondiales. Resultats En 30 ans d’enregistrement nous avons recense 725 cas de TGT et 175 cas de CP. Le taux standardise sur la population mondiale (TSM) d’incidence des TGT a double entre 1987 et 2016 (4,2/100 000 en 1987 et 9,3/100 000 en 2016). Il a ete multiplie par 2,63 dans la population des patients de 30 a 44 ans. On observe une baisse du taux de mortalite avec un TSM a 0,8/100 000 en 1987, et 0,4/100 000 en 2016. Le TSM d’incidence des CP est stable entre 1987 et 2016 (TSM entre 0,4 et 0,9/100 000). La mortalite est stable avec un TSM entre 0,1 et 0,3/100 000 entre 1987 et 2016. Conclusion L’incidence des TGT a fortement augmente dans l’Herault durant les 30 dernieres annees alors que l’on observe une diminution de la mortalite. La proportion des tumeurs germinales seminomateuses augmente ; elle est passee de 53 % a 60 % en 30 ans dans l’Herault. L’incidence et la mortalite du CP etaient stables dans l’Herault durant les 30 dernieres annees.

Poly(ADP-ribose) polymerase 1 inhibitor (PARPi) agents can improve progression-free survival of patients with breast cancer who carry a germline BRCA1 or BRCA2 pathogenic or likely pathogenic variant (gBRCA) in both the metastatic and adjuvant setting. Therefore, we need to reassess the frequency of gBRCA1 and gBRCA2 in order to redefine the criteria for women and tumor phenotype that should be tested.We studied the relative distribution of gBRCA1 and gBRCA2 in unselected populations of women with breast cancer and in unaffected individuals. We also analyzed the proportion of estrogen receptor (ER)-positive (ER+) tumors in unselected breast cancer patients with gBRCA.We performed a meta-analysis of studies of unselected breast cancer that analyzed the relative contribution of gBRCA1 versus gBRCA2 among unselected breast cancer cases in gBRCA carriers. We then performed a meta-analysis of gBRCA carriage in unaffected individuals from genome-wide population studies, the gnomAD databank, and case-control studies.TheThis meta-analysis showed that gBRCA2 carriage is predominant in unselected breast cancer patients and unaffected individuals. ER+ tumors among women with gBRCA-related breast cancer are predominant and have been underestimated. Because PARPi agents improve progression-free survival with ER+ gBRCA breast cancer in most clinical trials, breast cancer should be considered, regardless of ER status, for

Resume Objectifs On observe dans l’Herault une nette augmentation de l’incidence des cancers urologiques. Le registre des tumeurs de l’Herault (RTH) a recueilli 1961 tumeurs urologiques en 2016, soit 21,4 % de l’ensemble des tumeurs de l’Herault pour cette annee-la. La creation d’un registre specialise en onco-urologie nous est apparue necessaire. L’objectif de cet article est de decrire le fonctionnement de RHESOU et de donner quelques exemples de resultats. Materiel et methodes En novembre 2018, RHESOU (Registre de l’herault specialise en onco-urologie) a ete cree sur le meme mode de fonctionnement qu’un registre. Il permet de completer les donnees du RTH sur beaucoup d’autres parametres oncologiques. Pour chaque type de cancer urologique et genital masculin et urologique feminin, une fiche de recueil a ete realisee pour recueillir le maximum de donnees presentes dans le dossier des cas signales. Cette etude a evalue les donnees concernant les patients domicilies dans l’Herault pour l’annee 2017. Resultats Nous avons denombre pour l’annee 2017, 970 cancers de la prostate, 581 tumeurs de vessie, 212 cancers du rein, 51 tumeurs de la voie excretrice superieure, 28 cancers du testicule et 9 cancers du penis. Le recueil de ces donnees permet de creer des requetes et de fournir des analyses pertinentes et detaillees sur les cancers urologiques et genitaux masculins. Nous rapportons les donnees analysees sur le rein, la vessie et la prostate. Conclusions RHESOU est un outil accessible pour permettre une vue d’ensemble sur les cancers en urologie dans l’Herault et leur prise en charge. Avec l’apparition de nouveaux traitements, il saura s’adapter en permettant une evolution des fiches. Niveau de preuve 3.

International audience; Purpose: The metabolic changes associated with cachexia – sarcopenia syndrome might down-regulate antitumor immunity. We hypothesized that this syndrome reduces efficiency of immune checkpoint inhibitors (ICPI) in non-small cell lung cancer (NSCLC).Methods: The records of 142 consecutive NSCLC patients receiving first- or second-line anti-Programmed cell death protein 1) ICPI were reviewed. Response evaluation according to Response Evaluation Criteria in Solid Tumors 1.1 was performed at the eighth week of immunotherapy. Pretreatment cachexia was defined as a body-weight loss of 5% or more in the previous 6 months. Sarcopenia was estimated with the third lumbar skeletal muscle mass index (mSMI) and was evaluated before immunotherapy and at the eighth week. A decrease by 5% or more of the mSMI was considered as an evolving sarcopenia. The endpoints were disease control rate (DCR), progression-free (PFS) and overall survival (OS).Logistic regression model and Cox model took into account others covariables known to influence ICPI efficiency, particularly Programmed Death –Ligand 1 tumor cell score, Eastern Cooperative Oncology Group performance status and common somatic mutational status.Results: In multivariate analysis, cachexia – sarcopenia syndrome reduced the probability of achieving a disease control and were associated with a shorter survival. Patients without cachexia had a better probability to achieve disease control in comparison with those who did not experience cachexia (59.9 % and 41.1 %, respectively; odds ratio 95 % (confidence interval [95 %CI]): 2.60 (1.03–6.58)). Patients with cachexia had a shorter OS when compared with those without cachexia (hazard ratios [HR] (95 %CI): 6.26 (2.23–17.57)). Patients with an evolving sarcopenia had a shorter PFS and OS, with HR (95 %CI): 2.45 (1.09–5.53) and 3.87 (1.60–9.34) respectively.Conclusion: Cachexia – sarcopenia syndrome negatively influences patients’ outcome during anti-PD-1 ICPI therapy

Persistent shortage and heterogeneous quality of liver grafts encourages the optimization of donor-recipient matching in liver transplantation (LT). We explored whether or not there was a survival benefit (SB) of LT according to the quality of grafts assessed by the Donor Quality Index (DQI) and recipients’ disease severity, using the Model for End-Stage Liver Disease (MELD) in 8387 French patients wait-listed between 2009 and 2014. SB associated with LT was estimated using the sequential stratification method in different categories of MELD and DQI. For each transplantation, a stratum was created that matched one transplanted patient with all eligible control candidates. Strata were thereafter combined, and a stratified Cox model, adjusted for covariates, was fitted in order to estimate hazard ratios that qualified the SB according to each MELD and DQI sub-group. A significant SB was observed for all MELD and DQI sub-groups, with the exception of high MELD patients transplanted with “high-risk” grafts. More specifically, in decompensated-cirrhosis patients, “high-risk” grafts did not appear to be detrimental in medium MELD patients. Interestingly, in hepatocellular-carcinoma (HCC) patients, a significant SB was found for all MELD-DQI combinations. For MELD exceptions no SB was found. In terms of SB, “low-risk” grafts appeared appropriate for most severe patients (MELD > 30). Conversely, low/medium MELD and HCC patients presented an SB while allocated “high-risk” grafts. Thus, SB based matching rules for LT candidates might improve the survival of the LT population as a whole.

Multimorbidity is frequent in rheumatoid arthritis (RA) and could interfere with the therapeutic response. The aim of this study was to evaluate multimorbidity in the French cohort of early arthritis, the ESPOIR cohort, and its possible impact on the therapeutic response.We included patients fulfilling 2010 ACR/EULAR criteria for RA. An adapted MultiMorbidity Index (aMMI) was developed. Each patient was assigned scores of binary aMMI (0=no comorbidity, 1=at least 1 comorbidity) and counted and weighted aMMI. The primary endpoint was achievement of Clinical Disease Activity Index (CDAI) low disease activity after initiation of a first disease-modifying antirheumatic drug (DMARD) according to the aMMI. We collected data from the visit preceding the first DMARD initiation and the visit after at least 3 months of treatment. The impact of aMMI on therapeutic maintenance at 1, 3, 5 and 10 years was evaluated.Analyses involved 472 patients: 302 (64%) had at least 1 comorbidity. Overall, 45.3% and 44.7% with binary aMMI=0 or 1, respectively (non-significant), achieved CDAI low disease activity. Similar results were found with counted and weighted aMMI. Therapeutic maintenance was significantly better with binary aMMI=1 than binary aMMI=0 (OR at 10 years=14.0 [CI 95% 3.3-59.4]). Increased counted aMMI was associated with increased probability of still being on the first initiated DMARD at each time point.In the ESPOIR cohort, therapeutic response to a first DMARD was not affected by multimorbidity but therapeutic maintenance was better in multimorbid patients.

Simple Summary The analysis of circulating tumor cells (CTCs) as a “real-time liquid biopsy” in epithelial tumors for personalized medicine has received tremendous attention over the past years, with important clinical implications. In metastatic colorectal cancer (mCRC), the CellSearch® system has already demonstrated its prognostic value and interest in monitoring treatment response, but the number of recovered CTCs remains low. In this article, we evaluate the early prognostic and predictive value of viable CTCs in patients with mCRC treated with FOLFIRI–bevacizumab with an alternative approach, the functional EPISPOT assay. This study shows that viable CTCs can be detected in patients with mCRC before and during FOLFIRI–bevacizumab treatment and that CTC detection at D28 and the D0–D28 CTC kinetics evaluated with the EPISPOT assay are associated with response to treatment. Abstract Background: Circulating tumor cells (CTCs) allow the real-time monitoring of tumor course and treatment response. This prospective multicenter study evaluates and compares the early predictive value of CTC enumeration with EPISPOT, a functional assay that detects only viable CTCs, and with the CellSearch® system in patients with metastatic colorectal cancer (mCRC). Methods: Treatment-naive patients with mCRC and measurable disease (RECIST criteria 1.1) received FOLFIRI–bevacizumab until progression or unacceptable toxicity. CTCs in peripheral blood were enumerated at D0, D14, D28, D42, and D56 (EPISPOT assay) and at D0 and D28 (CellSearch® system). Progression-free survival (PFS) and overall survival (OS) were assessed with the Kaplan–Meier method and log-rank test. Results: With the EPISPOT assay, at least 1 viable CTC was detected in 21% (D0), 15% (D14), 12% (D28), 10% (D42), and 12% (D56) of 155 patients. PFS and OS were shorter in patients who remained positive, with viable CTCs between D0 and D28 compared with the other patients (PFS = 7.36 vs. 9.43 months, p = 0.0161 and OS = 25.99 vs. 13.83 months, p = 0.0178). The prognostic and predictive values of ≥3 CTCs (CellSearch® system) were confirmed. Conclusions: CTC detection at D28 and the D0–D28 CTC dynamics evaluated with the EPISPOT assay were associated with outcomes and may predict response to treatment.

Resume Objectifs L’asthme est la premiere pathologie chronique de l’enfant ; son controle et son traitement restent insuffisants. Notre objectif etait d’evaluer si l’utilisation du Childhood Asthma Control Test (C-ACT) en medecine generale avait un impact sur l’adaptation du traitement de fond. Methodes Notre etude quantitative, prospective, comparait 2 groupes de medecins generalistes. Tous ont eu les memes rappels sur l’asthme de l’enfant. Le C-ACT etait presente au groupe C-ACT uniquement. Les medecins du groupe controle devaient travailler de maniere habituelle, sans C-ACT. Les medecins incluaient des enfants asthmatiques de 6 a 11 ans les consultant pour leur asthme ou tout autre motif. Le critere de jugement principal etait l’adaptation du traitement de fond de l’asthme selon les paliers du Global INitative for Asthma (GINA). Les evaluations du groupe controle etaient comparees au C-ACT auto-administre sur internet apres la consultation. Resultats D’avril a octobre 2014, 61 medecins ont inclus 179 patients en 2 groupes comparables. Bien que non statistiquement significatif, avec le C-ACT, les medecins identifiaient 45 % d’asthmes non controles (contre 31 %). Lorsque le motif de consultation n’etait pas lie a l’asthme, ils en depistaient 25 % (contre 15 %). Les medecins utilisant le C-ACT faisaient 2 fois moins d’adaptations therapeutiques non recommandees par le GINA : 8 % contre 16 %. Dans le groupe controle, 25 % des evaluations etaient discordantes avec le C-ACT internet rempli par le patient. Apres correction par le C-ACT internet de ces evaluations initiales imprecises, il y avait en realite 25 % d’adaptations non recommandees : 3 fois plus que dans le groupe C-ACT (p = 0,014). Conclusion Utiliser le C-ACT en medecine generale permet de mieux evaluer le controle de l’asthme de l’enfant et de mieux adapter le traitement de fond.

Background: PARP inhibitor (PARPi) agents can improve progression-free survival of patients with breast cancer (BC) who carry a germline BRCA1 or BRCA2 pathogenic or likely pathogenic variant (gBRCA1/2) in both the metastatic and adjuvant setting. Therefore, we need to redefine the criteria of women and tumor phenotype that should be tested for gBRCA1/2. Objective: We studied the relative distribution of gBRCA1 and gBRCA2 in unselected populations of women with BC and in unaffected individuals. We also analyzed the proportion of estrogen receptor (ER)-positive (ER+) tumors in unselected BC patients with gBRCA1/2.Design: We performed a meta-analysis of studies of unselected BC that analyzed the relative contribution of gBRCA1 versus gBRCA2 and ER+ tumors among gBRCA1/2 carriers. We then performed a meta-analysis of gBRCA1/2 carriage in unaffected individuals, from genome-wide population studies, the gnomAD databank, and case–control studies. Results: The BRCA2 gene was involved in 54% of BC in unselected patients with gBRCA1/2 (n=108,699) and 59% of unaffected individuals (n=238,973) as compared with 38% of gBRCA1/2 family cohorts (n=29,700). The meta-analysis showed that 1.66% (95% CI 1.08-2.54) and 1.71% (95% CI 1.33-2.2) of unselected BC patients carried a gBRCA1 and gBRCA2, respectively. In unaffected individuals, the frequency of heterozygosity for gBRCA1 and gBRCA2 was estimated at 1/434 and 1/288, respectively. Nearly 0.5% of unaffected individuals in the studied populations carried a gBRCA1/2. Overall, 58% of breast tumors occurring in women carrying a gBRCA1/2 were ER+ (n=86,870).Conclusion: This meta-analysis showed that gBRCA2 carriage is predominant in unselected BC and in unaffected individuals. ER+ tumors among women with gBRCA1/2-related BC is predominant and has been underestimated. Because PARPi agents improve progression-free survival with ER+ gBRCA1/2 BC in both the adjuvant and metastatic setting, BC should be considered regardless of ER status for BRCA1/2 screening for therapeutic purposes.

Resume Objectif Dans le but de connaitre ce que les medecins specialistes attendent de la chimiotherapie du cancer du poumon (stade 3b et 4), nous les avons confrontes a un auto-questionnaire en ligne decrivant cinq situations differentes de prescription. Methode Trente specialistes experts ont ete invites ; 22 ont repondu (73 %). Pour chacune des differentes situations cliniques, il etait demande a l’expert de se positionner sur 3 items : curabilite, allongement de la survie, soulagement des symptomes. Le jugement porte sur chaque item se faisait sur une echelle de Likert impaire, entre −2 « pas du tout probable » et 2 « tout a fait probable ». Resultats Pour la curabilite, le pourcentage de reponse −2 differait significativement en fonction de la situation clinique (test de Fisher : p Conclusion Ce que les medecins specialistes attendent de la chimiotherapie differe en fonction du pronostic presuppose. A la situation de plus mauvais pronostic correspond l’attente la plus forte en termes de soulagement des symptomes et la plus faible en termes de curabilite.

Resume Objectif L’objectif de cette etude est de presenter l’evolution de l’epidemiologie du cancer du rein dans l’Herault a partir des donnees collectees par le registre des tumeurs de l’Herault (RTH) sur une periode de 30 ans. Materiels et methodes A partir de la base de donnees du RTH, nous avons etudie l’evolution du cancer du rein de 1987 a 2016. Nous avons analyse les donnees concernant l’incidence, la mortalite, l’anatomopathologie des tumeurs et leur stade au diagnostic. Nous avons compare ces resultats aux donnees nationales et internationales. Resultats Nous avons recense 3769 nouveaux cas de cancers du rein: 2628 chez l’homme (69,7 %) et 1141 chez la femme (30,3 %). En 2016, le cancer du rein etait le 8e cancer tous sexes confondus, le 7e cancer chez l’homme et le 11e chez la femme. Entre 1987 et 2016 le nombre de nouveaux cas de cancer du rein a ete multiplie par 4,2 chez l’homme et par 3,3 chez la femme. Le nombre de formes localisees a augmente de 9 % en 20 ans. En 2016 la probabilite, d’etre atteint d’un cancer du rein avant 75 ans est de 2,11 % pour un homme et de 0,62 % pour une femme. Conclusion En 30 ans, l’incidence du cancer du rein a fortement augmente dans l’Herault alors que l’on observe une diminution de sa mortalite. Ces donnees analytiques seront ameliorees par le developpement du Registre de l’Herault Specialise en Onco Urologie (RHESOU) Niveau de preuve 3.

Objectives To explore the 10-year tolerability profile of glucocorticoids (GC) use in patients with early RA. Methods Analysis of 10-year outcome from the early arthritis ESPOIR cohort. Patients were stratified in two groups, without or with GC treatment at least once during their follow-up. The primary outcome was a composite of deaths, cardiovascular diseases (CVD), severe infections and fractures. The weighted Cox time-dependent analysis model was used with inverse probability of treatment weighting (IPTW) propensity score method. Results Among the 608 patients [480 women, mean age of 47.5 (12.1) years], 397 (65%) received low-dose GC [median 1.9 mg/day (IQR 0.6–4.2), mean cumulative prednisone dose 8468 mg (8376), mean duration 44.6 months (40.1)]. In univariate analysis, over 95 total events (10 deaths, 18 CVDs, 32 fractures and 35 severe infections), patients taking GC experienced more events (n = 71) than those without GC (n = 24) (P =0.035). Highest cumulative exposure of GC (≥8.4 g) was associated with highest risk of occurrence of the primary outcome (24.3%, P =0.007), CVDs (7.9%, P =0.001) and severe infections (9.9%, P =0.024). The risk of events over time was significantly associated with GC, age, hypertension and ESR. The risk associated with GC treatment increased between the first follow-up visit [hazard ratio (HR) at 1 year = 0.46, 95% CI: 0.23, 0.90] and 10 years (HR = 6.83, 95% CI: 2.29, 20.35). Conclusion The 10-year analysis of this prospective early RA cohort supports a dose and time-dependent impact of low-dose GC treatment, with a long-term high risk of severe outcomes. Trial registration (ClinicalTrials.gov Identifier: NCT03666091).

Objectifs Le registre des tumeurs de l’Herault (RTH) est un registre general qualifie par le comite national des registres depuis 1987. L’objectif de cette etude est de presenter l’evolution de l’epidemiologie du cancer de la vessie dans le departement de l’Herault a partir des donnees collectees par le RTH sur une periode de 30 ans. Methodes A partir de la base de donnees du RTH, nous avons etudie l’incidence, les taux d’incidence standardises sur la population mondiale (TSM), la frequence relative, le sex-ratio, l’âge moyen au diagnostic, les donnees anatomopathologiques et les primo-traitements pour toutes les tumeurs de la vessie ≥ T1 dans la population de l’Herault entre 1987 et 2016. Les donnees de mortalite proviennent du service SC8 de l’INSERM (CepiDC). Nous avons compare ces resultats aux donnees nationales et internationales. Les estimations francaises proviennent des donnees FRANCIM et les donnees mondiales des registres sont regroupees par le Centre international de recherche sur le cancer (CIRC), situe a Lyon. Resultats Les TSM du cancer de la vessie pour 100 000 sont passes de 11,1 en 1987–1988 (21 hommes, 3,1 femmes) a 8,2 en 2015–2016 (15,2 hommes, 2,5 femmes). Sur 30 ans, le RTH a recense 5580 cas et 2718 deces. Le rapport mortalite/incidence etait de 48,7 % (45,9 % chez l’homme, 62,1 % chez la femme) et le sex-ratio etait de 4,7 hommes pour une femme. En 2016, il etait le 7e cancer dans l’Herault (5e chez l’homme). Les carcinomes urotheliaux representaient 91,7 % des cancers. En 2016, l’âge moyen au diagnostic etait de 74,8 ans (74,2 ans chez l’homme, 76,9 ans chez la femme) et la probabilite d’avoir un cancer de la vessie avant l’âge de 75 ans etait de 1,81 % pour un homme (1/55) et 0,26 % pour une femme (1/382) ( Fig. 1 ). Discussion L’incidence des tumeurs de la vessie a faiblement diminue chez l’homme dans l’Herault. Les registres ne recueillent que les tumeurs ≥ T1, ce qui differe des recommandations cliniques. En 2018, le Registre de l’Herault Specialise en Onco-Urologie (RHESOU) a vu le jour, dans le but d’apporter plus de coherence entre les donnees epidemiologiques et la pratique clinique actuelle. Conclusion L’incidence des tumeurs de la vessie a faiblement diminue chez l’homme dans l’Herault. Les registres ne recueillent que les tumeurs ≥ T1, ce qui differe des recommandations cliniques. En 2018, le Registre de l’Herault Specialise en Onco-Urologie (RHESOU) a vu le jour, dans le but d’apporter plus de coherence entre les donnees epidemiologiques et la pratique clinique actuelle.

Resume Objectif Evaluer le bilan 13–30 ARAMAV, un nouveau questionnaire d’autonomie et de qualite de vie developpe pour les patients en situation de handicap visuel. Methodes Nous avons realise une etude prospective monocentrique a l’institut ARAMAV en collaboration avec le CHU de Nimes. Les patients inclus etaient hospitalises pour une reeducation basse vision. Chaque patient a beneficie d’un bilan d’ergotherapie, du questionnaire de qualite de vie Short Forms 36 (SF36) et du bilan 13–30 ARAMAV au debut et en fin de reeducation. Nous avons verifie la reproductibilite, la sensibilite au changement ainsi que la coherence interne et externe du questionnaire. Resultats Nous avons inclus 231 patients sur une duree de 4 ans. Les patients presentaient tous un etat de cecite ou de malvoyance. Nous avons retrouve une excellente reproductibilite intra- et interutilisateur du questionnaire avec un coefficient de Lin > 0,9 (respectivement 0,99 et 0,91). En comparant les variations des differents scores entre avant et apres reeducation, nous avons retrouve une excellente sensibilite au changement pour la partie autonomie et pour la partie qualite de vie du questionnaire. Enfin, nous avons retrouve une tres bonne coherence interne et externe. Conclusion Nous proposons donc le bilan 13–30 ARAMAV comme un nouvel outil d’evaluation de l’autonomie et de la qualite de vie specifiquement destine au sujet deficient visuel et pouvant etre utilise pour evaluer l’impact d’une reeducation basse vision.

Background Flap surgery for deep pelvic pressure ulcers has already shown its effectiveness. Most studies relating to the postoperative period assessed complications rates and associated risk factors, but none focused on delayed wound healing. The objective of this study was to describe wound healing delay after primary flap surgery in patients with spinal cord injury (SCI) and to assess associated risk factors. Methods This observational retrospective study based on medical charts included all persons with SCI operated for primary flap surgery for pelvic PU in the Herault department of France between 2006 and 2014. Overall, 100 biomedical, psychological, socioeconomics and care management factors were studied. The primary outcome was wound healing delay, defined as time from surgery to complete cutaneous closure. Results 85 patients were included. Median healing time was 48 days (R: 20–406). Healing rate was 70% at 3 months and 90% at 4 months. After a multivariate analysis three factors were significantly associated with delayed wound healing: duration of hospitalization in the acute care unit (HR = 2.68; p = 0.004), local post-operative complication (HR = 10.75; p = 0.02), and post-operative sepsis (HR = 2.18; p = 0.02). Conclusion After primary skin flap surgery for PU in persons with SCI, delayed wound healing is related to local or general complications as well as care management organization. The risk of delayed wound healing justifies the implementation of a coordinated pre-operative management to prevent complications and a structured care network for an earlier transfer to a SCI rehabilitation center.

Introduction: This study aimed at generating a new simplified prognostic score (SPS) using common clinical and biological variables to discriminate a limited number of subgroups of patients with SCLC differing by their overall survival (OS). Methods: The SPS was developed exploring the Montpellier University Hospital retrospective database of 401 patients over a 16-year period. All patients had received etoposide - platinum-based chemotherapy as first-line treatment. The SPS development took into account significant determinants of OS in the Cox model, weighted by their regression β coefficients. Validation of the consequent SPS has been done separately in a combined population of 213 patients accrued from two different published trials (NCT03059667 and NCT00930891). Results: The significant independent determinants of OS included the following: (1) American Joint Committee on Cancer TNM stage IV (hazard ratio [HR]: 2.52; 95% confidence interval [CI]: 1.91–3.33); (2) Eastern Cooperative Oncology Group performance status greater than 1 (HR: 2.27; 95% CI: 1.79–2.87); (3) the presence of liver metastases (HR: 1.66; 95% CI: 1.29–2.15); and (4) neutrophil-to-lymphocyte ratio greater than 4 (HR: 1.39; 95% CI: 1.11–1.92). The SPS generated with these four variables, segregated three groups (good, intermediate, and poor prognosis) with respective median OS of 26.9 months (95% CI: 20.1–38.9), 11.5 months (95% CI: 9.8–13.0), and 6.8 months (95% CI: 5.8–8.3; log-rank p < 10–4). Harrell's C statistic estimate was 0.68 ± 0.012, suggesting goodness of calibration. In the validation cohort, the SPS segregated the aforementioned three subgroups in a nearly similar manner, with respective median OS: 27.2, 12.3, and 8.6 months (log-rank p < 10–3; Harrell’s C statistic: 0.58 ± 0.02). Conclusions: The SPS is easy to calculate in real-life practice and efficiently discriminates three populations with different prognoses. This study deserves further validation of this score in patients with SCLC receiving immunochemotherapy.

Resume Objectif L’objectif de l’etude etait de determiner la performance diagnostique de l’IRM dans la distinction des lesions endometriales begnines et malignes chez les patientes menopausees atteintes de metrorragies postmenopausiques ou d’un epaississement endometrial asymptomatique. Patientes et methodes Il s’agissait d’une etude prospective, de 2016 a 2018, incluant les patientes menopausees atteintes de metrorragies postmenopausiques ou d’un epaississement endometrial asymptomatique, en dehors d’un traitement par tamoxifene ou d’un traitement hormonal substitutif. Une IRM pelvienne comprenant des sequences morphologiques (T1, T2, T1 post-gadolinium) et fonctionnelles (diffusion, perfusion) a ete realisee. Les donnees des IRM ont ete comparees aux resultats anatomopathologiques. Resultats Sur 61 patientes incluses, 42 ont beneficie d’un prelevement de l’endometre ; il y avait 15 cancers de l’endometre (25 %), une hyperplasie atypique (1,6 %) et 35 lesions benignes (58 %). L’âge moyen etait de 63 ans. La presence d’un endometre epais (p Conclusion L’IRM pelvienne est performante pour differencier les lesions endometriales begnines et malignes chez les patientes menopausees atteintes de metrorragies postmenopausiques ou d’un epaississement endometrial asymptomatique.

Organ shortage leads to using non-optimal liver grafts. Thus, to determine the graft quality, the Donor Risk Index and the Eurotransplant Donor Risk Index have been proposed. In a previous study we showed that neither could be validated on the French database. Our aim was then dedicated to propose an adaptive Donor Quality Index (DQI) using data from 3961 liver transplantation (LT) performed in France between 2009 and 2013, with an external validation based on 1048 French LT performed in 2014. Using Cox models and three different methods of selection, we developed a new score and defined groups at risk. Model performance was assessed by means of three measures of discrimination corrected by the optimism using a bootstrap procedure. An external validation was also performed in order to evaluate its calibration and discrimination. Five donor covariates were retained: age, cause of death, intensive care unit stay, lowest MDRD creatinine clearance, and liver type. Three groups at risk could be discriminated. The performances of the model were satisfactory after internal validation. Calibration and discrimination were preserved in the external validation dataset. The DQI exhibited good properties and is potentially adaptive as an aid for better guiding decision making for LT.

International audience

According to clinical guidelines, the occurrence of very early-onset breast cancer (VEO-BC) (diagnosed ≤ age 30 years) or VEO ovarian cancer (VEO-OC) (diagnosed ≤ age 40 years) in families with BRCA1 or BRCA2 mutation (BRCAm) prompts advancing the age of risk-reducing strategies in relatives. This study aimed to assess the relation between the occurrence of VEO-BC or VEO-OC in families with BRCAm and age at BC or OC diagnosis in relatives. We conducted a retrospective multicenter study of 448 consecutive families with BRCAm from 2003 to 2018. Mean age and 5-year–span distribution of age at BC or OC in relatives were compared in families with or without VEO-BC or VEO-OC. Conditional probability calculation and Cochran–Mantel–Haenszel chi-square tests were used to investigate early-onset cancer occurrence in relatives of VEO-BC and VEO-OC cases. Overall, 15% (19/245) of families with BRCA1m and 9% (19/203) with BRCA2m featured at least one case of VEO-BC, 8% (37/245) and 2% (2/203) featured at least one case of VEO-OC, respectively. The cumulative prevalence of VEO-BC was 5.1% (95% CI 3.6–6.6) and 2.5% (95% CI 1.4–3.6) for families with BRCA1m and BRCA2m, respectively. The distribution of age and mean age at BC diagnosis in relatives did not differ by occurrence of VEO-BC for families with BRCA1m or BRCA2m. Conditional probability calculations did not show an increase of early-onset BC in VEO-BC families with BRCA1m or BRCA2m. Conversely, the probability of VEO-BC was not increased in families with early-onset BC. VEO-BC or VEO-OC occurrence may not be related to young age at BC or OC onset in relatives in families with BRCAm. This finding—together with a relatively high VEO-BC risk for women with BRCAm—advocates for MRI breast screening from age 25 regardless of family history.

Objectives By removing systematic differences across treatment groups, simple randomization is assumed to protect against bias. However, random differences may remain if the sample size is insufficiently large. We sought to determine the minimal sample size required to eliminate random differences, thereby allowing an unbiased estimation of the treatment effect. Study Design and Setting We reanalyzed two published multicenter, large, and simple trials: the International Stroke Trial (IST) and the Coronary Artery Bypass Grafting (CABG) Off- or On-Pump Revascularization Study (CORONARY). We reiterated 1,000 times the analysis originally reported by the investigators in random samples of varying size. We measured the covariates balance across the treatment arms. We estimated the effect of aspirin and heparin on death or dependency at 30 days after stroke (IST), and the effect of off-pump CABG on a composite primary outcome of death, nonfatal stroke, nonfatal myocardial infarction, or new renal failure requiring dialysis at 30 days (CORONARY). In addition, we conducted a series of Monte Carlo simulations of randomized trials to supplement these analyses. Results Randomization removes random differences between treatment groups when including at least 1,000 participants, thereby resulting in minimal bias in effects estimation. Later, substantial bias is observed. In a short review, we show such an enrollment is achieved in 41.5% of phase 3 trials published in the highest impact medical journals. Conclusions Conclusions drawn from completely randomized trials enrolling a few participants may not be reliable. In these circumstances, alternatives such as minimization or blocking should be considered for allocating the treatment.

Resume Introduction Un nombre important de patients atteints d’un cancer de la prostate (CP) est diagnostique et traite. L’objectif de cette etude est d’analyser, deux ans apres traitement, l’incontinence urinaire (IU) et les dysfonctionnements sexuels (DS) pouvant affecter les patients. Methodes Cette etude a suivi tous les cas de CP localise, diagnostiques entre 2008–2009, chez les hommes d’âge ≤ 65 ans en vie deux ans apres traitements. Quatre cent trente-sept personnes ont ete incluses dans l’enquete. Les donnees ont ete collectees par un questionnaire et par croisement avec les donnees du registre des cancers. Une analyse descriptive et comparative de la persistance des sequelles a deux ans a ete effectuee. Resultats A deux ans du traitement, l’IU a persiste pour 48,8 %, 41,2 % ont eu recours a des protections urinaires ; 39,2 % portaient au moins une protection/jour ; 55,2 % ont eu des difficultes financieres a l’achat des protections. Au total, 22,7 % n’ont pas consulte de specialiste pour l’IU. Les DS ont persiste pour 82,8 % ; 30,4 % n’ont pas consulte de specialiste. Les DS ont eu un impact negatif sur la vie sexuelle des patients et de leurs partenaires. Apres ajustement sur le stade, seule la prostatectomie est significativement associee a la persistance de l’IU et de la DS. Conclusion Le pourcentage de patients ayant une IU et/ou une DS persistante reste eleve. La persistance de ces sequelles a ete associee a la prostatectomie. Les differences de toxicites entre traitements doivent etre presentees aux patients avant toute prise en charge afin d’engager le patient dans une demarche de decision partagee.

Metastatic melanoma is one of the most aggressive and drug-resistant cancers with very poor overall survival. Circulating melanoma cells (CMCs) were first described in 1991. However, there is no general consensus on the clinical utility of CMC detection, largely due to conflicting results linked to the use of heterogeneous patient populations and different detection methods. Here, we developed a new EPithelial ImmunoSPOT (EPISPOT) assay to detect viable CMCs based on their secretion of the S100 protein (S100-EPISPOT). Then, we compared the results obtained with the S100-EPISPOT assay and the CellSearch&reg, CMC kit using blood samples from a homogeneous population of patients with metastatic melanoma. We found that S100-EPISPOT sensitivity was significantly higher than that of CellSearch&reg, Specifically, the percentage of patients with &ge, 2 CMCs was significantly higher using S100-EPISPOT than CellSearch&reg, (48% and 21%, respectively, p = 0.0114). Concerning CMC prognostic value, only the CellSearch&reg, results showed a significant association with overall survival (p = 0.006). However, due to the higher sensitivity of the new S100-EPISPOT assay, it would be interesting to determine whether this functional test could be used in patients with non-metastatic melanoma for the early detection of tumor relapse and for monitoring the treatment response.

BACKGROUND This prospective multicenter study evaluated the prognostic value of circulating tumor cells (CTCs) in relapsing nonoperable or metastatic head and neck squamous cell carcinoma (rHNSCC) treated by chemotherapy and cetuximab. METHODS In 65 patients suitable for analyses, peripheral blood was taken at day 0 (D0) D7, and D21 of treatment for CTC detection by CellSearch®, EPISPOT, and flow cytometry (FCM). Progression-free survival (PFS) was assessed with the Kaplan–Meier method and compared with the log-rank test (P < 0.05). RESULTS At D0, CTCs were detected with EPISPOT, CellSearch, and FCM in 69% (45/65), 21% (12/58), and 11% (7/61) of patients, respectively. In the patients tested with all 3 methods, EPISPOT identified 92% (36/39), 92% (35/38), and 90% (25/28) of all positive samples at D0, D7, and D21, respectively. Median PFS time was significantly lower in (a) patients with increasing or stable CTC counts (36/54) from D0 to D7 with EPISPOTEGFR (3.9 vs 6.2 months; 95% CI, 5.0–6.9; P = 0.0103) and (b) patients with ≥1 CTC detected with EPISPOT or CellSearch® (37/51) (P = 0.0311), EPISPOT or FCM (38/54) (P = 0.0480), and CellSearch or FCM (11/51) (P = 0.0005) at D7. CONCLUSIONS CTCs can be detected before and during chemotherapy in patients with rHNSCC. D0–D7 CTC kinetics evaluated with EPISPOTEGFR are associated with the response to treatment. This study indicates that CTCs can be used as a real-time liquid biopsy to monitor the early response to chemotherapy in rHNSCC. ClinicalTrials.gov Identifier NCT02119559

Objective.To evaluate the association of baseline serum level of vitamin D with disease activity, disability, and radiographic damage over the first year in early rheumatoid arthritis (RA).Methods.Among early arthritis patients included in the ESPOIR cohort, patients with early RA were evaluated. Levels of 25-hydroxy vitamin D2 and D3 were measured at baseline. Baseline associations between vitamin D level and 28-joint count Disease Activity Score based on erythrocyte sedimentation rate (DAS28-ESR), Health Assessment Questionnaire–Disability Index (HAQ-DI), and van der Heijde modified total Sharp score (mTSS) were assessed. Bivariate analysis was used to assess the association between vitamin D level and radiographic progression (mTSS increased by ≥ 1 point) or disability (HAQ-DI ≥ 0.5) over 12 months. Forward stepwise multiple logistic regression was used to evaluate the independent association of baseline variables and outcomes.Results.Among 813 patients with early arthritis, data for 645 patients with RA were analyzed. Vitamin D level was < 10 ng/mL (deficiency, group 1), 10–29.9 ng/mL (low level, group 2), and ≥ 30 ng/mL (normal, group 3) for 114 (17.7%), 415 (64.54%), and 114 (17.7%) patients, respectively. At baseline, DAS28-ESR and HAQ-DI were higher with vitamin D deficiency compared with groups 2 and 3 combined (P = 0.007 and P = 0.001, respectively), as was mean mTSS, but not significantly (p = 0.076). On multivariate analysis, baseline vitamin D deficiency was associated with HAQ-DI at 6 months (OR 1.70) and mTSS at 12 months (OR 1.76).Conclusion.Vitamin D deficiency was associated with more active and severe disease at baseline and may predict disability and radiographic progression over 1 year in early RA patients. [ClinicalTrials.gov: NCT03666091]

International audience; Background: Gram-positive organisms are a leading cause of infection in cardiovascular surgery. Furthermore, these patients have a high risk of developing postoperative renal failure in intensive care unit (ICU). Some antibiotic drugs are known to impair renal function. The aim of the study was to evaluate whether patients treated for Gram-positive cardiovascular infection with daptomycin (DAP) experienced a lower incidence of acute kidney injury (AKI) when compared to patients treated with vancomycin (VAN), with comparable efficacy.Methods: ICU patients who received either DAP or VAN, prior to or after cardiovascular surgery or mechanical circulatory support, from January 2010 to December 2012, were included in this observational retrospective cohort study. We excluded patients with end stage renal disease and antibiotic prophylaxis. The primary endpoint was the incidence of AKI within the first week of treatment. Secondary endpoints were the incidence of AKI within the first 14 days of treatment, the severity of AKI including renal replacement therapy (RRT), the rates of clinical failure (unsuccessful infection treatment) and of premature discontinuation and mortality. To minimize selection bias, we used a propensity score to compare the 2 groups. Univariate and multivariate analysis were performed to determine factors associated with AKI.Results: Seventy two patients, treated for infective endocarditis, cardiovascular foreign body infection, or surgical site infection were included (DAP, n = 28 and VAN, n = 44). AKI at day 7 was observed in 28 (64%) versus 6 (21%) of the VAN and DAP patients, respectively (p = 0.001). In the multivariate analysis adjusted to the propensity score, vancomycin treatment was the only factor associated with AKI (Odds Ratio 4.42; 95% CI: 1.39–15.34; p = 0.014). RRT was required for 2 (7%) DAP patients and 13 (30%) VAN patients, p = 0.035. Premature discontinuation and clinical failure occurred more frequently in VAN group than in DAP group (25% versus 4%, p = 0.022 and 42% versus 12%, respectively, p = 0.027).Conclusions: Daptomycin appears to be safer than vancomycin in terms of AKI risk in ICU patients treated for cardiovascular procedure-related infection. Daptomycin could be considered as a first line treatment to prevent AKI in high-risk patients.