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Douleurs pelviennes associées à l’endométriose, conseils pour la pratique clinique. Un consensus formalisé d’experts par le CNGOF & Convergences PP
No full textInternational audienceObjective: To develop best practice guidelines under the auspices of the CNGOF and Convergences PP for the management of pain associated with endometriosis.Method: We organised a literature review and a formal expert consensus. A multidisciplinary steering committee composed of 14 healthcare professionals and 2 patient association representatives drafted an argument based on literature analysis, resulting in 7 proposed definitions and 59 best practice recommendations. These proposals were then submitted for review by 108 French healthcare professionals from various specialties and professions. The first two rounds of rating were conducted online between June 2024 and November 2024, followed by a final videoconference meeting in January 2025.Results: The participation rate was 68% in the first round (74/108) and 76% in the second round (56/74). In total, 3 definitions and 45 best practice recommendations were retained and distributed across 6 sections: 1) Definition; 2) Assessment of chronic pelvic pain associated with endometriosis; 3) Non-pharmacological management; 4) Pharmacological management; 5) Surgical management; 6) Communication, health education, and therapeutic education.Conclusion: This formal expert consensus process has enabled the development of definitions and best practice guidelines to assist healthcare professionals in managing patients suffering from pain associated with endometriosis, thereby promoting better screening, characterization of pain, and therapeutic management.Objectif Élaborer des conseils de bonne pratique sous l’égide du CNGOF et de Convergences PP pour la prise en charge des douleurs associées à l’endométriose.Méthode Ces conseils de bonne pratique ont été élaborés selon la méthode de consensus d’experts formalisée. Un comité de pilotage pluridisciplinaire composé de 14 professionnels de santé et de deux représentantes d’associations de patientes a rédigé, après analyse de la littérature, un argumentaire et proposé 7 définitions et 59 conseils de bonne pratique. Ces propositions ont été soumises à 108 professionnels de santé français exerçant diverses spécialités et professions. Les deux premiers tours de cotation ont été effectués en ligne entre juin 2024 et novembre 2024, puis une réunion finale en visioconférence s’est déroulée en janvier 2025.Résultats Le taux de participation a été de 68 % au premier tour (74/108) et de 76 % au second (56/74). Au total, 3 définitions et 45 conseils de bonne pratique ont été retenus et ont été répartis en 6 sections : 1) définition ; 2) bilan de la douleur pelvienne chronique associée à l’endométriose ; 3) prise en charge non médicamenteuse ; 4) prise en charge médicamenteuse ; 5) prise en charge chirurgicale ; 6) communication, éducation en santé et éducation thérapeutique.Conclusion Ce consensus formalisé d’experts a permis d’élaborer des définitions et conseils de bonne pratique pour aider la communication des professionnels de santé prenant en charge les patientes souffrant de douleurs associées à l’endométriose, favorisant ainsi un meilleur dépistage, une meilleure caractérisation des douleurs et une meilleure prise en charge thérapeutique
Combination of encorafenib and binimetinib followed by ipilimumab and nivolumab versus ipilimumab and nivolumab in patients with advanced melanoma with BRAFV600E or BRAFV600K mutations (EBIN) : an international, open-label, randomised, controlled, phase 2 study
No full textInternational audienceBackground :Current first-line treatment for patients with metastatic melanoma with BRAFV600E or BRAFV600K mutations includes immunotherapy with immune checkpoint inhibitors and targeted therapy; however, the optimal sequencing of these treatments is unclear. We aimed to investigate the use of a targeted-therapy induction regimen before treatment with immune checkpoint inhibitors.Methods :This open-label, randomised, controlled, phase 2 trial (EBIN) was conducted at 37 centres in eight European countries. Eligible patients were 18 years or older and had previously untreated, unresectable, stage III or IV melanoma with BRAFV600E or BRAFV600K mutations and an Eastern Cooperative Oncology Group performance status of 0 or 1. Patients were randomly assigned (1:1) to one of two groups. Those in the induction group received targeted therapy (oral encorafenib 450 mg once a day plus oral binimetinib 45 mg twice a day for 12 weeks) followed by immune checkpoint inhibitors (intravenous nivolumab 3 mg/kg plus intravenous ipilimumab 1 mg/kg once every 3 weeks for four doses, followed by intravenous nivolumab 480 mg once every 4 weeks until unacceptable toxicity, disease progression, or 2 years of treatment). Patients in the control group received immune checkpoint inhibitors as above without any induction targeted therapy. Randomisation was conducted using a minimisation technique and was stratified by centre and a variable defined using stage and lactate dehydrogenase activity. The primary outcome was progression-free survival in the intention-to-treat population. Safety was assessed in all patients who initiated the protocol treatment. In this Article we report the primary analysis. The study is registered with ClinicalTrials.gov, NCT03235245, and is ongoing.Findings :Between Nov 12, 2018, and July 11, 2022, 271 patients were randomly assigned: 136 to the induction group and 135 to the control group. 103 (38%) patients were female, 168 (62%) were male, and the median age was 55 years (IQR 43–66). The median follow-up time was 21 months (IQR 13–33). There was no evidence of a longer progression-free survival in the induction group than in the control group (hazard ratio 0·87, 90% CI 0·67–1·12; p=0·36). The median progression-free survival was 9 months (95% CI 7–13) in the induction group and 9 months (5–14) in the control group. Grade 3–5 treatment-related adverse events occurred in 57 (42%) of 136 patients who started treatment in the induction group and in 42 (32%) of 131 patients who started treatment in the control group. The most common grade 3–4 treatment-related adverse event was hepatitis (17 [13%] of 136 patients in the induction group and nine [7%] of 131 patients in the control group). Serious treatment-related adverse events occurred in 45 (33%) of 136 patients in the induction group and 33 (25%) of 131 patients in the control group. There were three treatment-related deaths: two from cardiac events (heart failure and arrhythmia) in the induction group and one from meningitis in the control group.Interpretation :The targeted-therapy induction regimen did not improve progression-free survival compared with first-line treatment with immune checkpoint inhibitors in unselected patients with advanced melanoma with BRAFV600E or BRAFV600K mutations
How the work-related stress of French midwives has evolved over the COVID-19 pandemic: The COVISTRESS Midwives’ study
No full textInternational audienc
Adherent-invasive Escherichia coli in Crohn’s disease: the 25th anniversary
No full textInternational audienceIn 1998, Arlette Darfeuille-Michaud, Christel Neut and Jean-Frederic Colombel discovered a novel pathovar of Escherichia coli , adherent and invasive Escherichia coli (AIEC), in the ileum of patients with Crohn’s disease (CD), that was genetically distinct from diarrheagenic E. coli , could adhere to and invade intestinal epithelial cells and survive in macrophages. The consistent association between AIEC and CD (approximately 30% across the world), their ability to exploit CD-associated genetic traits, and virulence in preclinical colitis models but not healthy hosts spurred global research to elucidate their pathogenicity. Research focused on integrating AIEC with the microbiome, metabolome, metagenome, host response and the impact of diet and antimicrobials has linked the luminal microenvironment and AIEC metabolism to health and disease. This deeper understanding has led to therapeutic trials and precision medicine targeting AIEC-colonised patients. In November 2023, prominent members of the AIEC research community met to present and discuss the many facets of basic, translational and clinical AIEC fields at ‘AIEC: past, present and future’ in NYC. This review is a summary of this international meeting highlighting the history of AIEC, knowledge accumulated over the past 25 years about its pathogenic properties and proposes a standardised approach for screening patients for AIEC
Diagnostic d’une hémolyse non auto-immune chez l’adulte
No full textInternational audienceThe diagnosis of hemolysis is still based on straightforward biochemical parameters: haptoglobin (the most sensitive), lactate dehydrogenase (LDH), and unconjugated bilirubin. Anemia is not always present. Reticulocyte counts typically exceed 120×109/L, except in cases of associated vitamin deficiency or during the very early phase of acute hemolysis. When the Direct Antiglobulin Test is negative, a non-autoimmune cause of hemolysis should be considered. A thorough history, careful physical examination, and meticulous review of the peripheral blood smear help to rule out major emergencies such as malaria, thrombotic microangiopathy, severe infections, delayed hemolytic transfusion reaction, or toxic hemolysis. In the absence of a mechanical valve or other intravascular device that could induce hemolysis, second-line laboratory tests should be pursued: hemoglobin phenotyping, eosin-5'-maleimide (EMA) binding test, screening for paroxysmal nocturnal hemoglobinuria (PNH), and enzymatic assays. These tests usually lead to the diagnosis of most corpuscular non-autoimmune hemolytic anemias, including hemoglobinopathies (such as sickle cell disease, thalassemia syndromes, hemoglobin C disease, or unstable hemoglobins), membranopathies (such as hereditary spherocytosis or stomatocytosis), and enzyme deficiencies. The diagnosis of rare causes of hemolysis should be considered at a later stage or in specific contexts, such as alcoholism (Zieve's syndrome), advanced cirrhosis (spur cell anemia), or acute hemolysis in a young patient (Wilson's disease)
Brentuximab Vedotin addition to Gemcitabine in Relapsed or Refractory Peripheral T-cell Lymphoma: a LYSA Phase II Study
No full textInternational audienceWe aim to evaluate the efficacy of brentuximab vedotin (BV) combined with gemcitabine followed by BV maintenance in relapsed or refractory (R/R) peripheral T-cell lymphoma (PTCL). Patients (pts) with at least 5% CD30-positive cells by immunohistochemistry received 4 GBV induction (28d) cycles of gemcitabine 1000 mg/m2 (d1;d15) plus BV 1.8 mg/kg (d8) followed in responding pts by up to 12 BV maintenance (21d) cycles. Primary end point was overall response rate (ORR) after 4 induction cycles by CT-scan-based Lugano criteria. Of the 71 enrolled pts (median age of 66 years), 80.3% had received 1 prior line, 60.6% were refractory. The diagnoses per pathology central review were TFHL (47.9%), ALCL, [ALK- (19.7%) and ALK+ (7%)], PTCL-NOS (12.7%) and other entities (12.7%). In the intention-to-treat analysis, ORR was 46.5% with 19.7% complete response. Twenty-eight pts received maintenance. Grade 3-4 adverse events reported in ≥10% of pts during induction comprised: of neutropenia (55%), thrombocytopenia (14%), anemia (21%), infection (14%); during maintenance comprised of neutropenia (39%), thrombocytopenia (21%) and peripheral neuropathy (14%). With a median follow-up of 32.6 months, the median duration of response (DOR), progression-free (PFS) and overall survival were 15.8, 4.5 and 12.9 months, respectively. Efficacy, higher in ALCL, was present in the TFHL and PTCL-NOS group with and ORR, CR, PFS and DOR of 37.2%, 18.6%, 4 and 12.5 months, respectively. A negative association of high baseline soluble CD30 on both response and survival was found, which in ad hoc analysis appeared highly relevant in TFHL and PTCL-NOS patients. EudraCT 2017-000409-1 and NCT0349677
Barriers and facilitators to early post-stroke rehabilitation in stroke units: A nationwide survey in France
No full textInternational audienc
Personalized driving pressure-guided positive end-expiratory pressure in patients at risk of postoperative respiratory failure (IMPROVE-2): a multicenter, pragmatic, randomized clinical trial.
No full textInternational audiencePurpose: Airway driving pressure has garnered considerable attention for lung-protective ventilation. We evaluated the clinical effectiveness of airway driving pressure as a target to individualize positive-end-expiratory pressure (PEEP) setting in mechanically ventilated patients at risk for postoperative respiratory failure.Methods: We conducted a multicenter, pragmatic, assessor-masked, randomized trial among adult patients undergoing emergency abdominal surgery in 22 hospitals in France. Patients were assigned 1:1 to receive individually adjusted highest PEEP targeting a driving pressure < 13 cmH2O after an initial recruitment maneuver (intervention group) or to a fixed PEEP level of 5 cmH2O (control group). The primary outcome was a composite of postoperative respiratory failure (failure to wean from the ventilator or the composite of reintubation or curative non-invasive ventilation) or all-cause mortality at 30 days. Secondary outcomes included components of the composite primary outcome.Results: The primary outcome occurred in 87 out of 338 (25.7%) intervention patients and in 69 out of 341 (20.2%) control patients (difference, 5.5%; 95% confidence interval [CI] − 0.8 to 11.8; relative risk, 1.27; 95%CI 0.96–1.68; p = 0.08). The difference was primarily due to an increased incidence of reintubation or need for curative non-invasive ventilation among intervention patients (difference, 7.1%; 95% CI 2.5–11.9; relative risk, 1.97; 95% CI 1.24–3.11; p = 0.004). Other secondary outcomes did not differ.Conclusion: Among patients at risk for postoperative respiratory failure after emergency abdominal surgery, a strategy of individually adjusted highest PEEP in targeting driving pressure lower than 13 cmH2O did not reduce postoperative respiratory failure or deat
Polygenic risk scores for severe psychiatric disorders in bipolar disorders: associations with the clinical and dimensional expression, interactions with childhood maltreatment and mediation models
No full textInternational audiencePolygenic risk scores (PRSs) for several psychiatric disorders have been associated with the clinical presentation of bipolar disorder (BD). PRSs have also been suggested to moderate the associations between childhood maltreatment and BD severity. In this study, we investigated how PRSs for BD, schizophrenia, major depressive disorders (MDD) and attention-deficit/hyperactivity disorder (ADHD) might disentangle the clinical and dimensional heterogeneity of BD in a sample of 852 affected individuals. We used logistic and linear regressions, moderation and mediation models to test the associations between PRSs, dimensions in childhood/adulthood and clinical indicators of severity of BD. All models were adjusted for age, sex, BD type and depressive symptoms. None of the PRSs were significantly associated with the clinical expression of BD when considered in terms of mode of onset, course, or psychiatric comorbidities. Nevertheless, the PRS-ADHD significantly and positively correlated with the levels of childhood maltreatment, childhood ADHD symptoms, and of some adulthood measures (affective lability, impulsivity and hostility) with p values ranging from 3.10-8-4.10-4. None of the PRSs moderated the effects of childhood maltreatment on the clinical or dimensional variables. Mediation model suggested paths from both PRS-ADHD and PRS-MDD to childhood ADHD symptoms and childhood maltreatment. The links between PRS-ADHD to all adulthood dimensions were mediated by childhood ADHD symptoms (p < 0.002). In turn, some adulthood dimensions (mainly affect intensity and affective lability) were associated with the clinical severity of BD, as defined by rapid cycling, suicide attempts and anxiety disorders. In conclusion, this study disentangles the associations between the genetic liability for four psychiatric disorders and the clinical/dimensional heterogeneity of BD. We suggest a continuum from the genetic risk for ADHD and MDD through dimensions in childhood/adulthood to a severe/complex clinical expression of BD