Introduction Les inhibiteurs de points de contrôle immunitaire (ICI) ont révolutionné le traitement des cancers, mais exposent à des myotoxicités (myocardites, myosites) rares mais sévères. Les données populationnelles sur leur incidence et leurs facteurs de risque restent limitées. Cette étude évalue leur incidence, leurs facteurs de risque et leur impact sur la survie. Méthodes Nous avons réalisé une étude de cohorte rétrospective à partir du Système national des données de santé (SNDS), incluant tous les patients adultes ayant initié un ICI entre le 1ᵉʳ janvier 2012 et le 30 septembre 2022. Le critère principal était l’incidence cumulée des myotoxicités (myocardite et/ou myosite). Les facteurs de risque ont été analysés par des modèles de Fine et Gray, l’impact de la myotoxicité sur la survie globale à 1 an a été évaluée par des modèles de Cox avec exposition dépendante du temps. Les facteurs de risque de létalité à 1 et 3 mois ont été évalués par régression logistique. Résultats Parmi 172 363 patients initiant un ICI, l’incidence cumulée des myotoxicités était de 0,9 %, atteignant 7,1 % en cas de cancer thymique. L’incidence de la myocardite et de la myosite était de 0,4 % et 0,6%, respectivement, avec un chevauchement dans 23 % des cas. Les principaux facteurs de risque étaient le type de cancer (risque plus élevé si cancer thymique, mélanome, autres cancers cutanés), les antécédents de pathologies thymiques ou myasthéniques, la combinaison d’ICI et l’âge > 85 ans. La myotoxicité était le facteur le plus associé à la mortalité (HR 3,51 [3,17–3,89]), devant le statut métastatique (1,55 [1,52–1,58]). Chez les patients ayant eu une myotoxicité, la létalité à 1 mois atteignait 20,3 %, et était plus élevée en cas d’arythmie, d’insuffisance cardiaque ou respiratoire. Discussion/Conclusion Cette étude établit l’incidence, les facteurs de risque et la gravité des myotoxicités liées aux ICI, soulignant leur impact pronostique majeur et la nécessité d’une surveillance cardio-musculaire renforcée.

BACKGROUND:Individuals with severe obesity are at increased risk of severe influenza and may have impaired immune responses to vaccination. Recombinant influenza vaccine (RIV) may provide enhanced protection compared with egg-based standard-dose influenza vaccine (SD), but data in this high-risk population are limited. METHODS:The AP-HP FLUO trial (NCT05409612) was an open-label, randomized clinical trial conducted in 15 centers in France (November 2022-March 2023) with 6 months of follow-up. Adults with BMI ≥35 kg/m2 were randomized 1:1 to receive RIV or SD, using minimization by center, age (<50 vs ≥50 years), and BMI (<40 vs ≥40 kg/m2). The primary outcome was the ratio (RIV/SD) of geometric mean hemagglutinin-inhibition (HAI) titers (GMTs) for 4 influenza strains 28 days after vaccination. Safety and reactogenicity were also assessed. RESULTS:A total of 206 participants were included (104 RIV, 102 SD). Median age was 50 years, 60.2% were women, and median BMI was 41.0 kg/m2. At Day 28, GMT ratios favored RIV for A/H1N1 (1.6; 95% CI, 1.1-2.3), A/H3N2 (2.0; 95% CI, 1.3-3.2), and B/Yamagata (1.3; 95% CI, 1.0-1.8), but not for B/Victoria (0.9; 95% CI, 0.6-1.3). The effect did not vary significantly across the different age and BMI groups. By Day 180, titers did not differ significantly. Reactogenicity and safety profiles were similar between groups. CONCLUSIONS:In adults with severe obesity, RIV elicited stronger short-term humoral immune responses than an egg-based standard-dose vaccine, suggesting potential additional benefit for influenza prevention in this vulnerable population.

Importance:Levosimendan may facilitate weaning from venoarterial extracorporeal membrane oxygenation (VA-ECMO) and improve survival, but supporting evidence remains limited. Objective:To assess whether early administration of levosimendan reduces the time to successful VA-ECMO weaning in patients with severe but potentially reversible cardiogenic shock. Design, Setting, and Participants:Randomized, double-blind, placebo-controlled trial conducted across 11 intensive care units (ICUs) in France. Between August 27, 2021, and September 10, 2024, 205 adult patients with acute cardiogenic shock who had started VA-ECMO in the preceding 48 hours were enrolled. Final follow-up was completed on November 10, 2024. Interventions:Patients were randomized in a 1:1 ratio to receive levosimendan, 0.15 μg/kg per minute, to be increased to 0.20 μg/kg per minute after 2 hours (n = 101), or placebo (n = 104). Main Outcomes and Measures:The primary outcome was time to successful ECMO weaning within 30 days following randomization. Secondary outcomes included ECMO-, mechanical ventilation-, and organ failure-free days, ICU and hospital lengths of stay, serious adverse events, and all-cause 30- and 60-day mortality. Results:Among the 205 randomized patients (median age, 58 [IQR, 50-67] years; 149 [72.7%] male), main cardiogenic shock etiologies were postcardiotomy (79 [38.5%]), acute myocardial infarction (56 [27.3%]), and myocarditis (28 [13.7%]). Treatment dose was increased to 0.20 ± 0.01 μg/kg per minute in 93% of patients receiving levosimendan and in 96% of those receiving placebo. Within 30 days, 69 of 101 patients (68.3%) had a successful ECMO weaning in the levosimendan group compared with 71 of 104 (68.3%) in the placebo group (risk difference, 0.0% [95% CI, -12.8% to 12.7%]; subdistribution hazard ratio, 1.02 [95% CI, 0.74-1.39]; P = .92). In the levosimendan and placebo groups, respectively, median ECMO duration (5 [IQR, 4-7] days vs 6 [IQR, 4-11] days; P = .53), mean ICU length of stay (18 [SD, 15] days vs 19 [SD, 15] days; P = .42), and 60-day mortality (27.7% vs 25.0%; risk difference, 2.7% [95% CI, -9.0% to 15.3%]; P = .78) did not differ significantly. Ventricular arrhythmias occurred more frequently with levosimendan (18 [17.8%] vs 9 [8.7%]; absolute risk difference, 9.2% [95% CI, 0.4%-18.1%]). Conclusions and Relevance:Among patients with severe but potentially reversible cardiogenic shock supported by VA-ECMO, early levosimendan administration did not significantly reduce the time to successful weaning of ECMO compared with placebo. Trial Registration:ClinicalTrials.gov Identifier: NCT04728932.

Background: Pneumocystis jirovecii pneumonia (PJP) is a severe opportunistic infection in immune-mediated inflammatory diseases (IMID). Benefit and risk associated with PJP prophylaxis in IMID treated with high dose corticosteroids is not known. Methods: Between 2009 and 2022, we conducted a population-based retrospective cohort study (PARADISE) in the French national health data system (SNDS). The 377,094 patients with IMID, initiation of long-term high-dose corticosteroid therapy and no history of PJP were included. Propensity score weighting analysis was used to evaluate the effect of prophylaxis on PJP incidence and PJP-related death, and the effect of trimethoprim-sulfamethoxazole on adverse events. Findings: PJP cumulative incidence was 0·17% [0·16-0·19%] at 12 months after high-dose corticosteroid initiation with variations depending on IMID. A total of 630 PJP occurred with a 30-day mortality rate of 31·8% after PJP diagnosis. Eighty five percent of PJP occurred during the first 6 months. PJP prophylaxis was prescribed in 20,899 (5·5%) patients at least once during the first year after high-dose corticosteroid initiation. In the weighted analysis, prophylaxis showed a time-dependent effect, with a marked reduction in the risk of PJP (HR: 0·22 [0·09, 0·57]) and in the risk of PJP-related death (HR: 0·09 [0·01, 0·5]), during the first 100 days, and no significant reduction thereafter. Trimethoprim- sulfamethoxazole, the most commonly prescribed prophylaxis in the study, was associated with an increase in hematological, cutaneous and renal adverse events. Interpretation: PJP in IMID patients can be effectively prevented with early appropriate prophylaxis in high-risk population.Funding. Research grant from the French Ministry of Health [grant number PHRC-19-0147]

OBJECTIVE:Recent advances in giant cell arteritis (GCA) management aim to reduce glucocorticoid (GC). We described changes in treatment patterns over time in real life and assessed associations between cumulative GC use and adverse outcomes. METHODS:This retrospective population-based study used the French national health insurance database (Système National des Données de Santé) and included 18 301 incident GCA cases between 2010 and 2022. Latent class growth modelling identified GC use trajectories. We described trends in cumulative dose and sparing agent use. Multivariable survival models assessed factors associated with sustained GC-free remission and association between GC cumulative exposure and mortality, serious infections, major adverse cardiovascular events (MACE) and osteoporotic fractures. RESULTS:Four GC use trajectories were identified. Two high-dose trajectories declined over time. Yet, mean 2-year cumulative GC dose remained high, reaching 7.6 g among patients diagnosed in 2022. Methotrexate use increased until 2020 and plateaued thereafter while tocilizumab prescriptions rose, reaching over 25% in 2022. Male sex and baseline methotrexate or tocilizumab use were associated with faster GC tapering, while age >75 years, hypertension, kidney and neurodegenerative diseases were associated with slower tapering. Each gram of GC was associated with higher mortality (HR per gram 1.024, 95% CI 1.021 to 1.027). Yearly cumulative exposure to doses ≤5 mg/day was associated with increased infection (HR 1.13, 95% CI 1.00 to 1.29) and MACE (HR 1.04, 95% CI 1.01 to 1.08). CONCLUSION:Despite reductions in high-dose use, cumulative GC exposure in GCA remains substantial and associated with adverse outcomes, even at the lowest doses.

Experimental data suggest that COVID-19 vaccination could modulate immune checkpoint inhibitor (ICI) effects, but population evidence is limited. Using the French health data system (Système National des Données de Santé), we identified 95,015 adults initiating ICI therapy between December 2020 and March 2023. We assessed mRNA vaccination within 100 days before ICI initiation using inverse probability of treatment weighting and within 100 days after ICI initiation among previously unvaccinated patients using a cloning-censoring-weighting target-trial emulation. The primary outcome was all-cause mortality; secondary outcomes were cancer-specific and non-COVID-19 mortality. Follow-up extended to 31 December 2024 for all-cause mortality and to 31 December 2023 for cause-specific deaths. Pre-ICI mRNA vaccination was associated with lower early all-cause mortality (hazard ratio (HR) 0.90 (95% confidence interval (CI) 0.87-0.94) at 1-3 months and 0.96 (0.93-1.00) at 6 months) and no significant association after 12 months. Post-ICI mRNA vaccination showed a similar early association (HR 0.84 (95% CI 0.80-0.88) at 3 months and 0.86 (0.79-0.94) at 6 months), also with no significant association after 12 months. Estimates for non-COVID-19 and cancer-specific mortality were similar to those for overall survival. Similar early patterns with non-mRNA COVID-19 and other adult vaccines suggest modest, transient associations or healthy-vaccinee effects, rather than a specific mRNA COVID-19 vaccine effect.

OBJECTIVES:Giant cell arteritis (GCA) is a chronic large-vessel vasculitis affecting older adults, associated with significant cardiovascular (CV) complications. Understanding CV risk drivers among GCA, including classical CV risk factors and inflammation, is essential for improved patient management. We (i) assessed the association between GCA and risks of cardiovascular events, including aortic events, major adverse cardiovascular events (MACE), peripheral artery disease (PAD) events, and visceral artery events (ii) assessed the impact of traditional CV risk factors and GCA disease activity on these outcomes. METHODS:Using the French National Health Data System (SNDS), we included 23,193 patients aged ≥50 years diagnosed with incident GCA from 2012-2022. Patients were matched with a general population cohort (92,772 individuals) and a hospitalized cohort (92,772 individuals) using propensity score matching based on CV comorbidities. Primary outcomes were first incidence of aortic events, MACE, PAD events, and visceral artery events. RESULTS:Patients with GCA faced an increased risk of all CV outcomes compared with the general population cohort: aortic events (HR: 5.33; 95%CI, 4.50-6.32), MACE (HR: 2.15; 95% CI, 2.04-2.26), PAD events (HR: 2.72; 95%CI, 2.47-2.99), and visceral artery events (HR: 3.04; 95%CI, 2.33-3.97).When compared with the hospitalized cohort, GCA patients had increased risk of all outcomes except for MACE risk which did not significantly differ (HR: 1.01; 95%CI, 0.96-1.06). GCA disease activity was associated with increased MACE (HR: 1.98; 95%CI, 1.63-2.42). CONCLUSIONS:GCA significantly increases risks of vascular complications, highlighting the importance of cardiovascular risk management and inflammation control strategies.

QuestionIn patients with severe but potentially reversible cardiogenic shock who are receiving venoarterial extracorporeal membrane oxygenation (VA-ECMO), does early administration of levosimendan improve time to successful ECMO weaning within 30 days following randomization?FindingsIn this double-blind, placebo-controlled randomized clinical trial that included 205 patients receiving VA-ECMO, successful ECMO weaning at day 30 occurred in 69 (68.3%) in the levosimendan group compared with 71 (68.3%) in the placebo group, a nonsignificant difference.MeaningIn patients with potentially reversible cardiogenic shock supported by VA-ECMO, levosimendan did not reduce the time to successful weaning from ECMO compared with placebo. ImportanceLevosimendan may facilitate weaning from venoarterial extracorporeal membrane oxygenation (VA-ECMO) and improve survival, but supporting evidence remains limited.ObjectiveTo assess whether early administration of levosimendan reduces the time to successful VA-ECMO weaning in patients with severe but potentially reversible cardiogenic shock.Design, Setting, and ParticipantsRandomized, double-blind, placebo-controlled trial conducted across 11 intensive care units (ICUs) in France. Between August 27, 2021, and September 10, 2024, 205 adult patients with acute cardiogenic shock who had started VA-ECMO in the preceding 48 hours were enrolled. Final follow-up was completed on November 10, 2024.InterventionsPatients were randomized in a 1:1 ratio to receive levosimendan, 0.15 mu g/kg per minute, to be increased to 0.20 mu g/kg per minute after 2 hours (n = 101), or placebo (n = 104).Main Outcomes and MeasuresThe primary outcome was time to successful ECMO weaning within 30 days following randomization. Secondary outcomes included ECMO-, mechanical ventilation-, and organ failure-free days, ICU and hospital lengths of stay, serious adverse events, and all-cause 30- and 60-day mortality.ResultsAmong the 205 randomized patients (median age, 58 [IQR, 50-67] years; 149 [72.7%] male), main cardiogenic shock etiologies were postcardiotomy (79 [38.5%]), acute myocardial infarction (56 [27.3%]), and myocarditis (28 [13.7%]). Treatment dose was increased to 0.20 +/- 0.01 mu g/kg per minute in 93% of patients receiving levosimendan and in 96% of those receiving placebo. Within 30 days, 69 of 101 patients (68.3%) had a successful ECMO weaning in the levosimendan group compared with 71 of 104 (68.3%) in the placebo group (risk difference, 0.0% [95% CI, -12.8% to 12.7%]; subdistribution hazard ratio, 1.02 [95% CI, 0.74-1.39]; P = .92). In the levosimendan and placebo groups, respectively, median ECMO duration (5 [IQR, 4-7] days vs 6 [IQR, 4-11] days; P = .53), mean ICU length of stay (18 [SD, 15] days vs 19 [SD, 15] days; P = .42), and 60-day mortality (27.7% vs 25.0%; risk difference, 2.7% [95% CI, -9.0% to 15.3%]; P = .78) did not differ significantly. Ventricular arrhythmias occurred more frequently with levosimendan (18 [17.8%] vs 9 [8.7%]; absolute risk difference, 9.2% [95% CI, 0.4%-18.1%]).Conclusions and RelevanceAmong patients with severe but potentially reversible cardiogenic shock supported by VA-ECMO, early levosimendan administration did not significantly reduce the time to successful weaning of ECMO compared with placebo.Trial RegistrationClinicalTrials.gov Identifier: NCT04728932 This randomized clinical trial assesses the effect of levosimendan on weaning from venoarterial extracorporeal membrane oxygenation (VA-ECMO) within 30 days among patients with severe but potentially reversible cardiogenic shock.

BACKGROUND AND AIMS:Immune checkpoint inhibitor (ICI)-induced (cardio)-myotoxicities, including myocarditis and myositis, are uncommon but frequently severe adverse drug reactions seen in cancer patients. Real-life ICI myotoxicity incidence estimates span from limited-size cohorts, with risk factors and prognosticators poorly established, as well as their impact on survival. METHODS:This retrospective French National Health Data System cohort study included all adult patients starting ICI between 1 January 2012 and 30 September 2022. A 'narrow' and a 'broad' code combination (based on International Classification of Diseases-10 codes) were used for studied outcomes. The primary outcome was the occurrence of myotoxicities and secondary outcomes of myocarditis and myositis. Risk factors of these outcomes at 6 months were identified with Fine and Gray multivariable models, considering demographics, comorbidities, co-treatments, and cancer. Immune checkpoint inhibitor myotoxicity (as a time-dependent variable) association with overall survival was tested using Cox models. Risk factors of 1- and 3-month letality in ICI myotoxicity cases were assessed by multivariable logistic regression. RESULTS:In 172 363 ICI-treated adult patients, incidence of ICI myotoxicities at 6 months ranged between 0.7% and 0.9% (narrow or broad definitions, respectively), with up to 7.1% in patients with thymic cancer. Immune checkpoint inhibitor myocarditis and ICI myositis incidence ranged between 0.3% and 0.6%, co-occurring in ∼13%-23% of cases. The main risk factors for developing ICI myotoxicities (broad, n = 1520) were thymic tumour (sub-distribution hazard ratio [sHR] 12.94, 95% confidence interval [CI] 5.22-32.03), melanoma (2.41 [2.06-2.83]) and other skin cancers (2.07 [1.55-2.76]), history of thymic disorders (5.61 [2.66-11.86]), history of myasthenia gravis (2.50 [1.45-4.32]), combination of ICI (2.44 [1.99-2.98]), and age > 85 [1.79 [1.24-2.59] vs <45 years. Immune checkpoint inhibitor myotoxicity occurrence was the factor impacting most mortality after ICI start (HR 3.51 [95% CI 3.17-3.89] at 1 month), over metastatic status (1.55 [1.52-1.58]). In ICI myotoxicity patients, 1-month fatality was 20.3% and increased if severe arrhythmia (risk ratio 1.64 [95% CI 1.03-2.61]), heart failure (1.49 [1.06-2.07]), and respiratory failure (1.50 [1.05-2.15]) were reported. Additionally, results were consistent with secondary outcomes, using narrow and broad definitions. CONCLUSIONS:This pharmaco-epidemiological study assessed >170 000 French patients treated by ICI in real life, establishing the incidence and identifying risk factors of developing ICI myotoxicities, with severity surrogates associated with fatality.

Importance:Patients with giant cell arteritis (GCA) face an increased risk of major adverse cardiovascular events (MACE). The benefit of low-dose aspirin in these patients is unknown. Objective:To evaluate the 1-year association of low-dose aspirin with risk of MACE in primary prevention in patients with incident GCA and to evaluate the risk of major hemorrhage and net clinical benefit at predefined time points. Design, Setting, and Participants:This population-based cohort study used a target trial emulation framework with a cloning, censoring, and weighting approach within the French National Health Data System. Participants were individuals aged at least 50 years with incident GCA between 2010 and 2022, without previous cardiovascular events or antiplatelet or anticoagulant use at GCA diagnosis. Analysis was conducted from November 2024 to June 2025. Exposure:Initiation of low-dose aspirin vs not (control group) within 14 days of GCA diagnosis. Main Outcomes and Measures:The main outcome was MACE, a composite end point of ischemic stroke, myocardial infarction, and all-cause mortality. Major hemorrhages were evaluated as secondary outcomes. Results:A total of 14 528 individuals (median [IQR] age, 74 [67 to 80] years; 10 396 [72%] female), were included. Low-dose aspirin was initiated in 5220 individuals (36%). At 1 year, MACE risk was lower in the low-dose aspirin group (relative risk [RR], 0.86 [95% CI, 0.75 to 0.96]; risk difference [RD], -0.54% [95% CI, -0.99% to -0.12%]), while major hemorrhage risk was higher (RR, 1.29 [95% CI, 1.05 to 1.53]; RD, 0.51% [95% CI, 0.13% to 0.91%]). All-cause mortality was lower in the low-dose aspirin group at 1 year (RD, -0.43% [95% CI, -0.77% to -0.10%]). At 3 years, MACE events were less frequent in the low-dose aspirin group (RD, -1.08% [95% CI, -1.77% to -0.41%]), with no difference in major hemorrhages. A more pronounced association between low-dose aspirin and lower 1-year MACE was observed in women (RD, -0.78% [95% CI, -1.29% to -0.25%]) and patients with diabetes at GCA diagnosis (RD, -2.23% [95% CI, -3.48% to -1.02%]). Conclusions and Relevance:In this retrospective cohort study, low-dose aspirin at GCA diagnosis was associated with lower MACE at 1 and 3 years but higher hemorrhage risk at 1 year. Subgroup analyses suggested heterogeneity according to sex and diabetic status.

BACKGROUND:ESPERES, a prospective e-cohort study is designed to assess attitudes and perceptions of the COVID-19 pandemic among French health care workers. OBJECTIVES:We aimed to document (i) their confidence in the information directly transmitted by their health care institutions; (ii) the role of physicians in the development of normative beliefs about vaccines against COVID-19 among them; (iii) their view of issues related to governmental health institution communication; and (iv) the impact of this communication on their posture to promote vaccine adherence among patients. METHODS:We conducted semistructured interviews with health care workers from the ESPERES cohort (n = 50). We based our maximal variation strategy mainly on the social gradient. We proceeded to a thematic analysis following an inductive approach. RESULTS:Vaccine programs should rely on health care workers' high level of confidence in the information provided directly by their health care institutions. Moreover, our results indicated that in health care institutions, the behavior of physicians influences the normative beliefs and the personal motivation to get vaccinated through a trickle-down effect (from physicians to allied health professionals), as well as a trickle-around effect (between physicians). Additionally, it appeared that physicians' eagerness to be vaccinated against COVID-19 was a major determinant in promoting the reassurance of other health care workers. However, they all reported a lack of reliability of the information provided by governmental health institutions, which contributed to patients' vaccine hesitancy. In this context, in contrast to clinicians, nurses and assistant nurses did not promote vaccination against COVID-19 in order to preserve their relationship with hesitant patients, which highlights the need of future vaccine programs to better involve these professionals who work closely with patients. CONCLUSION:Our results are very informative for sustaining the implementation of vaccine programs among health care workers in the case of future pandemics.

BACKGROUND:Levodopa, dopamine agonists (DA) and monoamine oxidase inhibitors (MAOI) are all approved first-line therapies for Parkinson's disease (PD), as monotherapy or in combination. Data on their use in the early management of patients with PD in real-life are lacking. Our objective was to assess the impact of early therapeutic strategies on the development of motor and neuropsychiatric complications using a nationwide PD cohort. METHODS:NS-PARK is a cohort of patients with PD recruited between 2011 and 2021 from 26 expert centres for PD in France. We analysed the patients with less than 5-years disease duration and no motor complications at inclusion. We used interval censoring survival models to assess the associations between therapeutic strategies (levodopa monotherapy, levodopa alternative therapies or levodopa combinations) and motor fluctuations, dyskinesia, impulse control and related behaviours (ICRBs), apathy, psychosis/hallucination and daytime sleepiness. Analyses were adjusted for sex, age, disease duration, dopaminergic dose and disease severity. RESULTS:We included 1722 patients (38.4% female, median age 67.7 years). At inclusion, 41% received levodopa monotherapy, 31% received levodopa alternative therapies and 28% received levodopa combinations. Compared with levodopa monotherapy, levodopa alternative therapies were associated with a lower dyskinesia risk (hazard ratio (HR) 0.48, 95% confidence interval (CI)[0.28-0.84]), but there was no significant difference in motor fluctuations. Both levodopa alternative and combinations therapies increased ICRBs risk (HR 4.06, 95% CI [2.48-6.67]; HR 5.16, 95% CI [3.00-8.86]) and decreased apathy risk (HR 0.36, 95% CI [0.26-0.49]; HR 0.52, 95% CI [0.39-0.69]). No association was found with psychosis/hallucination or daytime sleepiness. CONCLUSIONS:In this real-life cohort, our data supported an association between levodopa alternative therapies and a lower risk of dyskinesia and apathy, but a higher risk of ICRBs compared with levodopa monotherapy. CLINICALTRIALS: GOV IDENTIFIER:NCT04888364. Registered June 2021.

OBJECTIVES:To investigate factors associated with DM complete clinical response and overall survival with a focus on the use of immunosuppressive therapies in patients with cancer-associated DM. METHODS:We performed a multicentre, retrospective cohort study. Multivariable survival analyses used a Cox model with time-dependent covariates and adjustments with inverse probability censoring weighting. RESULTS:We included 73 patients with cancer-associated DM. Median follow-up was 3.92 years. Overall, 40 (54.8%) patients achieved cancer remission, with DM complete clinical response in 28/40 (70.0%). DM complete clinical response was associated with cancer remission (hazard ratio [HR] 2.46, 95% CI [1.13-5.32]) and younger age (HR 0.68, 95% CI [0.49-0.95]). Risk of mortality was associated with sustained cancer activity (HR 12.93, 95% CI [2.42-69.25]), male sex (HR 2.82, 95% CI [1.19-6.70]), and older age (HR 1.86, 95% CI [1.26-2.79]) but not sustained DM activity (HR 0.40, 95% CI [0.13-1.26]). Oral corticosteroid use was a protective factor only on univariate analysis (HR 0.18, 95% CI [0.08-0.42]). CONCLUSION:This study provides strong evidence of a significant association between the evolutions of DM and cancer, both in terms of overall survival and DM complete clinical response. Immunosuppressive treatments for DM were not significantly associated with mortality. TRIAL REGISTRATION:ClinicalTrials.gov, NCT04637672.

BACKGROUND:Postural abnormalities (PA) and motor complications (MCs, including motor fluctuations - MFs- and levodopa-induced dyskinesia - LIDs) are hallmark of Parkinson's disease (PD) progression, yet their relationship remains poorly understood. OBJECTIVE:To investigate the association between PA and MCs, motor symptoms, and non-motor symptoms (NMS) in patients with PD, and to assess whether PA influences the development of MCs over time. METHODS:Data of the prospective NS-Park cohort (27 French PD Expert Centers) were analysed. PA was defined by a score ≥2 on item 3.13 of the MDS-UPDRS-III. Associations between PA and MCs, as well as with other motor symptoms and NMS, were assessed using logistic regression models. We used interval censoring survival models to assess the associations between PA at inclusion and the incidence of MCs. Analyses were adjusted for sex, age, disease duration, dopaminergic dose, and disease severity. RESULTS:Among 13,037 included PD patients (58.7 % male, median age at diagnosis 61 years), 724 (5.6 %) presented with PA. Patients with PA had longer disease duration, higher disease severity, and higher dopaminergic treatment. PA exhibited a higher prevalence of troublesome MFs (OR: 5.96; 95 % CI: 4.25-8.32) and LIDs (OR: 2.81; 95 % CI: 1.79-4.30), while associations with milder MCs were inconsistent. However, PA was not significantly associated with the development of MCs during follow-up. CONCLUSIONS:PA are associated with more frequent severe MCs, and a higher burden of motor and NMS, making patient care particularly challenging.

Background Immune checkpoint inhibitors (ICIs) may induce overlapping myositis/myasthenia gravis (MG) features, sparking current debate about pathophysiology and management of this emerging disease entity. We aimed to clarify whether ICI-induced (ir-) myositis and ir-MG represent distinct diseases or exist concurrently. Methods We performed a retrospective multicenter cohort study. Using the Paris University Hospitals database (n = 2,910,417), we screened all patients with International Classification of Diseases codes or free text related to myositis/MG signs and ICI (n = 620). ‘Ir-MG signs' were defined by fatigability, repetitive nerve stimulation (RNS) decrement, and/or acetylcholine receptor antibodies (AChR Abs). Findings Ir-MG signs were never observed in the absence of ir-myositis (pathological diagnosis (n = 12/14) or CK levels >8000 U/L (n = 2/14)). Among ir-myositis patients, fatigability (2%; n = 1/62) and RNS decrement (2%; n = 1/41) were demonstrated only in one patient with pre-existing MG. AChR Abs testing yielded positive results in 26% of ir-myositis patients (n = 14/53). We revealed that test results were already positive prior to ICI therapy (n = 8/9). Clinically, ir-myositis frequently presented with “MG-like” oculomotor disease (50%; n = 31/62), bulbar dysfunction affecting speech (29%; n = 18/62) and swallowing (42%; n = 26/62), and respiratory disorders (53%; n = 33/62). Extraocular and diaphragm muscles necropsies disclosed intense muscle inflammation (100%; n = 5/5). Interpretation In our extensive database, we found no evidence of isolated ir-MG, nor of clear neuromuscular junction dysfunction in ir-myositis. These findings suggest that patients with ir-MG suspicion frequently have ir-myositis and ir-MG might be rare. “MG-like” symptoms may stem from ir-myositis-specific predilection for oculo-bulbo-respiratory musculature. Indeed, we revealed florid inflammatory infiltration of the oculomotor and respiratory muscles. Additional studies are needed to confirm these results and to elucidate the role of pre-existing AChR Abs in ir-myositis. Funding None.

BACKGROUND AND OBJECTIVES:Status epilepticus (SE) is associated with high short-term mortality, but data on long-term outcomes, including recurrence and mortality, are limited. The aim of this study was to describe recurrence and postdischarge mortality rates up to 3 years after an initial SE and identify the associated risk factors. METHODS:We conducted a retrospective cohort study involving all patients, infants and adults, who survived their first hospitalization with an ICD-10 code of SE from January 1, 2011, to December 31, 2016, using the French National Health Data System, with a 3-year follow-up. Outcomes included SE recurrence, death, and cause of death from death certificates. Measures included patient characteristics, comorbidities, SE causes, intensive care unit admissions, and mechanical ventilation at the first SE. Multivariable Cox models assessed the relationships between these factors and recurrence or mortality. RESULTS:Among 37,930 patients (46.4% female, median age 55 years [interquartile range (IQR) 30-71]), the 3-year recurrence rate was 16.7% (95% CI 16.3-17.1) and the mortality rate was 25% (95% CI 24.5-25.4). Factors present at first SE associated with 3-year recurrence were younger age (hazard ratio [HR] 2.21, 95% CI 1.90-2.58, for age group <1 compared with 10-19 years), history of epilepsy before first SE (HR 1.73, IQR 1.63-1.84), alcohol consumption (HR 1.37, 95% CI 1.27-1.48), remote and progressive causes, comorbidities, and prolonged mechanical ventilation (HR 1.21, 95% CI 1.11-1.32). Progressive causes and higher number of comorbidities were also associated with mortality, but male sex (HR 1.24, 95% CI 1.19-1.30) and older age were specifically associated with mortality and not recurrence. Main causes of death at 3 years were tumors (32.1%), cardiovascular diseases (20.2%), and infectious or respiratory diseases (8.3%). DISCUSSION:Our study highlights a high risk of recurrence or death within 3 years after a first SE. We identified factors associated with increased risk of both recurrence and mortality and factors specifically associated with recurrence or mortality. A better understanding of these factors, which are mostly nonmodifiable at the time of discharge, could assist clinicians in better planning patient follow-up.