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Epidemiological and clinical insights into enterovirus circulation in Europe, 2018 - 2023: a multi-center retrospective surveillance study
No full textInternational audienceAbstract Background Enteroviruses (EV) cause yearly outbreaks with severe infections, particularly in young children. This study investigates EV circulation, age-distribution, and clinical presentations in Europe from 2018-2023. Methods Aggregated data were requested from ECDC National Focal Points for Surveillance and European Non-Polio Enterovirus Network. Data included detection month, specimen type, age-group, and clinical presentation for the ten most commonly reported EV types per year. Findings Twenty-eight institutions from 16 countries reported 563,654 EV-tests during the study-period with 33,265 (5.9%) EV-positive. Forty-two types were identified (n=11,605 cases) with echovirus (E)30, coxsackievirus (CV)A6, EV-D68, E9, E11, CVB5, E18, CVB4, EV-A71, and E6 most frequently reported. E30 detection declined after 2018/2019, while CVA6, CVB5, E9, E11, and EV-D68 were prevalent both before and after the COVID-19 pandemic, and CVB4 and E18 were prevalent after the pandemic. Over the study period, a shift in seasons (summer to fall) and specimen positivity (feces to respiratory) was observed. Neurological signs predominated among EV-A71, CVB4, CVB5, E6, E9, E11, E18, and E30 (30-72%). CVB4, CVB5, E9, E11, and E18 were also frequently reported among neonates (18-32%). CVA6 was frequently associated with HFMD, and EV-D68 with respiratory infections. Paralysis was reported among 22 infections, associated with ten non-polio types. Conclusion This study emphasizes the widespread circulation and severe nature of EV infections in Europe, particularly among neonates, as well as the (re-)emergence of specific types post-pandemic. Our findings highlight the need for continuous EV-surveillance to monitor variation in circulation, age, and clinical presentations, including paralysis among non-polio EV infections
P0611 Effectiveness comparisons between tofacitinib, filgotinib and upadacitinib in ulcerative colitis: results from the JAKARTA real-world evidence multicenter study
No full textInternational audienceAs no direct comparisons exist, we compared the effectiveness of tofacitinib (TOFA), filgotinib (FILGO) and upadacitinib (UPA) in patients with Ulcerative Colitis (UC). Methods In this retrospective multicenter study, we included all consecutive patients with UC ≥18 years-old, partial Mayo score > 2 who had started TOFA, FILGO or UPA after receiving ≥ 1 biologic. Following regimen were applied : TOFA (10mg b.i.d --> at W8: 5mg or 10 mg b.i.d according to physician’s judgement), FILGO (200mg q.d) and for UPA (45mg q.d --> at W8: 45mg, 30 mg or 15 mg q.d according to physician’s judgement). The primary endpoint was symptomatic remission (partial Mayo score ≤ 2) without corticosteroids (CFREM) at W16. Secondary endpoints were clinical-endoscopic remission (CFREM + endoscopic Mayo score ≤ 1), histological-endoscopic mucosal improvement (HEMI) (= clinical-endoscopic and histological remission (Nancy index ≤ 1)), drug retention and secondary loss of response. Comparisons were performed using propensity scores adjustment (IPTW). Results Overall 290 UC patients were included: TOFA=150, FILGO=79, UPA=61. The 3 groups were comparable except for higher proportion of patients with partial Mayo score > 6 or prior exposure > 3 biologics in UPA group (p < 0.001). Recommended maintenance dose (TOFA 5mg b.i.d/UPA 30 mg/FILGO 200 mg) from W8 after response to induction was applied in 41.3% (62/150), 65.8 % (52/79), and 59.0% (36/61), in TOFA, FILGO and UPA groups, respectively, and failed (need for dose re-escalation/drug discontinuation/no clinical remission at last follow-up) in 58.1% (36/62), 42.3% (22/52), 30.5% (11/36), in TOFA, FILGO and UPA groups, respectively, (p < 0.001). After IPTW, CFREM at W16 was higher in UPA (60.1%) compared to TOFA (38.9%) or FILGO groups (36.8%) (p < 0.001 for both). No predictor of efficacy/ failure was identified with these 3 JAK inhibitors. We failed to show any significant difference regarding clinical-endoscopic remission (UPA:16.5%, TOFA:16.5%, FILGO:12.8%) or HEMI (UPA:11.9%, TOFA: 4.4, FILGO: 12.7%). Among patients achieving CFREM at W16 (regardless of the dose), secondary loss of response (clinical relapse) was similar across the groups (TOFA:12.8%, FILGO: 19.2% and UPA: 10.3%; p = ns after IPTW). After adjustment, drug retention was longer for UPA compared to TOFA and FILGO groups (HR = 0.42 [0.21-0.85], p = 0.016) and shorter in FILGO than in TOFA group (HR = 1.60 [1.07-2.38], p = 0.021). No difference was demonstrated in terms of time to hospitalization or surgery between the 3 groups. Conclusion In this real-world evidence study, UPA was the most effective JAK inhibitor in UC at short and long-term but the large use of off-label maintenance doses in current practice needs further safety investigations
Effectiveness and safety of upadacitinib induction therapy for 223 patients with crohn's disease: A GETAID multicentre cohort study
No full textInternational audienceBackground: Real-world effectiveness and safety of upadacitinib in patients with Crohn's disease (CD) remain unclear.Aims: This study aimed to evaluate the effectiveness and safety of upadacitinib in a real-world cohort.Methods: From September 2022 to June 2024, all consecutive patients with refractory luminal CD treated with once daily upadacitinib 45 mg in 29 French GETAID centres were retrospectively included. The primary outcome was steroid-free clinical remission (SFCR) at week 12, defined as a Harvey-Bradshaw Index (HBI) of < 4. Clinical response (decrease of ≥ 3 points in HBI and/or HBI < 4), clinical remission, biomarker remission, endoscopic and/or radiologic response and safety were also assessed.Results: Among the 223 patients included, all were previously exposed to at least one biologic (median 4, IQR [3, 4]) and 119 (53.8%) had prior intestinal resection. At week 12, SFCR was achieved in 107/197 (54%), clinical response in 129/197 (65%) and clinical remission in 111/197 (56%). A total of, 90 out of 173 (52%) achieved biomarker remission. Endoscopic and/or radiologic response was observed in 18/38 (47%) patients. Clinical response of extraintestinal manifestations was observed in 37/47 (79%) patients and clinical remission in 29/47 (62%). A total of, 65 adverse events (AEs) occurred in 58 patients (26%), including 17 serious AEs, 16 disease exacerbation and one case of colonic EBV-associated lymphoproliferative disorder. Acne was reported in 24/223 (11%) patients.Conclusion: In this real-world cohort of highly refractory CD patients, upadacitinib induction resulted in a clinical response in about two-thirds of patients and in SFCR in half of the patients, with an acceptable safety profile
Mycoplasma pneumoniae infection in adult inpatients during the 2023–24 outbreak in France (MYCADO): a national, retrospective, observational study
No full textInternational audienceBackground. An epidemic of Mycoplasma pneumoniae infection has been observed in France since the fall of 2023. We aimed to: i) describe the characteristics of adults hospitalized for M. pneumoniae infection and ii) identify factors associated with severe outcomes of infection (i.e., intensive care unit [ICU)] admission or in-hospital death).Methods. MYCADO is a retrospective observational study including adults hospitalized for ≥24 hours in 76 French hospitals for a M. pneumoniae infection between 1 September 2023 and 29 February 2024. Clinical, laboratory and imaging data were collected from medical records.We identified factors associated with severe outcomes of infection, defined as need for ICU or in-hospital death, using multivariable logistic regression.Findings. Overall, 1309 patients with M. pneumoniae infection were included: 718 (54.9%) males; median age 43 years (IQR 31-63); 288 (22.0%) with chronic respiratory failure; 423 (32.3%) with cardiovascular comorbidities; 95 (7.3%) with immunosuppression. The most common symptoms were: cough (n=1098, 83.9%), fever (n=1023, 78.2%), dyspnoea (n=948, 72.4%), fatigue (n=550, 42.0%), headache (n=211, 16.1%), arthromyalgia (n=253, 19.3%), vomiting (n=132, 10.1%); 156 (11.9%) patients had extra-respiratory manifestations, including 36 (2.8%) erythema multiforme, 19 (1.5%) meningoencephalitis, 44 (3.4%) autoimmune haemolytic anaemia and 17 (1.3%) myocarditis. The median hospital stay duration was 8 days (IQR 6-11); 415 (31.7%) patients were admitted to ICU and 28 (2.1%) died at hospital. Men, patients with hypertension, obesity, respiratory or liver chronic failure, extra-respiratory manifestations, bilateral lung damage or consolidation on computed tomography scan, elevated inflammatory syndrome, lymphopenia, and those who did not receive any active antibiotic against M. pneumoniae prior to admission, were more likely to present with severe outcomes of infection.Interpretation. This national, observational study highlights unexpected, atypical radiologic presentations, a high proportion of transfers to ICU, and an association between severity and delayed administration of effective antibiotics.</p
Identification of the conditions and minimum requirements necessary for the release of autologous fresh CAR T-cell products under hospital exemption: a position paper from the WP-bioproduction of the UNITC consortium
No full textInternational audienc
Incremental prognostic value of late gadolinium enhancement granularity using cardiac MRI in patients with hypertrophic cardiomyopathy
No full textInternational audienceIntroductionTo enhance risk stratification for sudden cardiac death (SCD), the European Society of Cardiology (ESC) has recently added the extent of late gadolinium enhancement (LGE) using cardiac MRI in the guidelines, setting a threshold at ≥ 15% of left ventricular mass. While previous studies have showed the prognostic value of LGE extent to predict all-cause mortality, the prognostic impact of additional LGE features is not well established.ObjectiveWe aimed to assess the incremental prognostic value of the granularity of LGE using cardiac MRI including extent, location, and pattern in patients with HCM to predict all-cause death.MethodBetween 2008 and 2021, all patients referred for HCM assessment using cardiac MRI, without history of coronary artery disease (CAD) or clinical history of myocarditis were prospectively recruited in two French centers. The outcome was all-cause death using the French National Registry of Death. The concept of “LGE granularity” was defined as a model combining LGE extent, location, and pattern. Using nested Cox proportional hazard models, the additional predictive value was assessed by C-statistic increment, continuous net reclassification improvement (NRI), integrative discrimination index (IDI) and global Chi2.ResultsAmong 2672 included patients (52 ± 7 years, 56% males), 862 (32%) had LGE. After a median (IQR) follow-up of 9 (7–11) years, 447 (17%) patients died. The presence of LGE was strongly associated with the risk of all-cause death (log-rank P < 0.001, Figure 1A). Even after adjustment for known prognosticators, the presence of LGE was still associated with all-cause death (adjusted hazard ratio (HR) 3.96, 95% CI: 3.26–4.80, P < 0.001). In the subgroup of patients with LGE (n = 862), survival curves showed that the “LGE granularity model” was associated with a higher risk of all-cause death (all P < 0.001, Figure 1B). A nested Cox model adjusted on known prognosticators showed that the LGE extent, location and pattern were all independently associated with all-cause death (all P < 0.001, Figure 1C). The “LGE granularity model” combining all these LGE features showed the best improvement in model discrimination and reclassification over and above known prognosticators (C-statistic improvement: 0.90; NRI = 41.9%; IDI = 13.2%, Chi2 global = 450, all P < 0.001; LR-test P < 0.001).ConclusionIn a large cohort of HCM, LGE granularity model (extent, location, and pattern of LGE) had an incremental prognostic value above traditional prognosticators to predict all-cause death
High-dose chemotherapy with autologous haematopoietic stem cell transplantation in patients with isolated vitreoretinal lymphoma: a LOC network study
No full textInternational audienceDespite its indolent evolution, vitreoretinal lymphoma (VRL) has a poor prognosis due to a major risk of relapse in the central nervous system (CNS) and may necessitate aggressive therapy. However, the use of high-dose chemotherapy with autologous stem cell transplantation (HCT-ASCT) is poorly documented. We retrospectively analysed from the French LOC network database the adult immunocompetent patients treated with HCT-ASCT for isolated VRL. Thirty-eight patients underwent consolidation with HCT-ASCT for isolated VRL between 2008 and 2019 after induction chemotherapy. Twenty patients had primary VRL, and 18 had an isolated VRL relapse of a primary CNS lymphoma. Three patients underwent HCT-ASCT in first-line treatment, 24 in second-line treatment, and 11 in subsequent lines. At HCT-ASCT, the median age was 61 years, and the median KPS was 90. Thirty-two patients (84%) received high-dose thiotepa-based HCT. One patient (3%) died from HCT-ASCT toxicity. Nineteen (50%) patients relapsed after HCT-ASCT, including 17 cases occurring in the brain. The median progression-free survival, brain-free survival and overall survival from HCT-ASCT were 96, 113 and 92 months, respectively. HCT-ASCT represents an effective therapeutic strategy for select VRL patients, with a tolerable safety profile. However, the risk of subsequent brain relapse remains significant
Effect of a polyphenol-rich extract on LDL cholesterol in mild to moderate hypercholesterolemia: a randomized, double-blind, placebo-controlled trial
No full textInternational audienceBackground/ObjectiveHypercholesterolemia is a well-known risk factor for cardiovascular disease. This clinical trial evaluated the effects of TOTUM-070, a polyphenol-rich blend of plant extracts, on lipid metabolism in individuals with moderate hypercholesterolemia.Subjects/MethodsThis was a 6-month, multicenter, randomized, double-blind, placebo-controlled trial. Individuals not receiving lipid-lowering treatment and with fasting low-density lipoprotein cholesterol (LDL-C) between 1.3 and 1.9 g/L received TOTUM-070 (5 g/day) or placebo. The primary outcome was the change in fasting LDL-C. Secondary endpoints included safety, changes in the lipid profile, anthropometric measurements, and gut microbiome composition.ResultsA total of 120 subjects (mean age:53.1 ± 10.3 years; BMI: 25.9 ± 3.7 kg.m2; 69.2% women; baseline LDL-C: 1.44 ± 0.23 g/L) were included and randomized. TOTUM-070 was well tolerated. After 6 months, fasting LDL-C was reduced in the TOTUM-070 group compared with the placebo group (Mean estimate: 1.31 ± 0.03 [1.25 ; 1.37] vs 1.41 ± 0.03 [1.35 ; 1.47], p = 0.0041). Compared with placebo, TOTUM-070 also reduced total cholesterol (p < 0.01), non-high-density lipoprotein cholesterol (non-HDL-C) (p < 0.001), triglycerides (p < 0.05), apolipoprotein (apo)B100 (p < 0.01), the apoB100/apoA1 ratio (p < 0.01), oxidized LDL (p < 0.05), and body weight (–1.4 kg; p < 0.001). Furthermore, a decrease in the abundance of Dorea in fecal samples was observed in the TOTUM-070 group.ConclusionsThis clinical trial showed that supplementation with TOTUM-070 significantly lowers LDL-C and improves other lipid parameters in subjects with moderate hypercholesterolemia. As a polyphenol-rich plant-based blend, TOTUM-070 represents a promising non-pharmacological strategy that could complement lifestyle modifications for the management of early-stage hypercholesterolemia
Therapeutic Management During Pregnancy and Relapse Risk in Women With Multiple Sclerosis
No full textInternational audienceImportance: In women with multiple sclerosis (MS), disease-modifying therapy (DMT) management during pregnancy might impact relapse risk.Objective: To estimate the effect of DMT management during pregnancy on MS relapse rate and compare different therapeutic strategies.Design, setting, and participants: This was a multicenter retrospective cohort study using data from January 1990 to December 2023. Data were extracted in December 2023 from the French MS registry. Among 52 955 women in the registry, we included pregnancies identified through childbirths in patients with relapsing-onset MS who were monitored for at least 18 months before delivery and 9 months after. Pregnancies occurring less than 18 months apart or with missing month of birth were excluded.Exposures: Mediation analysis was used to estimate the total, direct, and indirect (mediated by DMT management) effects of pregnancy. Different therapeutic strategies were compared: DMT interruption, switching to or maintaining interferon β or glatiramer acetate, switching to or maintaining natalizumab until the third trimester, and switching to or maintaining intravenous anti-CD20 and interrupting it 3 months before conception.Main outcomes and measures: The primary outcome was the annualized relapse rate (ARR) during the preconception, gestation, and postpartum periods. Within a causal inference framework, counterfactual ARRs were estimated using longitudinal g-computation, combining a random forest algorithm for predicting DMTs, and a mixed-effects Poisson model for relapses.Results: We included 6341 pregnancies occurring in 4998 women (mean [SD] age at conception, 31.5 [4.5] years). DMT management during pregnancy significantly increased ARR during gestation (causal rate ratio [cRR], 1.13; 95% CI, 1.06-1.22) and postpartum (cRR, 1.08; 95% CI, 1.01-1.16) periods. This led to a deleterious total effect of pregnancy on ARR, particularly in women receiving natalizumab before pregnancy with prolonged interruption (ie, interruption before the second trimester or resumption more than 3 months after delivery; cRR, 2.18; 95% CI, 1.76-2.69), and in women receiving fingolimod (cRR, 2.15; 95% CI, 1.60-2.93). Compared to DMT interruption, anti-CD20 strategy was the most effective (cRR, 0.38; 95% CI, 0.25-0.52), followed by the natalizumab strategy with short interruption (cRR, 0.80; 95% CI, 0.71-0.90), whereas interferon β (cRR, 0.93; 95% CI, 0.86-0.99) and glatiramer acetate strategies (cRR, 0.91; 95% CI, 0.84-0.99) were less effective.Conclusion: In this study, DMT management during pregnancy significantly increased relapse risk, particularly in patients receiving natalizumab with prolonged interruption or fingolimod. The strategy based on the use of anti-CD20 before pregnancy was the most effective to mitigate this risk
