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Genotypic and phenotypic characterisation of respiratory syncytial virus after nirsevimab breakthrough infections: a large, multicentre, observational, real-world study
No full textInternational audienceBackgroundNirsevimab, a long-acting monoclonal antibody, has been approved for the prevention of respiratory syncytial virus (RSV) infection in infants. In France, more than 210 000 single doses were administered in infants younger than 1 year during the 2023–24 season. In this context, the selection and spread of escape variants might be a concern. Here, we aimed to characterise RSV associated with breakthrough infection.MethodsWe did a multicentre, national, observational study in France during the 2023–24 RSV season in RSV-infected infants (aged <1 year) who either received or did not receive a dose of nirsevimab before their first RSV season. We excluded infants with insufficient information about nirsevimab treatment or without parental consent. We used respiratory samples collected in each laboratory for full-length RSV RNA sequencing to analyse changes in the nirsevimab binding site Ø. We tested clinical RSV isolates for neutralisation by nirsevimab. We analysed F candidate substitutions by fusion-inhibition assay.FindingsOf the 695 RSV infected infants, we analysed 545 (78%) full-length RSV genome sequences: 260 (48%) from nirsevimab-treated breakthrough infections (236 [91%] RSV-A and 24 [9%] RSV-B) and 285 (52%) from untreated RSV-infected infants (236 [83%] RSV-A and 49 [17%] RSV-B). Analysis of RSV-A did not reveal any substitution in site Ø known to be associated with resistance to nirsevimab. Two (8%) of 24 RSV-B breakthrough infections had resistance-associated substitutions: F:N208D (dominant resistance-associated substitution) and a newly described F:I64M plus F:K65R combination (minority resistance-associated substitution), both of which induced high levels of resistance in the fusion-inhibition assay.InterpretationThis study is, to the best of our knowledge, the largest genotypic and phenotypic surveillance study of nirsevimab breakthrough infections to date. Nirsevimab breakthrough variants remain very rare despite the drug's widespread use. The detection of resistance-associated substitutions in the RSV-B F protein highlights the importance of active molecular surveillance
NANO-GBM trial of AGuIX nanoparticles with radiotherapy and temozolomide in the treatment of newly diagnosed Glioblastoma: Phase 1b outcomes and MRI-based biodistribution
No full textInternational audienceBackground: In glioblastoma (GBM), tumor progression occurs mainly within the irradiated tumor volume. To address this challenge, a radiosensitization strategy with intravenous gadolinium-based theranostic nanoparticles (AGuIX) is being explored in the NANO-GBM phase1b/2R trial (NCT04881032). Here, we present the results of the phase 1b part, which is the first-in-human use of these nanoparticles with radiotherapy and chemotherapy for the treatment of newly diagnosed GBM.Material and Methods: Eligible patients were aged 18 to 75 years with newly diagnosed and histologically confirmed GBM, with incomplete resection (biopsy or partial surgery). The phase 1b part was a dose escalation approach (Time-to-event Continuous Reassessment Method) with three dose levels: 50, 75, and 100 mg/kg. Patients were treated with RT (60 Gy), and concomitant and adjuvant TMZ, and 4 injections of AGuIX (D-3/-7, D1, D8, and D15). Dose-limiting-toxicity (DLT) was defined as any grade 3–4 adverse event (CTCAE v5.0), excluding alopecia, nausea, and rapidly controlled vomiting. Pharmacokinetic (PK), and biodistribution based on MRI were evaluated.Results: Between March 2022 and March 2023, eight patients were enrolled: 1 at 50 mg/kg, 1 at 75 mg/kg, and 6 at 100 mg/kg. All patients received the four AGuIX injections. Only one patient experienced a DLT (at 100 mg/kg): a grade 3 lymphopenia (related to TMZ). The RP2D of AGuIX was determined as 100 mg/kg. AGuIX mean AUC increased with dose. Regions of GBM with moderate (36–123 µM), and high (123–291 µM) or very high (>291 µM) AGuIX concentrations accounted in average for 38.7 and 26.8 %, respectively.Conclusion: These results confirm the lack of AGuIX-related toxicity and the widespread dispersion of nanoparticles throughout GBM. This supports progression to the randomized phase 2 part, utilizing an RP2D of AGuIX of 100 mg/kg (4 injections
Characteristics of Young Women Presenting With Acute Myocardial Infarction: The Prospective, Multicenter, Observational Young Women Presenting Acute Myocardial Infarction in France Study
No full textInternational audienceAbstractBackgroundThe percentage of women <50 years of age hospitalized with myocardial infarction is increasing. We describe the clinical, morphological, and biological characteristics, as well as the clinical outcomes of this population.Methods and ResultsThis prospective, observational study included consecutive women <50 years of age admitted for myocardial infarction at 30 centers in France (May 2017–June 2019). The primary outcome was the composite of net adverse clinical events: all‐cause death, cardiovascular death, recurrent myocardial infarction, stent thrombosis, any stroke, or major bleeding occurring during hospitalization with a 12‐month follow up. Three hundred fourteen women were included. The mean age was 43.0 (±5.7) years, 60.8% presented with ST‐segment–elevation myocardial infarction, 75.5% were current smokers, 31.2% had a history of complicated pregnancy, and 55.1% reported recent emotional stress. Most (91.6%) women presented with typical chest pain. Of patients on an estrogen‐containing contraceptive, 86.0% had at least 1 contraindication. Of patients with ST‐segment–elevation myocardial infarction, 17.8% had myocardial infarction with nonobstructive coronary arteries and 14.6% had spontaneous coronary artery dissection, whereas 29.3% presented with multivessel vessel disease. During hospitalization, 11 net adverse clinical events occurred in 9 (2.8%) women, but no deaths or stent thromboses occurred. By 12 months, 14 net adverse clinical events occurred in 10 (3.2%) women; 2 (0.6%) died (from progressive cancer) and 25 (7.9%) had an ischemia‐driven repeat percutaneous coronary intervention.ConclusionsMost young women with myocardial infarction reported typical chest pain and had modifiable cardiovascular risk factors. History of adverse pregnancy outcomes and prescription of combined oral contraceptive despite a contraindication were prevalent, emphasizing the need for comprehensive cardiological and gynecological evaluation and follow‐up
Endovascular treatment of unruptured intracranial aneurysms: Rate of thromboembolic events depicted by diffusion-weighted imaging in relation to different techniques
No full textInternational audienceBackground The rate of thromboembolic events (TEEs) associated with endovascular treatment (EVT) of intracranial aneurysms is not reported uniformly in the literature due to the various ways that are used to evaluate them. Analysis of Thromboembolic Complications after Endovascular Treatment of Unruptured Intracranial Aneurysms study (ACET) is a prospective, multicenter study, which analyzes the rate of TEEs using diffusion-weighted imaging (DWI) magnetic resonance imaging (MRI) in patients treated for unruptured aneurysms with different endovascular techniques. Methods Patients were prospectively included in six French centers. Postoperative DWI-MRI was performed within 72 hours post-procedure and independently evaluated. Univariate and multivariate analyses were conducted to determine factors associated with the occurrence of DWI lesions. Results Of the 233 included patients (54.5±11.2 years, 162 women, (69.5%)), 226 were effectively treated by EVT (coiling: 90 patients, 39.8%; balloon-assisted coiling (BAC): 62, 27.4%; stent-assisted coiling (SAC): 10, 4.4%; flow diversion (FD): 21, 9.3%; intrasaccular flow disruption (ISFD): 43, 19.0%) and had a postoperative MRI showing DWI lesions in 133 patients (58.8%). Univariate and multivariate analyses show the rate of patients with DWI lesions to be significantly higher with BAC (75.8%, P=0.001), SAC (90.0%, P=0.02), and FD (95.2%, P=0.001) compared with coiling alone (41.1%). Conclusions The rate of DWI lesions after EVT of unruptured aneurysms is primarily influenced by the EVT technique used. Techniques using transient (BAC) or permanent (SAC and FD) device placement in the parent artery are associated with a higher rate of DWI lesions. Trial registration number ACET: Unique identifier: NCT02862756
Comparison of self-management and spa therapy for upper-extremity musculoskeletal disorders: A randomized controlled trial
No full textInternational audienceBackground: Musculoskeletal disorders (MSDs) are common in the workplace and are a public health issue. Persistent pain despite conservative treatment or surgery may lead to poor long-term outcomes. Objective: To compare the effect of a combined 6-day program of exercise, self-management workshops and spa therapy with self-management on functional capacity in personal and professional daily life at 3 months in people with musculoskeletal disorders. Methods: We conducted a prospective, randomized controlled trial. Participants were employed (any type of work) and aged between 18 and 65 years, with latent or symptomatic upper extremity MSDs, with or without a history of sick leave. They were randomized to participate in 6 days (2 h per day) of spa therapy, exercise, and self-management workshops immediately (intervention) or at 3 months (control). The control group performed self-management until 3 months. The primary outcome was the score on the self-reported Quick Disability of Arm-Shoulder-Hand (QuickDASH) at 3 months. The primary analysis was conducted using analysis of covariance with baseline QuickDASH score as the covariate. Results: In total, 150 participants were randomized (85 % women): 78 to the control group and 72 to the intervention group. At 3 months, the QuickDASH total and work scores did not differ between groups (effectsize [ES] = -0.15, 95 %CI, -0.38 to 0.09, p = 0.215, and ES = -0.11, 95 % CI, -0.35 to 0.12, p = 0.343). However, QuickDASH sport/performing arts score was significantly different between randomization groups at 3 months (ES =-0.25, 95 % CI, -0.48 to -0.02, p = 0.035). Conclusions: This study provided no evidence in favor of a short-course, personalized self-management, intensive spa therapy intervention over self-management alone for the management of upper-extremity MSDs. Trial registration: ClinicalTrials.gov (NCT02702466) retrospectively registered
Preclinical and clinical evidence of the association of colibactin-producing Escherichia coli with anxiety and depression in colon cancer
No full textInternational audienceBACKGROUND The association between the intestinal microbiota and psychiatric disorders is becoming increasingly apparent. The gut microbiota contributes to colorectal carcinogenesis (CRC), as demonstrated with colibactin-producing Escherichia coli (CoPEC). AIM To evaluate the association between CoPEC prevalence and anxiety- and depressive-like behaviors with both preclinical and clinical approaches. METHODS Patients followed after a CRC surgery and for whom the prevalence of CoPEC has been investigated underwent a psychiatric interview. Results were compared according to the CoPEC colonization. In parallel C57BL6/J wild type mice and mice with a CRC susceptibility were chronically infected with a CoPEC strain. Their behavior was assessed using the Elevated Plus Maze test, the Forced Swimming Test and the Behavior recognition system PhenoTyper®. RESULTS In a limited cohort, all patients with CoPEC colonization presented with psychiatric disorders several years before cancer diagnosis, whereas only one patient (17%) without CoPEC did. This result was confirmed in C57BL6/J wild-type mice and in a CRC susceptibility mouse model (adenomatous polyposis colimultiple intestinal neoplasia/+). Mice exhibited a significant increase in anxiety- and depressive-like behaviors after chronic infection with a CoPEC strain. CONCLUSION This finding provides the first evidence that CoPEC infection can induce microbiota-gut-brain axis disturbances in addition to its procarcinogenic properties
Brexucabtagene autoleucel in relapsed or refractory mantle cell lymphoma, intention-to-treat use in the DESCAR-T registry
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Ophthalmic vascular manifestations in eosinophil-associated diseases: a comprehensive analysis of 57 patients from the CEREO and EESG networks and a literature review.
No full textInternational audienceIntroduction: Eosinophils have widespread procoagulant effects. In daily practice, eosinophil-related cardiovascular toxicity consists of endomyocardial damage, eosinophilic vasculitis and arterial or venous thrombosis. Here we aim to report on the clinical features and treatment outcomes of patients with unexplained ophthalmic vascular manifestations and eosinophilia.Methods: We conducted a retrospective, multicenter, observational study and a literature review of patients with eosinophilia (≥0.5 x109/L) and concomitant ophthalmic vascular manifestations independent of the underlying eosinophilic disease but with no alternative cause for ophthalmic manifestations.Results: Fifty-seven patients were included (20 from the observational study and 37 from the literature review). Ophthalmic vascular features were the initial manifestation of eosinophil-related disease in 34 (59%) patients and consisted of 29 central retinal artery occlusions, six branch retinal artery occlusions, five central retinal vein occlusions, two branch retinal vein occlusions, seven retinal vasculitides, two retinal vasospasms, 12 Purtscher’s retinopathies, 13 anterior ischemic optic neuropathies and two posterior ischemic optic neuropathies. The median [IQR] absolute eosinophil count at onset of ophthalmic vascular manifestations was 3.5 [1.7-7.8] x109/L. Underlying eosinophil-related diseases included eosinophilic granulomatosis with polyangiitis (n=32), clonal hypereosinophilic syndrome (HES) (n=1), idiopathic HES (n=13), lymphocytic HES (n=2), adverse drug reactions (n=3), parasitosis (n=2), polyarteritis nodosa (n=1), IgG4-related disease (n=1), eosinophilic fasciitis (n=1) and primary sclerosing cholangitis (n=1). Other extra-ophthalmologic arterial or venous thromboses related to eosinophilia were reported in four (7%) and nine (16%) patients, respectively. Visual prognosis was poor: only eight (10%) patients achieved full recovery of ophthalmologic symptoms. After a median follow-up of 10.5 [1-18] months, one patient (3%) had a recurrence of an ophthalmic vascular manifestation, and three patients (10%) had a recurrence of other vascular symptoms (deep vein thrombosis in two and pulmonary embolism in one patient). At the time of recurrence, absolute eosinophil counts were above 0.5 x109/L in all cases (n=4).Discussion: This study broadens the spectrum of vascular manifestations associated with hypereosinophilia by adding ophthalmic vascular manifestations. In patients with ophthalmological vascular manifestations and hypereosinophilia, aggressive treatment of the underlying pathology (and normalization of blood count) should be implemented
What competencies are needed to develop collaboration between general practitioners and pharmacists through initial interprofessional training? An analysis of training needs through a qualitative occupational didactic approach
No full textInternational audienceBackgroundCollaborative practice in primary health care increases care quality and security. In France, primary health care professionals increasingly work together. The link between general practitioners (GPs) and community pharmacists (CPs) is an important element. Nevertheless, effective collaboration between GPs and CPs is difficult to develop and formalize. Interprofessional education has been identified as a necessary step to prepare “collaborative practice-ready professionals”. We aimed to identify the interprofessional training needs of last-year GP and CP students to develop interprofessional collaborations.MethodWe conducted an analysis of training needs using a method inspired by occupational didactics. We collected data through individual semidirective interviews with CPs and GPs in 2022. At each stage we aimed to identify the elements of the occupational didactics to deduce the training needs in the form of a frame of reference: apparent competencies, emblematic situations and acting characteristics. We conducted an initial deductive thematic analysis to identify the apparent competencies of the two professions, the emblematic situations in which these competencies are used, and the acting characteristics used in these situations. We made an inductive categorization to define the collaborative competence and the families of situations and to model the actions of this GP-CP collaboration.ResultsWe defined the competency “to collaborate effectively in an interprofessional setting in order to respond to care issues in one’s territory” expressed in various professional situations. We described it by three capacities based on two interacting dynamics: one-off exchanges and structured collaborations. Various communication tools facilitate the implementation of these interactions. We modeled the actions of the GP-CP collaboration in the form of a conceptual map.ConclusionThe collaboration between the CP and the GP implements a competency that could be integrated into their professional referential.This competency, entitled “collaborating effectively in interprofessional settings to respond to care issues in one’s territory”, is expressed in a variety of professional situations. It is based on two parallel and interacting dynamics: one-off exchanges and a dynamic of lasting collaboration.This study thus lays the groundwork for the development of this collaborative skill among general practice and pharmacy residents
Radiation protection in a cohort of healthcare workers: knowledge, attitude, practices, feelings and IR-exposure in French hospitals
No full textInternational audienceThe number of healthcare workers occupationally exposed to ionizing radiation (IR) is increasing every year. As health effects from exposure to low doses IR have been reported, radiation protection (RP) in the context of occupational activities is a major concern. This study aims to assess the compliance of healthcare workers with RP policies, according to their registered cumulative dose, profession, and perception of radiation self-exposure and associated risk. Every healthcare worker from one of the participating hospitals in France with at least one dosimetric record for each year 2009, 2014, and 2019 in the SISERI registry was included and invited to complete an online questionnaire including information on the worker’s occupational exposure, perception of IR-exposure risk and RP general knowledge. H p (10) doses were provided by the SISERI system. Multivariate logistic regressions were used. Dosimeter wearing and RP practices compliance were strongly associated with ‘feeling of being IR-exposed’ (OR = 3.69, CI95% 2.04–6.66; OR = 4.60, CI95% 2.28–9.30, respectively). However, none of these factors was associated with RP training courses attendance. The main reason given for non-compliance is unsuitability or insufficient numbers of RP devices. This study provided useful information for RP policies. Making exposed workers aware of their own IR-exposure seems to be a key element to address in RP training courses. This type of questionnaire should be introduced into larger epidemiological studies. Dosimeter wearing and RP practices compliance are associated to feeling being IR-exposed. RP training courses should reinforce workers’ awareness of their exposure to IR