Management of copy number variants associated with incomplete penetrance and variable expressivity-Results of a French survey.

Increasing interest regarding neurodevelopmental disorders and democratization of chromosomal microarray analysis have led to growing identification of neuro-susceptibility copy number variations (CNVs). These CNVs have incomplete penetrance and variable expressivity (PIEV), which makes phenotypic features hard to predict. The French Consortium "AchroPuce" has provided a list of 17 CNVs that should be considered as PIEV CNVs. This list led to consensual French practices of healthcare professionals in postnatal diagnosis. However, no consensus was established in prenatal diagnosis and fetal pathology. 121 French health professionals were surveyed their opinions and practices regarding reporting of PIEV CNVs to patients, in order to identify key points so as to establish French recommendations. The survey showed that professionals in favor of reporting PIEV CNVs to patients in prenatal diagnosis and fetal pathology (respectively, 76% and 84% of respondents) considered highlighted that multidisciplinary consultation is the main point-of-care management before family survey. This statement is close to recommendations published worldwide. As a consequence, multidisciplinary expertise should be the basis of French recommendations concerning the reporting of PIEV CNVs and genetic counseling in prenatal diagnosis and fetal pathology.

Blister Beetle Dermatitis Outbreaks in Mali.

INTRODUCTION: Meloidae are distributed in temperate and arid regions but are also common in subtropical and tropical savannahs. These insects contain cantharidin, a vesicant substance that can cause poisoning by ingestion and dermatitis by direct contact. MATERIAL AND METHODS: We describe recurrent Meloidae-related dermatitis outbreaks and their health impact by analyzing medical consultation records and meteorological data. RESULTS: Between 2015 and 2019, dermatitis outbreaks took place at a French military base at the end of the rainy season, from July to August, with 100 cases reported in 2015, 74 in 2017, 100 in 2018, and 36 in 2019. In 2017, the incidence rate was 4.4% for the base's population. Initial medical consultations represented 31.5% of total medical care activity. Meloidae were identified as Cyaneolytta fryi. CONCLUSIONS: These outbreaks of burn-like lesions, although clinically benign, can place a considerable burden on the medical activity of health care facilities. The diagnosis of Meloidae dermatitis is exclusively anamnestic and clinical and requires reported contact with the insect. The treatment protocol is that of standard burn care, and the best preventive measure is to avoid bright white lights. Military personnel, foreign workers, and travelers venturing into the Sahel should be warned of the risks associated with these beetles.

Adverse Events and Infectious Complications in the Critically Ill Treated by Plasma Exchange: A Five-Year Multicenter Cohort Study.

OBJECTIVES: The aim of this study was to determine, in critically ill patients treated with therapeutic plasma exchange (TPE), the incidence of adverse events as well as the incidence of secondary infections and its predictive factors. DESIGN: A multicenter retrospective cohort study of an intensive care population treated with TPE to collect adverse events and infectious complications. The characteristics of patients who developed an infection after plasma exchange were compared with those of patients who did not. SETTING: Four ICUs of French university hospitals. PATIENTS: All adults admitted between January 1, 2015, and December 31, 2019, who received at least one plasma exchange session were included. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: A total of 711 TPE sessions were performed on 124 patients. The most frequent TPE indications were thrombotic microangiopathies (n = 32, 26%), myasthenia gravis (n = 25, 20%), and acute polyradiculoneuropathy (n = 12, 10%). Among the 124 patients, 22 (21%) developed arterial hypotension, 12 (12%) fever, and 9 (9%) electrolyte disturbance during TPE. Moreover, 60 (48%) presented at least one infectious complication: ventilator-associated pneumonia 42, pneumonia 13, bacteremia 18 (of which 6 catheter-related infections) viral reactivation 14. Independent risk factors for ICU-acquired infection were the ICU length of stay (24 vs. 7 d; hazard ratio [HR]: 1.09 [1.04-1.15], p < 0.001) and invasive mechanical ventilation (92% vs. 35%; HR: 16.2 [5.0-53.0], p < 0.001). CONCLUSIONS: In critically ill patients treated with TPE, adverse events occurring during the procedure remain moderately frequent and are mostly not life-threatening. Infectious complications, mainly ventilation-associated pneumonia, are frequent in this population. The need of mechanical ventilation and longer ICU stay is associated with an increased risk of infection.

Clinical and Product Features Associated with Outcome of DLBCL Patients to CD19-Targeted CAR T-Cell Therapy.

CD19-directed CAR T-cells have been remarkably successful in treating patients with relapsed/refractory (R/R) diffuse large B-cell lymphoma (DLBCL) and transformed follicular lymphoma (t-FL). In this cohort study, we treated 60 patients with axicabtagene ciloleucel or tisagenlecleucel. Complete and partial metabolic responses (CMR/PMR) were obtained in 40% and 23% of patients, respectively. After 6.9 months of median follow-up, median progression-free survival (mPFS) and overall survival (mOS) were estimated at 3.1 and 12.3 months, respectively. Statistical analyses revealed that CMR, PFS, and OS were all significantly associated with age-adjusted international prognostic index (aaIPI, p < 0.05). T-cell subset phenotypes in the apheresis product tended to correlate with PFS. Within the final product, increased percentages of both CD4 and CD8 CAR+ effector memory cells (p = 0.02 and 0.01) were significantly associated with CMR. Furthermore, higher CMR/PMR rates were observed in patients with a higher maximal in vivo expansion of CAR T-cells (p = 0.05) and lower expression of the LAG3 and Tim3 markers of exhaustion phenotype (p = 0.01 and p = 0.04). Thus, we find that aaIPI at the time of infusion, phenotype of the CAR T product, in vivo CAR T-cell expansion, and low levels of LAG3/Tim3 are associated with the efficacy of CAR T-cell therapy in DLBCL patients.

Morning blisters: cantharidin-related Meloidae burns.

We report several cases of Meloidae-related blisters in French soldiers deployed to Mali. Blister beetles of the Meloidae family produce cantharidin, a blistering agent, for defensive purposes. These virtually cosmopolitan Coleoptera can cause significant nuisance to travellers and deployed soldiers especially during the rainy season in the Sahel region.

Mind the eye-squirter! An Anthia sexmaculata sexmaculata-related necrotic burn.

We report the case of an Anthia sexmaculata sexmaculata-associated necrotic burn in a French expatriate in Mauritania. Anthia spp.-related injury is a common though underreported health issue in the Sahelo-Saharan area. Deployed soldiers and travellers should be aware of these beetles when adventuring in this region.