Les Accidents Sur les Sites d’Orpaillage Traditionnel : Un Danger Pour la Vision au Niger

Nous avons colligé sur 18 mois 36 yeux ayant été victimes de traumatisme chez les orpailleurs clandestins du Niger. Les atteintes étaient bilatérales dans tous les cas mais volontiers asymétriques et touchent une ou plusieurs structures de l’œil et ses annexes, la présence des corps étrangers multiple était vus dans tous les yeux, nous avons retrouvé 9 cas d’éclatement du globe ayant nécessité une éviscération d’emblée. Il y avaient des lésions d’autres systèmes qui étaient dans 55% maxillo-faciales et dans 27% des fractures de membres. Le pronostic visuel était mauvais dans 94,43% des cas. Le manque d’infrastructures d’exploitation adéquates, la mauvaise manipulation des explosifs artisanaux sont à l’origine des accidents responsables de ces traumatismes. L’absence de structures de premiers soins, le manque de moyens de déplacement compliquent d’avantage les cas graves. Une formation substantielle en matière de santé et de sécurité est à envisager de même que des apprentissages pour aider les travailleurs à comprendre les dangers et les moyens de réduire les risques auxquels ils sont exposés.   Over 18 months, we collected 36 eyes that were victims of trauma among niger illegal gold panners. The lesions were bilateral in all cases but willingly asymmetrical and affect one or more structures of the eye and its adnnexias. The presence of multiple foreign bodies was seen in all eyes, we found 9 cases of bursting of the globe requiring immediate evisceration. Other systems were also affected in 55% maxillofacial and in 27% limb fractures. The visual prognosis was poor in 94.43% of the cases. The lack of adequate operating infrastructure and the improper handling of homemade explosives are at the origin of the accidents responsible for these traumas. The absence of first aid structures and the lack of means of transportation further complicate serious cases. Substantial health and safety training should be considered, as well as apprenticeship to help workers understand the dangers and how to reduce the risks to which they are exposed

Inborn errors of OAS-RNase L in SARS-CoV-2-related multisystem inflammatory syndrome in children

Multisystem inflammatory syndrome in children (MIS-C) is a rare and severe condition that follows benign COVID-19. We report autosomal recessive deficiencies of OAS1, OAS2, or RNASEL in five unrelated children with MIS-C. The cytosolic double-stranded RNA (dsRNA)-sensing OAS1 and OAS2 generate 2'-5'-linked oligoadenylates (2-5A) that activate the single-stranded RNA-degrading ribonuclease L (RNase L). Monocytic cell lines and primary myeloid cells with OAS1, OAS2, or RNase L deficiencies produce excessive amounts of inflammatory cytokines upon dsRNA or severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) stimulation. Exogenous 2-5A suppresses cytokine production in OAS1-deficient but not RNase L-deficient cells. Cytokine production in RNase L-deficient cells is impaired by MDA5 or RIG-I deficiency and abolished by mitochondrial antiviral-signaling protein (MAVS) deficiency. Recessive OAS-RNase L deficiencies in these patients unleash the production of SARS-CoV-2-triggered, MAVS-mediated inflammatory cytokines by mononuclear phagocytes, thereby underlying MIS-C

Autoantibodies against type I IFNs in patients with life-threatening COVID-19

Interindividual clinical variability in the course of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is vast. We report that at least 101 of 987 patients with life-threatening coronavirus disease 2019 (COVID-19) pneumonia had neutralizing immunoglobulin G (IgG) autoantibodies (auto-Abs) against interferon-w (IFN-w) (13 patients), against the 13 types of IFN-a (36), or against both (52) at the onset of critical disease; a few also had auto-Abs against the other three type I IFNs. The auto-Abs neutralize the ability of the corresponding type I IFNs to block SARS-CoV-2 infection in vitro. These auto-Abs were not found in 663 individuals with asymptomatic or mild SARS-CoV-2 infection and were present in only 4 of 1227 healthy individuals. Patients with auto-Abs were aged 25 to 87 years and 95 of the 101 were men. A B cell autoimmune phenocopy of inborn errors of type I IFN immunity accounts for life-threatening COVID-19 pneumonia in at least 2.6% of women and 12.5% of men

Incidence and survival rates for adult malignant neuro-epithelial brain tumors in the Somme county (France): A retrospective, population-based study from 2003 to 2013

International audienceAims: To describe the incidence and survival rates for neuro-epithelial primary brain tumors (NPBTs) in adults in the Somme county between 2003 and 2013. Methods: By analyzing the Somme Cancer Registry, we calculated the age-standardized incidence rates (ASRs) for NPBTs. Independent effects of age, gender and period of diagnosis on the incidence were evaluated in a Poisson regression analysis. A Cox proportional hazards model was used to adjust the overall survival rates for age, gender, histologic group and period. Results: Of the 257 registered NPBTs, 193 (75.1%) were astrocytic tumors. The subpopulations most affected by NPBTs were men (incidence rate ratio (IRR) [95% confidence interval (CI)] females/males = 0.7 [0.55-0.90], p < 0.001) and the elderly (IRR [95% CI] = 1.02 [1.01-1.03] per year increment, p < 0.001). The ASR [95% CI] was 4.5 [3.9-5.1] cases per 100,000 person-years. The increase in incidence [95%CI] between 2003 and 2013 was estimated to be 7.6% [3.4-11.2%] per year (p < 0.001). Survival improved significantly between the 2003-2008 period and the 2009-2013 period (hazard ratio [95%CI] = 0.70 [0.50-0.96], p = 0.03). Conclusion: We observed an increase in the incidence of NPBTs and in survival rates between 2009 and 2013. These increases might have been due to broader, earlier access to diagnostic tools and/or improvements in treatment procedures

Mirvetuximab Soravtansine in FRα-Positive, Platinum-Resistant Ovarian Cancer

BACKGROUND: Mirvetuximab soravtansine-gynx (MIRV), a first-in-class antibody-drug conjugate targeting folate receptor α (FRα), is approved for the treatment of platinum-resistant ovarian cancer in the United States. METHODS: We conducted a phase 3, global, confirmatory, open-label, randomized, controlled trial to compare the efficacy and safety of MIRV with the investigator's choice of chemotherapy in the treatment of platinum-resistant, high-grade serous ovarian cancer. Participants who had previously received one to three lines of therapy and had high FRα tumor expression (≥75% of cells with ≥2+ staining intensity) were randomly assigned in a 1:1 ratio to receive MIRV (6 mg per kilogram of adjusted ideal body weight every 3 weeks) or chemotherapy (paclitaxel, pegylated liposomal doxorubicin, or topotecan). The primary end point was investigator-assessed progression-free survival; key secondary analytic end points included objective response, overall survival, and participant-reported outcomes. RESULTS: A total of 453 participants underwent randomization; 227 were assigned to the MIRV group and 226 to the chemotherapy group. The median progression-free survival was 5.62 months (95% confidence interval [CI], 4.34 to 5.95) with MIRV and 3.98 months (95% CI, 2.86 to 4.47) with chemotherapy (P<0.001). An objective response occurred in 42.3% of the participants in the MIRV group and in 15.9% of those in the chemotherapy group (odds ratio, 3.81; 95% CI, 2.44 to 5.94; P<0.001). Overall survival was significantly longer with MIRV than with chemotherapy (median, 16.46 months vs. 12.75 months; hazard ratio for death, 0.67; 95% CI, 0.50 to 0.89; P = 0.005). During the treatment period, fewer adverse events of grade 3 or higher occurred with MIRV than with chemotherapy (41.7% vs. 54.1%), as did serious adverse events of any grade (23.9% vs. 32.9%) and events leading to discontinuation (9.2% vs. 15.9%). CONCLUSIONS: Among participants with platinum-resistant, FRα-positive ovarian cancer, treatment with MIRV showed a significant benefit over chemotherapy with respect to progression-free and overall survival and objective response. (Funded by ImmunoGen; MIRASOL ClinicalTrials.gov number, NCT04209855.)

Biophysical Properties and Supramolecular Structure of Self-Assembled Liposome/ε-Peptide/DNA Nanoparticles: Correlation with Gene Delivery

Using solid-phase synthesis, lysine can be oligomerized by a reaction of the peptide carboxylate with the ε-amino group to produce nontoxic, biodegradable cationic peptides, ε-oligo(l-lysines). Here α-substituted derivatives of such ε-oligo(l-lysines) containing arginine and histidine in the side chain were tested as vectors for in vitro gene delivery. Combination of ε-oligolysines with the cationic lipid DOTAP and plasmid DNA resulted in transfection efficiency exceeding that of DOTAP alone, without significant increase in cytotoxicity. Synchrotron small-angle X-ray scattering studies revealed self-assembly of the DOTAP, ε-oligolysines, and DNA to ordered lamellar complexes. High transfection efficiency of the nanoparticles correlates with increase in zeta potential above +20 mV and requires particle size to be below 500 nm. The synergistic effect of branched ε-oligolysines and DOTAP in gene delivery can be explained by the increase in surface charge and by the supramolecular structure of the DOTAP/ε-oligolysine/DNA nanoparticles