Background: Complement pathway inhibition may provide benefit for severe acute respiratory illnesses caused by viral infections such as COVID-19. We present results from a nonrandomized proof-of-concept study of complement C5 inhibitor eculizumab for treatment of severe COVID-19. Methods: All patients (N = 80) with confirmed SARS-CoV-2 infection and severe COVID-19 admitted to our intensive care unit between March 10 and May 5, 2020 were included. Forty-five patients were treated with standard care and 35 with standard care plus eculizumab through expanded-access emergency treatment. The prespecified primary outcome was day-15 survival. Clinical laboratory values and biomarkers, complement levels, and treatment-emergent serious adverse events (TESAEs) were also assessed. Findings: At day 15, estimated survival was 82.9% (95% CI: 70.4%-95.3%) with eculizumab and 62.2% (48.1%-76.4%) without eculizumab (log-rank test, P = 0.04). Patients treated with eculizumab experienced a significantly more rapid decrease in lactate, blood urea nitrogen, total and conjugated bilirubin levels and a significantly more rapid increase in platelet count, prothrombin time, and in the ratio of arterial oxygen tension over fraction of inspired oxygen versus patients treated without eculizumab. Eculizumab-associated changes in complement levels, laboratory values, and biomarkers were consistent with terminal complement inhibition, reduced hypoxia, and decreased inflammation. TESAEs of special interest occurring in >5% of patients treated with/without eculizumab were ventilator-associated pneumonia (51%/24%), bacteremia (11%/2%), gastroduodenal hemorrhage (14%/16%), and hemolysis (3%/18%). Interpretation: Findings from this proof-of-concept study suggest eculizumab may improve survival and reduce hypoxia in patients with severe COVID-19. Randomized studies evaluating the efficacy and safety of this treatment approach are needed. Funding: Programme d'Investissements d'Avenir: ANR-18-RHUS60004.

BackgroundClinical features, complications and treatments of Gaucher’s disease (GD), a rare autosomal–recessive disorder due to a confirmed lysosomal enzyme (glucocerebrosidase) deficiency, are described.MethodsAll patients with known GD, living in France, with ≥1 consultations (1980–2010), were included in the French GD registry, yielding the following 4 groups: the entire cohort, with clinical description; and its subgroups: patients with ≥1 follow-up visits, to investigate complications; recently followed (2009–2010) patients; and patients treated during 2009–2010, to examine complications before and during treatment. Data are expressed as medians (range) for continuous variables and numbers (%) for categorical variables.ResultsAmong the 562 registry patients, 265 (49.6%) were females; 454 (85.0%) had type 1, 22 (4.1%) type 2, 37 (6.9%) perinatal–lethal type and 21 (3.9%) type 3. Median ages at first GD symptoms and diagnosis, respectively, were 15 (0–77) and 22 (0–84) years for all types. The first symptom diagnosing GD was splenomegaly and/or thrombocytopenia (37.6% and 26.3%, respectively). Bone-marrow aspiration and/or biopsy yielded the diagnosis for 54.7% of the patients, with enzyme deficiency confirming GD for all patients. Birth incidence rate was estimated at 1/50,000 and prevalence at 1/136,000. For the 378 followed patients, median follow-up was 16.2 (0.1–67.6) years. Major clinical complications were bone events (BE; avascular necrosis, bone infarct or pathological fracture) for 109 patients, splenectomy for 104, and Parkinson’s disease for 14; 38 patients died (neurological complications for 15 type-2 and 3 type-3 patients, GD complications for 11 type-1 and another disease for 9 type-1 patients). Forty-six had monoclonal gammopathy. Among 283 recently followed patients, 36 were untreated and 247 had been treated during 2009–2010; 216 patients received treatment in December 2010 (126 with imiglucerase, 45 velaglucerase, 24 taliglucerase, 21 miglustat). BE occurred before (130 in 67 patients) and under treatment (60 in 41 patients) with respective estimated frequencies (95% CI) of first BE at 10 years of 20.3% (14.1%–26.5%) and 19.8% (13.5%–26.1%).ConclusionThis registry enabled the epidemiological description of GD in France and showed that BE occur even during treatment.

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ObjectivesTo evaluate the feasibility and 6 months clinical result of sectioning of the transverse carpal ligament (TCL) and median nerve decompression after ultra-minimally invasive, ultrasound-guided percutaneous carpal tunnel release (PCTR) surgery.MethodsConsecutive patients with carpal tunnel syndrome were enrolled in this descriptive, open-label study. The procedure was performed in the interventional radiology room. Magnetic resonance imaging was performed at baseline and 1 month. The Boston Carpal Tunnel Questionnaire was administered at baseline, 1, and 6 months.Results129 patients were enrolled. Significant decreases in mean symptom severity scores (3.3 ± 0.7 at baseline, 1.7 ± 0.4 at Month 1, 1.3 ± 0.3 at Month 6) and mean functional status scores (2.6 ± 1.1 at baseline, 1.6 ± 0.4 at Month 1, 1.3 ± 0.5 at Month 6) were noted. Magnetic resonance imaging showed a complete section of all TCL and nerve decompression in 100% of patients. No complications were identified.ConclusionsUltrasound-guided PCTR was used successfully to section the TCL, decompress the median nerve, and reduce self-reported symptoms.

i Escherichia coli is the species most frequently associated with clinical infections by extended-spectrum-␤-lactamase (ESBL)-producing isolates, with the CTX-M ESBL enzymes being predominant and found in genetically diverse E. coli isolates. The main objective of this study was to compare, on the basis of a case-control design, the phylogenetic diversity of 152 CTX-M-producing and 152 non-ESBL-producing clinical E. coli isolates. Multilocus sequence typing revealed that even though CTX-M enzymes were largely disseminated across the diversity of E. coli isolates, phylogenetic group B2 showed a particularly heterogeneous situation. First, clone ST131 of group B2 was strongly associated with CTX-M production (55 [79%] of 70 isolates), with CTX-M-15 being predominant. Second, the remaining members of group B2 were significantly less frequently associated with CTX-M production (9 [12%] of 75) than E. coli phylogenetic groups A, B1, and D (88 [55%] of 159). CTX-M-producing ST131 E. coli isolates were significantly more frequent in patients hospitalized in geriatric wards or long-term care facilities. Besides, the non-ESBL ST131 isolates significantly more frequently showed resistance to penicillins than the non-ESBL, non-ST131 isolates did. In conclusion, the present study emphasizes the particular antimicrobial resistance and epidemiologic characteristics of clone ST131 within group B2, which could result from the higher antibiotic exposure of this clone, as it is the predominant clone of group B2 carried in the human gut. E scherichia coli is the Enterobacteriaceae species that causes the largest number of infections, but this species is also a widespread gut commensal of humans and animals. Strains of E. coli are therefore frequently exposed to antimicrobial agents, which has resulted in the emergence and rapid diffusion of antibioticresistant E. coli clinical isolates. Extended-spectrum ␤-lactamases (ESBLs), which confer resistance to extended-spectrum cephalosporins, were, until the year 2000, produced essentially by Klebsiella pneumoniae and Enterobacter sp. isolates responsible for nosocomial infections. However, E. coli has become dominant among the ESBL-producing enterobacterial species. This is especially worrisome as the human gut carriage of E. coli favors the dissemination of ESBLs in the community (31). Interestingly, the switch of dominant species among the ESBL-producing enterobacterial isolates occurred concomitantly with the emergence of novel ESBL enzymes that belong to the CTX-M family. The CTX-M enzymes have superseded the TEM and SHV ESBLs (2) and are found in genetically diverse E. coli isolates. Among CTX-M enzymes, CTX-M-15 predominates and has been associated with the dissemination of a particular E. coli clone of sequence type 131 (ST131) (23,27).The species E. coli is genetically diverse, and strains have been classified into a number of phylogenetic groups, the most frequent ones being A, B1, B2, and D (12, 14, 29, 32). The ST131 clone belongs to phylogenetic group B2 and is associated wi...

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Background: The preoperative number of dislocations has been previously proved to be a major factor influencing the results after Bankart repair with more preoperative dislocations correlated with higher recurrence rates and more reoperations. This could possibly be because of the lower quality of the tissue repaired during the procedure after multiple dislocations. On the other hand, the Latarjet procedure does not ''repair'' but rather reconstructs and augments the anterior glenoid.Purpose/Hypothesis: The main objective was to report the clinical outcomes of patients undergoing a Latarjet procedure after 1 dislocation versus multiple (2) dislocations. The hypothesis was that the preoperative number of dislocations would not influence clinical results.Study Design: Cohort study; Level of evidence, 3.Methods: Patients older than 18 years who had undergone a primary Latarjet procedure for shoulder instability with at least 2 years of follow-up were included. Three different techniques were used: a mini-open technique using 2 screws, an arthroscopic technique using 2 screws, and an arthroscopic technique using 2 cortical buttons. Patients were evaluated and answered a questionnaire to assess the number of episodes of dislocation before surgery, the time between the first dislocation and surgery, recurrence of the dislocation, revision surgery, the Walch-Duplay score, the Simple Shoulder Test score, and the visual analog scale (VAS) score for pain.Results: A total of 308 patients were included for analysis with a mean follow-up of 3.4 6 0.8 years. Of that, 83 patients were included in the first-time dislocation group and 225 in the recurrent dislocation group. At last follow-up, the rates of recurrence and reoperation were not significantly different between groups: 4.8% in the first-time dislocation group versus 3.65% in the recurrent dislocation group and 6.1% versus 4.0%, respectively. The overall Walch-Duplay scores at last follow-up were also comparable between the 2 groups, 67.3 6 24.85 and 71.8 6 25.1, even though the first-time dislocation group showed a lower pain subscore (15.0 6 8.6 vs 18.0 6 7.5; P = .003). The VAS for pain was also significantly higher in the first-time dislocation group compared with the recurrent dislocation group (1.8 6 2.3 vs 1.2 6 1.7; P = .03). Conclusion:The number of episodes of dislocation before surgery does not affect postoperative instability rates and reoperation rates after the Latarjet procedure. However, patients with first-time dislocations had more postoperative pain compared with patients with recurrent dislocations before surgery.

hThe adherence profile of HIV-infected patients predicts the therapeutic outcome, in particular during the early phase of antiretroviral therapy (ART). We conducted a prospective observational multicenter trial monitoring adherence and virological and immunological parameters over the initial 6 months of treatment. Thirty-five subjects were starting a treatment regimen including atazanavir, ritonavir, and emtricitabine-tenofovir. Adherence was assessed using self-completed questionnaires, announced pill counts, and the medication event monitoring system (