Surgical Outcomes in Benign Gynecologic Surgery Patients during the COVID-19 Pandemic (SOCOVID study)

Study Objective To determine the incidence of perioperative coronavirus disease (COVID-19) in women undergoing benign gynecologic surgery and to evaluate perioperative complication rates in patients with active, previous, or no previous severe acute respiratory syndrome coronavirus 2 infection. Design A multicenter prospective cohort study. Setting Ten institutions in the United States. Patients Patients aged >18 years who underwent benign gynecologic surgery from July 1, 2020, to December 31, 2020, were included. All patients were followed up from the time of surgery to 10 weeks postoperatively. Those with intrauterine pregnancy or known gynecologic malignancy were excluded. Interventions Benign gynecologic surgery. Measurements and Main Results The primary outcome was the incidence of perioperative COVID-19 infections, which was stratified as (1) previous COVID-19 infection, (2) preoperative COVID-19 infection, and (3) postoperative COVID-19 infection. Secondary outcomes included adverse events and mortality after surgery and predictors for postoperative COVID-19 infection. If surgery was delayed because of the COVID-19 pandemic, the reason for postponement and any subsequent adverse event was recorded. Of 3423 patients included for final analysis, 189 (5.5%) postponed their gynecologic surgery during the pandemic. Forty-three patients (1.3% of total cases) had a history of COVID-19. The majority (182, 96.3%) had no sequelae attributed to surgical postponement. After hospital discharge to 10 weeks postoperatively, 39 patients (1.1%) became infected with severe acute respiratory syndrome coronavirus 2. The mean duration of time between hospital discharge and the follow-up positive COVID-19 test was 22.1 ± 12.3 days (range, 4–50 days). Eleven (31.4% of postoperative COVID-19 infections, 0.3% of total cases) of the newly diagnosed COVID-19 infections occurred within 14 days of hospital discharge. On multivariable logistic regression, living in the Southwest (adjusted odds ratio, 6.8) and single-unit increase in age-adjusted Charlson comorbidity index (adjusted odds ratio, 1.2) increased the odds of postoperative COVID-19 infection. Perioperative complications were not significantly higher in patients with a history of positive COVID-19 than those without a history of COVID-19, although the mean duration of time between previous COVID-19 diagnosis and surgery was 97 days (14 weeks). Conclusion In this large multicenter prospective cohort study of benign gynecologic surgeries, only 1.1% of patients developed a postoperative COVID-19 infection, with 0.3% of infection in the immediate 14 days after surgery. The incidence of postoperative complications was not different in those with and without previous COVID-19 infections

LYST Controls the Biogenesis of the Endosomal Compartment Required for Secretory Lysosome Function

International audienceChediak-Higashi syndrome (CHS) is caused by mutations in the gene encoding LYST protein, the function of which remains poorly understood. Prominent features of CHS include defective secretory lysosome exocytosis and the presence of enlarged, lysosome-like organelles in several cell types. In order to get further insight into the role of LYST in the biogenesis and exocytosis of cytotoxic granules, we analyzed cytotoxic T lymphocytes (CTLs) from patients with CHS. Using confocal microscopy and correlative light electron microscopy, we showed that the enlarged organelle in CTLs is a hybrid compartment that contains proteins components from recycling-late endosomes and lysosomes. Enlargement of cytotoxic granules results from the progressive clustering and then fusion of normal-sized endolysosomal organelles. At the immunological synapse (IS) in CHS CTLs, cytotoxic granules have limited motility and appear docked while nevertheless unable to degranulate. By increasing the expression of effectors of lytic granule exocytosis, such as Munc13-4, Rab27a and Slp3, in CHS CTLs, we were able to restore the dynamics and the secretory ability of cytotoxic granules at the IS. Our results indicate that LYST is involved in the trafficking of the effectors involved in exocytosis required for the terminal maturation of perforin-containing vesicles into secretory cytotoxic granules

Iron depletion limits intracellular bacterial growth in macrophages

Many intracellular pathogens infect macrophages and these pathogens require iron for growth. Here we demonstrate in vitro that the intracellular growth of Chlamydia psittaci, trachomatis, and Legionella pneumophila is regulated by the levels of intracellular iron. Macrophages that express cell surface ferroportin, the only known cellular iron exporter, limit the intracellular growth of these bacteria. Hepcidin is an antimicrobial peptide secreted by the liver in response to inflammation. Hepcidin binds to ferroportin mediating its internalization and degradation. Addition of hepcidin to infected macrophages enhanced the intracellular growth of these pathogens. Macrophages from flatiron mice, a strain heterozygous for a loss-of-function ferroportin mutation, showed enhanced intracellular bacterial growth independent of the presence of exogenous hepcidin. Macrophages, from wild-type or flatiron mice, incubated with the oral iron chelator deferriprone or desferasirox showed reduced intracellular bacterial growth suggesting that these chelators might be therapeutic in chronic intracellular bacterial infections