Characteristics of the endoscopic procedures performed in a hybrid tertiary-level hospital during the first year of the COVID-19 pandemic.

Introduction: The COVID-19 pandemic caused many changes in gastrointestinal endoscopy units. Aim: To describe the changes that occurred in a gastrointestinal endoscopy unit of a hybrid hospital during the COVID-19 pandemic. Material and methods: We performed a retrospective study of endoscopies performed in the first year of the COVID-19 pandemic. We collected and described the data of interest to the study, which is presented with numbers and percentages or measures of central tendency and dispersion as appropriate. Fisher's exact test or the χ2 test were used as appropriate. Results: A total of 507 procedures were performed. There was a 92.5% reduction in the performance of endoscopic procedures. In all, 77 (15%) procedures were performed on patients with COVID-19. The most frequent procedures were esophagogastroduodenoscopy (EGD), colonoscopy, and endoscopic retrograde cholangiopancreatography (ERCP). The main indications were gastrointestinal bleeding, placement of enteral accesses, and alterations in the biliary and pancreatic ducts. Of these, 37 (48%) were therapeutic. Patients with COVID-19 were more susceptible to the development of complications. Conclusions: During the first year of the COVID-19 pandemic, the number of endoscopic procedures performed decreased significantly. The procedures most often required were EGD, colonoscopy, and ERCP, mainly indicated by gastrointestinal bleeding, placement of enteral accesses, and alterations of the bile and pancreatic ducts.

Biallelic variants in KARS1 are associated with neurodevelopmental disorders and hearing loss recapitulated by the knockout zebrafish.

PURPOSE: Pathogenic variants in Lysyl-tRNA synthetase 1 (KARS1) have increasingly been recognized as a cause of early-onset complex neurological phenotypes. To advance the timely diagnosis of KARS1-related disorders, we sought to delineate its phenotype and generate a disease model to understand its function in vivo. METHODS: Through international collaboration, we identified 22 affected individuals from 16 unrelated families harboring biallelic likely pathogenic or pathogenic in KARS1 variants. Sequencing approaches ranged from disease-specific panels to genome sequencing. We generated loss-of-function alleles in zebrafish. RESULTS: We identify ten new and four known biallelic missense variants in KARS1 presenting with a moderate-to-severe developmental delay, progressive neurological and neurosensory abnormalities, and variable white matter involvement. We describe novel KARS1-associated signs such as autism, hyperactive behavior, pontine hypoplasia, and cerebellar atrophy with prevalent vermian involvement. Loss of kars1 leads to upregulation of p53, tissue-specific apoptosis, and downregulation of neurodevelopmental related genes, recapitulating key tissue-specific disease phenotypes of patients. Inhibition of p53 rescued several defects of kars1-/- knockouts. CONCLUSION: Our work delineates the clinical spectrum associated with KARS1 defects and provides a novel animal model for KARS1-related human diseases revealing p53 signaling components as potential therapeutic targets.