RESUMEN
{beta}-Coronaviruses are a family of positive-strand enveloped RNA viruses that include the severe acute respiratory syndrome-CoV2 (SARS-CoV2). While much is known regarding their cellular entry and replication pathways, their mode of egress remains uncertain; however, this is assumed to be via the biosynthetic secretory pathway by analogy to other enveloped viruses. Using imaging methodologies in combination with virus-specific reporters, we demonstrate that {beta}-Coronaviruses utilize lysosomal trafficking for egress from cells. This pathway is regulated by the Arf-like small GTPase Arl8b; thus, virus egress is insensitive to inhibitors of the biosynthetic secretory pathway. Coronavirus infection results in lysosome deacidification, inactivation of lysosomal degradation and disruption of antigen presentation pathways. This coronavirus-induced exploitation of lysosomes provides insights into the cellular and immunological abnormalities observed in patients and suggests new therapeutic modalities.
RESUMEN
STUDY OBJECTIVE: For many hospitals, the non-operating room anesthesia (NORA) workload continues to expand. We developed a new NORA scheduling process with shared block time - a sandbox - amongst all of the gastroenterology groups and measured the efficacy of the intervention using basic operating room management metrics. DESIGN: Prospective analysis, statistical process control. SETTING: Academic, rural hospital; endoscopy suite; postoperative recovery area. PATIENTS: Adults and pediatric patients undergoing elective and/or urgent endoscopic procedures. INTERVENTIONS: In 2014, we divided the NORA block allocations on Thursdays into one afternoon block for pediatric GI, and 1.5 blocks to be shared between the two adult GI groups. We made a provision for an additional afternoon block available if necessary. No changes were made in the release policy. For scheduling, shared block time was released between the three endoscopy groups at 7days and then opened to the general pool at 48h. MEASUREMENTS: Case volumes, under-utilized time (opportunity-unused), elective time-in-block, over-utilized time. MAIN RESULTS: With the addition of a pediatric gastroenterologist, the number of cases per month increased after the change in scheduling procedure from a mean of 107 cases per month to 131, an increase of 23% (p=<0.01) (see Chart 1). Elective time-in-block increased after the intervention by 13% (p=0.09), while under-utilized time (opportunity-unused time) decreased in a reciprocal fashion (15%, p=0.03). Pre-intervention mean over-utilized time was 101min/month, while post-intervention over-utilized time decreased by 84.5% (99% CI ±3.29) to a mean of 16min/month. CONCLUSIONS: By using a multi-disciplinary, team-based approach, we were able to increase throughput without increasing under-utilized or over-utilized time, thereby increasing efficiency. Despite the additional cases brought in by the pediatric gastroenterologist, opportunity-unused time decreased only moderately-lending support to our prediction that opening an additional NORA block was not only unnecessary to accommodate expansion of the gastroenterology service, but was also financially unviable. One of the challenges in reducing under-utilized time lies in the relatively new role played by anesthesia in the NORA environment. In our study, we showed that the open access policy applies when the block allocations have under-utilized time. As anesthesiologists continue to expand their practice into the NORA environment, good communication, interdepartmental collaboration, and flexible scheduling processes are essential to improving efficiency.