Experience of using a regional network of hospitals in the care of older inpatients with COVID-19 in spring 2020.

Introduction: Frail, older patients with COVID-19 have an increased risk of hospital admission and death. Methods: We studied a regional model of care used for older patients with COVID-19 in spring 2020 across three settings: an acute teaching hospital, a district general hospital and a temporary emergency hospital. We also studied demographic and outcome data for these patients. Results: Increasing bed capacity in non-acute sites freed up beds in acute hospitals. Strict admission criteria and multidisciplinary team involvement allowed for the safe delivery of care in step-down sites. Conclusion: This model of care allowed for patient flow out of acute sites following the acute stage of their illness allowing for an increase in bed capacity while providing a safe setting for ongoing management.

Mechanisms of Resistance to KRASG12C Inhibitors.

KRAS is one of the most common human oncogenes, but concerted efforts to produce direct inhibitors have largely failed, earning KRAS the title of "undruggable". Recent efforts to produce subtype specific inhibitors have been more successful, and several KRASG12C inhibitors have reached clinical trials, including adagrasib and sotorasib, which have shown early evidence of efficacy in patients. Lessons from other inhibitors of the RAS pathway suggest that the effect of these drugs will be limited in vivo by the development of drug resistance, and pre-clinical studies of G12C inhibitors have identified evidence of this. In this review we discuss the current evidence for G12C inhibitors, the mechanisms of resistance to G12C inhibitors and potential approaches to overcome them. We discuss possible targets of combination therapy, including SHP2, receptor tyrosine kinases, downstream effectors and PD1/PDL1, and review the ongoing clinical trials investigating these inhibitors.