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Background: Senescent immune cells exhibit altered gene expression and resistance to apoptosis. The prevalence of these cells increases with age and emerging data implicate senescence-associated maladaptive signaling as a potential contributor to sepsis and septic shock. The senolytic drug fisetin promotes clearance of senescent cells and is hypothesized to mitigate septic responses to infection. Methods: We are conducting a multi-center, randomized, double-blinded, adaptive allocation phase 2 clinical trial to assess the efficacy of the senolytic drug fisetin in preventing clinical deterioration of elderly patients diagnosed with sepsis. We intend to enroll and randomize 220 elderly patients (age > 65) with the clinical diagnosis of sepsis to receive either fisetin as a single oral dose of 20 mg/kg, fisetin in two oral doses of 20 mg/kg each spaced 1 day apart, or placebo. The primary outcome will be changed in the composite of cardiovascular, respiratory, and renal sequential organ failure assessment scores at 7 days from enrollment. Secondary outcomes include quantification of senescent CD3 + cells at 7 days, and 28-day assessments of organ failure-free days, days in an intensive care unit, and all-cause mortality. Discussion: This multi-center, randomized, double-blinded trial will assess the efficacy of fisetin in preventing clinical deterioration in elderly patients with sepsis and measure the effects of this drug on the prevalence of senescent immune cells. We intend that the results of this phase 2 trial will inform the design of a larger phase 3 study. Trial registration: This trial is registered to ClinicalTrials.gov under identifier NCT05758246, first posted on March 7, 2023. [ABSTRACT FROM AUTHOR]

B Learning Objectives: b There has been a significant improvement in sepsis mortality rates in the recent years owing to improved quality of care, targeted programs and sepsis bundles. Not many studies have focused on factors affecting ICU sepsis readmission rates. B Conclusions: b Factors including a longer hospital stay, previous hospitalizations, receiving RBC transfusions and IV antibiotics at discharge during an initial ICU sepsis admission were associated with a higher risk of readmission within 30 days. [Extracted from the article]

B Learning Objectives: b Multiple studies have shown that use of a daily goal sheet improves overall quality of care in the ICU. As part of the quality improvement project and in conjunction with our ICU quality improvement committee, we followed the rates of central line and foley utilization during the time period as well as the rates of catheter-associated UTI and Central Line Associated Bloodstream infection. We followed the ICU quality metrics including central line and foley days and utilization rates every month starting from February 2018. [Extracted from the article]