Obesity is associated with improved early survival but increased late mortality in surgical patients with Sepsis: A propensity matched analysis.

BACKGROUND: While obesity is a risk factor for postoperative complications, its impact following sepsis is unclear. The primary objective of this study was to evaluate the association between obesity and mortality following admission to the surgical intensive care unit (SICU) with sepsis. METHODS: We conducted a single center retrospective review of SICU patients grouped into obese (n = 766, body mass index ≥30 kg/m 2 ) and nonobese (n = 574; body mass index, 18-29.9 kg/m 2 ) cohorts. Applying 1:1 propensity matching for age, sex, comorbidities, sequential organ failure assessment, and transfer status, demographic data, comorbidities, and sepsis presentation were compared between groups. Primary outcomes included in-hospital and 90-day mortality, ICU length of stay, need for mechanical ventilation (IMV) and renal replacement therapy (RRT). p < 0.05 was considered significant. RESULTS: Obesity associates with higher median ICU length of stay (8.2 vs. 5.6, p < 0.001), need for IMV (76% vs. 67%, p = 0.001), ventilator days (5 vs. 4, p < 0.004), and RRT (23% vs. 12%, p < 0.001). In-hospital (29% vs. 18%, p < 0.0001) and 90-day mortality (34% vs. 24%, p = 0.0006) was higher for obese compared with nonobese groups. Obesity independently predicted need for IMV (odds ratio [OR], 1.6; 95% confidence interval [CI], 1.2-2.1), RRT (OR, 2.2; 95% CI, 1.5-3.1), in-hospital (OR, 2.1; 95% CI, 1.5-2.8), and 90-day mortality (HR, 1.4; 95% CI, 1.1-1.8), after adjusting for sequential organ failure assessment, age, sex, and comorbidities. Comparative survival analyses demonstrate a paradoxical early survival benefit for obese patients followed by a rapid decline after 7 days (logrank p = 0.0009). CONCLUSION: Obesity is an independent risk factor for 90-day mortality for surgical patients with sepsis, but its impact appeared later in hospitalization. Understanding differences in systemic responses between these cohorts may be important for optimizing critical care management. LEVEL OF EVIDENCE: Prognostic and Epidemiological; Level III.

PD-1/PD-L1 inhibitor-induced immune thrombocytopenia: A pharmacovigilance study and systematic review.

INTRODUCTION: Programmed cell death-1 (PD-1) and programmed cell death ligand-1 (PD-L1) immune checkpoint inhibitors (ICIs) are used for a variety of cancers and are associated with a risk of developing immune-related adverse events, most commonly dermatitis, colitis, hepatitis, and pneumonitis. Immune-mediated hematologic toxicities have been reported, but are less well-described in the literature. Immune thrombocytopenia (ITP) is a rare autoimmune, hematologic adverse event that has been reported with PD-1/PD-L1 inhibitors. METHODS: We performed a retrospective observational analysis of the United States Food and Drug Administration Adverse Event Reporting System (FAERS) data. We searched for cases of ITP reported with exposure to PD-1/PD-L1 inhibitors from initial FDA approval for each agent to September 30, 2022. Disproportionality signal analysis was done by calculating the reporting odds ratio (ROR). Oxaliplatin was used as a positive control for sensitivity analysis as it is an anticancer therapy that has been associated with drug-induced ITP. A systematic review of the PubMed database was also conducted to identify published cases of PD-1/PD-L1 inhibitor-induced ITP. RESULTS: There were 329 reports of ITP with ICIs in the FAERS database that were reviewed for a disproportionality signal, including atezolizumab (n = 27), durvalumab (n = 17), nivolumab (n = 160), and pembrolizumab (n = 125). The ROR was significant for atezolizumab (ROR 5.39, 95 % CI 3.69-7.87), avelumab (ROR 10.32, 95 % CI 4.91-21.69), durvalumab (ROR 7.91, 95 % CI 4.91-12.75), nivolumab (ROR 9.76, 95 % CI 8.34-11.43), and pembrolizumab (ROR 12.6, 95 % CI 10.55-15.06). In our systematic review, we summated 57 cases of ICI-induced ITP. Nivolumab and pembrolizumab had the most reported cases of ITP in the literature. Most cases reported (53 %) included ITP-directed therapies beyond corticosteroids for the management of ICI-induced ITP. CONCLUSION: There is a significant reporting signal of ITP with several ICI agents. Clinicians should be aware of and monitor for signs of this potentially serious adverse event.