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BackgroundTo determine the impact of preoperative Liver Dysfunction (LD) on outcomes after elective Coronary Artery Bypass Grafting (CABG) and Valvular surgery (VS).MethodsThe Nationwide Inpatient Sample (2002–2010) was queried to identify patients with LD who had elective CABG or VS utilizing ICD-9-CM diagnosis and procedure codes. These patients were matched with the similar patients without LD (controls) by propensity score matching. Chi-square and Wilcoxon rank sum tests were used for analysis.ResultsWe identified 1197 patients with LD (CABG = 755; VS = 442) who were matched to 2394 controls. LD significantly increased hospital mortality after both CABG (OR = 5.19; 95%CI = 2.93–9.20) and VS (OR = 7.49; 95%CI = 3.12–17.96). Overall rates of complications after CABG with LD were greater than in non-complicated cases (OR = 1.73; 95%CI = 1.46–2.05). Among them, there was an increase in bleeding (OR = 1.81;95%CI = 1.44–2.28), respiratory (OR = 2.33;95%CI = 1.86–2.93), renal (OR = 2.79;95%CI = 2.04–3.81), and infectious (OR = 2.93;95%CI = 2.14–4.01) complications. In general, the rates of complications after VS with LD were also greater than in non-complicated cases (OR = 2.77;95%CI = 2.13–3.60), specifically for bleeding (OR = 3.07;95%CI = 2.17–4.34), respiratory (OR = 3.57;95%CI = 2.51–5.07), renal (OR = 4.40;95%CI = 2.80–6.92), and infectious (OR = 4.63;95%CI = 2.85–7.51) complications. The development of LD significantly increased mean hospital length of stay (LOS) and total hospital charges after both CABG (from7.0 ± 4.0 to 9.2 ± 9.1 days and from $100,265 ± 87,107 to $117,756 ± 99,320, respectively; P < 0.0001 for both) and VS (from 7.9 ± 5.0 to 11.4 ± 9.9 days and from $134,306 ± 114,216 to $176,620 ± 147,049, respectively; P < 0.0001 for both).ConclusionsLD worsened the outcomes after cardiac surgery. It increased rates of complications, hospital mortality, length of stay and total hospital charges after both procedures.

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Patients with relapsed or refractory lymphoma have limited treatment options, requiring newer regimens. In this Phase 1/2 study (NCT03769181), we assessed the safety, efficacy, and pharmacokinetics of isatuximab (Isa, anti‐CD38 antibody) in combination with cemiplimab (Cemi, anti‐programmed death‐1 [PD‐1] receptor antibody; Isa + Cemi) in patients with classic Hodgkin lymphoma (cHL), diffuse large B‐cell lymphoma (DLBCL), and peripheral T‐cell lymphoma (PTCL). In Phase 1, we characterized the safety and tolerability of Isa + Cemi with planned dose de‐escalation to determine the recommended Phase 2 dose (RP2D). Six patients in each cohort were treated with a starting dose of Isa + Cemi to determine the RP2D. In Phase 2, the primary endpoints were complete response in Cohort A1 (cHL anti‐PD‐1/programmed death‐ligand 1 [PD‐L1] naïve), and objective response rate in Cohorts A2 (cHL anti‐PD‐1/PD‐L1 progressors), B (DLBCL), and C (PTCL). An interim analysis was performed when the first 18 (Cohort A1), 12 (Cohort A2), 17 (Cohort B), and 11 (Cohort C) patients in Phase 2 had been treated and followed up for 24 weeks. Isa + Cemi demonstrated a manageable safety profile with no new safety signals. No dose‐limiting toxicities were observed at the starting dose; thus, the starting dose of each drug was confirmed as the RP2D. Based on the Lugano 2014 criteria, 55.6% (Cohort A1), 33.3% (Cohort A2), 5.9% (Cohort B), and 9.1% (Cohort C) of patients achieved a complete or partial response. Pharmacokinetic analyses suggested no effect of Cemi on Isa exposure. Modest clinical efficacy was observed in patients with cHL regardless of prior anti‐PD‐1/PD‐L1 exposure. In DLBCL or PTCL cohorts, interim efficacy analysis results did not meet prespecified criteria to continue enrollment in Phase 2 Stage 2. Isa + Cemi did not have a synergistic effect in these patient populations.