The objective of this study was to validate the performance of Tutivia, a peripheral blood gene expression signature, in predicting early acute rejection (AR) post-kidney transplant. Recipients of living or deceased donor kidney transplants were enrolled in a nonrandomized, prospective, global, and observational study (NCT04727788). The main outcome was validation of the area under the curve (AUC) of Tutivia vs serum creatinine at biopsy alone, or Tutivia + serum creatinine at biopsy. Of the 151 kidney transplant recipients, the mean cohort age was 53 years old, and 64% were male. There were 71% (107/151) surveillance/protocol biopsies and 29% (44/151) for-cause biopsies, with a 31% (47/151) overall rejection rate. Tutivia (AUC 0.69 [95% CI: 0.59-0.77]) and AUC of Tutivia + creatinine at biopsy (0.68 [95% CI: 0.59-0.77]) were greater than the AUC of creatinine at biopsy alone (0.51.4 [95% CI: 0.43-0.60]). Applying a model cut-off of 50 (scale 0-100) generated a high- and low-risk category for AR with a negative predictive value of 0.79 (95% CI: 0.71-0.86), a positive predictive value of 0.60 (95% CI: 0.45-0.74), and an odds ratio of 5.74 (95% CI: 2.63-12.54). Tutivia represents a validated noninvasive approach for clinicians to accurately predict early AR, beyond the current standard of care.

Background: Ketamine has seen increased use for sedation in the intensive care unit. In contrast to propofol or dexmedetomidine, ketamine may provide a positive effect on hemodynamics. Objective: The objective of this study was to compare the development of clinically significant hypotension or bradycardia (ie, negative hemodynamic event) between critically ill adults receiving sedation with ketamine and either propofol or dexmedetomidine. Methods: This was a retrospective cohort study of adults admitted to an intensive care unit at an academic medical center between January 2016 and January 2021. Results: Patients in the ketamine group (n = 78) had significantly less clinically significant hypotension or bradycardia compared with those receiving propofol or dexmedetomidine (n = 156) (34.6% vs 63.5%; P < 0.001). Patients receiving ketamine also experienced smaller degree of hypotension observed by percent decrease in mean arterial pressure (25.3% [17.4] vs 33.8% [14.5]; P < 0.001) and absolute reduction in systolic blood pressure (26.5 [23.8] vs 42.0 [37.8] mm Hg; P < 0.001) and bradycardia (15.5 [24.3] vs 32.0 [23.0] reduction in beats per minute; P < 0.001). In multivariate logistic regression modeling, receipt of propofol or dexmedetomidine was the only independent predictor of a negative hemodynamic event (odds ratio [OR]: 3.3, 95% confidence interval [CI], 1.7 to 6.1; P < 0.001). Conclusion and Relevance: Ketamine was associated with less clinically relevant hypotension or bradycardia when compared with propofol or dexmedetomidine, in addition to a smaller absolute decrease in hemodynamic parameters. The clinical significance of these findings requires further investigation.

Study Objective: Vasodilatory shock is the most common type of shock. Catecholamine vasopressors are the cornerstone of hemodynamic therapy but carry risks. Angiotensin II (AT ₂ ) was recently approved, and other novel agents (selepressin and terlipressin) are under investigation and used outside the United States (terlipressin). We performed a systematic review to summarize the efficacy and safety of these novel vasopressors and to offer guidance on their appropriate use. Design: Systematic review of controlled trials. Methods: Numerous databases were searched using terms related to angiotensin II, selepressin, terlipressin, vasopressor, and shock. Twenty-one citations, including 16 prospective comparative trials and 5 post hoc analyses reporting effects of AT ₂ , selepressin, and terlipressin, were reviewed for data on outcomes related to hemodynamic measures, mortality, severity and duration of illness, concomitant vasopressor utilization, and adverse effects. Findings from eligible literature are described qualitatively using Cochrane methods. Results: Fourteen controlled trials were assessed after exclusion of 2 dated trials of a distinct AT ₂ formulation. Trials are limited for AT ₂ (n = 2) and selepressin (n = 1), while terlipressin was investigated in 11 small trials. Overall, the trials have an unclear risk of bias. Most report mean arterial pressure (MAP) as primary end point, and all indicate novel vasopressors increase MAP compared to placebo and to a similar degree as with catecholamine vasopressors. Mortality findings are preliminary, as they have been limited to specific subgroups in trials of terlipressin and post hoc analyses of one trial of AT ₂ . Trials reported safety concerns for each agent including thromboembolism with AT ₂ and ischemia with terlipressin/selepressin. Conclusion: In this systematic review, controlled trials of novel vasopressors in treatment of vasodilatory shock were limited and of low quality. Angiotensin II, selepressin, and terlipressin appear to significantly increase MAP, but further study is required, particularly for selepressin, to determine their safety, efficacy, and role in treatment of vasodilatory shock.

Background: Use of nonbenzodiazepine agents propofol and dexmedetomidine are first line for sedation in the intensive care unit (ICU). These agents have been implicated in the development of bradycardia and hypotension in critical illness. Objectives: To compare the development of clinically significant hypotension and/or bradycardia (ie, negative hemodynamic event) in adults with sepsis yet to require vasopressors receiving either propofol or dexmedetomidine for continuous sedation. Methods: This was a retrospective multicenter cohort study of adults with non–vasopressor-dependent sepsis admitted to an ICU at two academic medical centers between July 2013-September 2017. Results: Patients in the propofol (n = 64) and dexmedetomidine (n = 31) groups developed a clinically significant negative hemodynamic event at statistically similar frequencies (34.4% vs 16.1%, P = 0.065). Patients receiving propofol developed a larger degree of hypotension (47.3 vs 34.7 mm Hg reduction, P = 0.031). In multivariable logistic regression modeling, independent predictors of a negative hemodynamic event were a past medical history of chronic kidney disease (odds ratio [OR] = 3.8; 95% CI = 1.17-12.2; P = 0.027) and baseline heart rate (OR = 1.02; 95% CI = 1.00-1.10; P = 0.036). Conclusions and Relevance: A minority of patients with sepsis who received either propofol or dexmedetomidine experienced an event. Patients with sepsis without shock receiving continuous infusions of propofol and dexmedetomidine experienced a negative hemodynamic event at similar frequencies, though the degree of hypotension seen with propofol was greater. The clinical significance of these adverse effects requires cautious use in sepsis and further investigation.

Introduction Despite the use of unfractionated heparin (UFH) or low molecular weight heparin (LMWH), rates of thromboembolic disease, and subsequent morbidity and mortality remain unacceptably high in patients with severe novel coronavirus disease 2019 (COVID-19) disease. Direct oral anticoagulants (DOACs), such as apixaban, have numerous purported benefits although the safety and efficacy of their use in intensive care unit (ICU) patients with severe COVID-19 has yet to be evaluated.Materials and Methods Single-center, retrospective cohort study of 21 ICU patients with severe COVID-19 respiratory disease treated with apixaban for atrial fibrillation (AFib), venous thromboembolism (VTE), catheter-induced thrombosis, and/or COVID-19-induced coagulopathy. The primary objective was to evaluate the incidence of bleeding events and secondary objectives included thromboembolic events, coagulation parameters, and mortality.Results Ninety percent of patients were non-White, 43% were obese, 90% had acute respiratory distress syndrome, and 76% required mechanical ventilation. Nearly half of (47.6%) also experienced renal dysfunction and required renal replacement therapy. Eighty-six percent of patients received prophylaxis or treatment with UFH or LMWH within the 24-hour period prior to apixaban initiation. Patients were initiated on apixaban for the treatment of suspected or confirmed VTE (67%) or AFib (33%). All coagulation parameters remained abnormal but stable throughout the 10-day monitoring period. No patients experienced any major bleeding events or thrombosis throughout the study period. There were four deaths during the follow-up period, all deemed unrelated to coagulopathy or bleeding.Conclusion Apixaban appeared safe and efficacious in ICU patients with severe COVID-19 disease. These data encourage future trials seeking to optimize anticoagulation strategies in patients with severe COVID-19.

Introduction: Negative outcome studies of vasopressors in kidney transplant have not focused on patient populations that are predominantly Black or Hispanic. Project Aims: The evaluation sought to investigate the independent impact of perioperative vasopressors on postoperative renal allograft function in a sample drawn from a primarily Black and Hispanic population. Design: Retrospective, observational, single-center evaluation of patients > 18 years old who underwent kidney transplantation comparing outcomes based on vasopressor exposure. Results: The study included 150 patients of which 60 received vasopressors. The primary outcome differed between groups with delayed graft function occurring in 17(28%) versus 11(12.2%) occurring more often in those that received perioperative vasopressors (P = 0.02). The serum creatinine at postoperative day 7 was higher (2.69 vs1.52 mg/dL, P = 0.004), postoperative day 7 eGFR was worse (27.3 vs 52.9 mL/min/1.73m2, P = 0.002) in patients who received vasopressors. Patients who received perioperative vasopressors experienced more postoperative arrhythmias (15% vs 8%, P = 0.007), insulin infusion therapy (26.7% vs 13.3%, P = 0.04), and increased hospital length of stay (6 days vs 5 days, P = 0.006). Using IPWRA, patients receiving vasopressors were more likely to experience delayed function, relative risk difference of 22% (95% CI:0.08-0.35;P = 0.002) and in multivariate logistic regression modeling, an increased odds ratio of 3.2 (95% CI:1.1-8.62;P = 0.022). Conclusions: The use of perioperative vasopressors was independently associated with worsened early renal allograft function including delayed graft function, increased adverse events such as postoperative arrhythmias, and longer ICU length of stay. Further investigation is needed surrounding vasopressor use in this population.