Daily Ards Research Analysis

OBJECTIVES: Latent class assignment-derived subphenotyping algorithms may identify treatment-responsive subgroups of critically ill patients with sepsis and acute respiratory distress syndrome. It is unclear if these algorithms are generalizable to patients with comorbid malignancy, a state which may perturb influential inflammatory biomarkers. This study aimed to test whether malignancy or neutropenia modified the effect of subphenotype assignment by two algorithms as applied to a prospective cohort enriched for ICU patients with active malignancy. DESIGN: Prospective cohort study at a single U.S. quaternary referral center. SETTING/PATIENTS: ICU patients older than 18 admitted to an ICU with a primary admission indication of sepsis. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: We applied two published subphenotyping algorithms utilizing either interleukin (IL)-6 or IL-8 (in addition to soluble tumor necrosis factor receptor 1 and bicarbonate) to our cohort of 930 patients with sepsis, 396 (42%) of whom had active malignancy. A greater proportion of hematologic malignancy patients were assigned the "hyperinflammatory" subphenotype by the IL-8-utilizing algorithm than the IL-6 algorithm (58% vs. 32%). Patients with leukemia and neutropenia were overrepresented among those classified as hyperinflammatory by IL-8 algorithm. We constructed Cox proportional hazards models to assess for interaction between the presence of solid malignancy, hematologic malignancy, and severe neutropenia and the subphenotype/mortality association. Hematologic malignancy uniquely appeared to attenuate the associated mortality of the IL-6-assigned hyperinflammatory subphenotype (interaction; p = 0.037), but not the IL-8-assigned hyperinflammatory subphenotype (interaction; p = 0.260), which retained an independent association with mortality in hematologic malignancy subjects (hazard ratio, 1.50; 95% CI, 1.08-2.07; p = 0.014). CONCLUSIONS: As subphenotyping algorithms are being tested as point-of-care prognostic tools, it is important to understand their generalizability to patients with comorbid malignancy, which constitute an increasing proportion of ICU patients. The differential behavior of these algorithms in patients with hematologic malignancy suggests a need for independent derivation and validation in this specific population.

RATIONALE: Surgeries that require one-lung ventilation have high rates of postoperative cardiopulmonary complications with associated morbidity and mortality. Statins may limit inflammation involved in the development of these complications. OBJECTIVES: We tested the hypothesis that perioperative simvastatin use reduces postoperative cardiopulmonary complications, compared with placebo, in surgery requiring one-lung ventilation. METHODS: Randomised, double-blind, multicentre trial of simvastatin versus placebo in patients undergoing elective oesophagectomy, lobectomy or pneumonectomy at 15 sites throughout the UK. Planned sample size is 452 patients. Participants were randomised to either simvastatin 80 mg or placebo for 4 days preoperatively and up to 7 days postoperatively. MEASUREMENTS: The primary outcome measure was a composite endpoint of the incidence of acute respiratory distress syndrome, postoperative pulmonary complications, myocardial infarction and/or myocardial ischaemia during the first 7 days postoperatively or until hospital discharge. A modified intention-to-treat analysis excluded patients who did not receive the intervention preoperatively or proceed with the planned surgery. MAIN RESULTS: 251 patients were randomised, 126 assigned to simvastatin and 125 to placebo, with 208 included in the modified intention-to-treat population. The trial was stopped early because of futility following recommendations from the data monitoring and ethics committee. The primary outcome occurred in 45/106 patients (42.5%) in the simvastatin group and 39/102 patients (38.2%) in the placebo group (OR 1.19 (95% CI 0.68 to 2.08); p=0.54). Secondary and safety outcomes were similar between the groups. CONCLUSION: In patients undergoing one-lung ventilation, simvastatin did not reduce the incidence of postoperative cardiopulmonary complications. TRIAL REGISTRATION NUMBER: isrctn.org identifier, ISRCTN48095567.

OBJECTIVES: This study aimed to evaluate long-term pulmonary function, cardiopulmonary exercise capacity, chest CT findings, and health-related quality of life (HRQoL) in survivors of COVID-19 complicated by acute respiratory distress syndrome (ARDS). DESIGN, SETTING, AND PATIENTS: This is a multicentric case-control study conducted from February 2023 to December of 2023. Pulmonary function tests, cardiopulmonary exercise testing (CPET), chest CT, and HRQoL (using EuroQol 5D three-level [EQ-5D-3L]) were performed at least 12 months after hospital discharge among cases (COVID-19 complicated by ARDS) and at the time of inclusion among controls (family members/friends matched for sex and age). INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: A total of 114 COVID-19 ARDS survivors and 115 controls were included. The mean age was 54 years and 52.4% of the participants were men. Time from hospital discharge to evaluation was 22 months (20.99-41.41 mo) among cases. Persistent symptoms, including memory loss (48.2%), fatigue (42.1%), and anxiety (31.6%), were reported by 73.6% of the COVID-19 ARDS survivors. Cases had significantly reduced pulmonary function, with lower diffusing capacity for carbon monoxide (DLCO) of 6.85 mmol/min/Kpa (5.44-8.37 mmol/min/Kpa) vs. 7.36 mmol/min/Kpa (6.43-8.96 mmol/min/Kpa; p = 0.012) and % of predicted DLCO of 81.0% (70.2-90.4%) vs. 89.3% (78.9-99.9%; p < 0.001), compared with controls, as well as a higher frequency of moderate to severe DLCO impairment (10.5% vs. 0.8%; p = 0.002). In CPET, cases demonstrated lower peak oxygen consumption (21.9 mL/kg/min [18.2-29 mL/kg/min] vs. 25.8 mL/kg/min [21.6-31.9 mL/kg/min]; p < 0.001). Chest CT revealed a greater prevalence of ground-glass opacities in cases (53.5% vs. 16.5%; p < 0.001) and emphysema (6.1% vs. 0%; p = 0.043). HRQoL, using EQ-5D-3L utility scores, were significantly lower in cases, with worse mobility (p < 0.001), self-care (p < 0.001), and anxiety/depression (p = 0.04) dimension scores compared with controls. CONCLUSIONS: COVID-19 ARDS survivors exhibit significant long-term impairments in pulmonary function, exercise capacity, and quality of life and abnormal chest CT findings compared with family controls with same sex and age.