The goal of this study was to investigate factors associated with 30-day readmission in a multivariate model, including the CDC wound classes "clean," "clean/contaminated," "contaminated," and "dirty/infected."The 2017-2020 American College of Surgeons-National Surgical Quality Improvement Program (ACS-NSQIP) database was queried for all patients undergoing total hip replacement, coronary artery bypass grafting, Ivor Lewis esophagectomy, pancreaticoduodenectomy, distal pancreatectomy, pneumonectomy, and colectomies. ACS-defined wound classes were concordant with CDC definitions. Multivariate linear mixed regression was used to determine risk factors for readmission while adjusting for type of surgery as a random intercept.477,964 cases were identified, with 38,734 (8.1%) patients having experienced readmission within 30 days of surgery. There were 181,243 (37.9%) cases classified as wound class "clean", 215,729 (45.1%) cases classified as "clean/contaminated", 40,684 cases (8.5%) classified as "contaminated", and 40,308 (8.4%) cases classified as "dirty/infected". In the multivariate generalized mixed linear model adjusting for type of surgery, sex, body mass index, race, American Society of Anesthesiologists class, presence of comorbidity, length of stay, urgency of surgery, and discharge destination, "clean/contaminated" (p < .001), "contaminated" (p < .001), and "dirty/infected" (p < .001) wound classes (when compared to "clean") were significantly associated with 30-day readmission. Organ/space surgical site infection and sepsis were among the most common reasons for readmission in all wound classes.Wound classification was strongly prognostic for readmission in multivariable models, suggesting that it may serve as a marker of readmissions. Surgical procedures that are "non-clean" are at significantly greater risk for 30-day readmission. Readmissions may be due to infectious complications; optimizing antibiotic use or source control to prevent readmission are areas of future study.
The US Critical Illness and Injury Trials Group is funded to engage the relevant scientific communities and federal agencies to jointly advocate for clinical research. An inclusive, nationwide network of experts has been created to establish national priorities and pursue a strategic plan in conjunction with professional societies and existing research networks. Investigator-initiated clinical proposals will be presented and discussed at the inaugural National Institutes of Health meeting to promote collaboration and establish working groups to develop projects and core resources. Future US Critical Illness and Injury Trials Group meetings will convene triannually, providing a venue to gauge progress on strategic deliverables, foster development of the clinical projects, discuss education and training in clinical trial design, and address the ethical, legal, and social implications of research in the critically ill or injured patients.
Vascular dysfunction and capillary leak are common in critically ill COVID-19 patients, but identification of endothelial pathways involved in COVID-19 pathogenesis has been limited. Angiopoietin-like 4 (ANGPTL4) is a protein secreted in response to hypoxic and nutrient-poor conditions that has a variety of biological effects including vascular injury and capillary leak.To assess the role of ANGPTL4 in COVID-19-related outcomes.Two hundred twenty-five COVID-19 ICU patients were enrolled from April 2020 to May 2021 in a prospective, multicenter cohort study from three different medical centers, University of Washington, University of Southern California and New York University.Plasma ANGPTL4 was measured on days 1, 7, and 14 after ICU admission. We used previously published tissue proteomic data and lung single nucleus RNA (snRNA) sequencing data from specimens collected from COVID-19 patients to determine the tissues and cells that produce ANGPTL4.Higher plasma ANGPTL4 concentrations were significantly associated with worse hospital mortality (adjusted odds ratio per log2 increase, 1.53; 95% CI, 1.17-2.00; p = 0.002). Higher ANGPTL4 concentrations were also associated with higher proportions of venous thromboembolism and acute respiratory distress syndrome. Longitudinal ANGPTL4 concentrations were significantly different during the first 2 weeks of hospitalization in patients who subsequently died compared with survivors (p for interaction = 8.1 × 10-5). Proteomics analysis demonstrated abundance of ANGPTL4 in lung tissue compared with other organs in COVID-19. ANGPTL4 single-nuclear RNA gene expression was significantly increased in pulmonary alveolar type 2 epithelial cells and fibroblasts in COVID-19 lung tissue compared with controls.ANGPTL4 is expressed in pulmonary epithelial cells and fibroblasts and is associated with clinical prognosis in critically ill COVID-19 patients.
Preconditioning by sublethal stress can protect a cell from subsequent injury and apoptosis through a mechanism that has been unclear. Many such stresses stimulate the formation of stress granules: transient cytoplasmic foci that contain heat shock protein as well as translationally stalled mRNA and various mRNA-binding proteins. Recent research suggests that sequestration in stress granules of TRAF2, an adaptor protein that is required for tumor necrosis factor receptor 1 signaling, may underlie preconditioning by sublethal stresses.
The analysis of gene expression data in clinical medicine has been plagued by the lack of a critical evaluation of accepted methodologies for the collection, processing, and labeling of RNA. In the present report, the reliability of two commonly used techniques to isolate RNA from whole blood or its leukocyte compartment was compared by examining their reproducibility, variance, and signal-to-noise ratios. Whole blood was obtained from healthy subjects and was either untreated or stimulated ex vivo with Staphylococcus enterotoxin B (SEB). Blood samples were also obtained from trauma patients but were not stimulated with SEB ex vivo. Total RNA was isolated from whole blood with the PAXgene proprietary blood collection system or from isolated leukocytes. Biotin-labeled cRNA was hybridized to Affymetrix GeneChips. The Pearson correlation coefficient for gene expression measurements in replicates from healthy subjects with both techniques was excellent, exceeding 0.985. Unsupervised analyses, including hierarchical cluster analysis, however, revealed that the RNA isolation method resulted in greater differences in gene expression than stimulation with SEB or among different trauma patients. The intraclass correlation, a measure of signal-to-noise ratio, of the difference between SEB-stimulated and unstimulated blood from healthy subjects was significantly higher in leukocyte-derived samples than in whole blood: 0.75 vs. 0.46 ( P = 0.002). At the P < 0.001 level of significance, twice as many probe sets discriminated between SEB-stimulated and unstimulated blood with leukocyte isolation than with PAXgene. The findings suggest that the method of RNA isolation from whole blood is a critical variable in the design of clinical studies using microarray analyses.
