IMPORTANCE Patients with frailty have higher risk for postoperative mortality and complications; however, most research has focused on small groups of high-risk procedures. The associations among frailty, operative stress, and mortality are poorly understood.OBJECTIVE To assess the association between frailty and mortality at varying levels of operative stress as measured by the Operative Stress Score, a novel measure created for this study. DESIGN, SETTING, AND PARTICIPANTSThis retrospective cohort study included veterans in the Veterans Administration Surgical Quality Improvement Program from April 1, 2010, through March 31, 2014, who underwent a noncardiac surgical procedure at Veterans Health Administration Hospitals and had information available on vital status (whether the patient was alive or deceased) at 1 year postoperatively. A Delphi consensus method was used to stratify surgical procedures into 5 categories of physiologic stress. EXPOSURES Frailty as measured by the Risk Analysis Index and operative stress as measured by the Operative Stress Score. MAIN OUTCOMES AND MEASURES Postoperative mortality at 30, 90, and 180 days. RESULTS Of 432 828 unique patients (401 453 males [92.8%]; mean (SD) age, 61.0 [12.9] years), 36 579 (8.5%) were frail and 9113 (2.1%) were very frail. The 30-day mortality rate among patients who were frail and underwent the lowest-stress surgical procedures (eg, cystoscopy) was 1.55% (95% CI, 1.20%-1.97%) and among patients with frailty who underwent the moderate-stress surgical procedures (eg, laparoscopic cholecystectomy) was 5.13% (95% CI, 4.79%-5.48%); these rates exceeded the 1% mortality rate often used to define high-risk surgery. Among patients who were very frail, 30-day mortality rates were higher after the lowest-stress surgical procedures (10.34%; 95% CI, 7.73%-13.48%) and after the moderate-stress surgical procedures (18.74%; 95% CI, 17.72%-19.80%). For patients who were frail and very frail, mortality continued to increase at 90 and 180 days, reaching 43.00% (95% CI, 41.69%-44.32%) for very frail patients at 180 days after moderate-stress surgical procedures. CONCLUSIONS AND RELEVANCEWe developed a novel operative stress score to quantify physiologic stress for surgical procedures. Patients who were frail and very frail had high rates of postoperative mortality across all levels of the Operative Stress Score. These findings suggest that frailty screening should be applied universally because low-and moderate-stress procedures may be high risk among patients who are frail.

Background: MicroRNAs (miRNAs) have critical functions in various biological processes. MiRNA profiling is an important tool for the identification of differentially expressed miRNAs in normal cellular and disease processes. A technical challenge remains for high-throughput miRNA expression analysis as the number of miRNAs continues to increase with in silico prediction and experimental verification. Our study critically evaluated the performance of a novel miRNA expression profiling approach, quantitative RT-PCR array (qPCR-array), compared to miRNA detection with oligonucleotide microchip (microarray).

Monocyte/macrophage polarization in skeletal muscle regeneration is ill defined. We used CD11b-diphtheria toxin receptor transgenic mice to transiently deplete monocytes/macrophages at multiple stages before and after muscle injury induced by cardiotoxin. Fat accumulation within regenerated muscle was maximal when ablation occurred at the same time as cardiotoxin-induced injury. Early ablation (day 1 after cardiotoxin) resulted in the smallest regenerated myofiber size together with increased residual necrotic myofibers and fat accumulation. However, muscle regeneration after late (day 4) ablation was similar to controls. Levels of inflammatory cells in injured muscle following early ablation and associated with impaired muscle regeneration were determined by flow cytometry. Delayed, but exaggerated, monocyte [CD11b(+)(CD90/B220/CD49b/NK1.1/Ly6G)(-)(F4/80/I-Ab/CD11c)(-)Ly6C(+/-)] accumulation occurred; interestingly, Ly6C(+) and Ly6C(-) monocytes were present concurrently in ablated animals and control mice. In addition to monocytes, proinflammatory, Ly6C(+) macrophage accumulation following early ablation was delayed compared to controls. In both groups, CD11b(+)F4/80(+) cells exhibited minimal expression of the M2 markers CD206 and CD301. Nevertheless, early ablation delayed and decreased the transient accumulation of CD11b(+)F4/80(+)Ly6C(-)CD301(-) macrophages; in control animals, the later tissue accumulation of these cells appeared to correspond to that of anti-inflammatory macrophages, determined by cytokine production and arginase activity. In summary, impairments in muscle regeneration were associated with exaggerated monocyte recruitment and reduced Ly6C(-) macrophages; the switch of macrophage/monocyte subsets is critical to muscle regeneration.