Abstract-Interleukin-6 (IL-6) synthesized in response to diverse stimuli may play an important role in bridging the inflammatory and atherosclerotic processes. The acute-phase response after coronary artery bypass graft surgery (CABG) is associated with the induction and release of cytokines, such as IL-6. We have examined the effect of common polymorphisms in the IL-6 gene promoter (Ϫ174GϾC, Ϫ572GϾC, and Ϫ597GϾA) on IL-6 levels after elective CABG. DNA extracted from the peripheral blood of 127 patients was amplified by polymerase chain reaction. IL-6 genotypes were resolved by gel electrophoresis after restriction enzyme digestion. Serum IL-6 was measured before surgery and in serial samples at 6, 24, 48, and 72 hours after CABG. Genotype distribution was as expected for a population in Hardy-Weinberg equilibrium for all polymorphisms. Rare allele frequencies (Ϯ95% CIs) were similar to those reported previously: Ϫ597A 0.36 (0.30 to 0.42), Ϫ572C 0.07 (0.04 to 0.10), and Ϫ174C 0.37 (0.31 to 0.43). The Ϫ174GϾC and Ϫ597GϾA genotypes were in strong allelic association (⌬ϭ0.97, PϽ0.001). Baseline IL-6 levels did not significantly differ between patients with different genotypes for any polymorphism. However, 6 hours after CABG, peak IL-6 levels were significantly higher (Pϭ0.03) in carriers of the Ϫ572C allele than in those of the Ϫ572GG genotype (355Ϯ67 versus 216Ϯ13 pg/mL, respectively) and in those with genotype Ϫ174CC compared with Ϫ174G allele carriers (287Ϯ31 versus 227Ϯ15 pg/mL, respectively; Pϭ0.04). These effects remained statistically significant after adjusting for possible confounders, including age, sex, smoking, duration of cardiopulmonary bypass, aortic cross-clamp time, and total duration of surgery. These data demonstrate that IL-6 promoter polymorphisms influence peak IL-6 production after CABG, suggesting that these polymorphisms, which are functional in vitro, are also functional in vivo, suggesting a genetic influence on IL-6 levels after acute severe injury. (Arterioscler Thromb Vasc

This study aimed to evaluate the sensitivity and specificity of subepidermal moisture (SEM), a biomarker employed for early detection of pressure injuries (PI), compared to the "Gold Standard" of clinical skin and tissue assessment (STA), and to characterize the timing of SEM changes relative to the diagnosis of a PI. This blinded, longitudinal, prospective clinical study enrolled 189 patients (n = 182 in intent-totreat [ITT]) at acute and post-acute sites (9 USA, 3 UK). Data were collected from patients' heels and sacrums using a biocapacitance measurement device beginning at admission and continuing for a minimum of 6 days to: (a) the patient developing a PI,from care, or (c) a maximum of 21 days. Standard of care clinical interventions prevailed, uninterrupted. Principal investigators oversaw the study at each site. Blinded Generalists gathered SEM data, and blinded Specialists diagnosed the presence or absence of PIs. Of the ITT population, 26.4% developed a PI during the study; 66.7% classified as Stage 1 injuries, 23% deep tissue injuries, the remaining being Stage 2 or Unstageable. Sensitivity was 87.5% (95% CI: 74.8%-95.3%) and specificity was 32.9% (95% CI: 28.3%-37.8%). Area under the receiver operating characteristic curve (AUC) was 0.6713 (95% CI 0.5969-0.7457, P < .001). SEM changes were observed 4.7 (± 2.4 days) earlier than diagnosis of a PI via STA alone. Latency between the SEM biomarker and later onset of a PI, in combination with standard of care interventions administered to at-risk patients, may have confounded specificity. Aggregate SEM sensitivity and specificity and 67.13% AUC exceeded that of clinical judgment alone. While acknowledging specificity limitations, these data Funding information Bruin Biometrics, LLC suggest that SEM biocapacitance measures can complement STAs, facilitate earlier identification of the risk of specific anatomies developing PIs, and inform earlier anatomy-specific intervention decisions than STAs alone. Future work should include cost-consequence analyses of SEM informed interventions.