Project description:Lambda interferons (IFNλs, type III IFNs or interleukins-28/29) were described fifteen years ago as novel cytokines sharing structural and functional homology with IL-10 and type I IFNs, respectively. IFNλs engage a unique receptor complex comprising IFNLR1 and IL10R2, nevertheless they share signaling cascade and many functions with type I IFNs, questioning their possible non-redundant roles and overall biological importance. Here, we review the latest evidence establishing the primacy of IFNλs in front line protection at anatomical barriers, mediating antiviral immunity before type I IFNs. We also discuss their emerging role in regulating inflammation and limiting host damage, a major difference to type I IFNs. IFNλs come thus to light as dual function cytokines mediating antiviral immunity and damage control.
Project description:BackgroundWith increasing emphasis on readmissions as an important quality metric, there is an interest in regionalization of care to high-volume centers. As a result, care of readmitted cardiac surgery patients may be fragmented if readmission occurs at a nonindex hospital. This study characterizes the frequency, risk factors, and outcomes of nonindex hospital readmission after cardiac surgery.MethodsIn this multicenter, population-based, nationally representative sample, we used weighted 2010-2015 National Readmission Database claims to identify all US adult patients who underwent 2 of the major cardiac surgeries, isolated coronary artery bypass grafting (CABG) or isolated surgical aortic valve replacement (SAVR), during their initial hospitalization. We examined characteristics, predictors, and outcomes after nonindex readmission.ResultsOverall, 1,070,073 procedures were included (844,206 CABG and 225,866 SAVR). Readmission at 30 days was 12.8% for CABG and 14.5% for SAVR. Nonindex readmissions accounted for 23% and 26% at 30 days; these were primarily noncardiac in etiology. The proportion of nonindex readmissions did not change significantly from 2010 to 2015. For CABG and SAVR, in-hospital mortality (adjusted odds ratios of 1.26 and 1.37, respectively) and major complications (odds ratios of 1.17 and 1.25, respectively) were significantly higher during nonindex versus index readmission, even after adjusting for patient risk profile, case mix, and hospital characteristics. Older age, higher income, and increased comorbidity burden were all independent predictors of nonindex readmission.ConclusionsA considerable proportion of patients readmitted after cardiac surgery are readmitted to nonindex hospitals. This fragmentation of care may account for worse outcomes associated with nonindex readmissions in this complex population.
Project description:BACKGROUND:Mechanisms of postoperative delirium remain poorly understood, limiting development of effective treatments. We tested the hypothesis that intraoperative oxidative damage is associated with delirium and neuronal injury and that disruption of the blood-brain barrier modifies these associations. METHODS:In a prespecified cohort study of 400 cardiac surgery patients enrolled in a clinical trial of atorvastatin to reduce kidney injury and delirium, we measured plasma concentrations of F2-isoprostanes and isofurans using gas chromatography-mass spectrometry to quantify oxidative damage, ubiquitin carboxyl-terminal hydrolase isozyme L1 to quantify neuronal injury, and S100 calcium-binding protein B using enzyme-linked immunosorbent assays to quantify blood-brain barrier disruption before, during, and after surgery. We performed the Confusion Assessment Method for the Intensive Care Unit twice daily to diagnose delirium. We measured the independent associations between intraoperative F2-isoprostanes and isofurans and delirium (primary outcome) and postoperative ubiquitin carboxyl-terminal hydrolase isozyme L1 (secondary outcome), and we assessed if S100 calcium-binding protein B modified these associations. RESULTS:Delirium occurred in 109 of 400 (27.3%) patients for a median (10th, 90th percentile) of 1.0 (0.5, 3.0) days. In the total cohort, plasma ubiquitin carboxyl-terminal hydrolase isozyme L1 concentration was 6.3 ng/ml (2.7, 14.9) at baseline and 12.4 ng/ml (7.9, 31.2) on postoperative day 1. F2-isoprostanes and isofurans increased throughout surgery, and the log-transformed sum of intraoperative F2-isoprostanes and isofurans was independently associated with increased odds of postoperative delirium (odds ratio, 3.70 [95% CI, 1.41 to 9.70]; P = 0.008) and with increased postoperative ubiquitin carboxyl-terminal hydrolase isozyme L1 (ratio of geometric means, 1.42 [1.11 to 1.81]; P = 0.005). The association between increased intraoperative F2-isoprostanes and isofurans and increased postoperative ubiquitin carboxyl-terminal hydrolase isozyme L1 was amplified in patients with elevated S100 calcium-binding protein B (P = 0.049). CONCLUSIONS:Intraoperative oxidative damage was associated with increased postoperative delirium and neuronal injury, and the association between oxidative damage and neuronal injury was stronger among patients with increased blood-brain barrier disruption.
Project description:Ischemic events in humans are not evenly distributed across the day. To discriminate between temporal differences in the incidence of ischemia and susceptibility to ischemic events, we examined the outcome of global ischemia in a murine model at three time points during the day. Global cerebral ischemia in mice during the light phase impairs survival and exacerbates outcome compared to ischemia at other times of the day. Specifically, mice that underwent cardiac arrest during the light phase had greater numbers of degenerating neurons, greater microglial activation, and increased proinflammatory cytokine production in the ischemia-vulnerable hippocampus, as well as increased locomotor activity. Time-of-day differences were not altered by the melatonin receptor antagonist luzindole. Our results document that brain tissue displays endogenous fluctuations in susceptibility to ischemic damage and demonstrate that small differences in time of onset can significantly influence ischemic outcomes.
Project description:This is a post-hoc analysis to assess the effect of anesthesia, surgical trauma, and extracorporeal circuit on endothelial integrity, microvascular permeability, and extracellular fluid balance, as well as on skeletal muscle catabolism, in patients undergoing elective cardiac surgery. We included 127 well-nourished patients undergoing "on-pump" elective cardiac surgery. One day prior to surgery (D0) and again on postoperative day 7 (POD7), body mass index, body composition assessment, hand-grip strength (HGS), and mid-upper arm muscle circumference (MAMC) were measured. Patients were assigned to early recovery (ER) and late recovery (LR) groups, depending on the duration of ICU stay (cut-off 48 hours). The magnitude of change (Δ) in all parameters studied was assessed in ER versus LR groups, regarding (i) epithelial tissue dysfunction (Δ-Extra-Cellular Water percentage (Δ-ECW%), Δ-Phase Angle (Δ-PhA)), (ii) skeletal muscle mass catabolism (Δ-Skeletal muscle mass reduction%, Δ-Hand Grip Strength (Δ-HGS) and Δ-Mid Upper-Arm Muscle Circumference (Δ-MAMC)). Baseline measurements were similar in both groups. A significant difference was observed in all Δ-parameters studied (Δ-ECW%, Δ-PhA and muscle catabolism, Δ-HGS, Δ-MAMC), the worse results being correlated to the LR group. The results raise the issue that patients with early recovery may silently have pathological conditions, continuing even on the day of discharge - further research should be planned.
Project description:Background:The optimal treatment of failed back surgery syndrome (FBSS) is controversial. Limited studies have demonstrated the satisfactory outcomes of percutaneous adhesiolysis in FBSS, which can be performed as a 1 day or 3 days procedure. In the current randomized clinical trial, we compared the clinical and functional outcomes of these 2 techniques. Methods:In this study, 60 patients with FBSS were randomly assigned into 2 equal groups: 1 day group and 3 days group. Before and at 4 and 12 weeks after the procedure, pain intensity was measured using visual analogue scale (VAS). The Oswestry disability index (ODI) was also completed. Pain reduction of 50% or more was defined as treatment success. Results:Significant pain relief and ODI improvement were obtained in the 2 groups with adhesiolysis (P < 0.001). However, pain intensity remained the same before and at 4 and 12 weeks after adhesiolysis. ODI score was significantly lower in 1 day group in the 1 month visit (P < 0.001). Treatment was successful in 76.7% and 83.3% of the patients in 1 day and 3 days groups, respectively (P = 0.519). Conclusions:Adhesiolysis is an effective treatment for pain relief and functional improvement in FBSS. The results of 1 day and 3 days procedures are comparable. Based on these findings, the authors recommend using 1 day technique, which can potentially decrease the patients' discomfort, hospital stay, and cost of treatment.
Project description:BackgroundAtrial fibrillation after cardiac surgery is associated with increased rates of death, complications, and hospitalizations. In patients with postoperative atrial fibrillation who are in stable condition, the best initial treatment strategy--heart-rate control or rhythm control--remains controversial.MethodsPatients with new-onset postoperative atrial fibrillation were randomly assigned to undergo either rate control or rhythm control. The primary end point was the total number of days of hospitalization within 60 days after randomization, as assessed by the Wilcoxon rank-sum test.ResultsPostoperative atrial fibrillation occurred in 695 of the 2109 patients (33.0%) who were enrolled preoperatively; of these patients, 523 underwent randomization. The total numbers of hospital days in the rate-control group and the rhythm-control group were similar (median, 5.1 days and 5.0 days, respectively; P=0.76). There were no significant between-group differences in the rates of death (P=0.64) or overall serious adverse events (24.8 per 100 patient-months in the rate-control group and 26.4 per 100 patient-months in the rhythm-control group, P=0.61), including thromboembolic and bleeding events. About 25% of the patients in each group deviated from the assigned therapy, mainly because of drug ineffectiveness (in the rate-control group) or amiodarone side effects or adverse drug reactions (in the rhythm-control group). At 60 days, 93.8% of the patients in the rate-control group and 97.9% of those in the rhythm-control group had had a stable heart rhythm without atrial fibrillation for the previous 30 days (P=0.02), and 84.2% and 86.9%, respectively, had been free from atrial fibrillation from discharge to 60 days (P=0.41).ConclusionsStrategies for rate control and rhythm control to treat postoperative atrial fibrillation were associated with equal numbers of days of hospitalization, similar complication rates, and similarly low rates of persistent atrial fibrillation 60 days after onset. Neither treatment strategy showed a net clinical advantage over the other. (Funded by the National Institutes of Health and the Canadian Institutes of Health Research; ClinicalTrials.gov number, NCT02132767.).
Project description:BackgroundAlthough damage control (DC) surgery is widely assumed to reduce mortality in critically injured patients, survivors often suffer substantial morbidity, suggesting that it should only be used when indicated. The purpose of this systematic review was to determine which indications for DC have evidence that they are reliable and/or valid (and therefore in which clinical situations evidence supports use of DC or that DC improves outcomes).MethodsWe searched 11 databases (1950-April 1, 2019) for studies that enrolled exclusively civilian trauma patients and reported data on the reliability (consistency of surgical decisions in a given clinical scenario) or content (surgeons would perform DC in that clinical scenario or the indication predicted use of DC in practice), construct (were associated with poor outcomes), or criterion (were associated with improved outcomes when DC was conducted instead of definitive surgery) validity for suggested indications for DC surgery or DC interventions.ResultsAmong 34,979 citations identified, we included 36 cohort studies and three cross-sectional surveys in the systematic review. Of the 59 unique indications for DC identified, 10 had evidence of content validity [e.g., a major abdominal vascular injury or a packed red blood cell (PRBC) volume exceeding the critical administration threshold], nine had evidence of construct validity (e.g., unstable patients with combined abdominal vascular and pancreas gunshot injuries or an iliac vessel injury and intraoperative acidosis), and six had evidence of criterion validity (e.g., penetrating trauma patients requiring > 10 U PRBCs with an abdominal vascular and multiple abdominal visceral injuries or intraoperative hypothermia, acidosis, or coagulopathy). No studies evaluated the reliability of indications.ConclusionsFew indications for DC surgery or DC interventions have evidence supporting that they are reliable and/or valid. DC should be used with respect for the uncertainty regarding its effectiveness, and only in circumstances where definitive surgery cannot be entertained.