Objectives Perioperative bleeding is common among patients undergoing cardiac surgery; however, the definition of perioperative bleeding is variable and lacks standardization. We propose a universal ...definition for perioperative bleeding (UDPB) in adult cardiac surgery in an attempt to precisely describe and quantify bleeding and to facilitate future investigation into this difficult clinical problem. Methods The multidisciplinary International Initiative on Haemostasis Management in Cardiac Surgery identified a common definition of perioperative bleeding as an unmet need. The functionality and usefulness of the UDPB for clinical research was then tested using a large single-center, nonselected, cardiac surgical database. Results A multistaged definition for perioperative bleeding was created based on easily measured clinical end points, including total blood loss from chest tubes within 12 hours, allogeneic blood products transfused, surgical reexploration including cardiac tamponade, delayed sternal closure, and the need for salvage treatment. Depending on these components, bleeding is graded as insignificant, mild, moderate, severe, or massive. When applied to an established cardiac surgery dataset, the UDPB provided insight into the incidence and outcome of bleeding after cardiac surgery. Conclusions The proposed UDPB in adult cardiac surgery provides a precise classification of bleeding that is useful in everyday practice as well as in clinical research. Once fully validated, the UDPB may be useful as an institutional quality measure and serve as an important end point in future cardiac surgical research.
Mixed lineage kinase domain-like (MLKL) is the terminal protein in the pro-inflammatory necroptotic cell death program. RIPK3-mediated phosphorylation is thought to initiate MLKL oligomerization, ...membrane translocation and membrane disruption, although the precise choreography of events is incompletely understood. Here, we use single-cell imaging approaches to map the chronology of endogenous human MLKL activation during necroptosis. During the effector phase of necroptosis, we observe that phosphorylated MLKL assembles into higher order species on presumed cytoplasmic necrosomes. Subsequently, MLKL co-traffics with tight junction proteins to the cell periphery via Golgi-microtubule-actin-dependent mechanisms. MLKL and tight junction proteins then steadily co-accumulate at the plasma membrane as heterogeneous micron-sized hotspots. Our studies identify MLKL trafficking and plasma membrane accumulation as crucial necroptosis checkpoints. Furthermore, the accumulation of phosphorylated MLKL at intercellular junctions accelerates necroptosis between neighbouring cells, which may be relevant to inflammatory bowel disease and other necroptosis-mediated enteropathies.
In this study, patients were randomly assigned to a transfusion threshold of 9 or 7.5 g per deciliter after cardiac surgery. There was no significant between-group difference in infectious or ...ischemic events, but more deaths were associated with the lower threshold.
Perioperative anemia is common after cardiac surgery and is associated with significant increases in morbidity and mortality.
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The transfusion of allogeneic red cells is the preferred treatment for acute anemia and is also used in patients undergoing cardiac surgery; typically, more than 50% of patients receive a perioperative transfusion,
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which uses a substantial proportion of blood supplies.
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Observational studies suggest that transfusion is harmful after cardiac surgery; associations have been reported between transfusion and infection, low cardiac output, acute kidney injury, and death.
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In contrast, randomized, controlled trials of red-cell transfusion with restrictive thresholds (i.e., transfusions . . .
Acute kidney injury (AKI) risk prediction scores are an objective and transparent means to enable cohort enrichment in clinical trials or to risk stratify patients preoperatively. Existing scores are ...limited in that they have been designed to predict only severe, or non-consensus AKI definitions and not less severe stages of AKI, which also have prognostic significance. The aim of this study was to develop and validate novel risk scores that could identify all patients at risk of AKI.
Prospective routinely collected clinical data (n = 30,854) were obtained from 3 UK cardiac surgical centres (Bristol, Birmingham and Wolverhampton). AKI was defined as per the Kidney Disease: Improving Global Outcomes (KDIGO) Guidelines. The model was developed using the Bristol and Birmingham datasets, and externally validated using the Wolverhampton data. Model discrimination was estimated using the area under the ROC curve (AUC). Model calibration was assessed using the Hosmer-Lemeshow test and calibration plots. Diagnostic utility was also compared to existing scores.
The risk prediction score for any stage AKI (AUC = 0.74 (95% confidence intervals (CI) 0.72, 0.76)) demonstrated better discrimination compared to the Euroscore and the Cleveland Clinic Score, and equivalent discrimination to the Mehta and Ng scores. The any stage AKI score demonstrated better calibration than the four comparison scores. A stage 3 AKI risk prediction score also demonstrated good discrimination (AUC = 0.78 (95% CI 0.75, 0.80)) as did the four comparison risk scores, but stage 3 AKI scores were less well calibrated.
This is the first risk score that accurately identifies patients at risk of any stage AKI. This score will be useful in the perioperative management of high risk patients as well as in clinical trial design.
ObjectivesGoal-directed optimisation of cerebral oxygenation using near-infrared spectroscopy (NIRS) during cardiopulmonary bypass is widely used. We tested the hypotheses that the use of NIRS ...cerebral oximetry results in reductions in cerebral injury (neurocognitive function, serum biomarkers), injury to other organs including the heart and brain, transfusion rates, mortality and resource use.DesignSystematic review and meta-analysis.SettingTertiary cardiac surgery centres in North America, Europe and Asia.ParticipantsA search of Cochrane Central Register of Controlled Trials, ClinicalTrials.gov, Medline, Embase, and the Cumulative Index to Nursing and Allied Health Literature Plus from inception to November 2016 identified 10 randomised trials, enrolling a total of 1466 patients, all in adult cardiac surgery.InterventionsNIRS-based algorithms designed to optimise cerebral oxygenation versus standard care (non-NIRS-based) protocols in cardiac surgery patients during cardiopulmonary bypass.Outcome measuresMortality, organ injury affecting the brain, heart and kidneys, red cell transfusion and resource use.ResultsTwo of the 10 trials identified in the literature search were considered at low risk of bias. Random-effects meta-analysis demonstrated similar mortality (risk ratio (RR) 0.76, 95% CI 0.30 to 1.96), major morbidity including stroke (RR 1. 08, 95% CI 0.40 to 2.91), red cell transfusion and resource use in NIRS-treated patients and controls, with little or no heterogeneity. Grades of Recommendation, Assessment, Development and Evaluation of the quality of the evidence was low or very low for all of the outcomes assessed.ConclusionsThe results of this systematic review did not support the hypotheses that cerebral NIRS-based algorithms have clinical benefits in cardiac surgery.Trial registration numberPROSPERO CRD42015027696.
Red blood cell transfusion can both benefit and harm. To inform decisions about transfusion, we aimed to quantify associations of transfusion with clinical outcomes and cost in patients having ...cardiac surgery.
Clinical, hematology, and blood transfusion databases were linked with the UK population register. Additional hematocrit information was obtained from intensive care unit charts. Composite infection (respiratory or wound infection or septicemia) and ischemic outcomes (myocardial infarction, stroke, renal impairment, or failure) were prespecified as coprimary end points. Secondary outcomes were resource use, cost, and survival. Associations were estimated by regression modeling with adjustment for potential confounding. All adult patients having cardiac surgery between April 1, 1996, and December 31, 2003, with key exposure and outcome data were included (98%). Adjusted odds ratios for composite infection (737 of 8516) and ischemic outcomes (832 of 8518) for transfused versus nontransfused patients were 3.38 (95% confidence interval CI, 2.60 to 4.40) and 3.35 (95% CI, 2.68 to 4.35), respectively. Transfusion was associated with increased relative cost of admission (any transfusion, 1.42 times 95% CI, 1.37 to 1.46, varying from 1.11 for 1 U to 3.35 for >9 U). At any time after their operations, transfused patients were less likely to have been discharged from hospital (hazard ratio HR, 0.63; 95% CI, 0.60 to 0.67) and were more likely to have died (0 to 30 days: HR, 6.69; 95% CI, 3.66 to 15.1; 31 days to 1 year: HR, 2.59; 95% CI, 1.68 to 4.17; >1 year: HR, 1.32; 95% CI, 1.08 to 1.64).
Red blood cell transfusion in patients having cardiac surgery is strongly associated with both infection and ischemic postoperative morbidity, hospital stay, increased early and late mortality, and hospital costs.
BACKGROUND:In an apparent paradox, morbidity and mortality are lower in obese patients undergoing cardiac surgery, although the nature of this association is unclear. We sought to determine whether ...the obesity paradox observed in cardiac surgery is attributable to reverse epidemiology, bias, or confounding.
METHODS:Data from the National Adult Cardiac Surgery registry for all cardiac surgical procedures performed between April 2002 and March 2013 were extracted. A parallel systematic review and meta-analysis (MEDLINE, Embase, SCOPUS, Cochrane Library) through June 2015 were also accomplished. Exposure of interest was body mass index categorized into 6 groups according to the World Health Organization classification.
RESULTS:A total of 401 227 adult patients in the cohort study and 557 720 patients in the systematic review were included. A U-shaped association between mortality and body mass index classes was observed in both studies, with lower mortality in overweight (adjusted odds ratio, 0.79; 95% confidence interval, 0.76–0.83) and obese class I and II (odds ratio, 0.81; 95% confidence interval, 0.76–0.86; and odds ratio, 0.83; 95% confidence interval, 0.74–0.94) patients relative to normal-weight patients and increased mortality in underweight individuals (odds ratio, 1.51; 95% confidence interval, 1.41–1.62). In the cohort study, a U-shaped relationship was observed for stroke and low cardiac output syndrome but not for renal replacement therapy or deep sternal wound infection. Counter to the reverse epidemiology hypotheses, the protective effects of obesity were less in patients with severe chronic renal, lung, or cardiac disease and greater in older patients and in those with complications of obesity, including the metabolic syndrome and atherosclerosis. Adjustments for important confounders did not alter our results.
CONCLUSIONS:Obesity is associated with lower risks after cardiac surgery, with consistent effects noted in multiple analyses attempting to address residual confounding and reverse causation.
Many neuromuscular disorders can have a differential impact on a specific myofibre type, forming the central premise of this review. The many different skeletal muscles in mammals contain a spectrum ...of slow‐ to fast‐twitch myofibres with varying levels of protein isoforms that determine their distinctive contractile, metabolic, and other properties. The variations in functional properties across the range of classic ‘slow’ to ‘fast’ myofibres are outlined, combined with exemplars of the predominantly slow‐twitch soleus and fast‐twitch extensor digitorum longus muscles, species comparisons, and techniques used to study these properties. Other intrinsic and extrinsic differences are discussed in the context of slow and fast myofibres. These include inherent susceptibility to damage, myonecrosis, and regeneration, plus extrinsic nerves, extracellular matrix, and vasculature, examined in the context of growth, ageing, metabolic syndrome, and sexual dimorphism. These many differences emphasise the importance of carefully considering the influence of myofibre‐type composition on manifestation of various neuromuscular disorders across the lifespan for both sexes. Equally, understanding the different responses of slow and fast myofibres due to intrinsic and extrinsic factors can provide deep insight into the precise molecular mechanisms that initiate and exacerbate various neuromuscular disorders. This focus on the influence of different myofibre types is of fundamental importance to enhance translation for clinical management and therapies for many skeletal muscle disorders.
Ischemia-reperfusion (IR) injury to the kidney occurs in a range of clinically important scenarios including hypotension, sepsis and in surgical procedures such as cardiac bypass surgery and kidney ...transplantation, leading to acute kidney injury (AKI). Mitochondrial oxidative damage is a significant contributor to the early phases of IR injury and may initiate a damaging inflammatory response. Here we assessed whether the mitochondria targeted antioxidant MitoQ could decrease oxidative damage during IR injury and thereby protect kidney function. To do this we exposed kidneys in mice to in vivo ischemia by bilaterally occluding the renal vessels followed by reperfusion for up to 24h. This caused renal dysfunction, measured by decreased creatinine clearance, and increased markers of oxidative damage. Administering MitoQ to the mice intravenously 15 min prior to ischemia protected the kidney from damage and dysfunction. These data indicate that mitochondrial oxidative damage contributes to kidney IR injury and that mitochondria targeted antioxidants such as MitoQ are potential therapies for renal dysfunction due to IR injury.
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