Platelet Transfusion in Cardiac Surgery: An Entropy-Balanced, Weighted, Multicenter Analysis.

BACKGROUND: Platelet transfusion is common in cardiac surgery, but some studies have suggested an association with harm. Accordingly, we investigated the association of perioperative platelet transfusion with morbidity and mortality. METHODS: We conducted a retrospective analysis of prospectively collected data from the Australian Society of Cardiac and Thoracic Surgeons National Cardiac Surgery Database. We included consecutive adults from 2005 to 2018 across 40 centers. We used inverse probability of treatment weighting via entropy balancing to investigate the association of perioperative platelet transfusion with our 2 primary outcomes, operative mortality (composite of both 30-day and in-hospital mortality) and 90-day mortality, as well as multiple other clinically relevant secondary outcomes. RESULTS: Among 119,132 eligible patients, 25,373 received perioperative platelets and 93,759 were considered controls. After entropy balancing, platelet transfusion was associated with reduced operative mortality (odds ratio [OR], 0.63; 99% confidence interval [CI], 0.47-0.84; P < .0001) and 90-day mortality (OR, 0.66; 99% CI, 0.51-0.85; P < .0001). Moreover, it was associated with reduced odds of deep sternal wound infection (OR, 0.57; 99% CI, 0.36-0.89; P = .0012), acute kidney injury (OR, 0.84; 99% CI, 0.71-0.99; P = .0055), and postoperative renal replacement therapy (OR, 0.71; 99% CI, 0.54-0.93; P = .0013). These positive associations were observed despite an association with increased odds of return to theatre for bleeding (OR, 1.55; 99% CI, 1.16-2.09; P < .0001), pneumonia (OR, 1.26; 99% CI, 1.11-1.44; P < .0001), intubation for longer than 24 hours postoperatively (OR, 1.13; 99% CI, 1.03-1.24; P = .0012), inotrope use for >4 hours postoperatively (OR, 1.14; 99% CI, 1.11-1.17; P < .0001), readmission to hospital within 30 days of surgery (OR, 1.22; 99% CI, 1.11-1.34; P < .0001), as well as increased drain tube output (adjusted mean difference, 89.2 mL; 99% CI, 77.0 mL-101.4 mL; P < .0001). CONCLUSIONS: In cardiac surgery patients, perioperative platelet transfusion was associated with reduced operative and 90-day mortality. Until randomized controlled trials either confirm or refute these findings, platelet transfusion should not be deliberately avoided when considering odds of death.

Association of perioperative transfusion of fresh frozen plasma and outcomes after cardiac surgery.

BACKGROUND: Fresh frozen plasma (FFP) transfusion is used to manage coagulopathy and bleeding in cardiac surgery patients despite uncertainty about its safety and effectiveness. METHODS: We performed a propensity score matched analysis of the Australian and New Zealand Society of Cardiac and Thoracic Surgeons National Cardiac Surgery Database including patients from 39 centres from 2005 to 2018. We investigated the association of perioperative FFP transfusion with mortality and other clinical outcomes. RESULTS: Of 119,138 eligible patients, we successfully matched 13,131 FFP recipients with 13,131 controls. FFP transfusion was associated with 30-day mortality (odds ratio (OR), 1.41; 99% CI, 1.17-1.71; p < .0001), but not with long-term mortality (hazard ratio (HR), 0.92; 99% CI, 0.85-1.00; p = .007, Holm-Bonferroni α = 0.0004). FFP was also associated with return to theatre for bleeding (OR, 1.97; 99% CI, 1.66-2.34; p < .0001), prolonged intubation (OR, 1.15; 99% CI, 1.05-1.26; p < .0001) and increased chest tube drainage (Mean difference (MD) in mL, 131; 99% CI, 120-141; p < .0001). It was also associated with reduced postoperative creatinine levels (MD in g/L, -6.33; 99% CI, -10.28 to -2.38; p < .0001). CONCLUSION: In a multicentre, propensity score matched analysis, perioperative FFP transfusion was associated with increased 30-day mortality and had variable associations with secondary clinical outcomes.

Sex Differences in Opioid Administration After Cardiac Surgery.

OBJECTIVES: To assess whether there are sex-based differences in the administration of opioid analgesic drugs among inpatients after cardiac surgery. DESIGN: A retrospective cohort study. SETTING: At a tertiary academic referral center. PARTICIPANTS: Adult patients who underwent cardiac surgery from 2014 to 2019. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The primary outcome was the cumulative oral morphine equivalent dose (OMED) for the postoperative admission. Secondary outcomes were the daily difference in OMED and the administration of nonopioid analgesics. The authors developed multivariate regression models controlling for known confounders, including weight and length of stay. A total of 3,822 patients (1,032 women and 2,790 men) were included. The mean cumulative OMED was 139 mg for women and 180 mg for men, and this difference remained significant after adjustment for confounders (adjusted mean difference [aMD], -33.21 mg; 95% CI, -47.05 to -19.36 mg; p < 0.001). The cumulative OMED was significantly lower in female patients on postoperative days 1 to 5, with the greatest disparity observed on day 5 (aMD, -89.83 mg; 95% CI, -155.9 to -23.80 mg; p = 0.009). By contrast, women were more likely to receive a gabapentinoid (odds ratio, 1.91; 95% CI, 1.42-2.58; p < 0.001). The authors found no association between patient sex and the administration of other nonopioid analgesics or specific types of opioid analgesics. The authors found no association between patient sex and pain scores recorded within the first 48 hours after extubation, or the number of opioids administered in close proximity to pain assessments. CONCLUSIONS: Female sex was associated with significantly lower amounts of opioids administered after cardiac surgery.

The prognostic value of elevated neutrophil-lymphocyte ratio for cardiac surgery-associated acute kidney injury: A systematic review and meta-analysis.

BACKGROUND: Patients undergoing cardiac surgery are at significant risk of developing postoperative acute kidney injury (AKI). Neutrophil-lymphocyte ratio (NLR) is a widely available inflammatory biomarker which may be of prognostic value in this setting. METHODS: We conducted a systematic review and meta-analysis of studies reporting associations between perioperative NLR with postoperative AKI. We searched Medline, Embase and the Cochrane Library, without language restriction, from inception to May 2022 for relevant studies. We meta-analysed the reported odds ratios (ORs) with 95% confidence intervals (CIs) for both elevated preoperative and postoperative NLR with risk of postoperative AKI and need for renal replacement therapy (RRT). We conducted a meta-regression to explore inter-study statistical heterogeneity. RESULTS: Twelve studies involving 10,724 participants undergoing cardiac surgery were included, with eight studies being deemed at high risk of bias using PROBAST modelling. We found statistically significant associations between elevated preoperative NLR and postoperative AKI (OR 1.45, 95% CI 1.18-1.77), as well as postoperative need for RRT (OR 2.37, 95% CI 1.50-3.72). Postoperative NLR measurements were not of prognostic significance. CONCLUSIONS: Elevated preoperative NLR is a reliable inflammatory biomarker for predicting AKI following cardiac surgery.

The Prognostic Significance of Red Cell Distribution Width in Cardiac Surgery: A Systematic Review and Meta-Analysis.

RED CELL DISTRIBUTION WIDTH (RDW) is a routinely available biomarker of likely erythropoietic dysfunction, which may be associated with adverse outcomes after cardiac surgery. This systematic review and meta-analysis aimed to clarify the prognostic value of RDW in patients undergoing cardiac surgery. The authors searched MEDLINE, Embase, and the Cochrane Library from inception to May 10, 2022 for studies investigating the association between elevated RDW (as defined by the authors of included studies) and adverse outcomes after cardiac surgery. Herein, the authors extracted maximally adjusted hazard ratios (HRs) and odds ratios (ORs) with associated CIs, and pooled them using random-effects inverse- variance modeling. The authors explored interstudy heterogeneity using metaregression. The authors included 26 studies involving 48,092 patients who had undergone cardiac surgery. Elevated preoperative RDW was associated with long-term mortality (pooled HR 1.63, 95% CI 1.05-2.52), short-term mortality (pooled OR 2.16, 95% CI 1.21-3.87), acute kidney injury (AKI; pooled OR 1.30, 95% CI 1.19-1.41) and postoperative atrial fibrillation (POAF; pooled OR 1.44, 95% CI 1.05-1.96). Some studies suggested a significant association between preoperative RDW elevation and neurologic complications; however, their number was insufficient for meta-analysis. The postoperative RDW levels were less consistently reported and could not be meta-analyzed. In conclusion, the authors found that elevated preoperative RDW was associated with increased short- and long-term mortality, POAF, and AKI after cardiac surgery. Further research is needed to investigate its role in the risk stratification of patients undergoing cardiac surgery.

Platelet Transfusion After Cardiac Surgery.

OBJECTIVES: To investigate the independent association of platelet transfusion with hospital mortality and key relevant clinical outcomes in cardiac surgery. DESIGN: A single-center, propensity score-matched, retrospective, cohort study. SETTING: At an American tertiary teaching hospital data from the Medical Information Mart for Intensive Care III and IV databases from 2001 to 2019. PARTICIPANTS: Consecutive adults undergoing coronary artery bypass graft and/or cardiac valvular surgery. INTERVENTIONS: Platelet transfusion during perioperative intensive care unit (ICU) admission. MEASUREMENTS AND MAIN RESULTS: Overall, 12,043 adults met the study inclusion criteria. Of these, 1,621 (13.5%) received apheresis-leukoreduced platelets, with a median of 1.19 units per recipient (IQR: 0.93-1.19) at a median of 1.78 hours (IQR: 0.75-4.25) after ICU admission. The platelet count was measured in 1,176 patients (72.5%) before transfusion, with a median count of 120 × 109/L (IQR: 89.0-157.0), and only 53 (3.3%) had platelet counts below 50 × 109/L. After propensity matching of 1,046 platelet recipients with 1,046 controls, perioperative platelet transfusion carried no association with in-hospital mortality (odds ratio [OR]: 1.28; 99% CI: 0.49-3.35; p = 0.4980). However, it was associated with a pattern of decreased odds of suspected infection (eg, respiratory infection, urinary tract infection, septicaemia, or other; OR: 0.70; 99% CI: 0.50-0.97; p = 0.0050), days in the hospital (adjusted mean difference [AMD]: 0.86; 99% CI: -0.27 to 1.98; p = 0.048), or days in intensive care (AMD 0.83; 99% CI: -0.15 to 1.82; p = 0.0290). CONCLUSIONS: Platelet transfusion was not associated with hospital mortality, but it was associated with decreased odds of suspected infection and with shorter ICU and hospital stays.

Fresh frozen plasma transfusion after cardiac surgery.

INTRODUCTION: Fresh frozen plasma (FFP) transfusion in the intensive care unit (ICU) is commonly used to treat coagulopathy and bleeding in cardiac surgery, despite suggestion that it may increase the risk of morbidity and mortality through mechanisms such as fluid overload and infection. METHODS: We retrospectively studied consecutive adults undergoing cardiac surgery from the Medical Information Mart for Intensive Care III and IV databases. We applied propensity score matching to investigate the independent association of within-ICU FFP transfusion with mortality and other key clinical outcomes. RESULTS: Of our 12,043 adults who met inclusion criteria, 1585 (13.2%) received perioperative FFP with a median of 2.48 units per recipient (interquartile range [IQR]: 2.04, 4.33) at a median time of 1.83 h (IQR: 0.75, 3.75) after ICU admission. After propensity matching of 952 FFP recipients to 952 controls, we found no significant association between FFP use and hospital mortality (odds ratio (OR): 1.58; 99% confidence interval (CI): 0.57, 3.71), suspected infection (OR: 0.72; 99% CI: 0.49, 1.08), or acute kidney injury (OR: 1.23; 99% CI: 0.91, 1.67). However, FFP was associated with increased days in hospital (adjusted mean difference (AMD): 1.28; 99% CI: 0.27, 2.41; p = .0050), days in intensive care (AMD: 1.28; 99% CI: 0.27, 2.28; p = .0011), and chest tube output in millilitres up to 8 h after transfusion (AMD: 92.98; 99% CI: 52.22, 133.74; p < .0001). CONCLUSIONS: After propensity matching, FFP transfusion was not associated with increased hospital mortality, but was associated with increased length of stay and no decrease in bleeding in the early post-transfusion period.

Cryoprecipitate Transfusion After Cardiac Surgery.

OBJECTIVES: The association of cryoprecipitate transfusion with patient outcomes after cardiac surgery is unclear. We aimed to investigate the predictors of, and outcomes associated with, postoperative cryoprecipitate transfusion in cardiac surgery patients. METHODS: We used the Medical Information Mart for Intensive Care III and IV databases. We included adults undergoing cardiac surgery, and propensity score matched cryoprecipitate-treated patients to controls. Using the matched cohort, we investigated the association of cryoprecipitate use with clinical outcomes. The primary outcome was in-hospital mortality. Secondary outcomes were infection, acute kidney injury, intensive care unit length of stay, hospital length of stay, and chest tube output at 2-hour intervals. RESULTS: Of 12,043 eligible patients, 283 (2.35%) patients received cryoprecipitate. The median dose was 5.83 units (IQR 4.17-7.24) given at a median first transfusion time of 1.75 hours (IQR 0.73-4.46) after intensive care unit admission. After propensity scoring, we matched 195 cryoprecipitate recipients to 743 controls. Postoperative cryoprecipitate transfusion was not significantly associated with in-hospital mortality (odds ratio [OR] 1.10; 99% confidence interval [CI] 0.43-2.84; p=0.791), infection (OR 0.77; 99% CI 0.45-1.34; p=0.220), acute kidney injury (OR 1.03; 99% CI 0.65-1.62; p=0.876) or cumulative chest tube output (adjusted mean difference 8 hrs post transfusion, 11 mL; 99% CI -104 to 125; p=0.804). CONCLUSIONS: Although cryoprecipitate was typically given to sicker patients with more bleeding, its administration was not associated with worse outcomes. Large, multicentred studies are warranted to further elucidate cryoprecipitate's safety profile and patterns of use in cardiac surgery.

Elevated Cardiac Troponin to Detect Acute Cellular Rejection After Cardiac Transplantation: A Systematic Review and Meta-Analysis.

Cardiac troponin is well known as a highly specific marker of cardiomyocyte damage, and has significant diagnostic accuracy in many cardiac conditions. However, the value of elevated recipient troponin in diagnosing adverse outcomes in heart transplant recipients is uncertain. We searched MEDLINE (Ovid), Embase (Ovid), and the Cochrane Library from inception until December 2020. We generated summary sensitivity, specificity, and Bayesian areas under the curve (BAUC) using bivariate Bayesian modelling, and standardised mean differences (SMDs) to quantify the diagnostic relationship of recipient troponin and adverse outcomes following cardiac transplant. We included 27 studies with 1,684 cardiac transplant recipients. Patients with acute rejection had a statistically significant late elevation in standardised troponin measurements taken at least 1 month postoperatively (SMD 0.98, 95% CI 0.33-1.64). However, pooled diagnostic accuracy was poor (sensitivity 0.414, 95% CrI 0.174-0.696; specificity 0.785, 95% CrI 0.567-0.912; BAUC 0.607, 95% CrI 0.469-0.723). In summary, late troponin elevation in heart transplant recipients is associated with acute cellular rejection in adults, but its stand-alone diagnostic accuracy is poor. Further research is needed to assess its performance in predictive modelling of adverse outcomes following cardiac transplant. Systematic Review Registration: identifier CRD42021227861.

Perioperative Neutrophil-Lymphocyte Ratio Predicts Mortality After Cardiac Surgery: Systematic Review and Meta-Analysis.

OBJECTIVES: Neutrophil-lymphocyte ratio (NLR) is an inflammatory biomarker that has been evaluated across a variety of surgical disciplines and is widely predictive of poor postoperative outcome, but its value in cardiac surgery is unclear. The authors did this systematic review and meta-analysis to determine the impact of elevated perioperative NLR on survival after cardiac surgery. DESIGN: Systematic review and meta-analysis of study-level data. SETTING: Multiple hospitals involved in an international pool of studies. PARTICIPANTS: Adults undergoing cardiac surgery. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The authors searched multiple databases from inception until November 2020. They generated summary hazard ratios (HR) and odds ratios (OR) for the association of elevated preoperative NLR with long-term and short-term mortality following cardiac surgery. They separately reported on elevated postoperative NLR. Between-study heterogeneity was explored using metaregression. The authors included 12 studies involving 13,262 patients undergoing cardiac surgery. Elevated preoperative NLR was associated with worse long-term (>30 days) (hazard ratio [HR] 1.56; 95% CI [confidence interval], 1.18-2.06; 8 studies) and short-term (<30 days) mortality (OR 3.18; 95% CI, 1.90-5.30; 7 studies). One study reported the association of elevated postoperative NLR with long-term mortality (HR 8.58; 95% CI, 2.55-28.85). There was considerable between-study heterogeneity for the analysis of long-term mortality (I2 statistic 94.39%), which mostly was explained by study-level variables, such as the number of variables adjusted for by included studies and how many of these significantly increased the risk of long-term mortality, high risk of bias, and number of study centers, as well as participant level factors, such as average participant age and hypertension prevalence. CONCLUSIONS: Perioperative NLR is an independent predictor of short-term and long-term postoperative mortality following cardiac surgery. Further research is required to determine which patient-level factors modify the prognostic value of NLR and to evaluate its role in routine clinical practice.

Machine learning to predict adverse outcomes after cardiac surgery: A systematic review and meta-analysis.

BACKGROUND: Machine learning (ML) models are promising tools for predicting adverse postoperative outcomes in cardiac surgery, yet have not translated to routine clinical use. We conducted a systematic review and meta-analysis to assess the predictive performance of ML approaches. METHODS: We conducted an electronic search to find studies assessing ML and traditional statistical models to predict postoperative outcomes. Our primary outcome was the concordance (C-) index of discriminative performance. Using a Bayesian meta-analytic approach we pooled the C-indices with the 95% credible interval (CrI) across multiple outcomes comparing ML methods to logistic regression (LR) and clinical scoring tools. Additionally, we performed critical difference and sensitivity analysis. RESULTS: We identified 2792 references from the search of which 51 met inclusion criteria. Two postoperative outcomes were amenable for meta-analysis: 30-day mortality and in-hospital mortality. For 30-day mortality, the pooled C-index and 95% CrI were 0.82 (0.79-0.85), 0.80 (0.77-0.84), 0.78 (0.74-0.82) for ML models, LR, and scoring tools respectively. For in-hospital mortality, the pooled C-index was 0.81 (0.78-0.84) and 0.79 (0.73-0.84) for ML models and LR, respectively. There were no statistically significant results indicating ML superiority over LR. CONCLUSION: In cardiac surgery patients, for the prediction of mortality, current ML methods do not have greater discriminative power over LR as measured by the C-index.

The influence of patient resilience and health status on satisfaction after total hip and knee arthroplasty.

BACKGROUND AND PURPOSE: Our research aimed to identify and characterise relationships between patient resilience, health status, and satisfaction following total hip and knee arthroplasty (THA/TKA). A secondary aim was to compare two frequently used instruments for measuring patient satisfaction: The Satisfaction Visual Analogue Scale (Satis VAS) and the Net Promoter Score (NPS). METHODS: 140 patients (mean age 69, 60% female) underwent primary THA or TKA at a centre in regional Australia and were recruited to complete questionnaires about their resilience, health status, and satisfaction following arthroplasty. We selected validated instruments to measure patient-reported outcomes: Satis VAS, NPS, EuroQol Group 5D-5L, EuroQol Group Visual Analogue Scale, and the Connor-Davidson 10-item Resilience Scale. RESULTS: Our research demonstrates a strong positive correlation between patient resilience and patient-reported health status. A moderate positive correlation exists between resilience and satisfaction (both Satis VAS and NPS). Resilient patients demonstrated higher health scores and higher satisfaction (by both measures) than lower-resilience patients. CONCLUSIONS: Patient satisfaction following arthroplasty, captured by Satis VAS and NPS, may be partly predicted by patient resilience post operatively, with higher-resilience patients demonstrating less dissatisfaction than lower-resilience patients.

Machine Learning Outperforms Existing Clinical Scoring Tools in the Prediction of Postoperative Atrial Fibrillation During Intensive Care Unit Admission After Cardiac Surgery.

OBJECTIVE(S): Using the Medical Information Mart for Intensive Care III (MIMIC-III) database, we compared the performance of machine learning (ML) to the to the established gold standard scoring tool (POAF Score) in predicting postoperative atrial fibrillation (POAF) during intensive care unit (ICU) admission after cardiac surgery. METHODS: Random forest classifier (RF), decision tree classifier (DT), logistic regression (LR), K neighbours classifier (KNN), support vector machine (SVM), and gradient boosted machine (GBM) were compared to the POAF Score. Cross-validation was used to assess the area under the receiver operating characteristic curve (AUC), sensitivity, and specificity of ML models. POAF Score performance confidence intervals were generated using 1,000 bootstraps. Risk profiles for GBM were generated using Shapley additive values. RESULTS: A total of 6,349 ICU admissions encompassing 6,040 patients were included. POAF occurred in 1,364 of the 6,349 admissions (21.5%). For predicting POAF during ICU admission after cardiac surgery, GBM, LR, RF, KNN, SVM and DT achieved an AUC of 0.74 (0.71-0.77), 0.73 (0.71-0.75), 0.72 (0.69-0.75), 0.68 (0.67-0.69), 0.67 (0.66-0.68) and 0.59 (0.55-0.63) respectively. The POAF Score AUC was 0.63 (0.62-0.64). Shapley additive values analysis of GBM generated patient level explanations for each prediction. CONCLUSION: Machine learning models based on readily available preoperative data can outperform clinical scoring tools for predicting POAF during ICU admission after cardiac surgery. Explanatory models are shown to have potential in personalising POAF risk profiles for patients by illustrating probabilistic input variable contributions. Future research is required to evaluate the clinical utility and safety of implementing ML-driven tools for POAF prediction.

Systematic review and meta-analysis of postoperative troponin as a predictor of mortality and major adverse cardiac events after vascular surgery.

BACKGROUND: The prognostic value of asymptomatic perioperative troponin rise in vascular surgery is unclear. We conducted this systematic review and meta-analysis to determine the significance of clinical and subclinical troponin elevation after vascular surgery. METHODS: We searched MEDLINE (Ovid), Embase (Ovid), and the Cochrane Library, without language restriction, from inception to May 2019 and included studies that reported associations between elevated postoperative troponin and short-term mortality, major adverse cardiac events (MACEs), or long-term mortality in a vascular surgery cohort. We synthesized study-level data on the maximally adjusted estimates using mixed effects modeling to generate summary odds ratios (ORs) for fixed-interval outcomes and summary hazard ratios for long-term mortality. Between-study heterogeneity was assessed with meta-regression. Methodologic quality and publication bias were formally assessed. RESULTS: We included 24 studies involving 11,657 participants. Postoperative troponin was found to have a strong, positive association with short-term mortality (OR, 4.95; 95% confidence interval [CI], 2.87-8.52; 7 studies; 2661 people) and MACEs (OR, 5.33; 95% CI, 1.59-17.82; 12 studies; 5047 people) independent of meeting the criteria for myocardial infarction. Subclinical postoperative troponin elevation was further demonstrated to be associated with greater long-term mortality (hazard ratio, 1.94; 95% CI, 1.56-2.42; 13 studies; 7630 people; median follow-up, 24 months). Time to troponin sampling, hypertension, and type of surgery partially accounted for between-study heterogeneity. The methodologic quality of included studies was variable, and publication bias was not detected. CONCLUSIONS: Elevated postoperative troponin is strongly prognostic of worse survival and greater likelihood of MACEs after vascular surgery, regardless of whether symptoms of myocardial ischemia are present. These data support the benefit of postoperative troponin monitoring in identifying patients at increased risk of worse outcomes and who may be candidates for personalized preventive interventions.

The Prognostic Value of Elevated Perioperative Neutrophil-Lymphocyte Ratio in Predicting Postoperative Atrial Fibrillation After Cardiac Surgery: A Systematic Review and Meta-Analysis.

BACKGROUND: The neutrophil-lymphocyte ratio (NLR) is an emerging inflammatory perioperative biomarker which has been studied to predict the incidence of postoperative atrial fibrillation (POAF) after cardiac surgery. This systematic review and meta-analysis aimed to evaluate the prognostic accuracy of elevated perioperative NLR in predicting POAF after cardiac surgery. METHODS: Multiple databases were searched from inception to May 2019 for prognostic studies on perioperative NLR and POAF following cardiac surgery. Maximally adjusted odds ratios (OR) with associated confidence intervals were obtained from each included study and pooled using random effects inverse variance modelling for preoperative NLR measurements, while standardised mean differences were pooled for postoperative NLR values. The significance of inter- and intra-study heterogeneity was explored using meta-regression. RESULTS: 1,799 unique studies satisfied selection criteria, from which 12 studies incorporating 9,262 participants were included. Elevated preoperative NLR significantly predicted POAF, with a pooled OR of 1.42 (95% CI 1.16-1.72). Multiple predefined covariates contributed to inter-study heterogeneity; however, only prevalence of hypertension (p=0.0055), history of congestive cardiac failure (p=0.0282) and average ejection fraction (p=0.0359) were significant effect modifiers. Elevated postoperative NLR was not a significant predictor of POAF (standardised mean difference 1.60 [95% CI -0.56-3.77] between POAF+ and POAF- groups). CONCLUSIONS: Elevated preoperative NLR is a promising prognostic biomarker for POAF, but residual sources of heterogeneity remain. Larger scale validation studies are required to justify the integration of preoperative NLR testing into routine clinical practice.

Topical cystic fibrosis transmembrane conductance regulator gene replacement for cystic fibrosis-related lung disease.

BACKGROUND: Cystic fibrosis is caused by a defective gene encoding a protein called the cystic fibrosis transmembrane conductance regulator (CFTR), and is characterised by chronic lung infection resulting in inflammation and progressive lung damage that results in a reduced life expectancy. OBJECTIVES: To determine whether topical CFTR gene replacement therapy to the lungs in people with cystic fibrosis is associated with improvements in clinical outcomes, and to assess any adverse effects. SEARCH METHODS: We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group Trials Register comprising references identified from comprehensive electronic database searches, handsearching relevant journals and abstract books of conference proceedings.Date of most recent search: 05 May 2016.An additional search of the National Institutes for Health (NIH) Genetic Modification Clinical Research Information System (GeMCRIS) was also performed for the years 1992 to 2015.Date of most recent search: 20 April 2016. SELECTION CRITERIA: Randomised controlled studies comparing topical CFTR gene delivery to the lung, using either viral or non-viral delivery systems, with placebo or an alternative delivery system in people with confirmed cystic fibrosis. DATA COLLECTION AND ANALYSIS: The authors independently extracted data and assessed study quality. Authors of included studies were contacted and asked for any available additional data. Meta-analysis was limited due to differing study designs. MAIN RESULTS: Four randomised controlled studies met the inclusion criteria for this review, involving a total of 302 participants lasting from 29 days to 13 months; 14 studies were excluded. The included studies differed in terms of CFTR gene replacement agent and study design, which limited the meta-analysis. One study only enrolled adult males, the remaining studies included both males and females aged 12 years and over.Risk of bias in the studies was moderate. Random sequence generation and allocation concealment was only described in the more recent study; the remaining three studies were judged to have an unclear risk of bias. All four studies documented double-blinding to the intervention, but there is some uncertainty with regards to participant blinding in one study. Some outcome data were missing from all four studies.There were no differences in either the number of respiratory exacerbations or the number of participants with an exacerbation between replacement therapy or placebo groups at any time point. Meta-analysis of most respiratory function tests showed no difference between treatment and placebo groups, but the smallest study (n = 16) reported forced vital capacity (litres) increased more in the placebo group at up to 24 hours. A further study reported a significant improvement in forced expiratory volume at one second (litres) at 30 days after participants had received their first dose of favouring the gene therapy agent, but this finding was not confirmed when combined with at second study in the meta-analysis. The more recent study (n = 140) demonstrated a small improvement in forced vital capacity (per cent predicted) at two and three months and again at 11 and 12 months for participants receiving CFTR gene replacement therapy compared to those receiving placebo. The same study reported a significant difference in the relative change in forced expiratory volume at one second (per cent predicted) at two months, three months and 12 months.One small study reported significant concerns with "influenza-like" symptoms in participants treated with CFTR gene replacement therapy; this was not reported on repeated use of the same agent in a larger recent study.There was no other evidence of positive impact on outcomes, in particular improved quality of life or reduced treatment burden.Two studies measured ion transport in the lower airways; one (n = 16) demonstrated significant changes toward normal values in the participants who received gene transfer agents (P < 0.0001), mean difference 6.86 (95% confidence interval 3.77 to 9.95). The second study (n = 140) also reported significant changes toward normal values (P = 0.032); however, aggregate data were not available for analysis. In the most recent study, there was also evidence of increased salt transport in cells obtained by brushing the lower airway. These outcomes, whilst important, are not of direct clinical relevance. AUTHORS' CONCLUSIONS: One study of liposome-based CFTR gene transfer therapy demonstrated some improvements in respiratory function in people with CF, but this limited evidence of efficacy does not support this treatment as a routine therapy at present. There was no evidence of efficacy for viral-mediated gene delivery.Future studies need to investigate clinically important outcome measures.

Paying attention to cardiac surgical risk: An interpretable machine learning approach using an uncertainty-aware attentive neural network.

Machine learning (ML) is increasingly applied to predict adverse postoperative outcomes in cardiac surgery. Commonly used ML models fail to translate to clinical practice due to absent model explainability, limited uncertainty quantification, and no flexibility to missing data. We aimed to develop and benchmark a novel ML approach, the uncertainty-aware attention network (UAN), to overcome these common limitations. Two Bayesian uncertainty quantification methods were tested, generalized variational inference (GVI) or a posterior network (PN). The UAN models were compared with an ensemble of XGBoost models and a Bayesian logistic regression model (LR) with imputation. The derivation datasets consisted of 153,932 surgery events from the Australian and New Zealand Society of Cardiac and Thoracic Surgeons (ANZSCTS) Cardiac Surgery Database. An external validation consisted of 7343 surgery events which were extracted from the Medical Information Mart for Intensive Care (MIMIC) III critical care dataset. The highest performing model on the external validation dataset was a UAN-GVI with an area under the receiver operating characteristic curve (AUC) of 0.78 (0.01). Model performance improved on high confidence samples with an AUC of 0.81 (0.01). Confidence calibration for aleatoric uncertainty was excellent for all models. Calibration for epistemic uncertainty was more variable, with an ensemble of XGBoost models performing the best with an AUC of 0.84 (0.08). Epistemic uncertainty was improved using the PN approach, compared to GVI. UAN is able to use an interpretable and flexible deep learning approach to provide estimates of model uncertainty alongside state-of-the-art predictions. The model has been made freely available as an easy-to-use web application demonstrating that by designing uncertainty-aware models with innately explainable predictions deep learning may become more suitable for routine clinical use.

Tree-based survival analysis improves mortality prediction in cardiac surgery.

Objectives: Machine learning (ML) classification tools are known to accurately predict many cardiac surgical outcomes. A novel approach, ML-based survival analysis, remains unstudied for predicting mortality after cardiac surgery. We aimed to benchmark performance, as measured by the concordance index (C-index), of tree-based survival models against Cox proportional hazards (CPH) modeling and explore risk factors using the best-performing model. Methods: 144,536 patients with 147,301 surgery events from the Australian and New Zealand Society of Cardiac and Thoracic Surgeons (ANZSCTS) national database were used to train and validate models. Univariate analysis was performed using Student's T-test for continuous variables, Chi-squared test for categorical variables, and stratified Kaplan-Meier estimation of the survival function. Three ML models were tested, a decision tree (DT), random forest (RF), and gradient boosting machine (GBM). Hyperparameter tuning was performed using a Bayesian search strategy. Performance was assessed using 2-fold cross-validation repeated 5 times. Results: The highest performing model was the GBM with a C-index of 0.803 (0.002), followed by RF with 0.791 (0.003), DT with 0.729 (0.014), and finally CPH with 0.596 (0.042). The 5 most predictive features were age, type of procedure, length of hospital stay, drain output in the first 4 h (ml), and inotrope use greater than 4 h postoperatively. Conclusion: Tree-based learning for survival analysis is a non-parametric and performant alternative to CPH modeling. GBMs offer interpretable modeling of non-linear relationships, promising to expose the most relevant risk factors and uncover new questions to guide future research.

Troponin as a predictor of outcomes in transcatheter aortic valve implantation: systematic review and meta-analysis.

BACKGROUND: Transcatheter aortic valve implantation (TAVI) is emerging as a therapeutic gold standard in the management of aortic stenosis. However, post-procedural complications of this procedure are being increasingly recognised. We therefore performed this systematic review and meta-analysis on the prognostic value of elevated troponin prior to TAVI to predict risk of post-procedural complications. METHODS: We searched Medline (Ovid), Embase (Ovid), and the Cochrane Library from inception until May 2022, and included studies on the association between elevated pre-procedural troponin with 30-day mortality, long-term mortality, and post-procedural myocardial injury (PPMI). We generated summary odds ratios (OR) and hazards ratios (HR) using random-effects meta-analysis and performed subgroup analyses to evaluate differences in troponin threshold selection. Inter-study heterogeneity was tested using the I2 test. RESULTS: We included 10 studies involving 4200 patients. Serum troponin elevation prior to TAVI was significantly associated with long-term mortality [HR = 2.09 (95% CI 1.30-3.36)], but not with 30-day mortality [OR 1.76 (95% CI 0.96-3.22)]. Subgroup analysis showed a trend towards increased effect size and statistical significance for 30-day mortality as troponin elevation was more narrowly defined. Two studies reported on PPMI and found no statistically significant mean difference between groups. CONCLUSIONS: Raised serum troponin is associated with increased long-term mortality following TAVI. Further clarification on the optimal troponin threshold for risk identification is required. High-quality studies that utilise ROC analysis for threshold selection are warranted.

Association of Perioperative Cryoprecipitate Transfusion and Mortality After Cardiac Surgery.

BACKGROUND: Cryoprecipitate is often transfused in patients undergoing cardiac surgery. However, its safety and effectiveness remain uncertain. METHODS: This study was a propensity score-matched analysis of data from the Australian and New Zealand Society of Cardiac and Thoracic Surgeons National Cardiac Surgery Database. The study included adults undergoing cardiac surgery between 2005 and 2018 across 38 sites. The association between perioperative cryoprecipitate transfusion and clinical outcomes was estimated, with a primary outcome of operative mortality. RESULTS: Of 119,132 eligible patients, 11,239 (9.43%) patients received cryoprecipitate. The median cumulative dose was 8 U (interquartile range, 5-10 U). After propensity score matching, we matched 9055 cryoprecipitate recipients to 9055 control subjects. Postoperative cryoprecipitate transfusion was associated with reduced operative mortality (odds ratio [OR], 0.82; 99% CI, 0.69-0.97; P = .002) and long-term mortality (hazard ratio, 0.92; 99% CI, 0.87-0.97; P = .0042). It was also associated with a reduction in acute kidney injury (OR, 0.85; 99% CI, 0.73-0.98; P = .0037) and all-cause infection (OR, 0.77; 99% CI, 0.67-0.88; P < .0001). These findings were observed despite increased rates of return to the operating room (OR, 1.36; 99% CI, 1.22-1.51; P < .0001) and cumulative 4-hour postoperative chest tube output (adjusted mean difference in mL, 97.69; 99% CI, 81.65;113.74; P < .0001). CONCLUSIONS: In a large, multicenter cohort study and after propensity score matching, perioperative transfusion of cryoprecipitate was associated with reduced operative and long-term mortality.