Prophylactic corticosteroids for cardiopulmonary bypass in adult cardiac surgery.

BACKGROUND: Cardiac surgery triggers a strong inflammatory reaction, which carries significant clinical consequences. Corticosteroids have been suggested as a potential perioperative strategy to reduce inflammation and help prevent postoperative complications. However, the safety and effectiveness of perioperative corticosteroid use in adult cardiac surgery is uncertain. This is an update of the 2011 review with 18 studies added. OBJECTIVES: Primary objective: to estimate the effects of prophylactic corticosteroid use in adults undergoing cardiac surgery with cardiopulmonary bypass on the: - co-primary endpoints of mortality, myocardial complications, and pulmonary complications; and - secondary outcomes including atrial fibrillation, infection, organ injury, known complications of steroid therapy, prolonged mechanical ventilation, prolonged postoperative stay, and cost-effectiveness. SECONDARY OBJECTIVE: to explore the role of characteristics of the study cohort and specific features of the intervention in determining the treatment effects via a series of prespecified subgroup analyses. SEARCH METHODS: We used standard, extensive Cochrane search methods to identify randomised studies assessing the effect of corticosteroids in adult cardiac surgery. The latest searches were performed on 14 October 2022. SELECTION CRITERIA: We included randomised controlled trials in adults (over 18 years, either with a diagnosis of coronary artery disease or cardiac valve disease, or who were candidates for cardiac surgery with the use of cardiopulmonary bypass), comparing corticosteroids with no treatments. There were no restrictions with respect to length of the follow-up period. All selected studies qualified for pooling of results for one or more endpoints. DATA COLLECTION AND ANALYSIS: We used standard Cochrane methods. Our primary outcomes were all-cause mortality, and cardiac and pulmonary complications. Secondary outcomes were infectious complications, gastrointestinal bleeding, occurrence of new post-surgery atrial fibrillation, re-thoracotomy for bleeding, neurological complications, renal failure, inotropic support, postoperative bleeding, mechanical ventilation time, length of stays in the intensive care unit (ICU) and hospital, patient quality of life, and cost-effectiveness. We used GRADE to assess the certainty of evidence for each outcome. MAIN RESULTS: This updated review includes 72 randomised trials with 17,282 participants (all 72 trials with 16,962 participants were included in data synthesis). Four trials (6%) were considered at low risk of bias in all the domains. The median age of participants included in the studies was 62.9 years. Study populations consisted mainly (89%) of low-risk, first-time coronary artery bypass grafting (CABG) or valve surgery. The use of perioperative corticosteroids may result in little to no difference in all-cause mortality (risk with corticosteroids: 25 to 36 per 1000 versus 33 per 1000 with placebo or no treatment; risk ratio (RR) 0.90, 95% confidence interval (CI) 0.75 to 1.07; 25 studies, 14,940 participants; low-certainty evidence). Corticosteroids may increase the risk of myocardial complications (68 to 86 per 1000) compared with placebo or no treatment (66 per 1000; RR 1.16, 95% CI 1.04 to 1.31; 25 studies, 14,766 participants; low-certainty evidence), and may reduce the risk of pulmonary complications (risk with corticosteroids: 61 to 77 per 1000 versus 78 per 1000 with placebo/no treatment; RR 0.88, 0.78 to 0.99; 18 studies, 13,549 participants; low-certainty evidence). Analyses of secondary endpoints showed that corticosteroids may reduce the incidence of infectious complications (risk with corticosteroids: 94 to 113 per 1000 versus 123 per 1000 with placebo/no treatment; RR 0.84, 95% CI 0.76 to 0.92; 28 studies, 14,771 participants; low-certainty evidence). Corticosteroids may result in little to no difference in incidence of gastrointestinal bleeding (risk with corticosteroids: 9 to 17 per 1000 versus 10 per 1000 with placebo/no treatment; RR 1.21, 95% CI 0.87 to 1.67; 6 studies, 12,533 participants; low-certainty evidence) and renal failure (risk with corticosteroids: 23 to 35 per 1000 versus 34 per 1000 with placebo/no treatment; RR 0.84, 95% CI 0.69 to 1.02; 13 studies, 12,799; low-certainty evidence). Corticosteroids may reduce the length of hospital stay, but the evidence is very uncertain (-0.5 days, 0.97 to 0.04 fewer days of length of hospital stay compared with placebo/no treatment; 25 studies, 1841 participants; very low-certainty evidence). The results from the two largest trials included in the review possibly skew the overall findings from the meta-analysis. AUTHORS' CONCLUSIONS: A systematic review of trials evaluating the organ protective effects of corticosteroids in cardiac surgery demonstrated little or no treatment effect on mortality, gastrointestinal bleeding, and renal failure. There were opposing treatment effects on cardiac and pulmonary complications, with evidence that corticosteroids may increase cardiac complications but reduce pulmonary complications; however, the level of certainty for these estimates was low. There were minor benefits from corticosteroid therapy for infectious complications, but the evidence on hospital length of stay was very uncertain. The inconsistent treatment effects across different outcomes and the limited data on high-risk groups reduced the applicability of the findings. Further research should explore the role of these drugs in specific, vulnerable cohorts.

Effect of on-pump vs. off-pump coronary artery bypass grafting in patients with non-dialysis-dependent severe renal impairment: propensity-matched analysis from the UK registry dataset.

Introduction: On-pump coronary artery bypass (ONCABG) grafting in patients with a pre-existing poor renal reserve is known to carry significant morbidity and mortality. There is limited controversial evidence on the benefit of off-pump coronary artery bypass (OPCABG) grafting in these high-risk groups of patients. We compared early clinical outcomes in propensity-matched cohorts of patients with non-dialysis-dependent pre-operative severe renal impairment undergoing OPCABG vs. ONCABG, captured in a large national registry dataset. Methods: All data for patients with a pre-operative creatinine clearance of less than 50 mL/min who underwent elective or urgent isolated OPCABG or ONCABG from 1996 to 2019 were extracted from the UK National Adult Cardiac Surgery Audit (NACSA) database. Propensity score matching was performed using 1:1 nearest neighbor matching without replacement using several baseline characteristics. We investigated the effect of ONCABG vs. OPCABG in the matched cohort using cluster-robust standard error regression. Results: We identified 8,628 patients with severe renal impairment undergoing isolated CABG, of whom 1,142 (13.23%) underwent OPCABG during the study period. We compared 1,141 propensity-matched pairs of patients undergoing OPCABG vs. ONCABG. The median age of the matched population was 78 years in both groups, with no significant imbalance post-matching in the rest of the variables. There was no difference between OPCABG and ONCABG in in-hospital mortality rates, post-operative dialysis, and stroke rates. However, the return to theatre for bleeding or tamponade was higher in ONCABG vs. OPCABG (P > 0.02); however, OPCABG reduced the total length of stay in the hospital by 1 day (P = 0.008). After double adjustment in the matched population using cluster-robust standard regression, ONCABG did not increase mortality compared to OPCABG (OR, 1.05, P = 0.78), postoperative stroke (OR, 1.7, P = 0.12), and dialysis (OR, 0.7, P = 0.09); however, ONCABG was associated with an increased risk of bleeding (OR, 1.53, P = 0.03). Discussion: In this propensity analysis of a large national registry dataset, we found no difference in early mortality and stroke in patients with pre-operative severe renal impairment undergoing OPCABG or ONCABG surgery; however, ONCABG was associated with an increased risk of return to theatre for bleeding and an increased length of hospital stay.

Impact of explanted valve type on aortic valve reoperations: nationwide UK experience.

OBJECTIVES: This nationwide retrospective cohort study assessed the impact of the explanted valve type on reoperative outcomes in aortic valve surgery within the UK over a 23-year period. METHODS: Data were sourced from the National Institute for Cardiovascular Outcomes Research (NICOR) database. All patients undergoing first-time isolated reoperative aortic valve replacement between 1996 and 2019 in the UK were included. Concomitant procedures, homograft implantation or aortic root enlargement were excluded. Propensity score matching was utilized to compare outcomes and risk factors for in-hospital mortality was evaluated through multivariable logistic regression. Final model selection was conducted using Akaike Information Criterion through bootstrapping. The primary end point was in-hospital mortality, and secondary end points included postoperative morbidities. RESULTS: Out of 2371 patients, 24.9% had mechanical and 75% had bioprosthetic valves implanted during the primary procedure. Propensity matched groups of 324 patients each, were compared. In-hospital mortality for mechanical and bioprosthetic valve explants was 7.1% and 5.9%, respectively (P = 0.632). On multivariable logistic regression analysis, valve type was not a risk factor for mortality [odds ratio (OR) 0.62, 95% confidence interval (CI) 0.37-1.05; P = 0.1]. Age (OR 1.03, 95% CI 1.01-1.05; P < 0.05), left ventricular ejection fraction (OR 1.62, 95% CI 1.08-2.42; P < 0.05), creatinine ≥ 200 mg/dl (OR 2.21, 95% CI 1.17-4.04; P < 0.05) and endocarditis (OR 2.66, 95% CI 1.71-4.14; P < 0.05) emerged as risk factors for mortality. CONCLUSIONS: The type of valve initially implanted (mechanical or bioprosthetic) did not determine mortality. Instead, age, left ventricular ejection fraction, renal impairment and endocarditis were significant risk factors for in-hospital mortality.

Corrigendum: Patterns of cytokine release and association with new onset of post-cardiac surgery atrial fibrillation.

[This corrects the article DOI: 10.3389/fsurg.2023.1205396.].

Trend in mitral valve prostheses of choice and early outcomes in the United Kingdom.

OBJECTIVE: Despite the superiority of mitral valve repair, surgical mitral valve replacement (SMVR) remains an important intervention for patients with valve stenosis, infective endocarditis and complex mitral valve degeneration. There has been an increasing popularity in the worldwide use of biological valves due to the avoidance of long-term anti-coagulation and recent advancements in transcatheter techniques. We aim to evaluate the trend, early clinical outcomes and the choice of prostheses use in isolated SMVR over a 23 years period in the United Kingdom. METHODS: All patients (n = 13,147) who underwent elective or urgent isolated SMVR from March 1996 to April 2019 were identified from the National Adult Cardiac Surgery Audit database. Trends in clinical outcomes, predicted/observed mortality of patients and the utilization of biological prostheses across 5 different age groups: <50, 50-59, 60-69, 70-79 and ≥80 years old were investigated. Early clinical outcomes associated with the use of mechanical and biological mitral valve prostheses in patients between the age of 60-70 years old were analysed. RESULTS: The number of isolated SMVR performed has remained stable with approximately 600 cases annually since 2010. The in-hospital/30-day mortality rate has decreased from 7.41% (1996) to 3.92% (2018), despite the EuroScore II increasing from 1.42% in 1996 to 2.43% in 2018. Biological prostheses usage increased across all age group, and particularly in the 60-69 and 70-79 group, from 17.86% and 53.85% in 1996 to 48.85% and 82.38% in 2018, respectively. The use of mechanical prostheses was reduced in patients between the age of 50-59 from 100% in 1996 to 80.65% in 2018. There were no differences in short term outcomes among patients aged 60-70 years who received either a biological or mechanical prostheses. CONCLUSION: There has been a significant reduction in surgical mitral valve replacement early in-hospital mortality, despite an observed increase in the risk profile of patients over 23 years. A shifting trend in valve replacement choices was observed with a rise in the use of biological prostheses, particularly within the 60-69 and 70-79 age group. Early in hospital outcomes for patients aged 60-70 were not determined by the implanted valve type.

Development and Evaluation of a Natural Language Processing System for Curating a Trans-Thoracic Echocardiogram (TTE) Database.

BACKGROUND: Although electronic health records (EHR) provide useful insights into disease patterns and patient treatment optimisation, their reliance on unstructured data presents a difficulty. Echocardiography reports, which provide extensive pathology information for cardiovascular patients, are particularly challenging to extract and analyse, because of their narrative structure. Although natural language processing (NLP) has been utilised successfully in a variety of medical fields, it is not commonly used in echocardiography analysis. OBJECTIVES: To develop an NLP-based approach for extracting and categorising data from echocardiography reports by accurately converting continuous (e.g., LVOT VTI, AV VTI and TR Vmax) and discrete (e.g., regurgitation severity) outcomes in a semi-structured narrative format into a structured and categorised format, allowing for future research or clinical use. METHODS: 135,062 Trans-Thoracic Echocardiogram (TTE) reports were derived from 146967 baseline echocardiogram reports and split into three cohorts: Training and Validation (n = 1075), Test Dataset (n = 98) and Application Dataset (n = 133,889). The NLP system was developed and was iteratively refined using medical expert knowledge. The system was used to curate a moderate-fidelity database from extractions of 133,889 reports. A hold-out validation set of 98 reports was blindly annotated and extracted by two clinicians for comparison with the NLP extraction. Agreement, discrimination, accuracy and calibration of outcome measure extractions were evaluated. RESULTS: Continuous outcomes including LVOT VTI, AV VTI and TR Vmax exhibited perfect inter-rater reliability using intra-class correlation scores (ICC = 1.00, p < 0.05) alongside high R2 values, demonstrating an ideal alignment between the NLP system and clinicians. A good level (ICC = 0.75-0.9, p < 0.05) of inter-rater reliability was observed for outcomes such as LVOT Diam, Lateral MAPSE, Peak E Velocity, Lateral E' Velocity, PV Vmax, Sinuses of Valsalva and Ascending Aorta diameters. Furthermore, the accuracy rate for discrete outcome measures was 91.38% in the confusion matrix analysis, indicating effective performance. CONCLUSIONS: The NLP-based technique yielded good results when it came to extracting and categorising data from echocardiography reports. The system demonstrated a high degree of agreement and concordance with clinician extractions. This study contributes to the effective use of semi-structured data by providing a useful tool for converting semi-structured text to a structured echo report that can be used for data management. Additional validation and implementation in healthcare settings can improve data availability and support research and clinical decision-making.

Trends and outcomes of concomitant aortic valve replacement and coronary artery bypass grafting in the UK and a survey of practices.

OBJECTIVES: Concomitant revascularization of coronary artery disease at the same time as treatment for aortic valvopathy favourably impacts survival. However, combined surgery may be associated with increased adverse outcomes compared to aortic valve replacement (AVR) or coronary artery bypass grafting in isolation. METHODS: We retrospectively analyzed all patients who underwent AVR with bypass grafting between February 1996 and March 2019 using data from the National Adult Cardiac Surgery Audit. We used a generalized mixed-effects model to assess the effect of the number and type of bypass grafts associated with surgical AVR on in-hospital mortality, postoperative stroke, and the need for renal dialysis. Furthermore, we conducted an international cross-sectional survey of cardiac surgeons to explore their views about concomitant AVR with coronary bypass grafting interventions. RESULTS: Fifty-one thousand two hundred and seventy-two patients were included in the study. Patients receiving 2 or more bypass grafts demonstrated more significant preoperative comorbidity and disease severity. Patients undergoing 2 and >2 grafts in addition to AVR had increased mortality as compared to patients undergoing AVR and only 1 graft [odds ratio (OR) 1.17, 95% confidence interval (CI) [1.05-1.30], P = 0.005 and OR 1.15, 95% CI [1.02-1.30], P = 0.024 respectively]. A single arterial conduit was associated with a reduction in mortality (OR 0.75, 95% CI [0.68-0.82], P < 0.001) and postoperative dialysis (OR 0.87, 95% CI [0.78-0.96], P = 0.006), but this association was lost with >1 arterial conduit. One hundred and three surgeons responded to our survey, with only a small majority believing that the number of bypass grafts can influence short- or long-term postoperative outcomes in these patients, and an almost equal split in responders supporting the use of staged or hybrid interventions for patients with concomitant pathology. CONCLUSIONS: The number of grafts performed during combined AVR and coronary artery bypass grafting is associated with increased morbidity and mortality. The use of an arterial graft was also associated with reduced mortality. Future studies are needed to assess the effect of incomplete revascularization and measure long-term outcomes. Based on our data, current published evidence, and the collective expert opinion we gathered, we endorse future work to investigate the short and long-term efficacy and safety of hybrid intervention for patients with concomitant advanced coronary and aortic valve disease.

Trend and early clinical outcomes of off-pump coronary artery bypass grafting in the UK.

OBJECTIVES: The popularity of off-pump coronary artery bypass grafting (CABG) varies across the world, ranging from 20% in Europe and the USA to 56% in Asia. We present the trend and early clinical outcomes in off pump in the UK. METHODS: All patients who underwent elective or urgent isolated CABG from 1996 to 2019 were extracted from the National Adult Cardiac Surgery Audit database. The trend in operating surgeons and units volume and training in off pump were analysed. Early clinical outcomes between off- and on-pump CABG were compared using propensity score matching. RESULTS: A total of 351 422 patients were included. The overall off-pump rate during the study period was 15.17%, it peaked in 2008 (19.8%), followed by a steady decreased to 2018 (7.63%). Its adoption varied across centres and surgeons, ranging from <1% to 48.36% and <1% to 85.5%, respectively, of total cases performed. After propensity score matching for the period 1996-2019, off pump, when compared to on pump, was associated with a lower in-hospital/30-day mortality (1.2% vs 1.5%, P < 0.001), return to theatre (3.7% vs 4.5%, P < 0.001), cerebrovascular accident (transient ischaemic attack: 0.3% vs 0.6%, stroke: 0.3% vs 0.6%, P < 0.001) and deep sternal wound infection (0.8% vs 1.2%, P ≤ 0.001). In a sub-analysis from the introduction of EuroScore II (2012-2019), there were no differences in-hospital/30-day mortality (1.0% vs 1.0%, P = 0.71). However, on pump, had a higher return to theatre (4.2% vs 2.7%, P < 0.001), cerebrovascular accident (transient ischaemic attack: 0.4% vs 0.2%, stroke: 0.5% vs 0.3%, P = 0.003) and deep sternal wound infection (1.0% vs 0.6%, P = 0.004). CONCLUSIONS: Our data show a decreasing trend in the use of off pump in the UK since 2008. This is likely to be multifactorial and raises the question of whether it should be a specialized revascularization technique.

Cardiac surgery risk prediction using ensemble machine learning to incorporate legacy risk scores: A benchmarking study.

Objective: The introduction of new clinical risk scores (e.g. European System for Cardiac Operative Risk Evaluation (EuroSCORE) II) superseding original scores (e.g. EuroSCORE I) with different variable sets typically result in disparate datasets due to high levels of missingness for new score variables prior to time of adoption. Little is known about the use of ensemble learning to incorporate disparate data from legacy scores. We tested the hypothesised that Homogenenous and Heterogeneous Machine Learning (ML) ensembles will have better performance than ensembles of Dynamic Model Averaging (DMA) for combining knowledge from EuroSCORE I legacy data with EuroSCORE II data to predict cardiac surgery risk. Methods: Using the National Adult Cardiac Surgery Audit dataset, we trained 12 different base learner models, based on two different variable sets from either EuroSCORE I (LogES) or EuroScore II (ES II), partitioned by the time of score adoption (1996-2016 or 2012-2016) and evaluated on holdout set (2017-2019). These base learner models were ensembled using nine different combinations of six ML algorithms to produce homogeneous or heterogeneous ensembles. Performance was assessed using a consensus metric. Results: Xgboost homogenous ensemble (HE) was the highest performing model (clinical effectiveness metric (CEM) 0.725) with area under the curve (AUC) (0.8327; 95% confidence interval (CI) 0.8323-0.8329) followed by Random Forest HE (CEM 0.723; AUC 0.8325; 95%CI 0.8320-0.8326). Across different heterogenous ensembles, significantly better performance was obtained by combining siloed datasets across time (CEM 0.720) than building ensembles of either 1996-2011 (t-test adjusted, p = 1.67×10-6) or 2012-2019 (t-test adjusted, p = 1.35×10-193) datasets alone. Conclusions: Both homogenous and heterogenous ML ensembles performed significantly better than DMA ensemble of Bayesian Update models. Time-dependent ensemble combination of variables, having differing qualities according to time of score adoption, enabled previously siloed data to be combined, leading to increased power, clinical interpretability of variables and usage of data.

Patterns of cytokine release and association with new onset of post-cardiac surgery atrial fibrillation.

Introduction: Postoperative Atrial Fibrillation (POAF) is a common complication of cardiac surgery, associated with increased mortality, stroke risk, cardiac failure and prolonged hospital stay. Our study aimed to assess the patterns of release of systemic cytokines in patients with and without POAF. Methods: A post-hoc analysis of the Remote Ischemic Preconditioning (RIPC) trial, including 121 patients (93 males and 28 females, mean age of 68 years old) who underwent isolated coronary artery bypass grafting (CABG) and aortic valve replacement (AVR). Mixed-effect models were used to analyze patterns of release of cytokines in POAF and non-AF patients. A logistic regression model was used to assess the effect of peak cytokine concentration (6 h after the aortic cross-clamp release) alongside other clinical predictors on the development of POAF. Results: We found no significant difference in the patterns of release of IL-6 (p = 0.52), IL-10 (p = 0.39), IL-8 (p = 0.20) and TNF-α (p = 0.55) between POAF and non-AF patients. Also, we found no significant predictive value in peak concentrations of IL-6 (p = 0.2), IL-8 (p = >0.9), IL-10 (p = >0.9) and Tumour Necrosis Factor Alpha (TNF-α)(p = 0.6), however age and aortic cross-clamp time were significant predictors of POAF development across all models. Conclusions: Our study suggests no significant association exists between cytokine release patterns and the development of POAF. Age and Aortic Cross-clamp time were found to be significant predictors of POAF.

Risk Factors and Outcomes of Reoperative Surgical Aortic Valve Replacement in the United Kingdom.

BACKGROUND: Mortality after reoperative aortic valve surgery continues to decline but remains high compared with primary isolated replacement. We sought to examine temporal trends, morbidity, and mortality among patients undergoing isolated first-time reoperative aortic valve surgery. METHODS: The study included all patients undergoing reoperative aortic valve surgery in the United Kingdom between January 2007 and March 2019. Patients undergoing isolated reoperative aortic valve replacement (AVR) were compared with a propensity matched cohort of patients undergoing isolated primary AVR. Outcomes measured included inhospital mortality, neurologic dysfunction, postoperative dialysis, deep sternal wound infections, and hospital length of stay. RESULTS: During the study period, 40,858 primary isolated AVRs and 3015 first-time isolated reoperative AVRs were carried out in the United Kingdom. In the propensity matched reoperative group, median age of participants was 69.8 years (60.8-76.2) with median duration between the initial surgery and the reoperation being 7.69 years. Overall mortality was 3.1% (94) for reoperative AVR compared with 1.9% (56) for primary AVR. Mortality of both primary and reoperative AVR declined during the study period. Reoperation, age, New York Heart Association class, and chronic kidney disease were independently associated with early mortality. CONCLUSIONS: Reoperative isolated AVR can be performed with acceptable inhospital mortality and provides a benchmark against which alternative strategies should be compared.

In-hospital outcomes predictors and trends of redo sternotomy aortic root replacements: insights from a UK registry analysis.

Background: Redo sternotomy aortic root surgery is technically demanding, and the evidence on outcomes is mostly from retrospective, small sample, single-centre studies. We report the trend, early clinical results and outcome predictors of redo aortic root replacement over 20 years in the United Kingdom. Methods: We retrospectively analysed collected data from the UK National Adult Cardiac Surgery Audit (NACSA) on all redo sternotomy aortic root replacements performed between 30th January 1998 and 19th March 2019. We analysed trends in the volume of operations, characteristics of hospital survivors vs. non-survivors, and predictors of in-hospital outcomes. Results: During the study period, 1,107 redo sternotomy aortic root replacements were performed (median age 59, 26% of patients were females). Eighty-four per cent of cases (N = 931) underwent a composite root replacement, 11% (N = 119) had homograft root replacement and valve-sparing root replacement was performed in 5.1% (N = 57) of cases. There was a steady increase in the volume of redo sternotomy root replacements beyond 2006, from an annual volume of 22 procedures in 2006 to 106 procedures in 2017. Hospital mortality was 17% (n = 192), postoperative stroke or TIA occurred in 5.2% (n = 58), and postoperative dialysis was required in 11% (n = 109) of patients. Return to the theatre for bleeding/tamponade was required in 9% (n = 102) and median in-hospital stay was 9 days. Age >59 (OR: 2.99, CI: 1.92-4.65, P < 0.001), recent myocardial infarction (OR: 6.42, CI: 2.24-18.41, P = 0.001) were associated with increased in-hospital mortality. Emergency surgery (OR: 3.95, 2.27-6.86, P < 0.001), surgery for endocarditis (OR: 2.05, CI: 1.26-3.33, P = 0.001), salvage coronary artery bypass grafting (OR: 2.20, CI: 1.37-3.54, P < 0.001), arch surgery (OR: 2.47, CI: 1.30-3.61, P = 0.018) and aortic cross-clamp longer than 169 min (OR: 2.17, CI: 1.00-1.01, P = 0.003) were associated with increased risk of mortality. We found no effect of the centre or surgeon volume on mortality (P > 0.05). Conclusions: Redo sternotomy aortic root replacement still carries significant morbidity and mortality and is sporadically performed across surgeons and centres in the UK.

On- versus off-pump CABG in octogenarians: A propensity-matched analysis from the UK National Database.

INTRODUCTION: Coronary artery bypass grafting (CABG) remains a good revascularization strategy in octogenarians with excellent clinical outcomes and quality of life postoperatively. However, the benefits of off-pump over on-pump CABG in the elderly population are still controversial. We investigated this issue in the UK National Audit database. METHOD: We retrospectively analyzed all octogenarians undergoing nonemergency, isolated CABG from 1996 to 2019. Propensity score matching (PSM) was conducted to adjust for imbalance in the baseline characteristics between the off-pump and on-pump groups. Primary outcome was in-hospital mortality and postoperative cerebrovascular accidents. Secondary outcomes were bleeding requiring reoperation, deep sternal wound infection, and postoperative dialysis. RESULT: A total of 6436 patients were included for analysis. No differences were observed between off- and on-pump group in-hospital mortality (4% vs. 3.8%, p = .89), return to theater rate (5.4% vs. 6.2%, p = .16) and incidence of deep sternal wound infection (1.1% vs. 1.6%, p = .34). However, octogenarian undergoing off-pump CABG were less likely to experience postoperative transient ischemic attack (TIA)/stroke (1.4% vs. 2.3%, p = .004) but more likely to require renal dialysis (4.8% vs. 3.5%, p = .03). CONCLUSION: The data show similar in-hospital mortality in octogenarians regardless of the revascularization technique used. Off-pump when compared with on-pump CABG is associated with a lower incidence in postoperative neurological events but a higher need for renal dialysis.

Females have an increased risk of short-term mortality after cardiac surgery compared to males: Insights from a national database.

OBJECTIVES: Female sex is considered a risk factor for mortality and morbidity following cardiac surgery. This study is the first to review the UK adult cardiac surgery national database to compare outcomes following surgical coronary revascularisation and valvular procedures between females and males. METHODS: Using data from National Adult Cardiac Surgery Audit, we identified all elective and urgent, isolated coronary artery by-pass grafting (CABG), aortic valve replacement (AVR) and mitral valve replacement/repair (MVR) procedures from 2010 to 2018. We compared baseline data, operative data and outcomes of mortality, stroke, renal failure, deep sternal wound infection, return to theater for bleeding, and length of hospital stay. Multivariable mixed-effect logistical/linear regression models were used to assess relationships between sex and outcomes, adjusting for baseline characteristics. RESULTS: Females, compared to males, had greater odds of experiencing 30-day mortality (CABG odd ratio [OR] 1.76, confidence interval [CI] 1.47-2.09, p < .001; AVR OR 1.59, CI 1.27-1.99, p < .001; MVR OR 1.37, CI 1.09-1.71, p = .006). After CABG, females also had higher rates of postoperative dialysis (OR 1.31, CI 1.12-1.52, p < .001), deep sternal wound infections (OR 1.43, CI 1.11-1.83, p = .005) and longer length of hospital stay (ß 1.2, CI 1.0-1.4, p < .001) compared to males. Female sex was protective against returning to theater for postoperative bleeding following CABG (OR 0.76, CI 0.65-0.87, p < .001) and AVR (OR 0.72, CI 0.61-0.84, p < .001). CONCLUSION: Females in the United Kingdom have an increased risk of short-term mortality after cardiac surgery compared to males. This highlights the need to focus on the understanding of the causes behind these disparities and implementation of strategies to improve outcomes in females.

Trend and factors associated with multiple arterial revascularization in coronary artery bypass grafting in the UK.

OBJECTIVES: Benefits of using multiple arterial grafting (MAG), over single arterial grafting in major adverse cardiac event rates and the need for repeat revascularization, have been widely reported. Several guidelines have recommended the use of MAG in selected patients. We report the trend of MAG in patients undergoing isolated coronary artery bypass grafting (CABG) in the UK. METHODS: This is a retrospective analysis of a prospectively collected UK national database in patients undergoing non-emergency, isolated CABG from 1996 to 2018. Patients were divided into single arterial grafting and MAG, and trends in perioperative characteristics were analysed. RESULTS: A total of 336 321 patients were included, of whom 284 003 (84.44%) received single arterial grafting and 52 318 (15.56%) received MAG. The use of MAG after an initial increase from 1996 to 2001, steadily decreased thereafter, particularly in the use of radial artery. MAG was likely to be performed in younger patients [66.72 (standard deviation: 9.22) vs 62.30 (standard deviation: 10.06), P < 0.001] and males (85% vs 81%, P < 0.001). After propensity score matching, the single arterial grafting group was more likely to undergo on-pump CABG (90% vs 69%, P < 0.001), experienced a lower in-hospital mortality (1.1% vs 1.3%, P < 0.001) and incidence of return to theatre for bleeding (2.5% vs 3.0%, P < 0.001). CONCLUSIONS: Our data show that the use of MAG in CABG in the UK after an initial increase from 1996 to 2001 steadily decreased thereafter until 2018. This is likely to be multifactorial and a better understanding of the main causes may contribute to establishing the best indication for MAG in everyday clinical practice.

Trend and early outcomes in isolated surgical aortic valve replacement in the United Kingdom.

Objective: Surgical aortic valve replacement (SAVR) is traditionally the gold-standard treatment in patients with aortic valve disease. The advancement of transcatheter aortic valve replacement (TAVR) provides an alternative treatment to patients with high surgical risks and those who had previous cardiac surgery. We aim to evaluate the trend, early clinical outcomes, and the choice of prosthesis use in isolated SAVR in the United Kingdom. Methods: All patients (n = 79,173) who underwent elective or urgent isolated surgical aortic valve replacement (SAVR) from 1996 to 2018 were extracted from the National Adult Cardiac Surgery Audit database. Patients who underwent additional procedures and emergency or salvage SAVR were excluded from the study. Trend and clinical outcomes were investigated in the whole cohort. Patients who had previous cardiac surgery, high-risk groups (EuroSCORE II >4%), and predicted/observed mortality were evaluated. Furthermore, the use of biological prostheses in five different age groups, that are <50, 50-59, 60-69, 70-79, and >80, was investigated. Clinical outcomes between the use of mechanical and biological aortic valve prostheses in patients <65 years old were analyzed. Results: The number of isolated SAVR increased across the study period with an average of 4,661 cases performed annually after 2010. The in-hospital/30-day mortality rate decreased from 5.28% (1996) to 1.06% (2018), despite an increasing trend in EuroSCORE II. The number of isolated SAVR performed in octogenarians increased from 596 to 2007 (the first year when TAVR was introduced in the UK) to 872 in 2015 and then progressively decreased to 681 in 2018. Biological prosthesis usage increased across all age groups, particularly in the 60-69 group, from 24.59% (1996) to 81.87% (2018). There were no differences in short-term outcomes in patients <65 years old who received biological or mechanical prostheses. Conclusion: Surgical aortic valve replacement remains an effective treatment for patients with isolated aortic valve disease with a low in-hospital/30-day mortality rate. The number of patients with high-risk and octogenarians who underwent isolated SAVR and those requiring redo surgery has reduced since 2016, likely due to the advancement in TAVR. The use of biological aortic prostheses has increased significantly in recent years in all age groups.

Co-culture of monocytes and zona fasciculata adrenal cells: An in vitro model to study the immune-adrenal cross-talk.

The hypothalamic-pituitary-adrenal axis is the primary neuroendocrine system activated to re-establish homeostasis during periods of stress, including critical illness and major surgery. During critical illness, evidence suggests that locally induced inflammation of the adrenal gland could facilitate immune-adrenal cross-talk and, in turn, modulate cortisol secretion. It has been hypothesized that immune cells are necessary to mediate the effect of inflammatory stimuli on the steroidogenic pathway that has been observed in vivo. To test this hypothesis, we developed and characterized a trans-well co-culture model of THP1 (human monocytic cell)-derived macrophages and ATC7 murine zona fasciculata adrenocortical cells. We found that co-culture of ATC7 and THP1 cells results in a significant increase in the basal levels of IL-6 mRNA in ATC7 cells, and this effect was potentiated by treatment with LPS. Addition of LPS to co-cultures of ATC7 and THP1 significantly decreased the expression of key adrenal steroidogenic enzymes (including StAR and DAX-1), and this was also found in ATC7 cells treated with pro-inflammatory cytokines. Moreover, 24-h treatment with the synthetic glucocorticoid dexamethasone prevented the effects of LPS stimulation on IL-6, StAR and DAX-1 mRNA in ATC7 cells co-cultured with THP1 cells. Our data suggest that the expression of IL-6 and steroidogenic genes in response to LPS depends on the activation of intra-adrenal immune cells. Moreover, we also show that the effects of LPS can be modulated by glucocorticoids in a time- and dose-dependent manner with potential implications for clinical practice.

Prophylactic corticosteroids for paediatric heart surgery with cardiopulmonary bypass.

BACKGROUND: Corticosteroids are routinely given to children undergoing cardiac surgery with cardiopulmonary bypass (CPB) in an attempt to ameliorate the inflammatory response. Their use is still controversial and the decision to administer the intervention can vary by centre and/or by individual doctors within that centre. OBJECTIVES: This review is designed to assess the benefits and harms of prophylactic corticosteroids in children between birth and 18 years of age undergoing cardiac surgery with CPB. SEARCH METHODS: We searched CENTRAL, MEDLINE, Embase and Conference Proceedings Citation Index-Science in June 2020. We also searched four clinical trials registers and conducted backward and forward citation searching of relevant articles. SELECTION CRITERIA: We included studies of prophylactic administration of corticosteroids, including single and multiple doses, and all types of corticosteroids administered via any route and at any time-point in the perioperative period. We excluded studies if steroids were administered therapeutically. We included individually randomised controlled trials (RCTs), with two or more groups (e.g. multi-drug or dose comparisons with a control group) but not 'head-to-head' trials without a placebo or a group that did not receive corticosteroids. We included studies in children, from birth up to 18 years of age, including preterm infants, undergoing cardiac surgery with the use of CPB. We also excluded studies in patients undergoing heart or lung transplantation, or both; studies in patients already receiving corticosteroids; in patients with abnormalities of the hypothalamic-pituitary-adrenal axis; and in patients given steroids at the time of cardiac surgery for indications other than cardiac surgery. DATA COLLECTION AND ANALYSIS: We used the Covidence systematic review manager to extract and manage data for the review. Two review authors independently assessed studies for inclusion, extracted data, and assessed risks of bias. We resolved disagreements by consensus or by consultation with a third review author. We assessed the certainty of evidence with GRADE. MAIN RESULTS: We found 3748 studies, of which 888 were duplicate records. Two studies had the same clinical trial registration number, but reported different populations and interventions. We therefore included them as separate studies. We screened titles and abstracts of 2868 records and reviewed full text reports for 84 studies to determine eligibility. We extracted data for 13 studies. Pooled analyses are based on eight studies. We reported the remaining five studies narratively due to zero events for both intervention and placebo in the outcomes of interest. Therefore, the final meta-analysis included eight studies with a combined population of 478 participants. There was a low or unclear risk of bias across the domains. There was moderate certainty of evidence that corticosteroids do not change the risk of in-hospital mortality (five RCTs; 313 participants; risk ratio (RR) 0.83, 95% confidence interval (CI) 0.33 to 2.07) for children undergoing cardiac surgery with CPB. There was high certainty of evidence that corticosteroids reduce the duration of mechanical ventilation (six RCTs; 421 participants; mean difference (MD) 11.37 hours lower, 95% CI -20.29 to -2.45) after the surgery. There was high-certainty evidence that the intervention probably made little to no difference to the length of postoperative intensive care unit (ICU) stay (six RCTs; 421 participants; MD 0.28 days lower, 95% CI -0.79 to 0.24) and moderate-certainty evidence that the intervention probably made little to no difference to the length of the postoperative hospital stay (one RCT; 176 participants; mean length of stay 22 days; MD -0.70 days, 95% CI -2.62 to 1.22). There was moderate certainty of evidence for no effect of the intervention on all-cause mortality at the longest follow-up (five RCTs; 313 participants; RR 0.83, 95% CI 0.33 to 2.07) or cardiovascular mortality at the longest follow-up (three RCTs; 109 participants; RR 0.40, 95% CI 0.07 to 2.46). There was low certainty of evidence that corticosteroids probably make little to no difference to children separating from CPB (one RCT; 40 participants; RR 0.20, 95% CI 0.01 to 3.92). We were unable to report information regarding adverse events of the intervention due to the heterogeneity of reporting of outcomes. We downgraded the certainty of evidence for several reasons, including imprecision due to small sample sizes, a single study providing data for an individual outcome, the inclusion of both appreciable benefit and harm in the confidence interval, and publication bias. AUTHORS' CONCLUSIONS: Corticosteroids  probably do not change the risk of mortality for children having heart surgery using CPB at any time point. They probably reduce the duration of postoperative ventilation in this context, but have little or no effect on the total length of postoperative ICU stay or total postoperative hospital stay. There was inconsistency in the adverse event outcomes reported which, consequently, could not be pooled. It is therefore impossible to provide any implications and policy-makers will be unable to make any recommendations for practice without evidence about adverse effects. The review highlighted the need for well-conducted RCTs powered for clinical outcomes to confirm or refute the effect of corticosteroids versus placebo in children having cardiac surgery with CPB. A core outcome set for adverse event reporting in the paediatric major surgery and intensive care setting is required.