Few UK studies have explored the epidemiology of postoperative acute kidney injury after diverse types of elective major non-cardiac surgery. Fewer still have compared postoperative acute kidney injury risk factors with conditions such as peri-operative myocardial injury that might have similar pathophysiology. This study aimed to characterise postoperative acute kidney injury and its clinical consequences in elective major non-cardiac surgery, and to assess risk factors for postoperative acute kidney injury including those related to peri-operative myocardial injury.

All elective major non-cardiac surgical episodes, occurring between 2015 and 2020, were identified retrospectively. Patients without measured peri-operative renal parameters were not studied. Our primary outcome was 7-day postoperative acute kidney injury rate, defined using Kidney Disease Improving Global Outcomes criteria. Multivariable logistic regression modelling was used to assess risk factors for postoperative acute kidney injury.

Postoperative acute kidney injury occurred in 1334/13,790 (9.7%) episodes, with 663 (49.7%) occurring on day 1. Postoperative acute kidney injury was associated with increased peri-operative complications (OR 1.8, 95%CI 1.6-2.1, p < 0.001), unanticipated critical care admissions (OR 2.4, 95%CI 1.6-3.5, p < 0.001) and in-hospital mortality (OR 8.0, 95%CI 5.1-12.5, p < 0.001). Independent risk factors for postoperative acute kidney injury include: raised creatinine; hypertension; anaemia; platelet: lymphocyte ratio; heart rate; male sex: renin-angiotensin-aldosterone system blockade; and intra-abdominal surgery.

Postoperative acute kidney injury is common and is associated with adverse outcomes. Prevalence peaks initially within the first 48 h, with a secondary rise seen from day 5 onwards, suggesting a different aetiology. It is determined by a combination of patient and surgical risk factors, with the former relating to physiological, rather than chronological, renal age. In common with peri-operative myocardial injury, postoperative acute kidney injury is independently associated with factors affecting autonomic tone and myeloid skewing.

Recent findings from Gutierrez del Arroyo and colleagues identified distinct sub-phenotypes in patients undergoing major noncardiac surgery based on biomarkers such as N terminal pro-brain natriuretic peptide, renin, aldosterone, and angiotensin-converting enzyme 2, which were associated with varying risks of postoperative myocardial injury. Although their findings highlight the potential of sub-phenotyping for advancing perioperative precision medicine, further research is needed to validate these sub-phenotypes and explore their role in tailoring perioperative management strategies.

To identify the association between preoperative inflammatory state and myocardial injury after noncardiac surgery (MINS) in older patients using systemic inflammation indicators neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and systemic immune-inflammation index (SII) and to compare their clinical predictive values.

This study included patients aged ≥65 years who underwent noncardiac surgery between January 2017 and August 2019. The relationship between preoperative inflammatory state and MINS was investigated using univariate and multivariate logistic regression analyses. The predictive values of NLR, PLR, and SII were determined by receiver operating characteristic (ROC) curve analysis. Based on the basic model we constructed, the predictive values were compared through separately adding NLR, PLR and SII.

Among 12464 patients, 965 (7.74%) developed MINS. The optimal cut-off values of NLR, PLR, and SII were 597×109, 2.59, and 923. Univariate and multivariate analyses show that preoperative inflammatory state is associated with MINS. In the multivariate analysis, the OR values for NLR, PLR, and SII were (OR: 1.61, 95% CI: 1.36-1.89, p<0.001), (OR: 1.28, 95% CI: 1.07-1.52, p=0.006), and (OR: 1.43, 95% CI: 1.20-1.70, p<0.001). ROC curve analysis indicated that NLR was more predictive of MINS (area under the curve [AUC]: 0.671, 95% CI: 0.652-0.689) than PLR (AUC: 0.635, 95% CI: 0.616-0.655) and SII (AUC: 0.648, 95% CI: 0.628-0.667). The addition of the NLR to a basic prediction model improved its predictive ability to a greater extent than the addition of PLR and SII.

Higher preoperative inflammation levels are associated with an increased risk of MINS. The NLR, PLR, and SII are independent risk factors for MINS and NLR demonstrated better predictive value than that of PLR and SII.

Recent epidemiological studies suggest that chronic pain is a clinically under-recognised cause for cardiovascular morbidity and mortality. Up to 30% of patients undergoing surgery report chronic pain, but the impact of pre-existing pain on postoperative cardiovascular outcomes is not known. Chronic pain and cardiovascular dysfunction share fundamental pathological mechanisms. Chronic pain is a modifiable risk factor for perioperative cardiovascular morbidity.

To investigate the consistency of associations between modified frailty index-5 (mFI-5) and postoperative adverse outcomes in head and neck cancer (HNC) reconstruction.

American College of Surgeons National Surgical Quality Improvement Program (ACS-NSQIP) database from 2017 to 2022 was utilized to identify HNC patients undergoing locoregional or microvascular free tissue transfers. Kaplan-Meier estimates and multivariable Cox regression analyses were utilized to compare risk of infections, bleeding, readmissions, reoperations, major adverse cardiovascular events (MACE), and mortality within the first postoperative month for each mFI-5 score with mFI-5 = 0 as reference. Further analyses investigated associations between individual mFI-5 components and the outcomes of interest.

We included 5,573 patients (median age: 64; 31.5% female), 63% (n = 3,519) of whom underwent microvascular free tissue transfers. Unadjusted univariate analyses associated higher mFI-5 scores with longer hospital stays. In locoregional tissue transfers, adjusted hazard ratios (aHRs) for reoperation were 1.37 (p = 0.03) for mFI-5 = 1 and 2.19 (p = 0.03) for mFI-5 ≥ 3. In microvascular free tissue transfers, aHRs for MACE were 1.93 (p = 0.04) for mFI-5 = 2 and 6.53 (p < 0.001) for mFI-5 ≥ 3, while aHRs for mortality was 3.88 (p = 0.04) for mFI-5 ≥ 3. No associations were observed between increasing mFI-5 scores and increased relative risk of infection, bleeding, or readmission. Individual component analysis associated congestive heart failure with aHRs of 3.92 (1.84-8.35; p < 0.001) for MACE and 5.30 (2.03-13.88; p < 0.001) for mortality. Additionally, COPD was associated with an aHR of 1.39 (1.16-1.67; p < 0.001) for infections.

The associations of higher mFI-5 scores with postoperative adverse outcomes following oncoplastic head and neck reconstruction were inconsistent and possibly driven by individual effects of its components.

Level III (three) Laryngoscope, 2025.

Perioperative myocardial injury (PMI) with different cut-off values has showed to be associated with different prognostic effect after cardiac surgery. Machine learning (ML) method has been widely used in perioperative risk predictions during cardiac surgery. However, the utilization of ML in PMI has not been studied yet. Therefore, we sought to develop and validate the performances of ML for PMI with different cut-off values in cardiac surgery with cardiopulmonary bypass (CPB).

This was a second analysis of a multicenter clinical trial (OPTIMAL) and requirement for written informed consent was waived due to the retrospective design. Patients aged 18-70 undergoing elective cardiac surgery with CPB from December 2018 to April 2021 were enrolled in China. The models were developed using the data from Fuwai Hospital and externally validated by the other three cardiac centres. Traditional logistic regression (LR) and eleven ML models were constructed. The primary outcome was PMI, defined as the postoperative maximum cardiac Troponin I beyond different times of upper reference limit (40x, 70x, 100x, 130x) We measured the model performance by examining the area under the receiver operating characteristic curve (AUROC), precision-recall curve (AUPRC), and calibration brier score.

A total of 2983 eligible patients eventually participated in both the model development (n = 2420) and external validation (n = 563). The CatboostClassifier and RandomForestClassifier emerged as potential alternatives to the LR model for predicting PMI. The AUROC demonstrated an increase with each of the four cutoffs, peaking at 100x URL in the testing dataset and at 70x URL in the external validation dataset. However, it's worth noting that the AUPRC decreased with each cutoff increment. Additionally, the Brier loss score decreased as the cutoffs increased, reaching its lowest point at 0.16 with a 130x URL cutoff. Moreover, extended CPB time, aortic duration, elevated preoperative N-terminal brain sodium peptide, reduced preoperative neutrophil count, higher body mass index, and increased high-sensitivity C-reactive protein levels were identified as risk factors for PMI across all four cutoff values.

The CatboostClassifier and RandomForestClassifer algorithms could be an alternative for LR in prediction of PMI. Furthermore, preoperative higher N-terminal brain sodium peptide and lower high-sensitivity C-reactive protein were strong risk factor for PMI, the underlying mechanism require further investigation.

Laparotomy surgery, which involves making an incision in the abdominal cavity to treat serious abdominal disease and save the patient's life, causes significant deaths in both developed and developing countries, including Ethiopia. The number studies examining in-hospital mortality rates among individuals that undergone laparotomy surgery and associated risk factors is limited.

To assess the magnitude of in-hospital mortality and its associated factors among patients undergone laparotomy at tertiary hospitals, West Oromia, Ethiopia, 2022.

An institutional based retrospective cross-sectional study was conducted from January 1, 2017, to December 31, 2021. Data were collected using systematic random sampling and based on structured and pretested abstraction sheets from 548 medical records and patient register log. Data were checked for completeness and consistency, coded, imported using Epi-data version 4.6, cleaned and analyzed using SPSS version 25 software. Variables with p < 0.2 in the Bi-variable logistic regression analysis were included in the multivariate logistic regression analysis. The fit of the model was checked by the Hosmer‒Lemeshow test. Using the odds ratio adjusted to 95% CI and a p value of 0.05, statistical significance was declared.

A total of 512 patient charts were reviewed, and the response rate was 93.43%. The overall magnitude of in-hospital mortality was 7.42% [95% CI: 5.4-9.8]. American society of Anesthesiology physiological status greater than III [AOR = 7.64 (95% CI: 3.12-18.66)], systolic blood pressure less than 90 mmHg [AOR = 6.11 (95% CI: 1.98-18.80)], preoperative sepsis [AOR = 3.54 (95% CI: 1.53-8.19)], ICU admission [AOR = 4.75 (95% CI: 1.50-14.96)], and total hospital stay greater than 14 days [(AOR = 6.76 (95% CI: 2.50-18.26)] were significantly associated with mortality after laparotomy surgery.

In this study, overall in- hospital mortality was high. Early identification patient's American Society of Anesthesiologists physiological status and provision of early appropriate intervention, and pays special attention to patients admitted with low systolic blood pressure, preoperative sepsis, intensive care unit admission and prolonged hospital stay to improve patient outcomes after laparotomy surgery.

Postoperative complications increase mortality, disability and costs. Advanced understanding of the risk factors for postoperative complications is needed to improve surgical outcomes. This paper discusses the rationale and profile of the BIGPROMISE (biomarkers to guide perioperative management and improve outcome in high-risk surgery) cohort, that aims to investigate risk factors, pathophysiology and outcomes related to postoperative complications.

Adult patients undergoing major surgery in two tertiary teaching hospitals. Clinical data and blood samples are collected before surgery, at the end of surgery and on the first, second and third postoperative day. At each time point a panel of cardiovascular, inflammatory, renal, haematological and metabolic biomarkers is assessed. Aliquots of plasma, serum and whole blood of each time point are frozen and stored. Data on severe complications are prospectively collected during 30 days after surgery. Functional status is assessed before surgery and after 120 days using the WHO Disability Assessment Schedule (WHODAS) 2.0. Mortality is followed up until 2 years after surgery.

The first patient was enrolled on 8 October 2021. Currently (1 January 2024) 3086 patients were screened for eligibility, of whom 1750 (57%) provided informed consent for study participation. Median age was 66 years (60; 73), 28% were female, and 68% of all patients were American Society of Anaesthesiologists (ASA) physical status class 3. Most common types of major surgery were cardiac (49%) and gastro-intestinal procedures (26%). The overall incidence of 30-day severe postoperative complications was 16%.

By the end of the recruitment phase, expected in 2026, approximately 3000 patients with major surgery will have been enrolled. This cohort allows us to investigate the role of pathophysiological perioperative processes in the cause of postoperative complications, and to discover and develop new biomarkers to improve risk stratification for adverse postoperative outcomes.

NCT05199025.

Perioperative myocardial injury (PMI) is associated with increased mobility and mortality after noncoronary cardiac surgery. However, limited studies have developed a predictive model for PMI. Therefore, we used hybrid feature selection (FS) methods to establish a predictive model for PMI in noncoronary cardiac surgery with cardiopulmonary bypass (CPB).

This was a single-center retrospective study conducted at the Fuwai Hospital in China. Patients aged 18-70 years who underwent elective noncoronary surgery with CPB at our institution from December 2018 to April 2021 were enrolled. The primary outcome was PMI, defined as the postoperative cardiac troponin I (cTnI) levels exceeding 220 times of upper reference limit (URL). Statistical analyses were conducted by Python (Python Software Foundation, version 3.9.7 and integrated development environment Jupyter Notebook 1.1.0) and SPSS software version 26.0 (IBM Corp., Armonk, New York, USA).

A total of 1130 patients were eventually eligible for this study. The incidence of PMI was 20.3% (229/1130) in the overall patients, 20.6% (163/791) in the training dataset, and 19.5% (66/339) in the testing dataset. The logistic regression model performed the best AUC of 0.6893 (95 CI%: 0.6371-0.7382) by the traditional selection method, and the random forest model performed the best AUC of 0.6937 (95 CI%: 0.6416-0.7423) by the union of Wrapper and Embedded method, and the CatBoost model performed the best AUC of 0.6828 (95 CI%: 0.6304-0.7320) by the union of Embedded and forward logistic regression technique, and the Naïve Bayes model achieved the best AUC with 0.7254 (95 CI%: 0.6746-0.7723) by forwarding logistic regression method. Moreover, the decision tree, KNeighborsClassifier, and support vector machine models performed the worse AUC in all selection forms. Furthermore, the SHapley Additive exPlanations plot showed that prolonged CPB, aortic clamp time, and preoperative low platelets count were strongly related to the PMI risk.

In total, four category feature selection methods were utilized, comprising five individual selection techniques and 15 combined methods. Notably, the combination of logistic regression and embedded methods demonstrated outstanding performance in predicting PMI risk. We also concluded that the machine learning model, including random forest, catboost, and Naive Bayes, were suitable candidates for establishing PMI predictive model. Nevertheless, additional investigation and validation are imperative for substantiating these finding.

Although cardiovascular diseases (CVDs) are the leading cause of death worldwide, their pharmacotherapy remains suboptimal. Thus, there is a clear unmet need to develop more effective and safer pharmacological strategies. In this review, we summarize the most relevant advances in cardiovascular pharmacology in 2023, including the approval of first-in-class drugs that open new avenues for the treatment of atherosclerotic CVD and heart failure (HF). The new indications of drugs already marketed (repurposing) for the treatment of obstructive hypertrophic cardiomyopathy, hypercholesterolaemia, type 2 diabetes, obesity, and HF; the impact of polypharmacy on guideline-directed drug use is highlighted as well as results from negative clinical trials. Finally, we end with a summary of the most important phase 2 and 3 clinical trials assessing the efficacy and safety of cardiovascular drugs under development for the prevention and treatment of CVDs.

Assay-specific increases in circulating cardiac troponin are observed in 20-40% of patients after noncardiac surgery, depending on patient age, type of surgery, and comorbidities. Increased cardiac troponin is consistently associated with excess morbidity and mortality after noncardiac surgery. Despite these findings, the underlying mechanisms are unclear. The majority of interventional trials have been designed on the premise that ischaemic cardiac disease drives elevated perioperative cardiac troponin concentrations. We consider data showing that elevated circulating cardiac troponin after surgery could be a nonspecific marker of cardiomyocyte stress. Elevated concentrations of circulating cardiac troponin could reflect coordinated pathological processes underpinning organ injury that are not necessarily caused by ischaemia. Laboratory studies suggest that matching of coronary artery autoregulation and myocardial perfusion-contraction coupling limit the impact of systemic haemodynamic changes in the myocardium, and that type 2 ischaemia might not be the likeliest explanation for cardiac troponin elevation in noncardiac surgery. The perioperative period triggers multiple pathological mechanisms that might cause cardiac troponin to cross the sarcolemma. A two-hit model involving two or more triggers including systemic inflammation, haemodynamic strain, adrenergic stress, and autonomic dysfunction might exacerbate or initiate acute myocardial injury directly in the absence of cell death. Consideration of these diverse mechanisms is pivotal for the design and interpretation of interventional perioperative trials.

Gastrointestinal symptoms are a common postoperative complication in patients with congenital heart disease (CHD), affecting their postoperative recovery. Probiotic intervention may be a promising therapeutic approach to alleviate postoperative gastrointestinal symptoms. This study aimed to evaluate the potential of Lactobacillus plantarum 24-7 (L. plantarum 24-7) in mitigating postoperative gastrointestinal symptoms and promoting patient recovery. Adult CHD patients scheduled for surgical intervention were recruited. One hundred and twenty patients were randomized and received L. plantarum or placebo intervention twice daily for ten days. Gastrointestinal symptoms were assessed utilizing the Gastrointestinal Symptom Rating Scale (GSRS). Various postoperative variables were analyzed across both groups. Alterations in gut microbiota were evaluated through 16S rRNA sequencing. 112 patients completed the study, with 55 in the probiotic group and 57 in the placebo group. While the disparity in overall postoperative GSRS scores between the two groups did not reach statistical significance (P = 0.067), marked differences were observed in bloating (P = 0.004) and hard stool (P = 0.030) scores. Furthermore, individuals within the probiotic group exhibited lower postoperative neutrophil counts (P = 0.007) and concurrently higher lymphocyte counts (P = 0.001). Variations in the diversity and composition of postoperative gut microbiota were discerned between the probiotic and placebo groups. Remarkably, no probiotic-related adverse events were documented. Supplementation with L. plantarum was well-tolerated and demonstrated partial efficacy in ameliorating gastrointestinal symptoms in postoperative CHD patients. Modulating the gut microbiota may be a potential mechanism by which L. plantarum exerts clinical benefits.

The release of danger signals from tissues in response to trauma during cardiac surgery creates conditions to reprogram the immune system to subsequent challenges posed by pathogens in the postoperative period. To demonstrate this, we tested immunoreactivity before surgery as the baseline (tbaseline), followed by subsequent challenges during the acute phase (t24h), convalescence (t7d), and long-term recovery (t3m). For 108 patients undergoing elective heart surgery, whole blood was stimulated with lipopolysaccharide (LPS), Influenza A virus subtype N2 (H3N2), or the Flublok™ vaccine to represent common pathogenic challenges. Leukocytosis, platelet count, and serum C-reactive protein (CRP) were used to measure non-specific inflammation. Cytokines were measured after 18 h of stimulation to reflect activation of the various cell types (activated neutrophils-IL-8; activated T cells-IL-2, IFNγ, activated monocyte (MO)-TNFα, IL-6, and deactivated or atypically activated MO and/or T cells-M-CSF, IL-10). IL-2 and IL-10 were increased at t7d, while TNFα was suppressed at t24h when LPS was utilized. Interestingly, M-CSF and IL-6 production was elevated at seven days in response to all stimuli compared to baseline. While some non-specific markers of inflammation (white cell count, IL-6, and IL-8) returned to presurgical levels at t3m, CRP and platelet counts remained elevated. We showed that surgical stimulus reprograms leukocyte response to LPS with only partial restoration of non-specific markers of inflammation.

Spinal cord injury is a frequent debilitating neurologic condition with increasing prevalence and related morbidity over the last decades. The neutrophil-to-lymphocyte ratio is a promising biomarker for determining different medical conditions' disease course and outcome such as traumatic brain injury (TBI). This study aimed to investigate the predictive value of neutrophil to lymphocyte ratio (NLR) in the outcome of SCI.

In a retrospective cross-sectional study from April 2019 to April 2022, all patients 18 to 65 years old, following spinal cord injury who were referred to Imam Khomeini Hospital and met inclusion and exclusion criteria enrolled in the study. A checklist including demographic data, lab, and clinical findings at admission, 24h, 48 h, and discharge were recorded. IBM SPSS Statistics software was used to analyze the data. A P-value of less than 0.05 was considered significant.

Six hundred patients met our inclusion criteria and enrolled in the study. The mean age of the patients was 40.93 ± 12.77, with 75% male and 25% female. There was a significant correlation between the N/L ratio at different time points (p.value=0.001), injury type, and ASIA score at admission and discharge (0.001). Furthermore, the NLR had approached significant value alone to predict outcomes in patients enrolled in the study (0.06).

A high NLR is unequivocally linked with poor outcomes in patients suffering from acute SCI and should be considered a negative prognostic factor; however, the NLR had approached significant predicting value in patients enrolled in the study.

Perioperative myocardial infarction/injury (PMI) is a surprisingly common yet difficult-to-predict cardiac complication in patients undergoing noncardiac surgery. We aimed to assess the incremental value of preoperative cardiac troponin (cTn) concentration in the prediction of PMI.

Among prospectively recruited patients at high cardiovascular risk (age ≥65 years or ≥45 years with preexisting cardiovascular disease), PMI was defined as an absolute increase in high-sensitivity cTnT (hs-cTnT) concentration of ≥14 ng/L (the 99th percentile) above the preoperative concentration. Perioperative myocardial infarction/injury was centrally adjudicated by two independent cardiologists using serial measurements of hs-cTnT. Using logistic regression, three models were derived: Model 1 including patient- and procedure-related information, Model 2 adding routinely available laboratory values, and Model 3 further adding preoperative hs-cTnT concentration. Models were also compared vs. preoperative hs-cTnT alone. The findings were validated in two independent cohorts. Among 6944 patients, PMI occurred in 1058 patients (15.2%). The predictive accuracy as quantified by the area under the receiver operating characteristic curve was 0.73 [95% confidence interval (CI) 0.71-0.74] for Model 1, 0.75 (95% CI 0.74-0.77) for Model 2, 0.79 (95% CI 0.77-0.80) for Model 3, and 0.74 for hs-cTnT alone. Model 3 included 10 preoperative variables: age, body mass index, known coronary artery disease, metabolic equivalent >4, risk of surgery, emergency surgery, planned duration of surgery, haemoglobin, platelet count, and hs-cTnT. These findings were confirmed in both independent validation cohorts (n = 722 and n = 966).

Preoperative cTn adds incremental value above patient- and procedure-related variables as well as routine laboratory variables in the prediction of PMI.

Higher levels of inflammatory biomarkers are associated with an increased risk of perioperative atrial fibrillation and myocardial injury after non-cardiac surgery (MINS). Colchicine is an anti-inflammatory drug that might reduce the incidence of these complications.

COP-AF was a randomised trial conducted at 45 sites in 11 countries. Patients aged 55 years or older and undergoing major non-cardiac thoracic surgery were randomly assigned (1:1) to receive oral colchicine 0·5 mg twice daily or matching placebo, starting within 4 h before surgery and continuing for 10 days. Randomisation was done with use of a computerised, web-based system, and was stratified by centre. Health-care providers, patients, data collectors, and adjudicators were masked to treatment assignment. The coprimary outcomes were clinically important perioperative atrial fibrillation and MINS during 14 days of follow-up. The main safety outcomes were a composite of sepsis or infection, and non-infectious diarrhoea. The intention-to-treat principle was used for all analyses. This trial is registered with ClinicalTrials.gov, NCT03310125.

Between Feb 14, 2018, and June 27, 2023, we enrolled 3209 patients (mean age 68 years [SD 7], 1656 [51·6%] male). Clinically important atrial fibrillation occurred in 103 (6·4%) of 1608 patients assigned to colchicine, and 120 (7·5%) of 1601 patients assigned to placebo (hazard ratio [HR] 0·85, 95% CI 0·65 to 1·10; absolute risk reduction [ARR] 1·1%, 95% CI -0·7 to 2·8; p=0·22). MINS occurred in 295 (18·3%) patients assigned to colchicine and 325 (20·3%) patients assigned to placebo (HR 0·89, 0·76 to 1·05; ARR 2·0%, -0·8 to 4·7; p=0·16). The composite outcome of sepsis or infection occurred in 103 (6·4%) patients in the colchicine group and 83 (5·2%) patients in the placebo group (HR 1·24, 0·93-1·66). Non-infectious diarrhoea was more common in the colchicine group (134 [8·3%] events) than the placebo group (38 [2·4%]; HR 3·64, 2·54-5·22).

In patients undergoing major non-cardiac thoracic surgery, administration of colchicine did not significantly reduce the incidence of clinically important atrial fibrillation or MINS but increased the risk of mostly benign non-infectious diarrhoea.

Canadian Institutes of Health Research, Accelerating Clinical Trials Consortium, Innovation Fund of the Alternative Funding Plan for the Academic Health Sciences Centres of Ontario, Population Health Research Institute, Hamilton Health Sciences, Division of Cardiology at McMaster University, Canada; Hanela Foundation, Switzerland; and General Research Fund, Research Grants Council, Hong Kong.

Perioperative myocardial injury evidenced by elevated cardiac biomarkers (both natriuretic peptides and troponin) is common after major non-cardiac surgery. However, it is unclear if the rise in cardiac biomarkers represents global or more localised cardiac injury. We have previously shown isolated right ventricular (RV) dysfunction in patients following lung resection surgery, with no change in left ventricular (LV) function. Given that perioperative RV dysfunction (RVD) can manifest insidiously, we hypothesise there may be a substantial burden of covert yet clinically important perioperative RVD in other major non-cardiac surgical groups. The Incidence, impact and Mechanisms of Perioperative Right VEntricular dysfunction (IMPRoVE) study has been designed to address this knowledge gap.

A multicentre prospective observational cohort study across four centres in the West of Scotland and London. One hundred and seventy-five patients will be recruited from five surgical specialties: thoracic, upper gastrointestinal, vascular, colorectal and orthopaedic surgery (35 patients from each group). All patients will undergo preoperative and postoperative (day 2-4) echocardiography, with contemporaneous cardiac biomarker testing. Ten patients from each surgical specialty (50 patients in total) will undergo T1-cardiovascular magnetic resonance (CMR) imaging preoperatively and postoperatively. The coprimary outcomes are the incidence of perioperative RVD (diagnosed by RV speckle tracking echocardiography) and the effect that RVD has on days alive and at home at 30 days postoperatively. Secondary outcomes include LV dysfunction and clinical outcomes informed by Standardised Endpoints in Perioperative Medicine consensus definitions. T1 CMR will be used to investigate for imaging correlates of myocardial inflammation as a possible mechanism driving perioperative RVD.

Approval was gained from Oxford C Research Ethics Committee (REC reference 22/SC/0442). Findings will be disseminated by various methods including social media, international presentations and publication in peer-reviewed journals.

NCT05827315.

Genetic polymorphisms contribute to patients' variability in pain perception and response to opioid treatment. The present study evaluated the association of calcitonin gene-related peptide (CGRP) 4218T/C polymorphisms with fentanyl consumption over 24 h postoperatively in patients after major abdominal surgery.

Eighty-five patients undergoing major abdominal surgery under general anaesthesia were recruited. For postoperative analgesia, epidural fentanyl and intravenous paracetamol were provided. The CGRP 4218T/C genotype was analysed, and the association between the genotype of the patient and the total consumption of fentanyl in the first 24 h after surgery was assessed. The association between different genotypes, the severity of postoperative pain and the side effects of opioids were also studied.

Our study population distribution included 52.9% of the T/T genotype (wild homozygote), 35.3% of the T/C genotype (heterozygote) and 11.8% of the C/C genotype (mutant homozygote). Mean (standard deviation) total fentanyl consumption in the first 24 h was found to be highest in the C/C group (212.0 [7.5] μg), followed by the T/T group (182.8 [9.9] μg) and was the least in the T/C group (159.6 [7.5] μg). The C/C group reported higher pain scores in all the study periods. There was no significant difference in the side effects of opioids, such as nausea, vomiting, sedation among different genotypes of CGRP 4218T/C.

The polymorphism of CGRP 4218T/C affects postoperative pain perception and analgesic consumption. Patients with the C/C genotype had higher postoperative fentanyl consumption and pain scores.

Increased inflammatory processes after non-cardiac surgery are very common. The association between postoperative inflammation and the occurrence of cardiovascular complications after non-cardiac surgery are still not entirely clear. Therefore, we will evaluate the association between postoperative inflammation and the occurrence of major cardiovascular complications in patients at-risk for cardiovascular complications undergoing non-cardiac surgery. We will further evaluate the association of postoperative inflammation and days-at-home within 30 days after surgery (DAH₃₀), the incidence of acute kidney injury, postoperative N-terminal probrain natriuretic peptide (NT-proBNP) concentrations and neurocognitive decline.

In this multicentre study, we will include 1400 patients at-risk for cardiovascular complications undergoing non-cardiac surgery. Our primary aim is to evaluate the association of postoperative maximum C-reactive protein concentration and the occurrence of a composite of five major cardiovascular complications (myocardial infarction, myocardial injury after non-cardiac surgery, new onset of atrial fibrillation, stroke and death) within 30 days after surgery using a Mann-Whitney-U test as well as a logistic regression model. As our secondary aim, we will evaluate the association of a composite of three inflammatory biomarkers (interleukin 6, procalcitonin and copeptin) on the occurrence of our composite of five cardiovascular complications within 30 days and 1 year after surgery, acute kidney injury, DAH₃₀ and NT-proBNP concentrations using linear or logistic regression models. We will measure inflammatory biomarkers before surgery, and on the first, second, third and fifth postoperative day. We will check medical records and conduct a telephone survey 30 days and 1 year after surgery. We evaluate neurocognitive function, using a Montreal Cognitive Assessment, before and 1 year after surgery.

This study was approved by the ethics committees at the Medical University of Vienna (2458/2020) and at the Medical University of Graz (33-274 ex 20/21).

NCT04753307.

Ischemic heart failure (IHF) is a leading cause of morbidity and mortality worldwide, for which heart transplantation remains the only definitive treatment. IHF manifests from myocardial infarction (MI) that initiates tissue remodeling processes, mediated by mechanical changes in the tissue (loss of contractility, softening of the myocardium) that are interdependent with cellular mechanisms (cardiomyocyte death, inflammatory response). The early remodeling phase is characterized by robust inflammation that is necessary for tissue debridement and the initiation of repair processes. While later transition toward an immunoregenerative function is desirable, functional reorientation from an inflammatory to reparatory environment is often lacking, trapping the heart in a chronically inflamed state that perpetuates cardiomyocyte death, ventricular dilatation, excess fibrosis, and progressive IHF. Therapies can redirect the immune microenvironment, including biotherapeutic and biomaterial-based approaches. In this review, we outline these existing approaches, with a particular focus on the immunomodulatory effects of therapeutics (small molecule drugs, biomolecules, and cell or cell-derived products). Cardioprotective strategies, often focusing on immunosuppression, have shown promise in pre-clinical and clinical trials. However, immunoregenerative therapies are emerging that often benefit from exacerbating early inflammation. Biomaterials can be used to enhance these therapies as a result of their intrinsic immunomodulatory properties, parallel mechanisms of action (e.g., mechanical restraint), or by enabling cell or tissue-targeted delivery. We further discuss translatability and the continued progress of technologies and procedures that contribute to the bench-to-bedside development of these critically needed treatments.

Perioperative atrial fibrillation (AF) and myocardial injury after noncardiac surgery (MINS) are common complications after noncardiac surgery. Inflammation has been implicated in the pathogenesis of both disorders. The COP-AF trial tests the hypothesis that colchicine reduces the incidence of perioperative AF and MINS in patients undergoing major noncardiac thoracic surgery.

The 'COlchicine for the Prevention of Perioperative Atrial Fibrillation' (COP-AF) trial is an international, blinded, randomized trial that compares colchicine to placebo in patients aged at least 55 years and undergoing major noncardiac thoracic surgery with general anesthesia. Exclusion criteria include a history of AF and a contraindication to colchicine (eg, severe renal dysfunction). Oral colchicine at a dose of 0.5 mg or matching placebo is given within 4 hours before surgery. Thereafter, patients receive colchicine 0.5 mg or placebo twice daily for a total of 10 days. The 2 independent co-primary outcomes are clinically important perioperative AF (including atrial flutter) and MINS during 14 days of follow-up. The main safety outcomes are sepsis or infection and non-infectious diarrhea. We aim to enroll 3,200 patients from approximately 40 sites across 11 countries to have at least 80% power for the independent evaluation of the 2 co-primary outcomes. The COP-AF main results are expected in 2023.

COP-AF is a large randomized and blinded trial designed to determine whether colchicine reduces the risk of perioperative AF or MINS in patients who have major noncardiac thoracic surgery.

Activation of central autonomic pathways, including those regulating the arterial baroreflex, might reduce acute pain. We tested the hypothesis that transcutaneous auricular nerve stimulation (TAN) reduces pain after orthopaedic trauma surgery through autonomic modulation.

A total of 86 participants aged >18 yr were randomly assigned to 50 min of either sham or active bilateral TAN, undertaken before, and again 24 h after, surgery for orthopaedic trauma. The primary outcome was absolute change in pain 24 h postoperatively, comparing the 100 mm visual analogue scale (VAS) before and after TAN. Secondary outcomes included the minimal clinically important difference in pain (>10 mm increase or reduction in VAS) before/after surgery, using intention-to-treat analysis. Holter monitoring, the analysis of which was masked to allocation, quantified autonomic modulation of heart rate.

From June 22, 2021 to July 7, 2022, 79/86 participants (49 yr; 45% female) completed TAN before and after surgery. For the primary outcome, the mean reduction in VAS was 19 mm (95% confidence interval [CI]: 12-26) after active TAN (n=40), vs 10 mm (95% CI: 3-17) after sham TAN (n=39; P=0.023). A minimally clinically important reduction in postoperative pain occurred in 31/40 (78%) participants after active TAN, compared with 15/39 (38%) allocated to sham TAN (odds ratio 5.51 [95% CI: 2.06-14.73]; P=0.001). Only active TAN increased heart rate variability (log low-frequency power increased by 0.19 ms2 [0.01-0.37 ms2]). Prespecified adverse events (auricular skin irritation) occurred in six participants receiving active TAN, compared with two receiving sham TAN.

Bilateral TAN reduces perioperative pain through autonomic modulation. These proof-of-concept data support a non-pharmacological, generalisable approach to improve perioperative analgesia.

Myocardial injury is a frequent complication of surgical patients after having non-cardiac surgery that is strongly associated with perioperative mortality. While intraoperative anesthesia-related deaths are exceedingly rare, about 1% of patients undergoing non-cardiac surgery die within the first 30 postoperative days. Given the number of surgeries performed annually, death following surgery is the second leading cause of death in the United States. Myocardial injury after non-cardiac surgery (MINS) is defined as an elevation in troponin concentrations within 30 days postoperatively. Although typically asymptomatic, patients with MINS suffer myocardial damage and have a 10% risk of death within 30 days after surgery and excess risks of mortality that persist during the first postoperative year. Many factors for the development of MINS are non-modifiable, such as preexistent coronary artery disease. Preventive measures, systematic approaches to surveillance and treatment standards are still lacking, however many factors are modifiable and should be considered in clinical practice: the importance of hemodynamic control, adequate oxygen supply, metabolic homeostasis, the use of perioperative medications such as statins, anti-thrombotic agents, beta-blockers, or anti-inflammatory agents, as well as some evidence regarding the choice of sedative and analgesic for anesthesia are discussed. Also, as age and complexity in comorbidities of the surgical patient population increase, there is an urgent need to identify patients at risk for MINS and develop prevention and treatment strategies. In this review, we provide an overview of current screening standards and promising preventive options in the perioperative setting and address knowledge gaps requiring further investigation.

Recent studies indicated that the prognosis of patients with gastrointestinal tumors is frequently influenced by its complications, notably myocardial injury. The main object is to investigate the occurrence and risk factors of myocardial injury in patients with gastrointestinal tumor.

1126 patients who received gastrointestinal tumor related surgery from May 2018 to June 2020 in the Sixth Affiliated Hospital of Sun Yat-sen University were retrospectively collected and divided into the non-myocardial injury group and the myocardial injury group (high-sensitive cardiac troponin I (hs-cTnI) ≥ 0.028 ng/ml). The occurrence and risk factors of myocardial injury in patients with gastrointestinal tumor are analyzed. The influence of myocardial injury on the ICU detention time in gastrointestinal tumor patients is also studied.

In total, 78 (6.93%) patients developed myocardial injuries. Compared with patients in the non-myocardial injury group, patients in the myocardial injury group have a higher prevalence of cardiovascular risk factors (including advanced age and higher smoking ratio), a higher prevalence of comorbidities (such as previous coronary artery disease, hypertension, atrium fibrillation and diabetes), and a higher rate of premedication (such as anticoagulation, β-blocker, Angiotensin-converting enzyme inhibitor/Angiotensin II receptor blocker, and diuretic) (all with P-value < 0.05). In addition, patients in the myocardial injury group also presented with a higher revised cardiac risk index (Lee index), higher neutrophil granulocyte ratio, lower hemoglobin, and higher likelihood of impaired cardiac structure and function (all with P-value < 0.05). There was a trend of statistical significance in the ICU detention time between the myocardial injury group and the non-myocardial injury group (1[1,3] vs. 2[1,10], P = 0.064). In this study, there were 7 patients presented with clinical symptoms in the myocardial injury group (chest discomfort in 4 cases, non-compressive precordial chest pain in 1 case, dyspnea in 2 cases). In the multivariate analysis, advanced age, increased Lee index score, increased neutrophil granulocyte ratio, decreased left ventricular ejection fraction (LVEF), increased interventricular septum were independent risk factors for myocardial injury.

In conclusion, advanced age, increased Lee index, increased neutrophil granulocyte ratio, decreased left ventricular ejection fraction, and increased ventricular septum were independent risk factors for preoperative myocardial injury in patients with gastrointestinal tumors. The proportion of clinical symptoms in gastrointestinal tumor patients with myocardial injury was low, indicating the necessity to closely monitor the cardiac status of individuals with gastrointestinal tumors.

The recovery from cardiac surgery involves resolving inflammation and remodeling with significant connective tissue turnover. Dynamics of smoldering inflammation and injury (white blood cells, platelets, CRP, IL-8, IL-6), vascular inflammation (IL-15, VEGF, RANTES), connective tissue remodeling (tenascin, MMP-9), cardiac injury and remodeling (YKL-40), and vascular remodeling (epiregulin, MCP-1, VEGF) were assessed up to 3 months after cardiac surgery. We hypothesize that at 3 months, studied markers will return to pre-surgical levels.

Patients (n = 139) scheduled for non-emergent heart surgery were included, except for patients with pre-existing immunological aberrancies. Blood was collected before surgery(t_baseline), 24 h later(t_24h) after the first sample, 7 days(t_7d), and 3 months(t_3m) after t_baseline. Serum markers were measured via multiplex or ELISA. Electronic medical records (EMR) were used to extract demographical, pre-existing conditions and clinical data. Disposition (discharge home, discharge to facility, death, re-admission) was determined at 28 days and 3 months from admission.

Not all inflammatory markers returned to baseline (CRP↑↑, leukocytosis, thrombocytosis, IL-8↓, IL-6↓). Tenascin and YKL-40 levels remained elevated even at t_3m. YKL-40 serum levels were significantly elevated at t_24h and t_7d while normalized at t_3m. VEGF returned to the baseline, yet MCP-1 remained elevated at 3 months. CCL28 increased at 3 months, while RANTES and IL-15 declined at the same time. Disposition at discharge was determined by serum MMP-9, while YKL-40 correlated with duration of surgery and APACHE II_24h.

The data demonstrated an ongoing extracellular matrix turnover at 3 months, while acute inflammation and vascular remodeling resolved only partially.

Perioperative hypotension has been repeatedly associated with organ injury and worse outcome, yet many interventions to reduce morbidity by attempting to avoid or reverse hypotension have floundered. In part, this reflects uncertainty as to what threshold of hypotension is relevant in the perioperative setting. Shifting population-based definitions for hypertension, plus uncertainty regarding individualised norms before surgery, both present major challenges in constructing useful clinical guidelines that may help improve clinical outcomes. Aside from these major pragmatic challenges, a wealth of biological mechanisms that underpin the development of higher blood pressure, particularly with increasing age, suggest that hypotension (however defined) or lower blood pressure per se does not account solely for developing organ injury after major surgery. The mosaic theory of hypertension, first proposed more than 60 yr ago, incorporates multiple, complementary mechanistic pathways through which clinical (macrovascular) attempts to minimise perioperative organ injury may unintentionally subvert protective or adaptive pathways that are fundamental in shaping the integrative host response to injury and inflammation. Consideration of the mosaic framework is critical for a more complete understanding of the perioperative response to acute sterile and infectious inflammation. The largely arbitrary treatment of perioperative blood pressure remains rudimentary in the context of multiple complex adaptive hypertensive endotypes, defined by distinct functional or pathobiological mechanisms, including the regulation of reactive oxygen species, autonomic dysfunction, and inflammation. Developing coherent strategies for the management of perioperative hypotension requires smarter, mechanistically solid interventions delivered by RCTs where observer bias is minimised.

The use of veno-arterial extracorporeal membrane oxygenation (VA-ECMO) is increasing, but mortality remains high. Early assessment of prognosis is challenging and valid markers are lacking. This study aimed to investigate Neutrophil-Lymphocyte Ratio (NLR), Platelet-Lymphocyte-Ratio (PLR) and Procalcitonin (PCT) for early assessment of prognosis in patients undergoing VA-ECMO. This retrospective single-center cohort study included 344 consecutive patients ≥ 18 years who underwent VA-ECMO due to cardiogenic shock. Main exposures were NLR, PLR and PCT measured within 24 h after VA-ECMO initiation. The primary endpoint was all-cause in-hospital mortality. In total, 92 patients were included into final analysis (71.7% male, age 57 ± 14 years). In-hospital mortality rate was 48.9%. Receiver operating characteristics (ROC) curve revealed an area under the curve (AUC) of 0.65 [95% confidence interval (CI) 0.53-0.76] for NLR. The AUCs of PLR and PCT were 0.47 [95%CI 0.35-0.59] and 0.54 [95%CI 0.42-0.66], respectively. Binary logistic regression showed an adjusted odds ratio of 3.32 [95%CI 1.13-9.76] for NLR, 1.0 [95%CI 0.998-1.002] for PLR and 1.02 [95%CI 0.99-1.05] for PCT. NLR is independently associated with in-hospital mortality in patients undergoing VA-ECMO. However, discriminative ability is weak. PLR and PCT seem not to be suitable for this purpose.

The Revised Cardiac Risk Index (RCRI) is a widely acknowledged prognostic model to estimate preoperatively the probability of developing in-hospital major adverse cardiac events (MACE) in patients undergoing noncardiac surgery. However, the RCRI does not always make accurate predictions, so various studies have investigated whether biomarkers added to or compared with the RCRI could improve this.

Primary: To investigate the added predictive value of biomarkers to the RCRI to preoperatively predict in-hospital MACE and other adverse outcomes in patients undergoing noncardiac surgery. Secondary: To investigate the prognostic value of biomarkers compared to the RCRI to preoperatively predict in-hospital MACE and other adverse outcomes in patients undergoing noncardiac surgery. Tertiary: To investigate the prognostic value of other prediction models compared to the RCRI to preoperatively predict in-hospital MACE and other adverse outcomes in patients undergoing noncardiac surgery.

We searched MEDLINE and Embase from 1 January 1999 (the year that the RCRI was published) until 25 June 2020. We also searched ISI Web of Science and SCOPUS for articles referring to the original RCRI development study in that period.

We included studies among adults who underwent noncardiac surgery, reporting on (external) validation of the RCRI and: - the addition of biomarker(s) to the RCRI; or - the comparison of the predictive accuracy of biomarker(s) to the RCRI; or - the comparison of the predictive accuracy of the RCRI to other models. Besides MACE, all other adverse outcomes were considered for inclusion.

We developed a data extraction form based on the CHARMS checklist. Independent pairs of authors screened references, extracted data and assessed risk of bias and concerns regarding applicability according to PROBAST. For biomarkers and prediction models that were added or compared to the RCRI in ≥ 3 different articles, we described study characteristics and findings in further detail. We did not apply GRADE as no guidance is available for prognostic model reviews.

We screened 3960 records and included 107 articles.   Over all objectives we rated risk of bias as high in ≥ 1 domain in 90% of included studies, particularly in the analysis domain. Statistical pooling or meta-analysis of reported results was impossible due to heterogeneity in various aspects: outcomes used, scale by which the biomarker was added/compared to the RCRI, prediction horizons and studied populations.  Added predictive value of biomarkers to the RCRI Fifty-one studies reported on the added value of biomarkers to the RCRI. Sixty-nine different predictors were identified derived from blood (29%), imaging (33%) or other sources (38%). Addition of NT-proBNP, troponin or their combination improved the RCRI for predicting MACE (median delta c-statistics: 0.08, 0.14 and 0.12 for NT-proBNP, troponin and their combination, respectively). The median total net reclassification index (NRI) was 0.16 and 0.74 after addition of troponin and NT-proBNP to the RCRI, respectively. Calibration was not reported. To predict myocardial infarction, the median delta c-statistic when NT-proBNP was added to the RCRI was 0.09, and 0.06 for prediction of all-cause mortality and MACE combined. For BNP and copeptin, data were not sufficient to provide results on their added predictive performance, for any of the outcomes. Comparison of the predictive value of biomarkers to the RCRI  Fifty-one studies assessed the predictive performance of biomarkers alone compared to the RCRI. We identified 60 unique predictors derived from blood (38%), imaging (30%) or other sources, such as the American Society of Anesthesiologists (ASA) classification (32%). Predictions were similar between the ASA classification and the RCRI for all studied outcomes. In studies different from those identified in objective 1, the median delta c-statistic was 0.15 and 0.12 in favour of  BNP and NT-proBNP alone, respectively, when compared to the RCRI, for the prediction of MACE. For C-reactive protein, the predictive performance was similar to the RCRI. For other biomarkers and outcomes, data were insufficient to provide summary results. One study reported on calibration and none on reclassification. Comparison of the predictive value of other prognostic models to the RCRI   Fifty-two articles compared the predictive ability of the RCRI to other prognostic models. Of these, 42% developed a new prediction model, 22% updated the RCRI, or another prediction model, and 37% validated an existing prediction model. None of the other prediction models showed better performance in predicting MACE than the RCRI. To predict myocardial infarction and cardiac arrest, ACS-NSQIP-MICA had a higher median delta c-statistic of 0.11 compared to the RCRI. To predict all-cause mortality, the median delta c-statistic was 0.15 higher in favour of ACS-NSQIP-SRS compared to the RCRI. Predictive performance was not better for CHADS2, CHA2DS2-VASc, R2CHADS2, Goldman index, Detsky index or VSG-CRI compared to the RCRI for any of the outcomes. Calibration and reclassification were reported in only one and three studies, respectively.

Studies included in this review suggest that the predictive performance of the RCRI in predicting MACE is improved when NT-proBNP, troponin or their combination are added. Other studies indicate that BNP and NT-proBNP, when used in isolation, may even have a higher discriminative performance than the RCRI. There was insufficient evidence of a difference between the predictive accuracy of the RCRI and other prediction models in predicting MACE. However, ACS-NSQIP-MICA and ACS-NSQIP-SRS outperformed the RCRI in predicting myocardial infarction and cardiac arrest combined, and all-cause mortality, respectively. Nevertheless, the results cannot be interpreted as conclusive due to high risks of bias in a majority of papers, and pooling was impossible due to heterogeneity in outcomes, prediction horizons, biomarkers and studied populations. Future research on the added prognostic value of biomarkers to existing prediction models should focus on biomarkers with good predictive accuracy in other settings (e.g. diagnosis of myocardial infarction) and identification of biomarkers from omics data. They should be compared to novel biomarkers with so far insufficient evidence compared to established ones, including NT-proBNP or troponins. Adherence to recent guidance for prediction model studies (e.g. TRIPOD; PROBAST) and use of standardised outcome definitions in primary studies is highly recommended to facilitate systematic review and meta-analyses in the future.