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Introduction Propofol is a widely used sedative-hypnotic agent for critically ill patients requiring invasive mechanical ventilation (IMV). Despite its clinical benefits, propofol is associated with increased risks of hypertriglyceridemia. Early identification of patients at risk for propofol-associated hypertriglyceridemia is crucial for optimising sedation strategies and preventing adverse outcomes. Machine-learning (ML) models offer a promising approach for predicting individualised patient risks of propofol-associated hypertriglyceridemia. Methods and analysis We propose the development of an ML model aimed at predicting the risk of propofol-associated hypertriglyceridemia in ICU patients receiving IMV. The study will use retrospective data from four Mayo Clinic sites. Nested cross validation (CV) will be employed, with a tenfold inner CV loop for model tuning and selection as well as an outer loop using leave-one-site-out CV for external validation. Feature selection will be conducted using Boruta and least absolute shrinkage and selection operator-penalised logistic regression. Data preprocessing steps include missing data imputation, feature scaling and dimensionality reduction techniques. Six ML algorithms will be tuned and evaluated. Bayesian optimisation will be used for hyperparameter selection. Global model explainability will be assessed using permutation importance, and local model explainability will be assessed using SHapley Additive exPlanations. Ethics and dissemination The proposed ML model aims to provide a reliable and interpretable tool for clinicians to predict the risk of propofol-associated hypertriglyceridemia in ICU patients. The final model will be deployed in a web-based clinical risk calculator. The model development process and performance measures obtained during nested CV will be described in a study publication to be disseminated in a peer-reviewed journal. The proposed study has received ethics approval from the Mayo Clinic Institutional Review Board (IRB #23–0 07 416).

Importance Eligibility criteria for randomized clinical trials (RCTs) are designed to select clinically relevant patient populations. However, not all eligibility criteria are strongly justified, potentially excluding marginalized groups, and limiting the generalizability of trial findings. Objective To summarize and evaluate the justification of exclusion criteria in published RCTs in critical care medicine. Evidence Review A systematic sampling review of parallel-group RCTs published in the top 5 general internal medicine journals by impact factor ( The Lancet, New England Journal of Medicine, Journal of the American Medical Association, British Medical Journal, and Annals of Internal Medicine ) between January 1, 2018, and February 23, 2023, was conducted. RCTs enrolling adults in intensive care units (ICUs) and RCTs enrolling critically ill patients who required life-sustaining interventions typically initiated in the ICU were included. All study exclusion criteria were categorized as either poorly justified, potentially justified, or strongly justified, adapting previously established criteria, independently and in duplicate. Findings In total, 225 studies were identified, 75 of which were included. The median (IQR) number of exclusion criteria per trial was 19 (14-24), with 1455 total exclusion criteria. Common exclusion criteria were related to the risk of adverse reaction to interventions (302 criteria [20.8%]), followed by inability to obtain consent (120 criteria [8.2%]), and treatment limitation decisions (97 criteria [6.7%]). Most exclusion criteria were either strongly justified (1080 criteria [74.2%]) or potentially justified (297 criteria [20.4%]), whereas 5.4% (78 criteria) were poorly justified. Of the 78 poorly justified exclusion criteria, the most common were pregnancy (19 criteria [24.4%]), communication barriers (11 criteria [14.1%]), lactation (10 criteria [12.8%]), and lack of health insurance (10 criteria [12.8%]). Overall, 45 of 75 studies (60.0%) had at least 1 poorly justified exclusion criteria. Conclusions and Relevance Most exclusion criteria in critical care medicine RCTs were strongly justifiable. Across poorly justified criteria, the most common exclusions were pregnant or lactating persons, those with communication barriers, and individuals without health insurance. This highlights the need to carefully consider exclusion criteria when designing trials to minimize the inappropriate exclusion of participants and enhance generalizability.

Background: PAINESD score was established as a predictor of periprocedural acute hemodynamic instability, long-term mortality and heart failure among patients undergoing catheter ablation for ventricular tachycardia (VT-CA). Objective: To assess the validity of PAINESD score and compare outcomes of high-risk patients undergoing catheter ablation for ventricular tachycardia (VT) with and without mechanical circulatory support (MCS) use during procedure. Methods: We conducted an observational dual-center study of consecutive patients with SHD undergoing VT-CA over a decade (2012-2022). The PAINESD score, based on 7 variables (COPD, age >60 years, general anesthesia, ischemic cardiomyopathy, NYHA class III or IV, ejection fraction <25%, VT storm, and diabetes mellitus), was calculated and categorized into low risk (<10), intermediate risk (10-16), and high risk (>16) as previously reported. Two survival analyses were performed to compare outcomes between different groups: one using all-cause mortality or heart transplant as the event, and another using recurrent or repeat ablation as the event. Multivariable Cox proportional hazards regression models were used to calculate hazard ratios for each PAINESD category and to determine the hazard ratio for the use of MCS among high-risk patients. Results: We found that between 2012 to 2022, 559 ablations were performed on 441 patients. There were 296 (53%), 182 (32.6%) and 81(14.5%) patients in low, medium, and high risk. Using low risk as reference, aHR for medium risk was 2.1 (1.24-3.7; p=0.006) and for high risk was 4.6(2.54-8.3; p <0.001). Among patients with high PAINESD score (n=81), 5 patients (6.2%) required MCS (Intra-arterial balloon pump (IABP)=1, ECMO only=1, ECMO+IABP=1, bypass=2). 4/5 (80%) patients on MCS stayed on them post procedure, except one patient on IABP. In this cohort, there was no difference between patients with and without MCS in primary outcome [aHR= 1.6 (0.48-5.4); p=0.43] and in secondary OUTCOME [1.29 (0.3-5.5; p=0.735)]. Conclusion: PAINESD was a significant predictor of mortality or heart failure, but it did not help in prediction of recurrence of VT, or repeat VT-CA.

Background: Patients undergoing epicardial access for ventricular tachycardia (VT) have a higher rate of complications and VT recurrence post-procedure. Data regarding electrophysiological factors driving the outcomes are scant. Objective: To compare the factors and outcomes associated with epicardial vs endocardial VT ablation. Methods: A single-center, retrospective study of patients undergoing catheter ablation for scar-related VT was conducted. Data collected included demographics, comorbidities, medications, relevant laboratory abnormalities, electrocardiograms, echocardiograms, detailed procedural characteristics, and outcomes. Results: Our cohort of 554 patients had 89 (16.1%) epicardial and 465 (83.9%) endocardial VT ablations. Patients undergoing epicardial ablation had a greater frequency of NICM, and more patients had undergone sympathetic modulation for VT (p < 0.05) but had lesser frequency of valve surgery, and CABG. Epicardial ablation was associated with greater use of both short-term (<3 months) and long-term (>6 months) anti-arrhythmic drugs (AAD) (p<0.01). Epicardial access was obtained by micropuncture or needle-in-needle technique for 22.5% (n=20) of patients. Except for more use of general anesthesia and the lesser usage of drugs for VT induction during epicardial procedures, there were no significant differences. Epicardial ablation had a higher risk of acute complications (<30 days) after the procedure (driven by pericarditis) (25% vs 7.8%, p<0.01). On survival analysis, epicardial access was associated with an increase in VT recurrence and repeat ablation (p<0.01) during a mean follow-up of 1072 days. On multivariate analysis, after adjusting for age, sex and comorbidities, epicardial access was an independent predictor of VT recurrence or repeat ablation [aHR 1.61 (CI: 1.18- 2.2)] Conclusion: Patients undergoing epicardial ablations with fewer comorbidities demonstrated increased AAD usage prior to and after the procedure, and a higher risk of acute complications after the procedure. Epicardial access was an independent predictor of VT recurrence or repeat ablation.

Background: Despite expert opinion recommending patient-tailored cardiac rehabilitation (CR) after acute aortic dissection, both patient participation in CR and the associated risk factor modification after CR following aortic dissection repair are poorly understood. Objectives: To describe the characteristics of patients referred to CR, as well as the enrollment rate and outcomes of those referred to CR following thoracic aortic dissection. Methods: We reviewed electronic health records of adults (≥18) discharged alive following thoracic aortic dissection surgery across the Mayo Clinic Enterprise (01/01/2020-11/15/2022) with follow-up to 05/15/2024 (IRB #24-001141). Data are presented using summary statistics. Results: During the study period, 85 patients were included (median [IQR] age: 65 [50-75] years; 40% female; Table 1 ). Across 84% (N=71) who were referred to CR at discharge, 55% (N=39) enrolled. In those patients referred versus not referred to CR, the prevalence of type A dissection (75% vs. 43%), end-organ involvement (27% vs. 0%), and underlying CAD (54% vs. 21%) were greater while current tobacco use (9% vs. 29%) was lower. Of those enrolled at Mayo Clinic (N=16), CR was started 35 (28-65) days following surgery. These patients completed 21 (13-30) CR sessions at an exercise intensity of 59% (50-65%) maximum predicted heart rate. CR was discontinued in 44% (N=7) due to non-cardiac reasons ( Table 2 ). Of the 9 patients who completed CR, general health status (Dartmouth index: 19 [17-21] vs. 26 [22-34]), depressive symptoms (PHQ-9: 1 [0-1] vs. 4 [1-4]), and exercise capacity (6MWT: 214 [196-244] vs. 384 [305-597] meters) improved ( Table 2 ). There were no reported complications or deaths, with stable aortic sizes reported at 18 months. Conclusions: CR improves functional capacity and well-being without complications in patients after thoracic aortic dissection surgery. Further investigation is needed to better assess CR efficacy and usage in this population.

Background: In recent years, catheter ablation has emerged as a sustainable, first-line therapy for the management of ventricular tachycardia (VT). Given the rise of the “obesity paradox” theory in atrial ablation outcomes, we sought to study the effect of BMI on patients undergoing structural VT ablation. Purpose: To assess the outcomes of VT ablation, specifically VT recurrence, in patients with elevated vs. normal BMI. Methods: Clinical characteristics and demographic data were collected for VT patients who underwent ablation at Mayo Clinic Rochester from 2012-2022. Patient BMI was classified as non-obese (<30 kg/m2), obese (30-40 kg/m2), and morbidly obese (≥40 kg/m2). The endpoint was a composite of initial monomorphic VT recurrence and repeat ablation after adjusting for age, sex, and comorbidities. Results: A total of 399 patients underwent 508 ablations. 51.4% of ablations had a BMI <30, 39.2% were between 30-40, and 9.4% were ≥40. There was a greater prevalence of hypertension and type 2 diabetes mellitus in morbidly obese patients (p <0.01). Morbidly obese individuals also had a significantly increased rate of general anesthesia during ablation and long VT cycle lengths. The Kaplan-Meier curve demonstrates no statistically significant differences in time to VT recurrence among the three BMI groups (p = 0.324). Neither morbid-obesity (aHR= 1.20; CI = 0.94-1.56, p = 0.14) nor nonmorbid-obesity (aHR = 0.92; CI = 0.76-1.10, p = 0.4), compared to non-obesity was a significant independent predictor of VT recurrence or repeat ablation on multivariate regression after adjusting for age, sex and comorbidities. Conclusion: There was no significant association between BMI groups and VT recurrence or repeat ablation, and no difference in complications. We did not find the obesity paradox to be relevant for VT ablation in our patient population. Further study would be needed with larger samples to corroborate these findings.

Abstract Background Ventricular tachycardia (VT) is a life-threatening arrhythmia that can complicate structural heart disease. While catheter ablation is effective in treating this condition, the recurrence of VT after the procedure continues to be a concern. Consequently, there is a need for a reliable system to evaluate the likelihood of arrhythmia recurrence following an ablation. Objective To predict recurrence or repeat ablation after a VT catheter ablation procedure using machine learning (ML) models. Methods We conducted a single-center, retrospective study of all patients undergoing catheter ablation for scar-related VT between 2012 and 2022. Data collected included demographics, comorbidities, medications, relevant laboratory abnormalities, electrocardiograms, echocardiograms, detailed procedural characteristics, and outcomes. Python version 3.8.5 for exploratory data analysis (EDA) and visualization. Using six different ML models from the training set (90:10 split), we used 34 variables to predict the primary outcome, including VT recurrence or repeat catheter ablation. The accuracy of these models was compared using ROC curves based on their performance on the test set. Results Out of 508 VT ablation procedures, 261 experienced a recurrence. Support Vector Classifier (SVM) performed the best, having an AUC of 0.73, followed by logistic regression at 0.69 (Figure A). SVM yielded sensitivity, specificity, positive and negative predictive values of 0.73, 0.73, 0.79, and 0.67, respectively. The F1 score was 0.70. Among the factors with the highest feature importance in the model, the most influential variable was the proceduralist’s experience level, followed by QRS width at baseline, LVEF, and patient’s age (Figure B). Conclusion Our model can predict recurrent VT after ablation with reasonable accuracy, outperforming the existing clinical risk scores significantly. Larger training sample sizes will help achieve more robust ML models and improve predictive accuracy further.Figure A: ROC curve depicting the AUROCB. Feature importance graph

Abstract Rationale Propofol is one of the first-line sedative-hypnotic agents for critically ill adults requiring mechanical ventilation. Although propofol can elevate triglyceride levels, and the latter is a risk factor for pancreatitis, the association between propofol and acute pancreatitis is unclear. Objectives We sought to determine the clinical impact and potential associations between propofol infusion, hypertriglyceridemia, and acute pancreatitis. Methods This is an observational multicenter study of adults (⩾18 yr old) who were admitted to an intensive care unit, who required mechanical ventilation and received continuous propofol infusion for at least 24 hours. The primary outcomes were the frequency of hypertriglyceridemia (&gt;400 mg/dl) and acute pancreatitis. Further analyses were done to determine the clinical impact of elevated triglyceride levels (i.e., sedation changes) and risk factors for pancreatitis development. Results Of 11,828 patients included, 33.2% (n = 3,922) had triglyceride levels measured, of whom 21.7% (n = 851) had hypertriglyceridemia at 4.5 days (SD = 6.8) after propofol initiation. Of those still requiring sedation, 70.4% (n = 576/818) received alternative sedatives after developing hypertriglyceridemia. Pancreatitis occurred in 1.2% of patients (n = 47/3,922) and was more frequent in those with hypertriglyceridemia (3.2%, 27/851; vs. 0.7%, 20/3,071; P &lt; 0.001). After adjustment for potential confounding variables, each 100 mg/dl increase in triglyceride levels was associated with an 11% increase in risk of pancreatitis. Propofol dose was not associated with pancreatitis development. Conclusions Acute pancreatitis is uncommon in patients receiving propofol infusion, and it occurs over a wide range of triglyceride levels, indicating a multifactorial pathophysiology. Hypertriglyceridemia frequently prompts the use of alternative sedatives. Further study is needed to determine how to best monitor and treat hypertriglyceridemia in critically ill patients receiving propofol infusion.

Objective: To assess the efficacy and safety of corticosteroids for the management of pediatric sepsis and septic shock. Data Sources: Ovid MEDLINE, Ovid Embase, CENTRAL, Web of Science (Core Collection) and China National Knowledge Infrastructure were systematically searched up to September 2023. Preprint servers, clinical trial registries and the reference sections of previous reviews were hand-searched. Study Selection: Randomized controlled trials that enrolled pediatric sepsis, septic shock or systemic inflammatory response syndrome patients, compared the use of corticosteroid regimens against standard sepsis care and reported eligible outcomes were included. Title/abstract and full-text screening were conducted in-duplicate. Data Extraction: Eligible articles were extracted using a standardized form in-duplicate. Outcomes extracted include mortality incidence, hospital and pediatric intensive care unit length of stay, duration of shock, incidence of adverse events and serious adverse events and incidence of corticosteroid-related adverse events. The risk of bias was assessed using the Revised Cochrane Risk of Bias Tool for Assessing Randomized Trials. Data Synthesis: Random-effects meta-analyses were conducted, and the quality of evidence was assessed using the Grading of Recommendations, Assessment, Development and Evaluations approach. Sixteen randomized controlled trials (N = 973) were included. Corticosteroid use may be associated with reduced mortality risks (risk ratio: 0.65, 95% CI: 0.50–0.85), shorter length of hospital stay (MD: −3.76 days, 95% CI: −6.66 to −0.86), and shorter pediatric intensive care unit length of stay (MD −2.34 days, 95% CI: −3.14 to −1.53 days). Corticosteroid use may be associated with gastrointestinal bleeding but not a higher risk of secondary infection. No studies reported on serious adverse events. All findings were based on low to very low quality of evidence. Conclusions: While corticosteroids show promise for managing pediatric sepsis and septic shock, the question of how to select the best candidate and the most optimal regimen remains unanswered. Future trials need to focus on assessing corticosteroid-related adverse events and stratifying patient inclusion by sepsis subphenotypes.

Objective: The objective of this study was to measure potential associations between surgeon sex and number of days alive and at home (DAH). Background: Patients treated by female surgeons appear to have lower rates of mortality, complications, readmissions, and healthcare costs when compared with male surgeons. DAH is a validated measure, shown to better capture the patient experience of postoperative recovery. Methods: We conducted a retrospective study of adults (≥18 years of age) undergoing common surgeries between January 01, 2007 and December 31, 2019 in Ontario, Canada. The outcome measures were the number of DAH within 30-, 90-, and 365-days. The data was summarized using descriptive statistics and adjusted using multivariable generalized estimating equations. Results: During the study period, 1,165,711 individuals were included, of which 61.9% (N = 721,575) were female. Those managed by a female surgeon experienced a higher mean number of DAH when compared with male surgeons at 365 days (351.7 vs. 342.1 days; P < 0.001) and at each earlier time point. This remained consistent following adjustment for covariates, with patients of female surgeons experiencing a higher number of DAH at all time points, including at 365 days (343.2 [339.5–347.1] vs. 339.4 [335.9–343.0] days). Multivariable regression modeling revealed that patients of male surgeons had a significantly lower number of DAH versus female surgeons. Conclusions: Patients of female surgeons experienced a higher number of DAH when compared with those treated by male surgeons at all time points. More time spent at home after surgery may in turn lower costs of care, resource utilization, and potentially improve quality of life. Further studies are needed to examine these findings across other care contexts.