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In the 30 years since the original description of ischaemic preconditioning, understanding of the pathophysiology of ischaemia/reperfusion injury and concepts of cardioprotection have been revolutionised. In the same period of time, management of patients with coronary artery disease has also been transformed: coronary artery and valve surgery are now deemed routine with generally excellent outcomes, and the management of acute coronary syndromes has seen decade on decade reductions in cardiovascular mortality. Nonetheless, despite these improvements, cardiovascular disease and ischaemic heart disease in particular, remain the leading cause of death and a significant cause of long-term morbidity (with a concomitant increase in the incidence of heart failure) worldwide. The need for effective cardioprotective strategies has never been so pressing. However, despite unequivocal evidence of the existence of ischaemia/reperfusion in animal models providing a robust rationale for study in man, recent phase 3 clinical trials studying a variety of cardioprotective strategies in cardiac surgery and acute ST-elevation myocardial infarction have provided mixed results. The investigators meeting at the Hatter Cardiovascular Institute workshop describe the challenge of translating strong pre-clinical data into effective clinical intervention strategies in patients in whom effective medical therapy is already altering the pathophysiology of ischaemia/reperfusion injury—and lay out a clearly defined framework for future basic and clinical research to improve the chances of successful translation of strong pre-clinical interventions in man. [ABSTRACT FROM AUTHOR]

Background: Remote ischemic preconditioning (RIPC) is reported to reduce biomarkers of ischemic and reperfusion injury in patients undergoing cardiac surgery, but uncertainty about clinical outcomes remains.Methods: We conducted a prospective, double-blind, multicenter, randomized, controlled trial involving adults who were scheduled for elective cardiac surgery requiring cardiopulmonary bypass under total anesthesia with intravenous propofol. The trial compared upper-limb RIPC with a sham intervention. The primary end point was a composite of death, myocardial infarction, stroke, or acute renal failure up to the time of hospital discharge. Secondary end points included the occurrence of any individual component of the primary end point by day 90.Results: A total of 1403 patients underwent randomization. The full analysis set comprised 1385 patients (692 in the RIPC group and 693 in the sham-RIPC group). There was no significant between-group difference in the rate of the composite primary end point (99 patients [14.3%] in the RIPC group and 101 [14.6%] in the sham-RIPC group, P=0.89) or of any of the individual components: death (9 patients [1.3%] and 4 [0.6%], respectively; P=0.21), myocardial infarction (47 [6.8%] and 63 [9.1%], P=0.12), stroke (14 [2.0%] and 15 [2.2%], P=0.79), and acute renal failure (42 [6.1%] and 35 [5.1%], P=0.45). The results were similar in the per-protocol analysis. No treatment effect was found in any subgroup analysis. No significant differences between the RIPC group and the sham-RIPC group were seen in the level of troponin release, the duration of mechanical ventilation, the length of stay in the intensive care unit or the hospital, new onset of atrial fibrillation, and the incidence of postoperative delirium. No RIPC-related adverse events were observed.Conclusions: Upper-limb RIPC performed while patients were under propofol-induced anesthesia did not show a relevant benefit among patients undergoing elective cardiac surgery. (Funded by the German Research Foundation; RIPHeart ClinicalTrials.gov number, NCT01067703.). [ABSTRACT FROM AUTHOR]

Background: It remains unclear if early enteral nutrition benefits patients with circulatory shock, particularly in those with prolonged use of vasopressors. This study aimed to assess the association between early enteral nutrition and clinical outcomes in patients with circulatory shock and whether the duration of circulatory shock (transient or persistent) impacts this association., Methods: Using data from a multicenter, cluster-randomized controlled trial, this secondary analysis involved patients with baseline circulatory shock as defined by a cardiovascular Sequential Organ Failure Assessment score of two or more. Patients were dichotomized into transient or persistent circulatory shock depending on the duration, while transient circulatory shock was defined by the resolution of shock within the first day of enrollment. Early enteral nutrition was defined as the initiation of enteral nutrition within 48 h after intensive care unit admission. The association between early enteral nutrition and a composite outcome (presence of any organ failure on study day 10 or 28-day mortality) was investigated by multivariable and propensity-score-weighted multivariable logistic regression analyses., Results: Seven hundred and eighty-five patients were included in the analysis, and early enteral nutrition was administered to 385 patients (49.0 %) in the whole study cohort. In patients with transient circulatory shock (n = 527), 221 patients (41.9 %) received early enteral nutrition, and in those with persistent circulatory shock (n = 258), 164 patients (63.6 %) did so. For the overall cohort, there was no difference in the incidence of primary composite outcome between early enteral nutrition and 'no early enteral nutrition ' groups (adjusted odd ratio 0.84, 95 % confidence interval 0.60-1.18) after adjustment for potential confounders. In patients with transient circulatory shock, receipt of early enteral nutrition, compared to no early enteral nutrition, was significantly associated with reduced incidence of the composite outcome (adjusted odd ratio 0.63, 95 % confidence interval 0.41-0.95, p = 0.027). On the contrary, there is no association between early enteral nutrition and the incidence of the composite outcome in patients with persistent circulatory shock (adjusted odd ratio 1.28, 95 % confidence interval 0.64-2.58, p = 0.485). The results of propensity-weighted multivariable analysis conform to the primary analysis., Conclusion: Early enteral nutrition was associated with improved clinical outcomes among patients with circulatory shock that resolved within the first day. RESEARCH REGISTRATION UNIQUE IDENTIFYING NUMBER (UIN) OF THE ORIGINAL NEED TRIAL: ISRCTN Registry, Registry number: ISRCTN12233792., Competing Interests: Conflict of interest The authors declare that they have no conflict of interest., (Copyright © 2025 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.)

Precision in critical care nutrition is paramount, as it focuses nutrition interventions on those patients most likely to benefit, or those who might potentially be harmed. Critical care nutrition must therefore be tailored to individual metabolic needs as determined by factors that control the capacity for tissue homeostasis and anabolic responses. This ideally involves the accurate and timely assessment of macronutrient and micronutrient requirements, a careful evaluation of metabolic response mechanisms and the identification of circumstances that might interfere with the productive utilization of dietary substrates. Specific surrogate markers of metabolic response, such as blood glucose levels, urea levels, or nitrogen balance, might be used to evaluate the metabolic readiness for nutrition and to establish the timing, nature, and clinical effectiveness of nutrition interventions. Despite the pressing need to further develop more targeted approaches in critically ill patients, indices of immediate metabolic responses that correlate with favorable clinical outcomes are lacking. In addition, the development of precision approaches might address timely adjustments in protein, energy, or micronutrient supplementation based on evolving clinical conditions. Here, we review why precision tools are needed in critical care nutrition, our progress thus far, as well as promising approaches and technologies by which multidisciplinary healthcare teams can improve quality of care and clinical outcomes by individualizing nutrition interventions., Competing Interests: Dr. Stoppe received funding from B. Braun, Fresenius, and Baxter. Dr. Hill’s institution received funding from Fresenius Kabi and Baxter; she received funding from the Medical Faculty RWTH Aachen—Stipend “Habilitationsstipendium.” The remaining authors have disclosed that they do not have any potential conflicts of interest., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the Society of Critical Care Medicine and Wolters Kluwer Health, Inc.)

Micronutrient (MN) status alterations (both depletion and deficiency) are associated with several complications and worse outcomes in critically ill patients. On the other side of the spectrum, improving MN status has been shown to be a potential co-adjuvant therapy. This review aims to collect existing data to better guide research in the critical care setting. This narrative review was conducted by the European Society of Intensive Care Medicine Feeding, Rehabilitation, Endocrinology, and Metabolism MN group. The primary objective was to identify studies focusing on individual MNs in critically ill patients, selecting the MNs that appear to be most relevant and most frequently investigated in the last decade: A, B 1 , B 2 , B 3 , B 6 , folate, C, D, E, copper, iron, selenium, zinc, and carnitine. Given the limited number of interventional studies for most MNs, observational studies were included. For each selected MN, the review summarizes the main form and functions, special needs and risk factors, optimal treatment strategies, pharmacological dosing, and clinical implications all specific to critically ill patients. A rigorous rebalancing of research strategies and priorities is needed to improve clinical practice. An important finding is that high-dose monotherapy of MNs is not recommended. Basal daily needs must be provided, with higher doses in diseases with known higher needs, and identified deficiencies treated. Finally, the review provides a list of ongoing trials on MNs in critically ill patients and identifies a priority list of future research topics., (© 2024 The Author(s). Journal of Parenteral and Enteral Nutrition published by Wiley Periodicals LLC on behalf of American Society for Parenteral and Enteral Nutrition.)

Background: Temporary mechanical circulatory support (tMCS) has become a standard treatment in cardiogenic shock but is associated with high complication rates. This study analyzes common complications associated with modern tMCS devices and their impact on mortality depending on the tMCS approach., Methods: We conducted a retrospective single-center analysis of patients with all-cause cardiogenic shock treated with veno-arterial extracorporeal life support, microaxial flow pump, and a combination of both (ECMELLA). The primary outcome was the impact of cumulative complications on mortality, evaluated separately for nonsurgical (non-PCCS) and cardiac surgical (PCCS) patients. Secondary outcomes included the impact of complications on mortality stratified by tMCS type and rates of bleeding, the need for renal replacement therapy (RRT), hemolysis, neurological complications, bloodstream infections, and ischemic limb complications., Results: We included 493 patients, totaling 4,881 days on tMCS support. Non-PCCS patients with 1 complication had a hazard ratio (HR) of 1.92 (95% confidence interval [CI]: 1.22, 3.00, p = 0.004) for mortality and 3.73 (95% CI: 2.48, 5.60, p < 0.001) for 2 or more complications compared to those without complications. In PCCS patients, 1 complication was associated with an HR of 2.22 (95% CI: 1.29, 3.81, p = 0.004) and 3.44 (95% CI: 2.04, 5.78, p < 0.001) for 2 or more complications. The most common complications in both non-PCCS and PCCS patients were bleeding (33% and 60%), need for RRT (31% and 43%), and severe hemolysis (26% and 35%)., Conclusion: Complications among tMCS-treated patients are common and clearly associated with an elevated mortality risk., (Copyright © 2025 The Authors. Published by Elsevier Inc. All rights reserved.)

Objectives: Recent multicenter trials suggest that higher protein delivery may result in worse outcomes in critically ill patients, but uncertainty remains. An updated Bayesian meta-analysis of recent evidence was conducted to estimate the probabilities of beneficial and harmful treatment effects., Data Sources: An updated systematic search was performed in three databases until September 4, 2024. The study adhered to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses 2020 guidelines and the protocol was preregistered in PROSPERO (CRD42024546387)., Study Selection: Randomized controlled trials that studied adult critically ill patients comparing protein doses delivered enterally and/or parenterally with similar energy delivery between groups were included., Data Extraction: Data extraction was performed by two authors independently, using a predefined worksheet. The primary outcome was mortality. Posterior probabilities of any benefit (relative risk [RR] < 1.00) or harm (RR > 1.00) and other important beneficial and harmful effect size thresholds were estimated. Risk of bias assessment was performed using the risk of bias 2.0 tool. All analyses were performed using a Bayesian hierarchical random-effects models, under vague priors., Data Synthesis: Twenty-two randomized trials (n = 4164 patients) were included. The mean protein delivery in the higher and lower protein groups was 1.5 ± 0.6 vs. 0.9 ± 0.4 g/kg/d. The median RR for mortality was 1.01 (95% credible interval, 0.84-1.16). The posterior probability of any mortality benefit from higher protein delivery was 43.6%, while the probability of any harm was 56.4%. The probabilities of a 1% (RR < 0.99) and 5% (RR < 0.95) mortality reduction by higher protein delivery were 38.7% and 22.9%, respectively. Conversely, the probabilities of a 1% (RR > 1.01) and 5% (RR > 1.05) mortality increase were 51.5% and 32.4%, respectively., Conclusions: There is a considerable probability of an increased mortality risk with higher protein delivery in critically ill patients, although a clinically beneficial effect cannot be completely eliminated based on the current data., Competing Interests: Dr. Deane is employed by an institution that has received lecture fees from Baxter Healthcare for his time. Dr. van de Poll received in kind support from Nutricia Research for the PRotEin provision in Critical IllneSs (PRECISe) trial and speaker and travel fees from Nutricia Research. The remaining authors have disclosed that they do not have any potential conflicts of interest., (Copyright © 2024 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved.)

Purpose: Gastrointestinal (GI) dysfunction is common in critically ill patients and associated with poor outcomes. There is a lack of standardised methods for daily monitoring of GI function. COSMOGI aimed to develop a Core Outcome Set (COS) for daily monitoring of GI function to improve consistency and comparability in future studies in critically ill patients., Methods: A modified Delphi consensus process engaging healthcare providers, clinical researchers, and patient representatives was performed. A systematic review identified existing parameters to monitor GI function, informing the development of potential outcomes. In Stage 1, participants rated outcomes (i.e., variables used for daily monitoring). In Stage 2, they refined and agreed on the definitions for the selected outcomes. The COS was ratified through consensus meetings., Results: 368 individuals registered for the Delphi process. 285 participants (77.4%) completed Stage 1, and 181 participants (63.5%) completed Stage 2. From 77 potential outcomes, 13 essential outcomes for daily monitoring of GI function in studies, each with an agreed-upon definition, were established: abdominal distension, bowel dilatation, intra-abdominal pressure, abdominal pain, stool passage, vomiting, GI bleeding (upper and lower), use of parenteral nutrition due to intolerance of enteral nutrition, prokinetics, postpyloric feeding due to gastroparesis, lower GI paralysis, gastroparesis, intolerance to enteral nutrition., Conclusions: Using a modified Delphi consensus process, COSMOGI established a COS for monitoring GI function in critically ill patients in research. This COS and definitions provide a framework to guide future research, enabling comparability across studies and allowing for future definitions of GI dysfunction., Trial Registration: This project was registered at ( www.comet-initiative.org ) on 27.03.2023 (number 2609) and was an ESICM-endorsed research project., Competing Interests: Declarations. Ethics approval and consent to participate: Not applicable, no ethical approval was needed for this study. Participants were invited and informed via participant information sheets available at https://cosmogi.site/documents . Consent for publication: All participants were informed about the aims of this study and the intent to publish. Participants who chose to be listed personally can be found in the online supplement. Competing interests: Varsha Asrani: No conflict of interest. Kaspar Felix Bachmann: No conflict of interest. Danielle E. Bear: Consulting fees from Baxter Healthcare, Fresenius Kabi, and Nestle Health Science. Giuliano Bolondi: No conflict of interest. Sabrina Boraso: No conflict of interest. Michael Casaer: Supported by the Research Foundation—Flanders, Belgium through a senior clinical investigator fellowship (1832822N). Zhigang Chang: No conflict of interest. Craig M. Coopersmith: Supported by the National Institutes of Health (R35GM148217). Antonella Cotoia: No conflict of interest. Thomas Davies: No conflict of interest. Angelique De Man: No conflict of interest. Gunnar Elke: No conflict of interest. Kursat Gundogan: No conflict of interest. Jan Gunst: Supported by the Research Foundation—Flanders, Belgium through a senior clinical investigator fellowship (1842724N). Bethan Jenkins: No conflict of interest. Slavica Kvolik: No conflict of interest. Marcus Laube: No conflict of interest. Matthias Lindner: No conflict of interest. Juan Carlos Lopez-Delgado: No conflict of interest. Cecilia Loudet: No conflict of interest. Ram Matsa: No conflict of interest. Emmanuel Pardo: EP received a research grant from Nestle Health Science. Simone Piva: No conflict of interest. Zudin Puthucheary: ZP has received honoraria for consultancy from Fresenius Kabi and Nutricia. Annika Reintam Blaser: ARB received speaker fee from Nutricia, consultancy fees from Fresenius Kabi and Nestle Health Science. Todd Rice: TWR has received consultancy fees from Nestle, Baxter, Abbott, and Fresenius Kabi. Sergio Ruiz-Santana: No conflict of interest. Stefan J. Schaller: SJS received grants and non-financial support from Baxter, Fresenius, and Nutricia. Joel Starkopf: No conflict of interest. Christian Stoppe: No conflict of interest. Arthur Van Zanten: ARHvZ reported receiving honoraria for advisory board membership from Baxter, Nutricia, and Fresenius Kabi, and research funding from Baxter., (© 2024. The Author(s).)

Evaluation of treatment outcomes in patients supported by temporary mechanical circulatory support (tMCS) currently relies mainly on mortality, which may not sufficiently address other patient benefits or harms. Bleeding and thrombosis are major contributors to mortality. Still, current bleeding scores are not designed for critically ill patients undergoing tMCS, only consider selected populations, and do not account for the high heterogeneity among bleeding and thrombotic adverse events. To improve clinical management, a group of European experts has proposed a revised scoring system based on the MOMENTUM 3 Hemocompatibility Score and the Society of Cardiac Angiography and Interventions (SCAI)classification of cardiogenic shock. The new system termed the Scoring Haemostasis Events and Assessment for Risk (SHEAR) score, is divided into a baseline characterization stage and four escalating scoring stages encompassing all aspects of clinical relevance. This report summarizes the literature on hemocompatibility-related adverse events associated with tMCS, including bleeding, stroke, vascular access complications, hemolysis, thrombosis, and device failure. The SHEAR score provides a simple and rapid bedside scoring system aiming to provide a univocal tool to increase physician awareness of hemocompatibility complications at baseline and beyond, improve clinical research, and enable the capture of device-related complications that will inform relevant outcomes beyond mortality., Competing Interests: Declaration of competing interest The authors declare the following financial interests and/or personal relationships that may be considered potential competing interests: All authors received honoraria from Abiomed., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Objectives: This study investigates our enhanced recovery after minimally invasive cardiac surgery program "enhanced recovery after minimally invasive cardiac surgery" (ERMICS) following a 'Zero ICU' concept compared to standard-of-care treatment in terms of safety and clinical efficacy., Methods: All patients who underwent minimally invasive mitral valve surgery for primary severe mitral valve regurgitation between 2021 and 2023 were included. Propensity score matching (2:1) was performed between patients who received standard-of-care treatment and those who underwent ERMICS. Patients treated with the ERMICS approach were transferred to the peripheral ward instead of the intensive care unit on the day of surgery (Zero ICU). Separate primary end-points were safety (mortality, stroke), postoperative ventilation time and hospital length of stay., Results: A total of 611 patients (566 standard of care vs 45 ERMICS) were included in the study. After 2:1 matching, the cohort comprised 135 patients (90 standard of care vs 45 ERMICS) and were well balanced in terms of pre- and intraoperative variables. Thirty-day mortality was 0% in both groups. Postoperative ventilation time [P = 0.018, odds ratio (OR) < 0.01, confidence interval (CI) < 0.001], postoperative pain (P = 0.005, OR = 0.36, CI 0.18-0.74) and hospital length of stay (P = 0.049, OR = 0.28, CI 0.08-0.98) was significantly lower in ERMICS patients, while postoperative complications did not differ., Conclusions: Our ERMICS 'Zero ICU' concept is safe and leads to significantly shorter postoperative ventilation time and hospital length of stay for patients undergoing minimally invasive mitral valve surgery for primary severe mitral valve regurgitation., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.)

Background: No specific triglyceride-lowering therapy is recommended in patients with hypertriglyceridemia-associated acute pancreatitis (HTG-AP), primarily because of the lack of quality evidence. This study aimed to describe practice variations in triglyceride-lowering therapies for early HTG-AP patients and assess whether more rapid triglyceride decline is associated with improving organ failure., Methods: This is a multicentre, prospective cohort study recruiting HTG-AP patients with elevated plasma triglyceride (> 11.3 mmol/L) admitted within 72 h from the onset of symptoms. Patients were dichotomised on study day 3 into either target reaching (plasma triglyceride ≤ 5.65 mmol/L) or not. The primary outcome was organ failure-free days (OFFD) to 14 days of enrolment. The association between target-reaching and OFFD was modelled. Additionally, the slope in plasma triglyceride over the first three days in response to treatment was calculated, and its association with OFFD was assessed as a sensitivity analysis., Results: Among the 300 enrolled patients, 211 underwent exclusive medical treatment, and 89 underwent various blood purification therapies. Triglyceride levels were available in 230 patients on study day 3, among whom 122 (53.0%) had triglyceride levels of ≤ 5.65 mmol/l. The OFFD was not different between these patients and those in whom plasma triglyceride remained > 5.65 mmol/L [median (IQR): 13 (10-14) vs. 14 (10-14), p = 0.46], even after adjustment for potential confounders. For the decline slopes, there was no significant change in OFFD with a steeper decline slope [risk difference, - 0.088, 95% CI, - 0.334 to 0.158, p = 0.48]., Conclusions: Triglyceride-lowering therapies vary greatly across centres. More rapid triglyceride decline was not associated with improving incidence and duration of organ failure., Competing Interests: Declarations Ethics approval and consent to participate The study was approved by the ethics committee of Jinling Hospital (ethical number: 2020NZKY-016–01) and registered with the Chinese Clinical Trial Registry (ChiCTR2000039541). The local hospital ethics committees of all the participating sites also approved the trial. Consent for publication Not applicable. Competing interests The authors declare that they have no competing interests., (© 2024. The Author(s).)

Background: Evidence on the benefits of fiber-supplemented enteral nutrition (EN) in critically ill patients is inconsistent, and critical care nutrition guidelines lack recommendations based on high-quality evidence. This systematic review and meta-analysis (SRMA) aims to provide a current synthesis of the literature on this topic., Methods: For this SRMA of randomized controlled trials (RCT), electronic databases (MEDLINE, EMBASE, CENTRAL) were searched systematically from inception to January 2024 and updated in June 2024. Trials investigating clinical effects of fiber-supplemented EN versus placebo or usual care in adult critically ill patients were selected. Two independent reviewers extracted data and assessed the risk of bias of the included studies. Random-effect meta-analysis and trial sequential analysis (TSA) were conducted. The primary outcome was overall mortality, and one of the secondary outcomes was diarrhea incidence. Subgroup analyses were also performed for both outcomes., Results: Twenty studies with 1405 critically ill patients were included. In conventional meta-analysis, fiber-supplemented EN was associated with a significant reduction of overall mortality (RR 0.66, 95% CI 0.47, 0.92, p = 0.01, I 2  = 0%; 12 studies) and diarrhea incidence (RR 0.70, 95% CI 0.51, 0.96, p = 0.03, I 2  = 51%; 11 studies). However, both outcomes were assessed to have very serious risk of bias, and, according to TSA, a type-1 error cannot be ruled out. No subgroup differences were found for the primary outcome., Conclusion: Very low-certainty evidence suggests that fiber-supplemented EN has clinical benefits. High-quality multicenter RCTs with large sample sizes are needed to substantiate any firm recommendation for its routine use in this group of patients. PROSPERO registration number: CRD42023492829., (© 2024. The Author(s).)

Purpose: Cardiac surgery, post-cardiotomy cardiogenic shock (PCCS), and temporary mechanical circulatory support (tMCS) provoke substantial inflammation. We therefore investigated whether a selenium-based, anti-inflammatory strategy would benefit PCCS patients treated with tMCS in a post-hoc analysis of the sustain CSX trial., Methods: Post-hoc analysis of patients receiving tMCS for PCCS in the Sustain CSX trial, which investigated the effects of high-dose selenium on postoperative organ dysfunction in cardiac surgery patients., Primary Outcome: duration of tMCS therapy., Secondary Outcomes: postoperative organ dysfunction and 30-day mortality., Results: Thirty-nine patients were treated with tMCS for PCCS. There was no difference in the median duration of tMCS between the selenium and the placebo group (3 days [IQR: 1-6] vs. 2 days [IQR: 1-7], p = 0.52). Median dialysis duration was longer in the selenium group (1.5 days [0-21.8] vs. 0 days [0-1.8], p = 0.048). There was no difference in 30-day mortality (53% vs. 41%, OR 1.44, 95% CI 0.32-6.47, p = 0.62)., Conclusion: In this explorative study, a perioperative high-dose selenium-supplementation did not show beneficial effects on organ dysfunctions and mortality rates in patients with PCCS receiving tMCS., Competing Interests: Declaration of competing interest S.O. received institutional research and study funds from Novartis Pharma GmbH and institutional research, study and educational grants, speaker fees, and advisory board fees from Abiomed outside this work. E. D. received speaker honoraria from Baxter outside this work. G.E. declares speaker honoraria from Baxter and Fresenius Kabi outside this work. B.O·B declares: British Heart Foundation for Tight K, The role of Potassium in AFACS prevention (Grant number CS/18/3/34063); National Institute for Health Research (NIHR) for Predicting AF after Cardiac Surgery - the PARADISE Scores: A Clinical Prediction Rule for AFACS (Grant number NIHR131227). All outside this work. All other authors declare no conflicts of interest., (Copyright © 2023. Published by Elsevier Inc.)

Importance: Supplementing potassium in an effort to maintain high-normal serum concentrations is a widespread strategy used to prevent atrial fibrillation after cardiac surgery (AFACS), but is not evidence-based, carries risks, and is costly., Objective: To determine whether a lower serum potassium concentration trigger for supplementation is noninferior to a high-normal trigger., Design, Setting, and Participants: This open-label, noninferiority, randomized clinical trial was conducted at 23 cardiac surgical centers in the United Kingdom and Germany. Between October 20, 2020, and November 16, 2023, patients with no history of atrial dysrhythmias scheduled for isolated coronary artery bypass grafting (CABG) surgery were enrolled. The last study patient was discharged from the hospital on December 11, 2023., Interventions: Patients were randomly assigned to a strategy of tight or relaxed potassium control (only supplementing if serum potassium concentration fell below 4.5 mEq/L or 3.6 mEq/L, respectively). Patients wore an ambulatory heart rhythm monitor, which was analyzed by a core laboratory masked to treatment assignment., Main Outcomes and Measures: The prespecified primary end point was clinically detected and electrocardiographically confirmed new-onset AFACS in the first 120 hours after CABG surgery or until hospital discharge, whichever occurred first. All primary outcome events were validated by an event validation committee, which was masked to treatment assignment. Noninferiority of relaxed potassium control was defined as a risk difference for new-onset AFACS with associated upper bound of a 1-sided 97.5% CI of less than 10%. Secondary outcomes included other heart rhythm-related events, clinical outcomes, and cost related to the intervention., Results: A total of 1690 patients (mean age, 65 years; 256 [15%] females) were randomized. The primary end point occurred in 26.2% of patients (n = 219) in the tight group and 27.8% of patients (n = 231) in the relaxed group, which is a risk difference of 1.7% (95% CI, -2.6% to 5.9%). There was no difference between the groups in the incidence of at least 1 AFACS episode detected by any means or by ambulatory heart rhythm monitor alone, non-AFACS dysrhythmias, in-patient mortality, or length of stay. Per-patient cost for purchasing and administering potassium was significantly lower in the relaxed group (mean difference, $111.89 [95% CI, $103.60-$120.19]; P <.001)., Conclusions and Relevance: For AFACS prophylaxis, supplementation only when serum potassium concentration fell below 3.6 mEq/L was noninferior to the current widespread practice of supplementing potassium to maintain a serum potassium concentration greater than or equal to 4.5 mEq/L. The lower threshold of supplementation was not associated with any increase in dysrhythmias or adverse clinical outcomes., Trial Registration: ClinicalTrials.gov Identifier: NCT04053816.

Background/aims: Metabolic syndrome is common in patients with acute pancreatitis and its components have been reported to be associated with infectious complications. In this post hoc analysis, we aimed to evaluate whether metabolic abnormalities impact the effect of immune-enhancing thymosin alpha-1 (Tα1) therapy in acute necrotizing pancreatitis (ANP) patients., Methods: All data were obtained from the database for a multicenter randomized clinical trial that evaluated the efficacy of Tα1 in ANP patients. Patients who discontinued the Tα1 treatment prematurely were excluded. The primary outcome was 90-day infected pancreatic necrosis (IPN) after randomization. Three post hoc subgroups were defined based on the presence of hyperglycemia, hypertriglyceridemia, or both at the time of randomization. In each subgroup, the correlation between Tα1 and 90-day IPN was assessed using the Cox proportional-hazards regression model. Multivariable propensity-score methods were used to control potential bias., Results: Overall, 502 participants were included in this post hoc analysis (248 received Tα1 treatment and 254 received matching placebo treatment). Among them, 271 (54.0%) had hyperglycemia, 371 (73.9%) had hypertriglyceridemia and 229 (45.6%) had both. Tα1 therapy was associated with reduced incidence of IPN among patients with hyperglycemia (18.8% vs 29.7%: hazard ratio, 0.80; 95% confidence interval, 0.37 to 0.97; p=0.03), but not in the other subgroups. Additional multivariate regression models using three propensity-score methods yielded similar results., Conclusions: Among ANP patients with hyperglycemia, immune-enhancing Tα1 treatment was associated with a reduced risk of IPN (ClinicalTrials.gov, Registry number: NCT02473406).

Background: With advancements in burn treatment and intensive care leading to decreased mortality rates, a growing cohort of burn survivors is emerging. These individuals may be susceptible to frailty, characterized by reduced physiological reserve and increased vulnerability to stressors commonly associated with aging, which significantly complicates their recovery process. To date, no study has investigated burns as a potential risk factor for frailty. This study aimed to determine the short-term prevalence of frailty among burn survivors' months after injury and compare it with that of the general population., Methods: A post hoc analysis was conducted on the Randomized Trial of Enteral Glutamine to Minimize the Effects of Burn Injury (RE-ENERGIZE) trial, an international randomized-controlled trial involving 1200 burn injury patients with partial- or full-thickness burns. Participants who did not complete the 36-Item Short Form Health Survey (SF-36) questionnaire were excluded. Data for the general population were obtained from the 2022 National Health Interview Survey (NHIS). Frailty was assessed using the FRAIL (Fatigue, Resistance, Ambulation, Illness, Loss of weight) scale. Due to lack of data on loss of weight, for the purposes of this study, malnutrition was used as the fifth variable. Illness and malnutrition were based on admission data, while fatigue, resistance, and ambulation were determined from post-discharge responses to the SF-36. The burn cohort and general population groups were matched using propensity score matching and compared in terms of frailty status. Within the burn group, patients were divided into different subgroups based on their frailty status, and the differences in their (instrumental) activities of daily living (iADL and ADL) were compared. A multivariable analysis was performed within the burn cohort to identify factors predisposing to frailty as well as compromised iADL and ADL., Results: Out of the 1200 burn patients involved in the study, 600 completed the required questionnaires [follow-up time: (5.5 ± 2.3) months] and were matched to 1200 adults from the general population in the U.S. In comparison to the general population, burn patients exhibited a significantly higher likelihood of being pre-frail (42.3% vs. 19.8%, P < 0.0001), or frail (13.0% vs. 1.0%, P < 0.0001). When focusing on specific components, burn patients were more prone to experiencing fatigue (25.8% vs. 13.5%, P < 0.0001), limited resistance (34.0% vs. 2.7%, P < 0.0001), and restricted ambulation (41.8% vs. 3.8%, P < 0.0001). Conversely, the incidence rate of illness was observed to be higher in the general population (1.2% vs. 2.8%, P = 0.03), while no significant difference was detected regarding malnutrition (2.3% vs. 2.6%, P = 0.75). Furthermore, in comparison with robust burn patients, it was significantly more likely for pre-frail and frail patients to disclose compromise in ADL and iADL. The frail cohort reported the most pronounced limitation., Conclusions: Our findings suggest a higher incidence of post-discharge frailty among burn survivors in the short-term following injury. Burn survivors experience compromised fatigue, resistance, and ambulation, while rates of illness and malnutrition were lower or unchanged, respectively. These results underscore the critical need for early identification of frailty after a burn injury, with timely and comprehensive involvement of a multidisciplinary team including burn and pain specialists, community physicians, physiotherapists, nutritionists, and social workers. This collaborative effort can ensure holistic care to address and mitigate frailty in this patient population., (© 2024. The Author(s).)

Background: With the antibiotic crisis, the topical antibacterial control including chronic wounds gains increasing importance. However, little is known regarding tolerance development when bacteria face repetitive exposure to the identical antiseptics as commonly found in clinical practice., Materials and Methods: Clinical isolates foremost of chronic wounds were exposed in vitro to dilutions of two antiseptics used for wound therapy: polyhexanide or octenidine. Adaptive response was determined by growth/kill curves, minimal inhibitory concentration (MIC), and whole genome sequencing. Antiseptic/bacteriophage combinations were studied by liquid-infection assays and bacterial plating., Results: Polyhexanide acted stronger against Escherichia coli and Proteus mirabilis while octenidine was more potent against Staphylococcus aureus . Otherwise, the antiseptic efficacy varied across isolates of Klebsiella pneumoniae , Pseudomonas aeruginosa , and Acinetobacter baumannii . Upon repetitive exposure with constant antiseptic concentrations P. aeruginosa and P. mirabilis adaptation was evident by a reduced lag-phase and a twofold increased MIC. Under increasing octenidine concentrations, P. aeruginosa adapted to an eightfold higher dosage with mutations in smvA , opgH , and kinB affecting an efflux pump, alginate and biofilm formation, respectively. S. aureus adapted to a fourfold increase of polyhexanide with a mutation in the multiple peptide resistance factor MprF, also conferring cross-resistance to daptomycin. Antiseptic/bacteriophage combinations enhanced bacterial inhibition and delayed adaptation., Conclusion: Different bacterial species/strains respond unequally to low-level antiseptic concentrations. Bacterial adaptation potential at phenotypic and genotypic levels may indicate the necessity for a more nuanced selection of antiseptics. Bacteriophages represent a promising yet underexplored strategy for supporting antiseptic treatment, which may be particularly beneficial for the management of critical wounds., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc.)

Competing Interests: CS has received consulting fees; travel compensation; and honoraria for lectures, presentations, or educational events from Fresenius Kabi, Baxter, Abiomed, and B Braun. CS has also received financial support for an investigator-initiated study from Fresenius Kabi. WHH has received support for attending meetings and travel from Fresenius Kabi and their institution has received a grant from Fresenius Kabi.

Aim: The cardiac surgery-related ischemia-reperfusion-related oxidative stress triggers the release of cytotoxic reactive oxygen and nitrogen species, contributing to organ failure and ultimately influencing patients' short- and long-term outcomes. Selenium is an essential co-factor for various antioxidant enzymes, thereby contributing to the patients' endogenous antioxidant and anti-inflammatory defense mechanisms. Given these selenium's pleiotropic functions, we investigated the effect of a high-dose selenium-based anti-inflammatory perioperative strategy on functional recovery after cardiac surgery., Materials and Methods: This prospective study constituted a nested sub-study of the SUSTAIN CSX trial, a double-blinded, randomized, placebo-controlled multicenter trial to investigate the impact of high-dose selenium supplementation on high-risk cardiac surgery patients' postoperative recovery. Functional recovery was assessed by 6-min walk distance, Short Form-36 (SF-36) and Barthel Index questionnaires., Key Findings: 174 patients were included in this sub-study. The mean age (SD) was 67.3 (8.9) years, and 78.7 % of the patients were male. The mean (SD) predicted 30-day mortality by the European System for Cardiac Operative Risk Evaluation II score was 12.6 % (9.4 %). There was no difference at hospital discharge and after three months in the 6-min walk distance between the selenium and placebo groups (131 m [IQR: not performed - 269] vs. 160 m [IQR: not performed - 252], p = 0.80 and 400 m [IQR: 299-461] vs. 375 m [IQR: 65-441], p = 0.48). The SF-36 and Barthel Index assessments also revealed no clinically meaningful differences between the selenium and placebo groups., Significance: A perioperative anti-inflammatory strategy with high-dose selenium supplementation did not improve functional recovery in high-risk cardiac surgery patients., Competing Interests: Declaration of competing interest Dr. Ott received institutional research and study funds from Novartis Pharma GmbH and institutional research, study and educational grants, speaker fees and advisory board fees from Abiomed. Dr. Stoppe reported grants and nonfinancial support from Biosyn Arzneimittel Gmbh and grants from Hecht Foundation during the conduct of the study and consultant fees from B. Braun, Baxter, and Fresenius Kabi and speaker fees from Biosyn Arzneimittel Gmbh outside the submitted work. Dr. Fremes was a site investigator of the SUSTAIN study and received fees for per-patient enrollment to their institution during the conduct of the study; received grants from Medtronic and Boston Scientific as a site co-investigator for SURTAVI and Low Risk trials and received fees for per-patient enrollment to their institution; received grants from Boston Scientific as a site co–principal investigator for the NeoAccurate IDE trial and received fees for per-patient enrollment to their institution; and received grants from the Canadian Institutes of Health Research as the nominated principal investigator of the ROMA trial outside the submitted work. Dr. Heyland reported nonfinancial support from Biosyn Arzneimittel Gmbh during the conduct of the study. No other disclosures were reported. Dr. O'Brien received research funding from the British Heart Foundation and the National Institute for Health Science Research and funding for work as a consultant for Teleflex. The other authors declare no conflicts of interest related to this manuscript., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)