Association of Preoperative Copeptin Levels with Risk of All-Cause Mortality in a Prospective Cohort of Adult Cardiac Surgery Patients.

We aimed to investigate the association of preoperative copeptin, a new cardiovascular biomarker, with short- and long-term mortality in a cohort of adult patients undergoing cardiac surgery, including its potential as a prognostic marker for clinical outcome. Preoperative blood samples of the Bern Perioperative Biobank, a prospective cohort of adults undergoing cardiac surgery during 2019, were analyzed. The primary and secondary outcome measures were 30-day and 1-year all-cause mortality. Optimal copeptin thresholds were calculated with the Youden Index. Associations of copeptin levels with the two outcomes were examined with multivariable logistic regression models; their discriminatory capacity was assessed with the area under the receiver operating characteristic (AUROC). A total of 519 patients (78.4% male, median age 67 y (IQR: 60-73 y)) were included, with a median preoperative copeptin level of 7.6 pmol/L (IQR: 4.7-13.2 pmol/L). We identified an optimal threshold of 15.9 pmol/l (95%-CI: 7.7 to 46.5 pmol/L) for 30-day mortality and 15.9 pmol/L (95%-CI: 9.0 to 21.3 pmol/L) for 1-year all-cause mortality. Regression models featured an AUROC of 0.79 (95%-CI: 0.56 to 0.95) for adjusted log-transformed preoperative copeptin for 30-day mortality and an AUROC of 0.76 (95%-CI: 0.64 to 0.88) for 1-year mortality. In patients undergoing cardiac surgery, the baseline levels of copeptin emerged as a strong marker for 1-year all-cause death. Preoperative copeptin levels might possibly identify patients at risk for a complicated, long-term postoperative course, and therefore requiring a more rigorous postoperative observation and follow-up.

Association of Indoleamine 2,3-Dioxygenase (IDO) Activity with Outcome after Cardiac Surgery in Adult Patients.

Indoleamine 2,3-deoxygenase (IDO) plays an important role in the catabolism of the amino acid tryptophan. Tryptophan and its metabolites are key immune modulators. Increased IDO activity has been observed in various diseases and is associated with worse clinical outcomes. However, comprehensive research regarding its role in cardiac surgery remains limited. Therefore, we aimed to investigate perioperative changes in IDO activity and pathway metabolites, along with their impact on clinical outcomes in adult patients undergoing cardiac surgery. As an observational cohort study conducted at the Inselspital in Bern from January to December 2019, we retrospectively analyzed the data of prospectively collected biobank samples of patients undergoing cardiac surgery with the use of cardiopulmonary bypass. IDO pathway metabolite analysis was conducted by mass spectrometry. Perioperative dynamics were descriptively assessed and associated with pre-defined clinical outcome measures (30-day mortality, 1-year mortality, incidence of stroke and myocardial infarction, and length of hospital stay) through a multi-step exploratory regression analysis. A cohort of 192 adult patients undergoing cardiac surgery with the use of cardiopulmonary bypass were included (median age 67.0, IQR 60.0-73.0, 75.5% male). A significant perioperative decrease in the kynurenine/tryptophan (Kyn/Trp) ratio (-2.298, 95% CI -4.028 to -596, p = 0.009) and significant perioperative dynamics in the associated metabolites was observed. No association of perioperative changes in IDO activity and pathway metabolites with clinical outcomes was found. A significant decrease in the Kyn/Trp ratio among adult patients undergoing cardiac surgery indicates a perioperative downregulation of IDO, which stands in contrast to other pro-inflammatory conditions. Further studies are needed to investigate IDO in the setting of perioperative immunomodulation, which is a key driver of postoperative complications in cardiac surgery patients.

In Vitro Investigation of Insulin Dynamics During 4 Hours of Simulated Cardiopulmonary Bypass.

BACKGROUND: Hyperglycemia is common in patients undergoing cardiovascular surgery with cardiopulmonary bypass. We hypothesize that intraoperative hyperglycemia may be, at least partially, attributable to insulin loss due to adhesion on artificial surfaces and/or degradation by hemolysis. Thus, our primary aim was to investigate the loss of insulin in 2 different isolated extracorporeal circulation circuits (ECCs), that is, a conventional ECC (cECC) with a roller pump, and a mini-ECC (MiECC) system with a centrifugal pump. The secondary aim was to assess and compare the relationship between changes in insulin concentration and the degree of hemolysis in our 2 ECC models. METHODS: Six cECC and 6 MiECC systems were primed with red packed blood cells and thawed fresh-frozen plasma (1:1). Four additional experiments were performed in cECC using only thawed fresh-frozen plasma. Human insulin (Actrapid) was added, targeting a plasma insulin concentration of 400 mU/L. Insulin concentration and hemolysis index were measured at baseline and hourly thereafter. The end points were the change in insulin level after 4 hours compared to baseline and hemolysis index after 4 hours. The insulin concentration and hemolysis index were analyzed by means of a saturated linear mixed-effect regression model with a random offset for each experiment to account for the repeated measure design of the study, resulting in mean estimates and 95% confidence intervals (CIs) of the primary end points as well as of pairwise contrasts with respect to ECC type. RESULTS: Insulin concentration decreased by 63% (95% CI, 48%-77%) in the MiECC and 92% (95% CI, 77%-106%) in the cECC system that contained red blood cells. Insulin loss was significantly higher in the cECC system compared to the MiECC (P = .022). In the cECC with only plasma, insulin did not significantly decrease (-4%; 95% CI, -21% to 14%). Hemolysis index in MiECC increased from 68 (95% CI, 46-91) to 76 (95% CI, 54-98) after 4 hours, in cECC from 81 (95% CI, 59-103) to 121 (95% CI, 99-143). Hemolysis index and percent change of insulin showed an excellent relationship (r = -0.99, P < .01). CONCLUSIONS: Our data showed that insulin levels substantially decreased during 4 hours of simulated cardiopulmonary bypass only in the ECC that contained hemoglobin. The decrease was more pronounced in the cECC, which also exhibited a greater degree of hemolysis. Our results suggest that insulin degradation by hemolysis products may be a stronger contributor to insulin loss than adhesion of insulin molecules to circuit surfaces.

Gender-specific prolactin thresholds to determine prolactinoma size: a novel Bayesian approach and its clinical utility.

Background: In clinical practice, the size of adenomas is crucial for guiding prolactinoma patients towards the most suitable initial treatment. Consequently, establishing guidelines for serum prolactin level thresholds to assess prolactinoma size is essential. However, the potential impact of gender differences in prolactin levels on estimating adenoma size (micro- vs. macroadenoma) is not yet fully comprehended. Objective: To introduce a novel statistical method for deriving gender-specific prolactin thresholds to discriminate between micro- and macroadenomas and to assess their clinical utility. Methods: We present a novel, multilevel Bayesian logistic regression approach to compute observationally constrained gender-specific prolactin thresholds in a large cohort of prolactinoma patients (N = 133) with respect to dichotomized adenoma size. The robustness of the approach is examined with an ensemble machine learning approach (a so-called super learner), where the observed differences in prolactin and adenoma size between female and male patients are preserved and the initial sample size is artificially increased tenfold. Results: The framework results in a global prolactin threshold of 239.4 µg/L (95% credible interval: 44.0-451.2 µg/L) to discriminate between micro- and macroadenomas. We find evidence of gender-specific prolactin thresholds of 211.6 µg/L (95% credible interval: 29.0-426.2 µg/L) for women and 1,046.1 µg/L (95% credible interval: 582.2-2,325.9 µg/L) for men. Global (that is, gender-independent) thresholds result in a high sensitivity (0.97) and low specificity (0.57) when evaluated among men as most prolactin values are above the global threshold. Applying male-specific thresholds results in a slightly different scenario, with a high specificity (0.99) and moderate sensitivity (0.74). The male-dependent prolactin threshold shows large uncertainty and features some dependency on the choice of priors, in particular for small sample sizes. The augmented datasets demonstrate that future, larger cohorts are likely able to reduce the uncertainty range of the prolactin thresholds. Conclusions: The proposed framework represents a significant advancement in patient-centered care for treating prolactinoma patients by introducing gender-specific thresholds. These thresholds enable tailored treatment strategies by distinguishing between micro- and macroadenomas based on gender. Specifically, in men, a negative diagnosis using a universal prolactin threshold can effectively rule out a macroadenoma, while a positive diagnosis using a male-specific prolactin threshold can indicate its presence. However, the clinical utility of a female-specific prolactin threshold in our cohort is limited. This framework can be easily adapted to various biomedical settings with two subgroups having imbalanced average biomarkers and outcomes of interest. Using machine learning techniques to expand the dataset while preserving significant observed imbalances presents a valuable method for assessing the reliability of gender-specific threshold estimates. However, external cohorts are necessary to thoroughly validate our thresholds.

Levels of Circulating Ketone Bodies in Patients Undergoing Cardiac Surgery on Cardiopulmonary Bypass.

Ketone bodies (KBs) are energy-efficient substrates utilized by the heart depending on its metabolic demand and substrate availability. Levels of circulating KBs have been shown to be elevated in acute and chronic cardiovascular disease and are associated with severity of disease in patients with heart failure and functional outcome after myocardial infarction. To investigate whether this pattern similarly applies to patients undergoing cardiac surgery involving cardiopulmonary bypass (CPB), we analysed prospectively collected pre- and postoperative blood samples from 192 cardiac surgery patients and compared levels and perioperative changes in total KBs with Troponin T as a marker of myocardial cell injury. We explored the association of patient characteristics and comorbidities for each of the two biomarkers separately and comparatively. Median levels of KBs decreased significantly over the perioperative period and inversely correlated with changes observed for Troponin T. Associations of patient characteristics with ketone body perioperative course showed notable differences compared to Troponin T, possibly highlighting factors acting as a "driver" for the change in the respective biomarker. We found an inverse correlation between perioperative change in ketone body levels and changes in troponin, indicating a marked decrease in ketone body concentrations in patients exhibiting greater myocardial cell injury. Further investigations aimed at better understanding the role of KBs on perioperative changes are warranted.

Decision Curve Analysis of In-Hospital Mortality Prediction Models: The Relative Value of Pre- and Intraoperative Data For Decision-Making.

BACKGROUND: Clinical prediction modeling plays a pivotal part in modern clinical care, particularly in predicting the risk of in-hospital mortality. Recent modeling efforts have focused on leveraging intraoperative data sources to improve model performance. However, the individual and collective benefit of pre- and intraoperative data for clinical decision-making remains unknown. We hypothesized that pre- and intraoperative predictors contribute equally to the net benefit in a decision curve analysis (DCA) of in-hospital mortality prediction models that include pre- and intraoperative predictors. METHODS: Data from the VitalDB database featuring a subcohort of 6043 patients were used. A total of 141 predictors for in-hospital mortality were grouped into preoperative (demographics, intervention characteristics, and laboratory measurements) and intraoperative (laboratory and monitor data, drugs, and fluids) data. Prediction models using either preoperative, intraoperative, or all data were developed with multiple methods (logistic regression, neural network, random forest, gradient boosting machine, and a stacked learner). Predictive performance was evaluated by the area under the receiver-operating characteristic curve (AUROC) and under the precision-recall curve (AUPRC). Clinical utility was examined with a DCA in the predefined risk preference range (denoted by so-called treatment threshold probabilities) between 0% and 20%. RESULTS: AUROC performance of the prediction models ranged from 0.53 to 0.78. AUPRC values ranged from 0.02 to 0.25 (compared to the incidence of 0.09 in our dataset) and high AUPRC values resulted from prediction models based on preoperative laboratory values. A DCA of pre- and intraoperative prediction models highlighted that preoperative data provide the largest overall benefit for decision-making, whereas intraoperative values provide only limited benefit for decision-making compared to preoperative data. While preoperative demographics, comorbidities, and surgery-related data provide the largest benefit for low treatment thresholds up to 5% to 10%, preoperative laboratory measurements become the dominant source for decision support for higher thresholds. CONCLUSIONS: When it comes to predicting in-hospital mortality and subsequent decision-making, preoperative demographics, comorbidities, and surgery-related data provide the largest benefit for clinicians with risk-averse preferences, whereas preoperative laboratory values provide the largest benefit for decision-makers with more moderate risk preferences. Our decision-analytic investigation of different predictor categories moves beyond the question of whether certain predictors provide a benefit in traditional performance metrics (eg, AUROC). It offers a nuanced perspective on for whom these predictors might be beneficial in clinical decision-making. Follow-up studies requiring larger datasets and dedicated deep-learning models to handle continuous intraoperative data are essential to examine the robustness of our results.

Atelectasis in obese patients undergoing laparoscopic bariatric surgery are not increased upon discharge from Post Anesthesia Care Unit.

Background: Obese patients frequently develop pulmonary atelectasis upon general anesthesia. The risk is increased during laparoscopic surgery. This prospective, observational single-center study evaluated atelectasis dynamics using Electric Impedance Tomography (EIT) in patients undergoing laparoscopic bariatric surgery. Methods: We included adult patients with ASA physical status I-IV and a BMI of ≥40. Exclusion criteria were known severe pulmonary hypertension, home oxygen therapy, heart failure, and recent pulmonary infections. The primary outcome was the proportion of poorly ventilated lung regions (low tidal variation areas) and the global inhomogeneity (GI) index assessed by EIT before discharge from the Post Anesthesia Care Unit compared to these same measures prior to initiation of anesthesia. Results: The median (IQR) proportion of low tidal variation areas at the different analysis points were T1 10.8% [3.6-15.1%] and T5 10.3% [2.6-18.9%], and the mean difference was -0.7% (95% CI: -5.8% -4.5%), i.e., lower than the predefined non-inferiority margin of 5% (p = 0.022). There were no changes at the four additional time points compared to T1 or postoperative pulmonary complications during the 14 days following the procedure. Conclusion: We found that obese patients undergoing laparoscopic bariatric surgery do not leave the Post Anesthesia Care Unit with increased low tidal variation areas compared to the preoperative period.

Gas6 in chronic liver disease-a novel blood-based biomarker for liver fibrosis.

The expression of the receptor tyrosine kinase Axl and its cleavage product soluble Axl (sAxl) is increased in liver fibrosis, cirrhosis, and hepatocellular carcinoma (HCC). In this multicenter study, we evaluated the diagnostic value of Gas6, the high-affinity ligand of Axl, in patients with chronic liver disease. Levels of sAxl and Gas6, and their albumin (alb) ratios were analyzed in serum samples of patients with biopsy-proven liver fibrosis, end-stage liver disease, HCC, and healthy controls, and were compared to Fibrosis-4 (FIB-4), enhanced liver fibrosis (ELF™) test, Child-Pugh score (CPS), model of end-stage liver disease (MELD) score, hepatic venous pressure gradient, and α-fetoprotein, respectively. A total of 1111 patients (median age 57.8 y, 67.3% male) was analyzed. Gas6/alb showed high diagnostic accuracy for the detection of significant (≥F2: AUC 0.805) to advanced fibrosis (≥F3: AUC 0.818), and was superior to Fib-4 for the detection of cirrhosis (F4: AUC 0.897 vs. 0.878). In addition, Gas6/alb was highly predictive of liver disease severity (Odds ratios for CPS B/C, MELD ≥ 15, and clinically significant portal hypertension (CSPH) were 16.534, 10.258, and 12.115), and was associated with transplant-free survival (Hazard ratio 1.031). Although Gas6 and Gas6/alb showed high diagnostic accuracy for the detection of HCC in comparison to chronic liver disease patients without cirrhosis (AUC 0.852, 0.868), they failed to discriminate between HCC in cirrhosis versus cirrhosis only. In conclusion, Gas6/alb shows a high accuracy to detect significant to advanced fibrosis and cirrhosis, and predicts severity of liver disease including CSPH.

Reporting quality of randomized controlled trials in prehabilitation: a scoping review.

BACKGROUND: Inadequate study reporting precludes interpretation of findings, pooling of results in meta-analyses, and delays knowledge translation. While prehabilitation interventions aim to enhance candidacy for surgery, to our knowledge, a review of the quality of reporting in prehabilitation has yet to be conducted. Our objective was to determine the extent to which randomized controlled trials (RCTs) of prehabilitation are reported according to methodological and intervention reporting checklists. METHODS: Eligibility criteria: RCTs of unimodal or multimodal prehabilitation interventions. SOURCES OF EVIDENCE: search was conducted in March 2022 using MEDLINE, Embase, PsychINFO, Web of Science, CINAHL, and Cochrane. CHARTING METHODS: identified studies were compared to CONSORT, CERT & Modified CERT, TIDieR, PRESENT, and CONSORT-SPI. An agreement ratio (AR) was defined to evaluate if applicable guideline items were correctly reported. Data were analyzed as frequency (n, %) and mean with standard deviation (SD). RESULTS: We identified 935 unique articles and included 70 trials published from 1994 to 2022. Most prehabilitation programs comprised exercise-only interventions (n = 40, 57%) and were applied before oncologic surgery (n = 32, 46%). The overall mean AR was 57% (SD: 20.9%). The specific mean ARs were as follows: CONSORT: 71% (SD: 16.3%); TIDieR: 62% (SD:17.7%); CERT: 54% (SD: 16.6%); Modified-CERT: 40% (SD:17.8%); PRESENT: 78% (SD: 8.9); and CONSORT-SPI: 47% (SD: 22.1). CONCLUSION: Altogether, existing prehabilitation trials report approximately half of the checklist items recommended by methodological and intervention reporting guidelines. Reporting practices may improve with the development of a reporting checklist specific to prehabilitation interventions.

Characteristics and neurological survival following intraoperative cardiac arrest in a Swiss University Hospital: a 7-year retrospective observational cohort study.

Introduction: Little is known about intraoperative cardiac arrest during anesthesia care. In particular, data on characteristics of cardiac arrest and neurological survival are scarce. Methods: We conducted a single-center retrospective observational study evaluating anesthetic procedures from January 2015 until December 2021. We included patients with an intraoperative cardiac arrest and excluded cardiac arrest outside of the operating room. The primary outcome was the return of spontaneous circulation (ROSC). Secondary outcomes were sustained ROSC over 20 min, 30-day survival, and favorable neurological outcome according to Clinical Performance Category (CPC) 1 and 2. Results: We screened 228,712 anesthetic procedures, 195 of which met inclusion criteria and were analyzed. The incidence of intraoperative cardiac arrest was 90 (CI 95% 78-103) in 100,000 procedures. The median age was 70.5 [60.0; 79.4] years, and two-thirds of patients (n = 135; 69.2%) were male. Most of these patients with cardiac arrest had ASA physical status IV (n = 83; 42.6%) or V (n = 47; 24.1%). Cardiac arrest occurred more frequently (n = 104; 53.1%) during emergency procedures than elective ones (n = 92; 46.9%). Initial rhythm was pre-dominantly non-shockable with pulseless electrical activity mostly. Most patients (n = 163/195, 83.6%; CI 95 77.6-88.5%) had at least one instance of ROSC. Sustained ROSC over 20 min was achieved in most patients with ROSC (n = 147/163; 90.2%). Of the 163 patients with ROSC, 111 (68.1%, CI 95 60.4-75.2%) remained alive after 30 days, and most (n = 90/111; 84.9%) had favorable neurological survival (CPC 1 and 2). Conclusion: Intraoperative cardiac arrest is rare but is more likely in older patients, patients with ASA physical status ≥IV, cardiac and vascular surgery, and emergency procedures. Patients often present with pulseless electrical activity as the initial rhythm. ROSC can be achieved in most patients. Over half of the patients are alive after 30 days, most with favorable neurological outcomes, if treated immediately.

Impact of Intraoperative Fluid Balance and Norepinephrine on Postoperative Acute Kidney Injury after Cystectomy and Urinary Diversion over Two Decades: A Retrospective Observational Cohort Study.

The use of norepinephrine and the restriction of intraoperative hydration have gained increasing acceptance over the last few decades. Recently, there have been concerns regarding the impact of this approach on renal function. The objective of this study was to examine the influence of norepinephrine, intraoperative fluid administration and their interaction on acute kidney injury (AKI) after cystectomy. In our cohort of 1488 consecutive patients scheduled for cystectomies and urinary diversions, the overall incidence of AKI was 21.6% (95%-CI: 19.6% to 23.8%) and increased by an average of 0.6% (95%-CI: 0.1% to 1.1%, p = 0.025) per year since 2000. The fluid and vasopressor regimes were characterized by an annual decrease in fluid balance (-0.24 mL·kg-1·h-1, 95%-CI: -0.26 to -0.22, p < 0.001) and an annual increase in the amount of norepinephrine of 0.002 µg·kg-1·min-1 (95%-CI: 0.0016 to 0.0024, p < 0.001). The interaction between the fluid balance and norepinephrine levels resulted in a U-shaped association with the risk of AKI; however, the magnitude and shape depended on the reference categories of confounders (age and BMI). We conclude that decreased intraoperative fluid balance combined with increased norepinephrine administration was associated with an increased risk of AKI. However, other potential drivers of the observed increase in AKI incidence need to be further investigated in the future.

[Interrater reliability and concurrent validity of 4AT for the detection of postoperative delirium: A prospective cohort study]. / Interrater Reliabilität und Übereinstimmungsvalidität des 4AT zur Erfassung des postoperativen Delirs.

Interrater reliability and concurrent validity of 4AT for the detection of postoperative delirium: A prospective cohort study Abstract. Background: Numerous tools for detecting postoperative delirium are available. Guidelines recommend the 4 A's Test (4AT). However, there is little evidence on the validity and reliability of the German version of 4AT. Aim: To assess the interrater reliability of the German version of 4AT test for the detection of postoperative delirium in general surgical and orthopedic-traumatological patients, and the concurrent validity with the Delirium Observation Screening Scale (DOS). Methods: The present work is part of a prospective cohort study with a sample of 202 inpatients (≥ 65 years) who underwent surgery. The interrater reliability of the 4AT (intraclass coefficients) was determined with a subsample of 33 subjects who were rated by two nurses. Concurrent validity between the DOS scale and the 4AT was calculated using Pearson's correlation coefficient. Results: Interrater reliability for the 4AT total score and dichotomized total score were 0.92 (95% CI 0.84-0.96) and 0.98 (95% CI 0.95-0.98), respectively. The correlation between DOS and 4AT (Pearson) was 0.54 (p < 0.001). Conclusions: The 4A test can be used by nurses as a screening instrument for the detection of postoperative delirium in older patients on general surgery and orthopedic traumatology wards. In case of positive 4AT results further assessment by nurse experts or physicians is required.

A Pilot Investigation Evaluating Relative Changes in Fronto-Occipital Alpha and Beta Spectral Power as Measurement of Anesthesia Hypnotic Depth.

BACKGROUND: Other than clinical observation of a patient's vegetative response to nociception, monitoring the hypnotic component of general anesthesia (GA) and unconsciousness relies on electroencephalography (EEG)-based indices. These indices exclusively based on frontal EEG activity neglect an important observation. One of the main hallmarks of transitions from wakefulness to GA is a shift in alpha oscillations (7.5-12.5 Hz activity) from occipital brain regions toward anterior brain regions ("alpha anteriorization"). Monitoring the degree of this alpha anteriorization may help to guide induction and maintenance of hypnotic depth and prevent intraoperative awareness. However, the occipital region of the brain is completely disregarded and occipital alpha as characteristic of wakefulness and its posterior-to-anterior shift during induction are missed. Here, we propose an application of Narcotrend's reduced power alpha beta (RPAB) index, originally developed to monitor differences in hemispheric perfusion, for determining the ratio of alpha and beta activity in the anterior-posterior axis. METHODS: Perioperative EEG data of 32 patients undergoing GA in the ophthalmic surgery department of Bern University Hospital were retrospectively analyzed. EEG was recorded with the Narcotrend® monitor using a frontal (Fp1-Fp2) and a posterior (T9-Oz) bipolar derivation with reference electrode over A2. The RPAB index was computed between both bipolar signals, defining the fronto-occipital RPAB (FO-RPAB). FO-RPAB was analyzed during wakefulness, GA maintenance, and emergence, as well as before and after the intraoperative administration of a ketamine bolus. FO-RPAB was compared with a classical quantitative EEG measure-the spectral edge frequency 95% (SEF-95). RESULTS: A significant shift of the FO-RPAB was observed during both induction of and emergence from GA ( P < .001). Interestingly, the additional administration of ketamine during GA did not lead to a significant change in FO-RPAB ( P = 0.81). In contrast, a significant increase in the SEF-95 in the frontal channel was observed during the 10-minute period after ketamine administration ( P < .001). CONCLUSIONS: FO-RPAB appears to qualify as a marker of unconsciousness, reflecting physiological fronto-occipital activity differences during GA. In contrast to frontal SEF-95, it is not disturbed by additional administration of ketamine for analgesia.

Airway management during ongoing chest compressions-direct vs. video laryngoscopy. A randomised manikin study.

BACKGROUND: Tracheal intubation is used for advanced airway management during cardiac arrest, particularly when basic airway techniques cannot ensure adequate ventilation. However, minimizing interruptions of chest compressions is of high priority. Video laryngoscopy has been shown to improve the first-pass success rate for tracheal intubation in emergency airway management. We aimed to compare first-pass success rate and time to successful intubation during uninterrupted chest compression using video laryngoscopy and direct laryngoscopy. METHODS: A total of 28 anaesthetists and 28 anaesthesia nurses with varied clinical and anaesthesiological experience were recruited for the study. All participants performed a tracheal intubation on a manikin simulator during ongoing chest compressions by a mechanical resuscitation device. Stratified randomisation (physicians/nurses) was performed, with one group using direct laryngoscopy and the other using video laryngoscopy. RESULTS: First-pass success rate was 100% (95% CI: 87.9% - 100.0%) in the video laryngoscopy group and 67.8% (95% CI: 49.3% - 82.1%) in the direct laryngoscopy group [difference: 32.2% (95% CI: 17.8% - 50.8%), p<0.001]. The median time for intubation was 27.5 seconds (IQR: 21.8-31.0 seconds) in the video laryngoscopy group and 30.0 seconds (IQR: 26.5-36.5 seconds) in the direct laryngoscopy group (p = 0.019). CONCLUSION: This manikin study on tracheal intubation during ongoing chest compressions demonstrates that video laryngoscopy had a higher first-pass success rate and shorter time to successful intubation compared to direct laryngoscopy. Experience in airway management and professional group were not significant predictors. A clinical randomized controlled trial appears worthwhile.

Determination of selective antegrade perfusion flow rate in aortic arch surgery to restore baseline cerebral near-infrared spectroscopy values: a single-centre observational study.

OBJECTIVES: Neuroprotection during aortic arch surgery involves selective antegrade cerebral perfusion. The parameters of cerebral perfusion, e.g. flow rate, are inconsistent across centres and are subject of debate. The aim of this study was to determine the cerebral perfusion flow rate during hypothermic circulatory arrest required to meet preoperative awake baseline regional cerebral oxygen saturation (rSO2). METHODS: Patients scheduled for aortic arch surgery with hypothermic circulatory arrest were enrolled in this prospective observational study. After initiation of hypothermic circulatory arrest, bilateral selective antegrade cerebral perfusion was established and cerebral flow rate was continuously increased. The primary end point was the difference of cerebral saturation from baseline during cerebral perfusion flow rates of 6, 8 and 10 ml/kg/min. RESULTS: A total of 40 patients were included. During antegrade cerebral perfusion, rSO2 was significantly lower than the baseline at 6 ml/kg/min [-7.3, 95% confidence interval (CI): -1.7, -12.9; P = 0.0015]. In contrast, flow rates of 8 and 10 ml/kg/min resulted in rSO2 that did not significantly differ from the baseline (-2; 95% CI: -4.3, 8.3; P > 0.99 and 1.8; 95% CI: -8.5%, 4.8%; P > 0.99). Cerebral saturation was significantly more likely to meet baseline values during selective antegrade cerebral perfusion with 8 ml/kg/min than at 6 ml/kg/min (44.1%; 95% CI: 27.4%, 60.8% vs 11.8%; 95% CI: 0.9%, 22.6%; P = 0.0001). CONCLUSIONS: At 8 ml/kg/min cerebral flow rate during selective antegrade cerebral perfusion, regional cerebral oximetry baseline values are significantly more likely to be achieved than at 6 ml/kg/min. Further increasing the cerebral flow rate to 10 ml/kg/min does not significantly improve rSO2.

Multimodal prehabilitation for major surgery in elderly patients to lower complications: protocol of a randomised, prospective, multicentre, multidisciplinary trial (PREHABIL Trial).

INTRODUCTION: The global volume of surgery is growing and the population ageing, and economic pressure is rising. Major surgery is associated with relevant morbidity and mortality. Postoperative reduction in physiological and functional capacity is especially marked in the elderly, multimorbid patient with low fitness level, sarcopenia and malnutrition. Interventions aiming to optimise the patient prior to surgery (prehabilitation) may reduce postoperative complications and consequently reduce health costs. METHODS AND ANALYSIS: This is a multicentre, multidisciplinary, prospective, 2-arm parallel-group, randomised, controlled trial with blinded outcome assessment. Primary outcome is the Comprehensive Complications Index at 30 days. Within 3 years, we aim to include 2×233 patients with a proven fitness deficit undergoing major surgery to be randomised using a computer-generated random numbers and a minimisation technique. The study intervention consists of a structured, multimodal, multidisciplinary prehabilitation programme over 2-4 weeks addressing deficits in physical fitness and nutrition, diabetes control, correction of anaemia and smoking cessation versus standard of care. ETHICS AND DISSEMINATION: The PREHABIL trial has been approved by the responsible ethics committee (Kantonale Ethikkomission Bern, project ID 2020-01690). All participants provide written informed consent prior to participation. Participant recruitment began in February 2022 (10 and 8 patients analysed at time of submission), with anticipated completion in 2025. Publication of the results in peer-reviewed scientific journals are expected in late 2025. TRIAL REGISTRATION NUMBER: NCT04461301.

Direct versus video laryngoscopy with standard blades for neonatal and infant tracheal intubation with supplemental oxygen: a multicentre, non-inferiority, randomised controlled trial.

BACKGROUND: Tracheal intubation in neonates and infants is a potentially life-saving procedure. Video laryngoscopy has been found to improve first-attempt tracheal intubation success and reduce complications compared with direct laryngoscopy in children younger than 12 months. Supplemental periprocedural oxygen might increase the likelihood of successful first-attempt intubation because of an increase in safe apnoea time. We tested the hypothesis that direct laryngoscopy is not inferior to video laryngoscopy when using standard blades and supplemental oxygen is provided. METHODS: We did a non-inferiority, international, multicentre, single-blinded, randomised controlled trial, in which we randomly assigned neonates and infants aged up to 52 weeks postmenstrual age scheduled for elective tracheal intubation to either direct laryngoscopy or video laryngoscopy (1:1 ratio, randomly assigned using a secure online service) at seven tertiary paediatric hospitals across Australia, Canada, Italy, Switzerland, and the USA. An expected difficult intubation was the main exclusion criteria. Parents and patients were masked to the assigned group of treatment. All infants received supplemental oxygen (1 L/Kg per min) during laryngoscopy until the correct tracheal tube position was confirmed. The primary outcome was the proportion of first-attempt tracheal intubation success, defined as appearance of end-tidal CO2 curve at the anaesthesia monitor, between the two groups in the modified intention-to-treat analysis. A 10% non-inferiority margin between direct laryngoscopy or video laryngoscopy was applied. The trial is registered with ClinicalTrials.gov (NCT04295902) and is now concluded. FINDINGS: Of 599 patients assessed, 250 patients were included between Oct 26, 2020, and March 11, 2022. 244 patients were included in the final modified intention-to-treat analysis. The median postmenstrual age on the day of intubation was 44·0 weeks (IQR 41·0-48·0) in the direct laryngoscopy group and 46·0 weeks (42·0-49·0) in the video laryngoscopy group, 34 (28%) were female in the direct laryngoscopy group and 38 (31%) were female in the video laryngoscopy group. First-attempt tracheal intubation success rate with no desaturation was higher with video laryngoscopy (89·3% [95% CI 83·7 to 94·8]; n=108/121) compared with direct laryngoscopy (78·9% [71·6 to 86·1]; n=97/123), with an adjusted absolute risk difference of 9·5% (0·8 to 18·1; p=0·033). The incidence of adverse events between the two groups was similar (-2·5% [95% CI -9·6 to 4·6]; p=0·490). Post-anaesthesia complications occurred seven times in six patients with no difference between the groups. INTERPRETATION: Video laryngoscopy with standard blades in combination with supplemental oxygen in neonates and infants might increase the success rate of first-attempt tracheal intubation, when compared with direct laryngoscopy with supplemental oxygen. The incidence of hypoxaemia increased with the number of attempts, but was similar between video laryngoscopy and direct laryngoscopy. Video laryngoscopy with oxygen should be considered as the technique of choice when neonates and infants are intubated. FUNDING: Swiss Pediatric Anaesthesia Society, Swiss Society for Anaesthesia and Perioperative Medicine, Foundation for Research in Anaesthesiology and Intensive Care Medicine, Channel 7 Telethon Trust, Stan Perron Charitable Foundation, National Health and Medical Research Council.

Discovery of plasma proteome markers associated with clinical outcome and immunological stress after cardiac surgery.

Background: Molecular mechanisms underlying perioperative acute phase reactions in cardiac surgery are largely unknown. We aimed to characterise perioperative alterations of the acute phase plasma proteome in a cohort of adult patients undergoing on-pump cardiac surgery using high-throughput mass spectrometry and to identify candidate proteins potentially relevant to postoperative clinical outcome through a novel, multi-step approach. Methods: This study is an analysis of the Bern Perioperative Biobank, a prospective cohort of adults who underwent cardiac surgery with the use of cardiopulmonary bypass (CPB) at Bern University Hospital between January and December 2019. Blood samples were taken before induction of anaesthesia and on postoperative day one. Proteomic analyses were performed by mass spectrometry. Through a multi-step, exploratory approach, hit-proteins were first identified according to their perioperative prevalence and dynamics. The set of hit-proteins were associated with predefined clinical outcome measures (all-cause one-year mortality, length of hospital stay, postoperative myocardial infarction and stroke until hospital discharge). Results: 192 patients [75.5% male, median age 67.0 (IQR 60.0-73.0)] undergoing cardiac surgery with the use of CPB were included in this analysis. In total, we identified and quantified 402 proteins across all samples, whereof 30/402 (7%) proteins were identified as hit-proteins. Three hit-proteins-LDHB, VCAM1 and IGFBP2-demonstrated the strongest associations with clinical outcomes. After adjustment both for age, sex, BMI and for multiple comparisons, the scaled preoperative levels of IGFBP2 were associated with 1-year all-cause mortality (OR 10.63; 95% CI: 2.93-64.00; p = 0.046). Additionally, scaled preoperative levels of LDHB (OR 5.58; 95% CI: 2.58-8.57; p = 0.009) and VCAM1 (OR 2.32; 95% CI: 0.88-3.77; p = 0.05) were found to be associated with length of hospital stay. Conclusions: We identified a subset of promising candidate plasma proteins relevant to outcome after on-pump cardiac surgery. IGFBP2 showed a strong association with clinical outcome measures and a significant association of preoperative levels with 1-year all-cause mortality. Other proteins strongly associated with outcome were LDHB and VCAM1, reflecting the dynamics in the acute phase response, inflammation and myocardial injury. We recommend further investigation of these proteins as potential outcome markers after cardiac surgery. Clinical Trial Registration: ClinicalTrials.gov; NCT04767685, data are available via ProteomeXchange with identifier PXD046496.

Delirium in elderly postoperative patients: A prospective cohort study.

AIM: To describe the incidence, time in days and risk factors for postoperative delirium in elderly patients. DESIGN: Prospective cohort study. METHODS: Patients over 65 years were daily screened with the 4A's Test and the Delirium Observation Screening Scale for postoperative delirium. A psychiatrist assessed according to the DSM-V. We performed descriptive and logistic regression analyses. RESULTS: From 202 patients, 7.5% (N = 15) had a diagnosed postoperative delirium, whereby 73.3% (N = 11) developed the delirium during the first 48 hr after surgery. The median duration was 1 day. Patients over 80 years suffering from heart failure with surgical drains, bladder catheter, central venous catheter had higher odds for developing a postoperative delirium. The incidence of postoperative delirium in our sample was lower compared with other surgical and ortho-geriatric populations. Despite age, several modifiable postoperative factors were associated with the occurrence of postoperative delirium.

Flow cytometry-based high-throughput RNAi screening for miRNAs regulating MHC class II HLA-DR surface expression.

HLA-DR isotype is a MHC-II cell-surface receptor found on APCs and plays a key role in initiating immune responses. In severely immunocompromised patients with conditions like sepsis, the number of HLA-DR molecules expressed on leukocytes is considered to correlate with infectious complications and patients' probability of survival. The underlying regulatory mechanisms of HLA-DR expression remain largely unknown. One probable path to regulation is through microRNAs (miRNAs), which have been implicated as regulatory elements of both innate and adaptive immune system development and function. In our study, flow cytometry-based high-throughput miRNA screening was performed in a stable HLA-DR-expressing human melanoma cell line, MelJuSo, for either up- or downregulating miRNAs of the surface HLA-DR expression. By the end of the screening, the top ten upregulators and top five downregulators were identified, and both the HLA-DR protein and mRNA regulations were further verified and validated. In-silico approaches were applied for functional miRNA-mRNA interaction prediction. The potential underlying gene regulations of different miRNAs were proposed. Our results promote the study of miRNA-mediated HLA-DR regulation under both physiological and pathological conditions, and may pave the way for potential clinical applications.