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Mitali Stevens,1 Todd Davis,1 Sibyl H Munson,2 Apeksha V Shenoy,2 Boye LA Gricar,2 Halit O Yapici,2 Andrew D Shaw3 1Global Health Economics & Reimbursement, Edwards Lifesciences, Irvine, CA, USA; 2Department of Health Economics and Outcomes Research, Boston Strategic Partners, Inc., Boston, MA, USA; 3Department of Anaesthesiology and Pain Medicine, University of Alberta, Edmonton, Alberta, CanadaCorrespondence: Andrew D ShawDepartment of Anaesthesiology and Pain Medicine, University of Alberta, 8440 112 St NW, Edmonton, Alberta T6G 2G3, CanadaEmail ashaw2@ualberta.caObjective: A monitoring pulmonary artery catheter (PAC) is utilized in approximately 34% of the US cardiac surgical procedures. Increased use of PAC has been reported to have an association with complication rates: significant decreases in new-onset heart failure (HF) and respiratory failure (RF), but increases in bacteremia and urinary tract infections. We assessed the impact of increasing PAC adoption on hospital costs among cardiac surgery patients for US-based healthcare systems.Methods: An Excel-based economic model calculated annualized savings for a US hospital with various cardiac surgical volumes and PAC adoption rates. A second model, for an integrated payer-provider health system, analyzed outcomes/costs resulting from the cardiac surgical admission and for the treatment of persistent HF and RF complications in the year following surgery. Model inputs were extracted from published literature, and one-way and probabilistic sensitivity analyses were performed.Results: For an acute care hospital with 500 procedures/year and 34% PAC adoption, annualized savings equalled $61,806 vs no PAC utilization. An increase in PAC adoption rate led to increased savings of $134,751 for 75% and $170,685 for 95% adoption. Savings ranged from $12,361 to $185,418 at volumes of 100 and 1500 procedures/year, respectively. For an integrated payer-provider health system with the base-case scenario of 3845 procedures/year and 34% PAC adoption, estimated savings were $596,637 for the combined surgical index admission and treatment for related complications over the following year.Conclusion: PAC utilization in adult cardiac surgery patients results in reduced costs for both acute care hospitals and payer-provider integrated health systems.Keywords: heart failure, respiratory failure, economic evaluation, cost analysis, acute care hospital, integrated payer-provider

Objective: Acute renal failure remains a major complication of coronary artery bypass graft surgery that is strongly associated with in-hospital mortality. Based on similar observations in other clinical settings, we tested the hypothesis that the diagnosis of acute renal failure associated with coronary artery bypass graft surgery is increasing in the United States.Design: Observational cohort study.Setting: The Nationwide Inpatient Sample database was used to test the hypothesis. This database contains discharge information from 20% of U.S. hospitals.Patients: Hospital discharges coded for coronary artery bypass graft surgery from 1988 to 2003 comprised the study population; those also coded for acute renal failure formed the subset of interest.Interventions: None.Measurements and Main Results: Multivariable regression models were constructed, including adjustment for risk factors and comorbidities, to identify the relationship between year of surgery and diagnosis of acute renal failure and mortality. The incidence of acute renal failure diagnosis increased significantly during the study period from 1.1% to 4.1% (p < .0001). The proportion of acute renal failure cases that required dialysis decreased from 15.8% to 8.7% (p < .0001). Despite an increase in comorbid disease burden, mortality in the acute renal failure subgroup declined from 39.5% to 17.9% (p < .0001). The percentage of acute renal failure survivors with postdischarge special-care requirements increased from 35.5% to 64.5% (p < .0001).Conclusions: Our findings suggest that the observed increase in acute renal failure diagnosis rates may be partly attributable to less restrictive criteria for acute renal failure diagnosis, consistent with acute renal failure patterns observed in other clinical settings. Although the need for dialysis is a relatively clear benchmark for diagnosing acute renal failure, use of alternate criteria to define this disorder has become more common, perhaps contributing to higher diagnosis rates. We conclude that the nationwide trend of acute renal failure associated with coronary artery bypass graft surgery has significantly increased from 1988 to 2003. Despite declining mortality, acute renal failure remains a burden on healthcare resources. [ABSTRACT FROM AUTHOR]

Irritable bowel syndrome (IBS) is a frequently occurring, benign functional gastrointestinal disorder with a complex poorly understood pathology which appears to be multifactorial in nature. There is no association with structural or biochemical abnormalities in the gastrointestinal tract. Functional variations in myoelectrical activity, visceral hypersensitivity and illness behaviours have all been observed in patients experimentally. In conjunction with environmental, psychological and alimentary factors, these mechanisms have been proposed as the major determinants of symptom genesis. Certainly, dietary factors are frequently perceived by sufferers as powerful symptom triggers, with many reporting multiple food intolerance. Physicians, however, remain divided upon the relevance of food to the disorder, with many eschewing a nutritional connection. This is unsurprising as, despite much experimental work to determine the clinical relevance of food intolerance and allergy to the aetiology of the disorder, the vast range of foodstuffs available for testing, inherent procedural problems with test foods, methodological insufficiencies and the continually evolving knowledge of the disorder, particularly the subgrouping of sufferers, have restricted the scientific validity of current findings. At the present time, it is difficult to make informed judgement upon the importance of food in IBS, and rigorously designed, large scale trials devised in the light of recent knowledge are required before conclusions can be drawn. [ABSTRACT FROM AUTHOR]

Abstract Background There is limited data available on the environmental and public health impact of the microbiological hazards associated with sputa from patients with cystic fibrosis [CF]. Pseudomonas aeruginosa, Burkholderia cenocepacia (formerly Burkholderia cepacia genomovar III), Staphylococcus aureus and Stenotrophomonas maltophilia are bacterial pathogens which are commonly found in the sputum of CF patients. A study was performed to ascertain the amount of sputum produced relating to microbial loading, as well as the diversity of bacteria present in a population of adult patients, with particular attention to pathogenic organisms. Methods Sputum from adult [>18 years old] CF patients [n = 20], chosen randomly from a population of 138 CF patients, was collected over a 24 h period on admission to the in-patient CF unit and enumerated quantitatively, as well as the sputa from 138 adult CF patients was examined qualitatively for the presence of infecting microflora. In addition, all different phenotypes from the sputum of each patient were identified phenotypically employing a combination of conventional identification methods [e.g. oxidase], as well as the API Identification schemes [API 20 NE, API 20 E]. Results This study demonstrated that patients with cystic fibrosis generate large numbers of bacteria in their sputum, approximating to 109 organisms per patient per day. Although these organisms are introduced to the environment from the respiratory tract mainly via sputum, relatively few represent true bacterial pathogens and therefore are not clinically important to the general public who are immunocompotent. The greatest risk of such environmental microbial loading is to other patients with CF and therefore CF patients should be made aware of the hazards of acquiring such organisms from the environment, as well as socializing with other CF patients with certain transmissible types, such as Pseudomonas aeruginosa and Burkholderia cenocepacia. Conclusions Environmental health professionals should therefore be aware that CF patients are a greater risk to their peer grouping rather than to the general public or health care workers and that good personal hygiene practices with CF patients should be encouraged to minimize environmental contamination and potential acquistion.

Purpose: Novel interventions for the prevention or treatment of acute kidney injury (AKI) are currently lacking. To facilitate the evaluation and adoption of new treatments, the use of the most appropriate design and endpoints for clinical trials in AKI is critical and yet there is little consensus regarding these issues. We aimed to develop recommendations on endpoints and trial design for studies of AKI prevention and treatment interventions based on existing data and expert consensus., Methods: At the 31st Acute Disease Quality Initiative (ADQI) meeting, international experts in critical care, nephrology, involving adults and pediatrics, biostatistics and people with lived experience (PWLE) were assembled. We focused on four main areas: (1) patient enrichment strategies, (2) prevention and attenuation studies, (3) treatment studies, and (4) innovative trial designs of studies other than traditional (parallel arm or cluster) randomized controlled trials. Using a modified Delphi process, recommendations and consensus statements were developed based on existing data, with > 90% agreement among panel members required for final adoption., Results: The panel developed 12 consensus statements for clinical trial endpoints, application of enrichment strategies where appropriate, and inclusion of PWLE to inform trial designs. Innovative trial designs were also considered., Conclusion: The current lack of specific therapy for prevention or treatment of AKI demands refinement of future clinical trial design. Here we report the consensus findings of the 31st ADQI group meeting which has attempted to address these issues including the use of predictive and prognostic enrichment strategies to enable appropriate patient selection., (© 2024. The Author(s).)

Fluid therapy is an integral component of perioperative management. In light of emerging evidence in this area, the Perioperative Quality Initiative (POQI) convened an international multiprofessional expert meeting to generate evidence-based consensus recommendations for fluid management in patients undergoing surgery. This article provides a summary of the recommendations for perioperative fluid management of surgical patients from the preoperative period until hospital discharge and for all types of elective and emergency surgery, apart from burn injuries and head and neck surgery. Where evidence was lacking, recommendations for future research were generated. Specific recommendations are made for fluid management in elective major noncardiac surgery, cardiopulmonary bypass, thoracic surgery, neurosurgery, minor noncardiac surgery under general anaesthesia, and critical illness. There are ongoing gaps in knowledge resulting in variation in practice and some disagreement with our consensus recommendations. Perioperative fluid management should be individualised, taking into account the type of surgery and important patient factors, including intravascular volume status and acute and chronic comorbidities. Recommendations are made for further research in perioperative fluid management to address important gaps., (Copyright © 2024 British Journal of Anaesthesia. Published by Elsevier Ltd. All rights reserved.)

The Society of Cardiovascular Anesthesiologists (SCA) is committed to improving the quality, safety, and value that cardiothoracic anesthesiologists bring to patient care. To fulfill this mission, the SCA supports the creation of peer-reviewed manuscripts that establish standards, produce guidelines, critically analyze the literature, interpret preexisting guidelines, and allow experts to engage in consensus opinion. The aim of this report, commissioned by the SCA President, is to summarize the distinctions among these publications and describe a novel SCA-supported framework that provides guidance to SCA members for the creation of these publications. The ultimate goal is that through a standardized and transparent process, the SCA will facilitate up-to-date education and implementation of best practices by cardiovascular and thoracic anesthesiologists to improve patient safety, quality of care, and outcomes., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2023 International Anesthesia Research Society.)

Revealing the acute cortical pharmacodynamics of an antidepressant dose of ketamine in humans with depression is key to determining the specific mechanism(s) of action for alleviating symptoms. While the downstream effects are characterised by increases in plasticity and reductions in depressive symptoms-it is the acute response in the brain that triggers this cascade of events. Computational modelling of cortical interlaminar and cortico-cortical connectivity and receptor dynamics provide the opportunity to interrogate this question using human electroencephalography (EEG) data recorded during a ketamine infusion. Here, resting-state EEG was recorded in a group of 30 patients with major depressive disorder (MDD) at baseline and during a 0.44 mg/kg ketamine dose comprising a bolus and infusion. Fronto-parietal connectivity was assessed using dynamic causal modelling to fit a thalamocortical model to hierarchically connected nodes in the medial prefrontal cortex and superior parietal lobule. We found a significant increase in parietal-to-frontal AMPA-mediated connectivity and a significant decrease in the frontal GABA time constant. Both parameter changes were correlated across participants with the antidepressant response to ketamine. Changes to the NMDA receptor time constant and inhibitory intraneuronal input into superficial pyramidal cells did not survive correction for multiple comparisons and were not correlated with the antidepressant response. These results provide evidence that the antidepressant effects of ketamine may be mediated by acute fronto-parietal connectivity and GABA receptor dynamics. Furthermore, it supports the large body of literature suggesting the acute mechanism underlying ketamine's antidepressant properties is related to GABA-A and AMPA receptors rather than NMDA receptor antagonism., (© 2024. The Author(s).)

Background: Microdosing psychedelics is a phenomenon with claimed cognitive benefits that are relatively untested clinically. Pre-clinically, psychedelics have demonstrated enhancing effects on neuroplasticity, which cannot be measured directly in humans, but may be indexed by non-invasive electroencephalography (EEG) paradigms. This study used a visual long-term potentiation (LTP) EEG paradigm to test the effects of microdosed lysergic acid diethylamide (LSD) on neural plasticity, both acutely while on the drug and cumulatively after microdosing every third day for six weeks. Healthy adult males (n = 80) completed the visual LTP paradigm at baseline, 2.5 h following a dose of 10 µg of LSD or inactive placebo, and 6 weeks later after taking 14 repeated microdoses. Visually induced LTP was used as indirect index of neural plasticity. Surface level event-related potential (ERPs) based analyses are presented alongside dynamic causal modelling of the source localised data using a generative thalamocortical model (TCM) of visual cortex to elucidate underlying synaptic circuitry., Results: Event-related potential (ERP) analyses of N1b and P2 components did not show evidence of changes in visually induced LTP by LSD either acutely or after 6 weeks of regular dosing. However modelling the complete timecourse of the ERP with the TCM demonstrated changes in laminar connectivity in primary visual cortex. This primarily included changes to self-gain and inhibitory input parameters acutely. Layer 2/3 to layer 5 excitatory connectivity was also different between LSD and placebo groups. After regular dosing only excitatory input from layer 2/3 into layer 5 and inhibitory input into layer 4 were different between groups., Conclusions: Without modulation of the ERPs it is difficult to relate the findings to other studies visually inducing LTP. It also indicates the classic peak analysis may not be sensitive enough to demonstrate evidence for changes in LTP plasticity in humans at such low doses. The TCM provides a more sensitive approach to assessing changes to plasticity as differences in plasticity mediated laminar connectivity were found between the LSD and placebo groups., Trial Registration:  ANZCTR registration number ACTRN12621000436875; Registered 16/04/2021 https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=381476 ., (© 2024. The Author(s).)

Objectives: Acute kidney injury (AKI) is increasingly recognized as a source of poor patient outcomes after cardiac surgery. The purpose of the present report is to provide perioperative teams with expert recommendations specific to cardiac surgery-associated AKI (CSA-AKI)., Methods: This report and consensus recommendations were developed during a joint, in-person, multidisciplinary conference with the Perioperative Quality Initiative and the Enhanced Recovery After Surgery Cardiac Society. Multinational practitioners with diverse expertise in all aspects of cardiac surgical perioperative care, including clinical backgrounds in anesthesiology, surgery and nursing, met from October 20 to 22, 2021, in Sacramento, California, and used a modified Delphi process and a comprehensive review of evidence to formulate recommendations. The quality of evidence and strength of each recommendation were established using the Grading of Recommendations Assessment, Development, and Evaluation methodology. A majority vote endorsed recommendations., Results: Based on available evidence and group consensus, a total of 13 recommendations were formulated (4 for the preoperative phase, 4 for the intraoperative phase, and 5 for the postoperative phase), and are reported here., Conclusions: Because there are no reliable or effective treatment options for CSA-AKI, evidence-based practices that highlight prevention and early detection are paramount. Cardiac surgery-associated AKI incidence may be mitigated and postsurgical outcomes improved by focusing additional attention on presurgical kidney health status; implementing a specific cardiopulmonary bypass bundle; using strategies to maintain intravascular euvolemia; leveraging advanced tools such as the electronic medical record, point-of-care ultrasound, and biomarker testing; and using patient-specific, goal-directed therapy to prioritize oxygen delivery and end-organ perfusion over static physiologic metrics., Competing Interests: Declaration of Competing Interest None., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Competing Interests: The authors declare no conflicts of interest.

The administration of fluids is one of the most common interventions in the intensive care unit. The effects and side effects of intravenous fluids depend on the amount administered and their specific composition. Intravenous fluid solutions are either considered crystalloids (for example 0.9% saline, lactated Ringer's solution) or colloids (artificial colloids such as gelatins, and albumin). This narrative review summarizes the physiological principles of fluid therapy and reviews the most important studies on crystalloids, artificial colloids and albumin in the context of critically ill patients., (© The Author(s) 2022. Published by Oxford University Press on behalf of the ERA.)

Synaptic loss occurs early in many neurodegenerative diseases and contributes to cognitive impairment even in the absence of gross atrophy. Currently, for human disease there are few formal models to explain how cortical networks underlying cognition are affected by synaptic loss. We advocate that biophysical models of neurophysiology offer both a bridge from preclinical to clinical models of pathology and quantitative assays for experimental medicine. Such biophysical models can also disclose hidden neuronal dynamics generating neurophysiological observations such as EEG and magnetoencephalography. Here, we augment a biophysically informed mesoscale model of human cortical function by inclusion of synaptic density estimates as captured by 11C-UCB-J PET, and provide insights into how regional synapse loss affects neurophysiology. We use the primary tauopathy of progressive supranuclear palsy (Richardson's syndrome) as an exemplar condition, with high clinicopathological correlations. Progressive supranuclear palsy causes a marked change in cortical neurophysiology in the presence of mild cortical atrophy and is associated with a decline in cognitive functions associated with the frontal lobe. Using parametric empirical Bayesian inversion of a conductance-based canonical microcircuit model of magnetoencephalography data, we show that the inclusion of regional synaptic density-as a subject-specific prior on laminar-specific neuronal populations-markedly increases model evidence. Specifically, model comparison suggests that a reduction in synaptic density in inferior frontal cortex affects superficial and granular layer glutamatergic excitation. This predicted individual differences in behaviour, demonstrating the link between synaptic loss, neurophysiology and cognitive deficits. The method we demonstrate is not restricted to progressive supranuclear palsy or the effects of synaptic loss: such pathology-enriched dynamic causal models can be used to assess the mechanisms of other neurological disorders, with diverse non-invasive measures of pathology, and is suitable to test the effects of experimental pharmacology., (© The Author(s) 2022. Published by Oxford University Press on behalf of the Guarantors of Brain.)

Introduction: Peroxisome proliferator-activated receptor δ (PPARδ) plays a central role in modulating mitochondrial function in ischemia-reperfusion injury. The novel PPARδ modulator, ASP1128, was evaluated., Methods: A randomized, double-blind, placebo-controlled, biomarker assignment-driven, multicenter study was performed in adult patients at risk for acute kidney injury (AKI) following cardiac surgery, examining efficacy and safety of a 3-day, once-daily intravenous dose of 100 mg ASP1128 versus placebo (1:1). AKI risk was based on clinical characteristics and postoperative urinary biomarker (TIMP2)•(IGFBP7). The primary end point was the proportion of patients with AKI based on serum creatinine within 72 hours postsurgery (AKI-SCr72h). Secondary endpoints included the composite end point of major adverse kidney events (MAKE: death, renal replacement therapy, and/or ≥25% reduction of estimated glomerular filtration rate [eGFR]) at days 30 and 90)., Results: A total of 150 patients were randomized and received study medication (81 placebo, 69 ASP1128). Rates of AKI-SCr72h were 21.0% and 24.6% in the placebo and ASP1128 arms, respectively ( P  = 0.595). Rates of moderate/severe AKI (stage 2/3 AKI-SCr and/or stage 3 AKI-urinary output criteria) within 72 hours postsurgery were 19.8% and 23.2%, respectively ( P  = 0.609). MAKE occurred within 30 days in 11.1% and 13.0% in the placebo and ASP1128 arms ( P  = 0.717), respectively; and within 90 days in 9.9% and 15.9% in the placebo and ASP1128 arms ( P  = 0.266), respectively. No safety issues were identified with ASP1128 treatment, but rates of postoperative atrial fibrillation were lower (11.6%) than in the placebo group (29.6%)., Conclusion: ASP1128 was safe and well-tolerated in patients at risk for AKI following cardiac surgery, but it did not show efficacy in renal endpoints., (© 2023 International Society of Nephrology. Published by Elsevier Inc.)

The first Cardiovascular Outcomes Research in Perioperative Medicine (COR-PM) conference took place on May 13, 2022, in Palm Springs, CA, and online. Here, we: (1) summarize the background, objective, and aims of the COR-PM meeting; (2) describe the conduct of the meeting; and (3) outline future directions for scientific meetings aimed at fostering high-quality clinical research in the broader perioperative medicine community., Competing Interests: Conflicts of Interest: See Disclosures at the end of the article., (Copyright © 2022 International Anesthesia Research Society.)

Cardiac surgery-associated acute kidney injury (CS-AKI) is common and is associated with increased risk for postoperative morbidity and mortality. Our recent survey of the Society of Cardiovascular Anesthesiologists (SCA) membership showed 6 potentially renoprotective strategies for which clinicians would most value an evidence-based review (ie, intraoperative target blood pressure, choice of specific vasopressor agent, erythrocyte transfusion threshold, use of alpha-2 agonists, goal-directed oxygen delivery on cardiopulmonary bypass [CPB], and the "Kidney Disease Improving Global Outcomes [KDIGO] bundle of care"). Thus, the SCA's Continuing Practice Improvement Acute Kidney Injury Working Group aimed to provide a practice update for each of these strategies in cardiac surgical patients based on the evidence from randomized controlled trials (RCTs). PubMed, EMBASE, and Cochrane library databases were comprehensively searched for eligible studies from inception through February 2021, with search results updated in August 2021. A total of 15 RCTs investigating the effects of the above-mentioned strategies on CS-AKI were included for meta-analysis. For each strategy, the level of evidence was assessed using the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) methodology. Across the 6 potentially renoprotective strategies evaluated, current evidence for their use was rated as "moderate," "low," or "very low." Based on eligible RCTs, our analysis suggested using goal-directed oxygen delivery on CPB and the "KDIGO bundle of care" in high-risk patients to prevent CS-AKI (moderate level of GRADE evidence). Our results suggested considering the use of vasopressin in vasoplegic shock patients to reduce CS-AKI (low level of GRADE evidence). The decision to use a restrictive versus liberal strategy for perioperative red cell transfusion should not be based on concerns for renal protection (a moderate level of GRADE evidence). In addition, targeting a higher mean arterial pressure during CPB, perioperative use of dopamine, and use of dexmedetomidine did not reduce CS-AKI (a low or very low level of GRADE evidence). This review will help clinicians provide evidence-based care, targeting improved renal outcomes in adult patients undergoing cardiac surgery., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2022 International Anesthesia Research Society.)

Objectives: Accurately assessing the probability of significant respiratory depression following opioid administration can potentially enhance perioperative risk assessment and pain management. We developed and validated a risk prediction tool to estimate the probability of significant respiratory depression (indexed by naloxone administration) in patients undergoing noncardiac surgery., Design: Retrospective cohort study., Setting: Single academic centre., Participants: We studied n=63 084 patients (mean age 47.1±18.2 years; 50% men) who underwent emergency or elective non-cardiac surgery between 1 January 2007 and 30 October 2017., Interventions: A derivation subsample reflecting two-thirds of available patients (n=42 082) was randomly selected for model development, and associations were identified between predictor variables and naloxone administration occurring within 5 days following surgery. The resulting probability model for predicting naloxone administration was then cross-validated in a separate validation cohort reflecting the remaining one-third of patients (n=21 002)., Results: The rate of naloxone administration was identical in the derivation (n=2720 (6.5%)) and validation (n=1360 (6.5%)) cohorts. The risk prediction model identified female sex (OR: 3.01; 95% CI: 2.73 to 3.32), high-risk surgical procedures (OR: 4.16; 95% CI: 3.78 to 4.58), history of drug abuse (OR: 1.81; 95% CI: 1.52 to 2.16) and any opioids being administered on a scheduled rather than as-needed basis (OR: 8.31; 95% CI: 7.26 to 9.51) as risk factors for naloxone administration. Advanced age (OR: 0.971; 95% CI: 0.968 to 0.973), opioids administered via patient-controlled analgesia pump (OR: 0.55; 95% CI: 0.49 to 0.62) and any scheduled non-opioids (OR: 0.63; 95% CI: 0.58 to 0.69) were associated with decreased risk of naloxone administration. An overall risk prediction model incorporating the common clinically available variables above displayed excellent discriminative ability in both the derivation and validation cohorts (c-index=0.820 and 0.814, respectively)., Conclusion: Our cross-validated clinical predictive model accurately estimates the risk of serious opioid-related respiratory depression requiring naloxone administration in postoperative patients., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

In this study, we define and validate a state of postoperative systemic inflammatory dysregulation (PSID) based on postoperative phenotypic extremes of plasma C-reactive protein concentration following major abdominal surgery. PSID manifested clinically with significantly higher rates of sepsis, complications, longer hospital stays and poorer short, and long-term outcomes. We hypothesized that PSID will be associated with, and potentially predicted by, altered patterns of genome-wide peripheral blood mononuclear cell differential DNA methylation and gene expression. We identified altered DNA methylation and differential gene expression in specific immune and metabolic pathways during PSID. Our findings suggest that dysregulation results in, or from, dramatic changes in differential DNA methylation and highlights potential targets for early detection and treatment. The combination of altered DNA methylation and gene expression suggests that dysregulation is mediated at multiple levels within specific gene sets and hence, nonspecific anti-inflammatory treatments such as corticosteroids alone are unlikely to represent an effective therapeutic strategy., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Objective: To examine the association/effect of intraoperative cerebral oximetry (CeOx) on major organ morbidity and mortality (MOMM) after adult cardiac surgery., Design: A retrospective, multicenter cohort study., Setting: Patients treated at any hospital within the Society of Thoracic Surgeons Adult Cardiac Surgery Database between July 1, 2011, and December 31, 2016, with a 30-day postoperative follow-up., Participants: Individuals ≥18 years old undergoing isolated coronary artery bypass graft (CABG) or valve repair or replacement, or any combination of procedures with cardiopulmonary bypass., Interventions: Intraoperative CeOx., Measurements and Main Results: MOMM includes operative mortality, stroke, renal failure, prolonged mechanical ventilation, deep sternal wound infection, or reoperation for any reason within 30 days. Of 1.19 million patients who met inclusion criteria within 1,180 facilities, ∼30% (n = 361,124) received CeOx versus nonrecipients (n = 838,675) with similar baseline patient characteristics. Using a propensity score-based 1:1 greedy matching method, 99.7% of CeOx recipients (n = 360,285) were matched with nonrecipients. The rates of MOMM were lower with versus without CeOx. The absolute risk reduction translated to a number needed to treat of 227 patients (95% CI: 166-363, p < 0.0001). In sensitivity analyses of prespecified subgroups, the benefit was strongest among patients undergoing aortic valve repair or replacement ± CABG (more than 7 fewer MOMM events per 1,000, p < 0.0001). However, intensive care unit stay >72 hours was higher with CeOx., Conclusion: Intraoperative cerebral oximetry is associated with less major organ morbidity and mortality after adult cardiac surgery. A large-scale clinical trial is warranted, given that desaturation is common and correctable., Competing Interests: Conflict of Interest None., (Published by Elsevier Inc.)

Background: Whilst intraoperative hypotension is associated with postoperative acute kidney injury (AKI), the link between intraoperative hypotension and acute kidney disease (AKD), defined as continuing renal dysfunction for up to 3 months after exposure, has not yet been studied., Methods: We conducted a retrospective multicentre cohort study using data from noncardiac, non-obstetric surgery extracted from a US electronic health records database. Primary outcome was the association between intraoperative hypotension, at three MAP thresholds (≤75, ≤65, and ≤55 mm Hg), and the following two AKD subtypes: (i) persistent (initial AKI incidence within 7 days of surgery, with continuation between 8 and 90 days post-surgery) and (ii) delayed (renal impairment without AKI within 7 days, with AKI occurring between 8 and 90 days post-surgery). Secondary outcomes included healthcare resource utilisation for patients with either AKD subtype or no AKD., Results: A total of 112 912 surgeries qualified for the study. We observed a rate of 2.2% for delayed AKD and 0.6% for persistent AKD. Intraoperative hypotension was significantly associated with persistent AKD at MAP ≤55 mm Hg (hazard ratio 1.1; 95% confidence interval: 1.38-1.22; P<0.004). However, IOH was not significantly associated with delayed AKD across any of the MAP thresholds. Patients with delayed or persistent AKD had higher healthcare resource utilisation across both hospital and intensive care admissions, compared with patients with no AKD., Conclusions: Intraoperative hypotension is associated with persistent but not delayed acute kidney disease. Both types of acute kidney disease appear to be associated with increased healthcare utilisation. Correction of intraoperative hypotension is a potential opportunity to decrease postoperative kidney injury and associated costs., (Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.)