SOX6 expression and aneurysms of the thoracic and abdominal aorta.

Abdominal and thoracic aortic aneurysms (AAAs, TAAs) remain a major cause of deaths worldwide, in part due to the lack of reliable prognostic markers or early warning signs. Sox6 has been found to regulate renin controlling blood pressure. We hypothesized that Sox6 may serve as an important regulator of the mechanisms contributing to hypertension-induced aortic aneurysms.

Intraoperative Oxygen Treatment, Oxidative Stress, and Organ Injury Following Cardiac Surgery: A Randomized Clinical Trial.

Importance: Liberal oxygen (hyperoxia) is commonly administered to patients during surgery, and oxygenation is known to impact mechanisms of perioperative organ injury.

Objective: To evaluate the effect of intraoperative hyperoxia compared to maintaining normoxia on oxidative stress, kidney injury, and other organ dysfunctions after cardiac surgery.

Design, Setting, And Participants: This was a participant- and assessor-blinded, randomized clinical trial conducted from April 2016 to October 2020 with 1 year of follow-up at a single tertiary care medical center.

Determinants and Practice Variability of Oxygen Administration during Surgery in the United States: A Retrospective Cohort Study.

Background: The best approaches to supplemental oxygen administration during surgery remain unclear, which may contribute to variation in practice. This study aimed to assess determinants of oxygen administration and its variability during surgery.

Methods: Using multivariable linear mixed-effects regression, the study measured the associations between intraoperative fraction of inspired oxygen and patient, procedure, medical center, anesthesiologist, and in-room anesthesia provider factors in surgical cases of 120 min or longer in adult patients who received general anesthesia with tracheal intubation and were admitted to the hospital after surgery between January 2016 and January 2019 at 42 medical centers across the United States participating in the Multicenter Perioperative Outcomes Group data registry.

Mitochondrial CypD Acetylation Promotes Endothelial Dysfunction and Hypertension.

Background: Nearly half of adults have hypertension, a major risk factor for cardiovascular disease. Mitochondrial hyperacetylation is linked to hypertension, but the role of acetylation of specific proteins is not clear. We hypothesized that acetylation of mitochondrial CypD (cyclophilin D) at K166 contributes to endothelial dysfunction and hypertension.

Perioperative Acute Kidney Injury: Implications, Approach, Prevention.

Acute kidney injury remains a common and significant contributor to perioperative morbidity. Acute kidney injury worsens patient outcomes, and anesthesiologists should make significant efforts to prevent, assess, and treat perioperative renal injury. The authors discuss the impact of renal injury on patient outcomes and putative underlying mechanisms, evidence underlying treatments for acute kidney injury, and practices that may prevent the development of perioperative renal injury.

Hyperoxia Increases Kidney Injury During Renal Ischemia and Reperfusion in Mice.

Background: Renal ischemia and reperfusion (IR) contribute to perioperative acute kidney injury, and oxygen is a key regulator of this process. We hypothesized that oxygen administration during surgery and renal IR would impact postoperative kidney function and injury in mice.

Methods: Mice were anesthetized, intubated, and mechanically ventilated with a fraction of inspired oxygen (F io2 ) 0.

Oxidative stress mediates associations between preoperative psychosocial phenotype and pain-related outcomes at 6 months following total knee arthroplasty: a longitudinal cohort study.

Objective: Greater preoperative depression, anxiety, and pain catastrophizing are associated with more severe long-term pain following total knee arthroplasty (TKA). In a secondary analysis of previously reported data, we tested the hypothesis that these associations are mediated by oxidative stress (OS).

Design: A mixed between/within-subjects longitudinal cohort design.

Targeting Soluble Guanylyl Cyclase during Ischemia and Reperfusion.

Ischemia and reperfusion (IR) damage organs and contribute to many disease states. Few effective treatments exist that attenuate IR injury. The augmentation of nitric oxide (NO) signaling remains a promising therapeutic target for IR injury.

Preoperative Predictors of Prolonged Opioid Use in the 6 Months After Total Knee Arthroplasty.

Objectives: Prolonged postoperative opioid use increases the risk for new postsurgical opioid use disorder. We evaluated preoperative phenotypic factors predicting prolonged postoperative opioid use.

Methods: We performed a secondary analysis of a prospective observational cohort (n=108) undergoing total knee arthroplasty (TKA) for osteoarthritis with 6-week and 6-month follow-up.

The Association Between Enhanced Recovery After Cardiac Surgery-Guided Analgesics and Postoperative Delirium.

Objectives: Delirium is a common postoperative complication associated with death and long-term cognitive impairment. The authors studied the association between opioid-sparing anesthetics, incorporating Enhanced Recovery After Cardiac Surgery (ERACS)-guided analgesics and postoperative delirium.

Design: The authors performed a retrospective review of nonemergent coronary, valve, or ascending aorta surgery patients.

Oxygen administration during surgery and postoperative organ injury: observational cohort study.

Objective: To examine whether supraphysiological oxygen administration during surgery is associated with lower or higher postoperative kidney, heart, and lung injury.

Design: Observational cohort study.

Setting: 42 medical centers across the United States participating in the Multicenter Perioperative Outcomes Group data registry.

Role of Axl in target organ inflammation and damage due to hypertensive aortic remodeling.

We have shown that excessive endothelial cell stretch causes release of growth arrest-specific 6 (GAS6), which activates the tyrosine kinase receptor Axl on monocytes and promotes immune activation and inflammation. We hypothesized that GAS6/Axl blockade would reduce renal and vascular inflammation and lessen renal dysfunction in the setting of chronic aortic remodeling. We characterized a model of aortic remodeling in mice following a 2-wk infusion of angiotensin II (ANG II).

SOLUBLE GUANYLYL CYCLASE ACTIVATION RESCUES HYPEROXIA-INDUCED DYSFUNCTION OF VASCULAR RELAXATION.

Introduction: Perioperative alterations in perfusion lead to ischemia and reperfusion injury, and supplemental oxygen is administered during surgery to limit hypoxic injury but can lead to hyperoxia. We hypothesized that hyperoxia impairs endothelium-dependent and endothelium-independent vasodilation but not the vasodilatory response to heme-independent soluble guanylyl cyclase activation. Methods: We measured the effect of oxygen on vascular reactivity in mouse aortas.

Society of Cardiovascular Anesthesiologists Clinical Practice Update for Management of Acute Kidney Injury Associated With Cardiac Surgery.

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).

Perioperative oxidative stress predicts subsequent pain-related outcomes in the 6 months after total knee arthroplasty.

Total knee arthroplasty (TKA) is effective for pain reduction in most patients, but 15% or more report unsatisfactory long-term pain outcomes. We tested whether oxidative stress (OS) related to extended tourniquet application during TKA and subsequent ischemic reperfusion (IR) contributed to adverse post-TKA pain outcomes. Blood samples were obtained in 91 patients with osteoarthritis (63% female) undergoing TKA before tourniquet placement (T1), 45 minutes after tourniquet inflation (T2), and 15 minutes after tourniquet removal (T3).

Preoperative Predictors of Complex Regional Pain Syndrome Outcomes in the 6 Months Following Total Knee Arthroplasty.

This prospective observational study evaluated preoperative predictors of complex regional pain syndrome (CRPS) outcomes in the 6 months following total knee arthroplasty (TKA). Participants were n = 110 osteoarthritis patients (64.5% female) undergoing unilateral TKA with no prior CRPS history.

Assessment of Awake Prone Positioning in Hospitalized Adults With COVID-19: A Nonrandomized Controlled Trial.

Importance: Awake prone positioning may improve hypoxemia among patients with COVID-19, but whether it is associated with improved clinical outcomes remains unknown.

Objective: To determine whether the recommendation of awake prone positioning is associated with improved outcomes among patients with COVID-19-related hypoxemia who have not received mechanical ventilation.

Design, Setting, And Participants: This pragmatic nonrandomized controlled trial was conducted at 2 academic medical centers (Vanderbilt University Medical Center and NorthShore University HealthSystem) during the COVID-19 pandemic.

Impact of Inhaled Oxygen on Reactive Oxygen Species Production and Oxidative Damage during Spontaneous Ventilation in a Murine Model of Acute Renal Ischemia and Reperfusion.

Introduction: Acute kidney injury (AKI) affects 10% of patients following major surgery and is independently associated with extra-renal organ injury, development of chronic kidney disease, and death. Perioperative renal ischemia and reperfusion (IR) contributes to AKI by, in part, increasing production of reactive oxygen species (ROS) and leading to oxidative damage. Variations in inhaled oxygen may mediate some aspects of IR injury by affecting tissue oxygenation, ROS production, and oxidative damage.

Impact of Intraoperative Data on Risk Prediction for Mortality After Intra-Abdominal Surgery.

Background: Risk prediction models for postoperative mortality after intra-abdominal surgery have typically been developed using preoperative variables. It is unclear if intraoperative data add significant value to these risk prediction models.

Methods: With IRB approval, an institutional retrospective cohort of intra-abdominal surgery patients in the 2005 to 2015 American College of Surgeons National Surgical Quality Improvement Program was identified.

Oxidative stress is associated with characteristic features of the dysfunctional chronic pain phenotype.

The dysfunctional chronic pain (Dysfunctional CP) phenotype is an empirically identifiable CP subtype with unclear pathophysiological mechanisms that cuts across specific medical CP diagnoses. This study tested whether the multidimensional pain and psychosocial features that characterize the dysfunctional CP phenotype are associated broadly with elevated oxidative stress (OS). Measures of pain intensity, bodily extent of pain, catastrophizing cognitions, depression, anxiety, sleep disturbance, pain interference, and function were completed by 84 patients with chronic osteoarthritis before undergoing total knee arthroplasty.

Potential Renoprotective Strategies in Adult Cardiac Surgery: A Survey of Society of Cardiovascular Anesthesiologists Members to Explore the Rationale and Beliefs Driving Current Clinical Decision-Making.

Objectives: The authors sought to (1) characterize the rationale underpinning anesthesiologists' use of various perioperative strategies hypothesized to affect renal function in adult patients undergoing cardiac surgery, (2) characterize existing belief about the quality of evidence addressing the renal impact of these strategies, and (3) identify potentially renoprotective strategies for which anesthesiologists would most value a detailed, evidence-based review.

Design: Survey of perioperative practice in adult patients undergoing cardiac surgery.

Setting: Online survey.

Intraoperative venous congestion and acute kidney injury in cardiac surgery: an observational cohort study.

Background: Increased intravascular volume has been associated with protection from acute kidney injury (AKI), but in patients with congestive heart failure, venous congestion is associated with increased AKI. We tested the hypothesis that intraoperative venous congestion is associated with AKI after cardiac surgery.

Methods: In patients enrolled in the Statin AKI Cardiac Surgery trial, venous congestion was quantified as the area under the curve (AUC) of central venous pressure (CVP) >12, 16, or 20 mm Hg during surgery (mm Hg min).

Perioperative high density lipoproteins, oxidative stress, and kidney injury after cardiac surgery.

Oxidative stress promotes acute kidney injury (AKI). Higher HDL cholesterol concentrations are associated with less AKI. To test the hypothesis that HDL antioxidant activity is associated with AKI after cardiac surgery, we quantified HDL particle (HDL-P) size and number, paraoxonase-1 (PON-1) activity, and isofuran concentrations in 75 patients who developed AKI and 75 matched control patients.

The incidence, risk, presentation, pathophysiology, treatment, and effects of perioperative acute kidney injury.

Purpose: Present clinical updates, current research findings, and consensus statements relevant to the care of the acute kidney injury (AKI) patient.

Principal Findings: Acute kidney injury is one of the most frequent and debilitating complications of surgery and critical illness. Consensus criteria use serum creatinine and urine output measurements to diagnose AKI and allow for objective diagnosis and more accurate comparisons across populations.