Effects of RBT-1 on preconditioning response biomarkers in patients undergoing coronary artery bypass graft or heart valve surgery: a multicentre, double-blind, randomised, placebo-controlled phase 2 trial.

Background: RBT-1 is a combination drug of stannic protoporfin (SnPP) and iron sucrose (FeS) that elicits a preconditioning response through activation of antioxidant, anti-inflammatory, and iron-scavenging pathways, as measured by heme oxygenase-1 (HO-1), interleukin-10 (IL-10), and ferritin, respectively. Our primary aim was to determine whether RBT-1 administered before surgery would safely and effectively elicit a preconditioning response in patients undergoing cardiac surgery. Methods: This phase 2, double-blind, randomised, placebo-controlled, parallel-group, adaptive trial, conducted in 19 centres across the USA, Canada, and Australia, enrolled patients scheduled to undergo non-emergent coronary artery bypass graft (CABG) and/or heart valve surgery with cardiopulmonary bypass. Patients were randomised (1:1:1) to receive either a single intravenous infusion of high-dose RBT-1 (90 mg SnPP/240 mg FeS), low-dose RBT-1 (45 mg SnPP/240 mg FeS), or placebo within 24-48 h before surgery. The primary outcome was a preoperative preconditioning response, measured by a composite of plasma HO-1, IL-10, and ferritin. Safety was assessed by adverse events and laboratory parameters. Prespecified adaptive criteria permitted early stopping and enrichment. This trial is registered with ClinicalTrials.gov, NCT04564833. Findings: Between Aug 4, 2021, and Nov 9, 2022, of 135 patients who were enrolled and randomly allocated to a study group (46 high-dose, 45 low-dose, 44 placebo), 132 (98%) were included in the primary analysis (46 high-dose, 42 low-dose, 44 placebo). At interim, the trial proceeded to full enrollment without enrichment. RBT-1 led to a greater preconditioning response than did placebo at high-dose (geometric least squares mean [GLSM] ratio, 3.58; 95% CI, 2.91-4.41; p < 0.0001) and low-dose (GLSM ratio, 2.62; 95% CI, 2.11-3.24; p < 0.0001). RBT-1 was generally well tolerated by patients. The primary drug-related adverse event was dose-dependent photosensitivity, observed in 12 (26%) of 46 patients treated with high-dose RBT-1 and in six (13%) of 45 patients treated with low-dose RBT-1 (safety population). Interpretation: RBT-1 demonstrated a statistically significant cytoprotective preconditioning response and a manageable safety profile. Further research is needed. A phase 3 trial is planned. Funding: Renibus Therapeutics, Inc.

Topical Versus Intravenous Tranexamic Acid in Patients Undergoing Cardiac Surgery: The DEPOSITION Randomized Controlled Trial.

BACKGROUND: Although intravenous tranexamic acid is used in cardiac surgery to reduce bleeding and transfusion, topical tranexamic acid results in lower plasma concentrations compared to intravenous tranexamic acid, which may lower the risk of seizures. We aimed to determine whether topical tranexamic acid reduces the risk of in-hospital seizure without increasing the risk of transfusion among cardiac surgery patients. METHODS: We conducted a multicenter, double dummy, blinded, randomized controlled trial of patients recruited by convenience sampling in academic hospitals undergoing cardiac surgery with cardiopulmonary bypass. Between September 17, 2019, and November 28, 2023, a total of 3242 patients from 16 hospitals in 6 countries were randomly assigned (1:1 ratio) to receive either intravenous tranexamic acid (control) through surgery or topical tranexamic acid (treatment) at the end of surgery. The primary outcome was seizure, and the secondary outcome was red blood cell transfusion. After the last planned interim analysis-when 75% of anticipated participants had completed follow up-the Data and Safety Monitoring Board recommended to terminate the trial, and upon unblinding, the Operations Committee stopped the trial for safety. RESULTS: Among 3242 randomized patients (mean age, 66.0 years; 77.7% male), in-hospital seizure occurred in 4 of 1624 patients (0.2%) in the topical group and in 11 of 1628 patients (0.7%) in the intravenous group (absolute risk difference, -0.5%; 95% CI, -0.9 to 0.03; P = .07). Red blood cell transfusion occurred in 570 patients (35.1%) in the topical group and in 433 (26.8%) in the intravenous group (absolute risk difference, 8.3%; 95% CI, 5.2 to 11.5; P = .007). The absolute risk difference in transfusion of ≥4 units of red blood cells in the topical group compared to the intravenous group was 8.2% (95% CI, 3.4 to 12.9). CONCLUSIONS: Among patients having cardiac surgery, topical administration of tranexamic acid resulted in an 8.3% absolute increase in transfusion without reducing the incidence of seizure, compared to intravenous tranexamic acid.

Case series of retinal vein occlusions showing early recovery using oral l-methylfolate.

This case series describes the aggregate rate of recovery in five consecutive subjects (six eyes) with retinal vein occlusion (RVO) who received l-methylfolate and other vitamins via Ocufolin®, a medical food. Subjects were followed for 10-33 months by a single ophthalmologist. Ocufolin® was prescribed at the time of diagnosis and subjects remained on the regimen throughout the time of observation. Examinations were performed in an un-masked fashion at 3-month intervals with recording of best corrected visual acuity (BCVA), average retinal nerve fiber layer (ARNFL) and central macular thickness (CMT), and fundus (examination of the retina, macula, optic nerve, and vessels) photography. Testing was done for vitamin deficiencies, vascular and coagulable risk factors, and methylenetetrahydrofolate reductase (MTHFR) polymorphisms. Vitamin deficiencies and vascular risk factors were found in all subjects, and all four tested subjects carried at least one MTHFR polymorphism. By the end of the study period BCVA in all subjects was 20/25 or better. Cystoid macular edema was identified and measured by optical coherence tomography (OCT). The percent change was calculated and plotted at 3-month intervals using the percent change in thickness from the time of diagnosis and percent change toward normative values for ARNFL and CMT. The total reduction in thickness of ARNFL and CMT from time of diagnosis was 44.19% and 30.27%, respectively. The comparison to normative data shows a reduction of ARNFL from 164.2% to 94% and CMT from 154.4% to 112.7% of normal thickness (100%). Plots showed the aggregate recovery was most rapid over the first 3 months and slowed over the next 3 months with most of the recovery taking place within 6 months of treatment. The rate of improvement in BCVA and resolution of retinal thickening was found to be better than predicted on historical grounds. No subjects progressed from nonischemic to ischemic RVO. Vitamin deficiencies, vascular risk factors, and genetic predisposition to oxidative stress were common in this RVO series. It appears that addressing these factors with Ocufolin® had a salutary effect on recovery.

The reliability of posterior malleolar ankle fracture assessment: a unique perspective.

AIM: This study aims to elucidate the pathology of PMFs in the South African population, establish correlations between fracture patterns and international classification guidelines and evaluate the interobserver reliability of current classifications. METHODS: A retrospective review was conducted in a multicentre analysis over a one-year period from January 2019 to December 2019 at our institution. Computer tomography scans for foot and ankle injuries were reviewed, and posterior malleolus fractures were included. Pathoanatomical data was collected and analysed according to known classification systems and subsequent treatment modalities evaluated. A panel of observers individually reviewed radiographic data to determine interobserver reliability. RESULTS: A total of 71 patients were included with a mean age of 41 ± 13.4 years (range 18-78) and a female predominant population (69%). A greater proportion of injuries were high energy (23.9%), with significant fragment comminution (53.5%), and half (52.1%) of all injuries were subluxated/dislocated at presentation. A total of 93% of injuries were managed operatively, despite theatre access limitations resulting in significant delays to fixation (19.1 days). Despite good pathoanatomical agreement with most international classifications, interobserver reliability was poor (Krippendorff α-coefficient < 0.667). Inconsistent treatment patterns in operative and non-operative strategies are reported. CONCLUSION: A unique patient population of younger, female individuals incurred posterior malleolar fractures due to higher energy mechanisms of injury. Whilst injury patterns were mostly comparable, significant interobserver variability was noted. Resource limitations, diagnostic challenges, poorly defined and inconsistent treatment strategies, inevitably impact outcomes within the South African population. LEVEL OF EVIDENCE: Level III.

Mortality and Severe Complications Among Newly Graduated Surgeons in the United States.

OBJECTIVE: To evaluate severe complications and mortality over years of independent practice among general surgeons. BACKGROUND: Despite concerns that newly graduated general surgeons may be unprepared for independent practice, it is unclear whether patient outcomes differ between early and later career surgeons. METHODS: We used Medicare claims for patients discharged between July 1, 2007 and December 31, 2019 to evaluate 30-day severe complications and mortality for 26 operations defined as core procedures by the American Board of Surgery. Generalized additive mixed models were used to assess the association between surgeon years in practice and 30-day outcomes while adjusting for differences in patient, hospital, and surgeon characteristics. RESULTS: The cohort included 1,329,358 operations performed by 14,399 surgeons. In generalized mixed models, the relative risk (RR) of mortality was higher among surgeons in their first year of practice compared with surgeons in their 15th year of practice [5.5% (95% CI: 4.1%-7.3%) vs 4.7% (95% CI: 3.5%-6.3%), RR: 1.17 (95% CI: 1.11-1.22)]. Similarly, the RR of severe complications was higher among surgeons in their first year of practice compared with surgeons in their 15th year of practice [7.5% (95% CI: 6.6%-8.5%) versus 6.9% (95% CI: 6.1%-7.9%), RR: 1.08 (95% CI: 1.03-1.14)]. When stratified by individual operation, 21 operations had a significantly higher RR of mortality and all 26 operations had a significantly higher RR of severe complications in the first compared with the 15th year of practice. CONCLUSIONS: Among general surgeons performing common operations, rates of mortality and severe complications were higher among newly graduated surgeons compared with later career surgeons.

Homocysteine Reduction for Stroke Prevention: Regarding the Recent AHA/ASA 2021 Prevention of Stroke in Patients With Stroke and Transient Ischemic Attack.

Reduction of secondary ischemic stroke risk following an initial stroke is an important goal. The 2021 Prevention of Stroke in Patients With Stroke and Transient Ischemic Attack assembles opportunities for up to 80% secondary stroke reduction. Homocysteine reduction was not included in the recommendations. The reduction of homocysteine with low doses of folic acid has been shown to reduce ischemic stroke and all stroke. This has been obscured by studies using high doses of folic acid and cyanocobalamin in patients with renal failure and Methylenetetrahydrofolate reductase (MTHFR) polymorphisms. The confounding impacts of high dose folic acid and cyanocobalamin toxicity in renal failure and MTHFR C677T subgroups are discussed. New studies show that their toxicity is due to non-bioequivalence to the natural dietary forms, L-methylfolate and methylcobalamin. Low doses of folic acid and cyanocobalamin are safer than high doses for these subpopulations. Even lower toxicity with greater effectiveness for reducing homocysteine is seen with L-methylfolate and methylcobalamin, which are safe at high doses. Retinal vascular imaging is a noninvasive method for evaluating central nervous system (CNS) microangiopathy. A formulation containing l-methylfolate and methylcobalamin has been shown to reduce homocysteine and increase perfusion in diabetic retinopathy. This supports homocysteine intervention for CNS ischemia. Future ischemic stroke intervention studies could benefit from monitoring retinal perfusion to estimate the impact of risk reduction strategies. The omission of a recommendation for homocysteine and secondary stroke reduction through the use of B vitamins should be reconsidered in light of re-analysis of major B vitamin intervention studies and new technologies for monitoring CNS perfusion. We recommend revision of the 2021 Guideline to include homocysteine reduction with low doses of folic acid and cyanocobalamin, or better yet, L-methylfolate and methylcobalamin, making a good clinical guideline better.

Hydrogen Storage with Aluminum Formate, ALF: Experimental, Computational, and Technoeconomic Studies.

Long-duration storage of hydrogen is necessary for coupling renewable H2 with stationary fuel cell power applications. In this work, aluminum formate (ALF), which adopts the ReO3-type structure, is shown to have remarkable H2 storage performance at non-cryogenic (>120 K) temperatures and low pressures. The most promising performance of ALF is found between 120 K and 160 K and at 10 bar to 20 bar. The study illustrates H2 adsorption performance of ALF over the 77 K to 296 K temperature range using gas isotherms, in situ neutron powder diffraction, and DFT calculations, as well as technoeconomic analysis (TEA), illustrating ALF's competitive performance for long-duration storage versus compressed hydrogen and leading metal-organic frameworks. In the TEA, it is shown that ALF's storage capacity, when combined with a temperature/pressure swing process, has advantages versus compressed H2 at a fraction of the pressure (15 bar versus 350 bar). Given ALF's performance in the 10 bar to 20 bar regime under moderate cooling, it is particularly promising for use in safe storage systems serving fuel cells.

Optical opening of the blood-brain barrier for targeted and ultra-sparse viral infection of cells in mouse cortex.

Adeno-associated viruses (AAVs) are used in a wide array of experimental situations for driving expression of biosensors, recombinases, and opto-/chemo-genetic actuators in the brain. However, conventional approaches for minimally invasive, spatially precise, and ultra-sparse AAV-mediated transduction of cells during imaging experiments have remained a significant challenge. Here, we show that intravenous injection of commercially available AAVs at different doses, combined with laser-based perforation of cortical capillaries through a cranial widow, allows for ultra-sparse, titratable, and micron-level precision for delivery of viral vectors with relatively little inflammation or tissue damage. Further, we show the utility of this approach for eliciting sparse expression of GCaMP6, channelrhodopsin, or fluorescent reporters in neurons and astrocytes within specific functional domains in normal and stroke-damaged cortex. This technique represents a facile approach for targeted delivery of viral vectors that should assist in the study of cell types and circuits in the cortex.

Prescribed Opioid Dosages, Payer Type, and Self-Reported Outcomes After Surgical Procedures in Michigan, 2018-2020.

Importance: Collaborative quality improvement (CQI) models, often supported by private payers, create hospital networks to improve health care delivery. Recently, these systems have focused on opioid stewardship; however, it is unclear whether reduction in postoperative opioid prescribing occurs uniformly across health insurance payer types. Objective: To evaluate the association between insurance payer type, postoperative opioid prescription size, and patient-reported outcomes in a large statewide CQI model. Design, Setting, and Participants: This retrospective cohort study used data from 70 hospitals within the Michigan Surgical Quality Collaborative clinical registry for adult patients (age ≥18 years) undergoing general, colorectal, vascular, or gynecologic surgical procedures between January 1, 2018, and December 31, 2020. Exposure: Insurance type, classified as private, Medicare, or Medicaid. Main Outcomes and Measures: The primary outcome was postoperative opioid prescription size in milligrams of oral morphine equivalents (OME). Secondary outcomes were patient-reported opioid consumption, refill rate, satisfaction, pain, quality of life, and regret about undergoing surgery. Results: A total of 40 149 patients (22 921 [57.1%] female; mean [SD] age, 53 [17] years) underwent surgery during the study period. Within this cohort, 23 097 patients (57.5%) had private insurance, 10 667 (26.6%) had Medicare, and 6385 (15.9%) had Medicaid. Unadjusted opioid prescription size decreased for all 3 groups during the study period from 115 to 61 OME for private insurance patients, from 96 to 53 OME for Medicare patients, and from 132 to 65 OME for Medicaid patients. A total of 22 665 patients received a postoperative opioid prescription and had follow-up data for opioid consumption and refill. The rate of opioid consumption was highest among Medicaid patients throughout the study period (16.82 OME [95% CI, 12.57-21.07 OME] greater than among patients with private insurance) but increased the least over time. The odds of refill significantly decreased over time for patients with Medicaid compared with patients with private insurance (odds ratio, 0.93; 95% CI, 0.89-0.98). Adjusted refill rates for private insurance remained between 3.0% and 3.1% over the study period; adjusted refill rates among Medicare and Medicaid patients decreased from 4.7% to 3.1% and 6.5% to 3.4%, respectively, by the end of the study period. Conclusions and Relevance: In this retrospective cohort study of surgical patients in Michigan from 2018 to 2020, postoperative opioid prescription size decreased across all payer types, and differences between groups narrowed over time. Although funded by private payers, the CQI model appeared to have benefitted patients with Medicare and Medicaid as well.

Exclusive Recognition of CO2 from Hydrocarbons by Aluminum Formate with Hydrogen-Confined Pore Cavities.

Exclusive capture of carbon dioxide (CO2) from hydrocarbons via adsorptive separation is an important technology in the petrochemical industry, especially for acetylene (C2H2) production. However, the physicochemical similarities between CO2 and C2H2 hamper the development of CO2-preferential sorbents, and CO2 is mainly discerned via C recognition with low efficiency. Here, we report that the ultramicroporous material Al(HCOO)3, ALF, can exclusively capture CO2 from hydrocarbon mixtures, including those containing C2H2 and CH4. ALF shows a remarkable CO2 capacity of 86.2 cm3 g-1 and record-high CO2/C2H2 and CO2/CH4 uptake ratios. The inverse CO2/C2H2 separation and exclusive CO2 capture performance from hydrocarbons are validated via adsorption isotherms and dynamic breakthrough experiments. Notably, the hydrogen-confined pore cavities with appropriate dimensional size provide an ideal pore chemistry to specifically match CO2 via a hydrogen bonding mechanism, with all hydrocarbons rejected. This molecular recognition mechanism is unveiled by in situ Fourier-transform infrared spectroscopy, X-ray diffraction studies, and molecular simulations.

Noncryogenic Air Separation Using Aluminum Formate Al(HCOO)3 (ALF).

Separating oxygen from air to create oxygen-enriched gas streams is a process that is significant in both industrial and medical fields. However, the prominent technologies for creating oxygen-enriched gas streams are both energy and infrastructure intensive as they use cryogenic temperatures or materials that adsorb N2 from air. The latter method is less efficient than the methods that adsorb O2 directly. Herein, we show, via a combination of gas adsorption isotherms, gas breakthrough experiments, neutron and synchrotron X-ray powder diffraction, Raman spectroscopy, and computational studies, that the metal-organic framework, Al(HCOO)3 (ALF), which is easily prepared at low cost from commodity chemicals, exhibits substantial O2 adsorption and excellent time-dependent O2/N2 selectivity in a range of 50-125 near dry ice/solvent (≈190 K) temperatures. The effective O2 adsorption with ALF at ≈190 K and ≈0.21 bar (the partial pressure of O2 in air) is ≈1.7 mmol/g, and at ice/salt temperatures (≈250 K), it is ≈0.3 mmol/g. Though the kinetics for full adsorption of O2 near 190 K are slower than at temperatures nearer 250 K, the kinetics for initial O2 adsorption are fast, suggesting that O2 separation using ALF with rapid temperature swings at ambient pressures is a potentially viable choice for low-cost air separation applications. We also present synthetic strategies for improving the kinetics of this family of compounds, namely, via Al/Fe solid solutions. To the best of our knowledge, ALF has the highest O2/N2 sorption selectivity among MOF adsorbents without open metal sites as verified by co-adsorption experiments..

Study protocol of a phase 2, randomised, placebo-controlled, double-blind, adaptive, parallel group clinical study to evaluate the efficacy and safety of recombinant alpha-1-microglobulin in subjects at high risk for acute kidney injury following open-chest cardiac surgery (AKITA trial).

INTRODUCTION: Acute kidney injury (AKI) is a common complication after cardiac surgery (CS) and is associated with adverse short-term and long-term outcomes. Alpha-1-microglobulin (A1M) is a circulating glycoprotein with antioxidant, heme binding and mitochondrial-protective mechanisms. RMC-035 is a modified, more soluble, variant of A1M and has been proposed as a novel targeted therapeutic protein to prevent CS-associated AKI (CS-AKI). RMC-035 was considered safe and generally well tolerated when evaluated in four clinical phase 1 studies. METHODS AND ANALYSIS: This is a phase 2, randomised, double-blind, adaptive design, parallel group clinical study that evaluates RMC-035 compared with placebo in approximately 268 cardiac surgical patients at high risk for CS-AKI. RMC-035 is administered as an intravenous infusion. In total, five doses will be given. Dosing is based on presurgery estimated glomerular filtration rate (eGFR), and will be either 1.3 or 0.65 mg/kg.The primary study objective is to evaluate whether RMC-035 reduces the incidence of postoperative AKI, and key secondary objectives are to evaluate whether RMC-035 improves postoperative renal function compared with placebo. A blinded interim analysis with potential sample size reassessment is planned once 134 randomised subjects have completed dosing. An independent data monitoring committee will evaluate safety and efficacy data at prespecified intervals throughout the trial. The study is a global multicentre study at approximately 30 sites. ETHICS AND DISSEMINATION: The trial was approved by the joint ethics committee of the physician chamber Westfalen-Lippe and the University of Münster (code '2021-778 f-A') and subsequently approved by the responsible ethics committees/relevant institutional review boards for the participating sites. The study is conducted in accordance with Good Clinical Practice, the Declaration of Helsinki and other applicable regulations. Results of this study will be published in a peer-reviewed scientific journal. TRIAL REGISTRATION NUMBER: NCT05126303.

Characterizing geographic variation in postoperative venous thromboembolism.

OBJECTIVE: Venous thromboembolism (VTE) after major surgery remains an important contributor to morbidity and mortality. Despite significant quality improvement efforts in prevention and prophylaxis strategies, the degree of hospital and regional variation in the United States remains unknown. METHODS: Medicare beneficiaries undergoing 13 different major surgeries at U.S. hospitals between 2016 and 2018 were included in this retrospective cohort study. We calculated the rates of 90-day VTE. We adjusted for a variety of patient and hospital covariates and used a multilevel logistic regression model to calculate the rates of VTE and coefficients of variation across hospitals and hospital referral regions (HRRs). RESULTS: A total of 4,115,837 patients from 4116 hospitals were included, of whom 116,450 (2.8%) experienced VTE within 90 days. The 90-day VTE rates varied substantially by procedure, from 2.5% for abdominal aortic aneurysm repair to 8.4% for pancreatectomy. Across the hospitals, there was a 6.6-fold variation in index hospitalization VTE and a 5.3-fold variation in the rate of postdischarge VTE. Across the HRRs, there was a 2.6-fold variation in 90-day VTE, with a 12.1-fold variation in the coefficient of variation. A subset of HRRs was identified with both higher VTE rates and higher variance across hospitals. CONCLUSIONS: Substantial variation exists in the rate of postoperative VTE across U.S. hospitals. Characterizing HRRs with high overall rates of VTE and those with significant variation across the hospitals will allow for targeted quality improvement efforts.

Evidence-Based Opioid Prescribing Guidelines and New Persistent Opioid Use After Surgery.

OBJECTIVE: Evaluate the association of evidence-based opioid prescribing guidelines with new persistent opioid use after surgery. SUMMARY BACKGROUND DATA: Patients exposed to opioids after surgery are at risk of new persistent opioid use, which is associated with opioid use disorder and overdose. It is unknown whether evidence-based opioid prescribing guidelines mitigate this risk. METHODS: Using Medicare claims, we performed a difference-in-differences study of opioid-naive patients who underwent 1 of 6 common surgical procedures for which evidence-based postoperative opioid prescribing guidelines were released and disseminated through a statewide quality collaborative in Michigan in October 2017. The primary outcome was the incidence of new persistent opioid use, and the secondary outcome was total postoperative opioid prescription quantity in oral morphine equivalents (OME). RESULTS: We identified 24,908 patients who underwent surgery in Michigan and 118,665 patients who underwent surgery outside of Michigan. Following the release of prescribing guidelines in Michigan, the adjusted incidence of new persistent opioid use decreased from 3.29% (95% CI 3.15-3.43%) to 2.51% (95% CI 2.35-2.67%) in Michigan, which was an additional 0.53 (95% CI 0.36-0.69) percentage point decrease compared with patients outside of Michigan. Simultaneously, adjusted opioid prescription quantity decreased from 199.5 (95% CI 198.3-200.6) mg OME to 88.6 (95% CI 78.7-98.5) mg OME in Michigan, which was an additional 55.7 (95% CI 46.5-65.4) mg OME decrease compared with patients outside of Michigan. CONCLUSIONS: Evidence-based opioid prescribing guidelines were associated with a significant reduction in the incidence of new persistent opioid use and the quantity of opioids prescribed after surgery.

Postoperative Opioid Prescribing and New Persistent Opioid Use: The Risk of Excessive Prescribing.

OBJECTIVE: Evaluate the association between postoperative opioid prescribing and new persistent opioid use. SUMMARY BACKGROUND DATA: Opioid-nave patients who develop new persistent opioid use after surgery are at increased risk of opioid-related morbidity and mortality. However, the extent to which postoperative opioid prescribing is associated with persistent postoperative opioid use is unclear. METHODS: Retrospective study of opioid-naïve adults undergoing surgery in Michigan from 1/1/2017 to 10/31/2019. Postoperative opioid prescriptions were identified using a statewide clinical registry and prescription fills were identified using Michigan's prescription drug monitoring program. The primary outcome was new persistent opioid use, defined as filling at least 1 opioid prescription between post-discharge days 4 to 90 and filling at least 1 opioid prescription between post-discharge days 91 to 180. RESULTS: A total of 37,654 patients underwent surgery with a mean age of 52.2 (16.7) years and 20,923 (55.6%) female patients. A total of 31,920 (84.8%) patients were prescribed opioids at discharge. Six hundred twenty-two (1.7%) patients developed new persistent opioid use after surgery. Being prescribed an opioid at discharge was not associated with new persistent opioid use [adjusted odds ratio (aOR) 0.88 (95% confidence interval (CI) 0.71-1.09)]. However, among patients prescribed an opioid, patients prescribed the second largest [12 (interquartile range (IQR) 3) pills] and largest [20 (IQR 7) pills] quartiles of prescription size had higher odds of new persistent opioid use compared to patients prescribed the smallest quartile [7 (IQR 1) pills] of prescription size [aOR 1.39 (95% CI 1.04-1.86) andaOR 1.97 (95% CI 1.442.70), respectively]. CONCLUSIONS: In a cohort of opioid-naïve patients undergoing common surgical procedures, the risk of new persistent opioid use increased with the size of the prescription. This suggests that while opioid prescriptions in and of themselves may not place patients at risk of long-term opioid use, excessive prescribing does. Consequently, these findings support ongoing efforts to mitigate excessive opioid prescribing after surgery to reduce opioid-related harms.

Association of Elective Surgical Volume With State Executive Order Curtailing Elective Surgery in Michigan During the COVID-19 Pandemic.

OBJECTIVE: Our objective was to evaluate changes in elective surgical volume in Michigan while an executive order (EO) was in place curtailing elective surgery during the COVID-19 pandemic. SUMMARY BACKGROUND DATA: Many state governors enacted EOs curtailing elective surgery to protect scare resources and generate hospital capacity for patients with COVID-19. Little is known of the effectiveness of an EO on achieving a sustained reduction in elective surgery. METHODS: This retrospective cohort study of data from a statewide claims-based registry in Michigan includes claims from the largest private payer in the state for a representative set of elective operations on adult patients from February 2 through August 1, 2020. We reported trends in surgical volume over the period the EO was in place. Estimated backlogs in elective surgery were calculated using case counts from the same period in 2019. RESULTS: Hospitals achieved a 91.7% reduction in case volume before the EO was introduced. By the time the order was rescinded, hospitals were already performing elective surgery at 60.1% of pre-pandemic case rates. We estimate that a backlog of 6419 operations was created while the EO was in effect. Had hospitals ceased elective surgery during this period, an additional 18% of patients would have experienced a delay in surgical care. CONCLUSIONS: Both the introduction and removal of Michigan's EO lagged behind the observed ramp-down and ramp-up in elective surgical volume. These data suggest that EOs may not effectively modulate surgical care and could also contribute to unnecessary delays in surgical care.

Assessment of Determinants of Value in Carotid Endarterectomy.

BACKGROUND: Over 150,000 carotid endarterectomies (CEA) are performed annually worldwide, accounting for $900 million in the United States alone. How cost/spending and quality are related is not well understood but remain essential components in maximizing value. We sought to identify determinants of variability in hospital 90-day episode value for CEA. METHODS: Medicare and private-payer admissions for CEA from January 2, 2014 to August 28, 2020 were linked to retrospective clinical registry data for hospitals in Michigan performing vascular surgery. Hospital-specific, risk-adjusted, 30-day composite complications (defined as reoperation, new neurologic deficit, myocardial infarction, additional procedure including CEA or carotid artery stenting, readmission, or mortality) and 30-day risk-adjusted, price-standardized total episode payments were used to categorize hospitals into low or high value by defining the intersection between complications and spending. RESULTS: A total of 6,595 patients across 39 hospitals were identified across both datasets. Patients at low-value hospitals had a higher rate of 30-day composite complications (17.9% vs. 10.1%, P < 0.001) driven by a significantly higher rate of reoperation (3.0% vs. 1.4%, P = 0.016), readmission (10.7% vs. 6.2%, P = 0.012), new neurologic deficit (4.6% vs. 2.3%, P = 0.017), and mortality (1.6% vs. 0.6%, P < 0.049). Mean total episode payments were $19,635 at low-value hospitals compared to $15,709 at high-value hospitals driven by index hospitalization ($10,800 vs. $9,587, P = 0.002), professional ($3,421 vs. $2,827, P < 0.001), readmission ($3,011 vs. $1,826, P < 0.001), and post-acute care payments ($2,335 vs. $1,486, P < 0.001). Findings were similar when only including patients who did not suffer a complication. CONCLUSIONS: There is tremendous variation in both quality and payments across hospitals included for CEA. Importantly, costs were higher at low-value hospitals independent of postoperative complication. There appears to be little to no relationship between total episode spending and surgical quality, suggesting that improvements in value may be possible by decreasing total episode cost without affecting surgical outcomes.

Impact of Cannabis Use on Outcomes after Lower Extremity Bypass.

BACKGROUND: Cannabis is one of the most commonly used substances in the United States, with national use on the rise. However, there is a paucity of data regarding the effects of cannabis and surgical outcomes. The aim of this study was to assess the association of cannabis use on postoperative outcomes after lower extremity bypass. METHODS: We queried a large statewide registry from 2014 to 2021 to assess patients who underwent lower extremity bypass procedures. Data were gathered regarding cannabis use and the association with postoperative outcomes at 30 days and 1 year. RESULTS: A total of 11,013 patients were identified. Ninety-one percent of patients (10,024) reported no cannabis use, whereas 9.0% (989) reported cannabis use in the past month. Compared with noncannabis users, patients using cannabis had higher opioid use at discharge (odds ratio [OR]: 1.56, 95% confidence interval [CI]: 1.28-1.90), decreased bypass patency at 30 days (OR: 0.52, 95% CI: 0.36-0.78) and 1 year (OR: 0.64, 95% CI 0.47-0.86), and an increased amputation rate at 1 year (OR: 1.25, 95% CI: 1.02-1.52) after lower extremity bypass. CONCLUSIONS: This study shows that cannabis use in vascular surgical patients was associated with decreased graft patency, increased amputation, and increased opioid use after lower extremity bypass procedures. Although future studies are needed, the present study provides novel data that can be used to counsel patients undergoing vascular surgery.

Aluminum formate, Al(HCOO)3: An earth-abundant, scalable, and highly selective material for CO2 capture.

A combination of gas adsorption and gas breakthrough measurements show that the metal-organic framework, Al(HCOO)3 (ALF), which can be made inexpensively from commodity chemicals, exhibits excellent CO2 adsorption capacities and outstanding CO2/N2 selectivity that enable it to remove CO2 from dried CO2-containing gas streams at elevated temperatures (323 kelvin). Notably, ALF is scalable, readily pelletized, stable to SO2 and NO, and simple to regenerate. Density functional theory calculations and in situ neutron diffraction studies reveal that the preferential adsorption of CO2 is a size-selective separation that depends on the subtle difference between the kinetic diameters of CO2 and N2. The findings are supported by additional measurements, including Fourier transform infrared spectroscopy, thermogravimetric analysis, and variable temperature powder and single-crystal x-ray diffraction.

Women benefit from endovenous ablation with fewer complications: Analysis of the Vascular Quality Initiative Varicose Vein Registry.

OBJECTIVE: To evaluate the association between gender and long-term clinician-reported and patient-reported outcomes after endovenous ablation procedures. METHODS: This retrospective cohort study of prospectively collected data from the Vascular Quality Initiative's Varicose Vein Registry included patients undergoing endovenous ablation procedures on truncal veins with or without treatment of perforating veins between 2015 and 2019. A univariate analysis included comparisons of preprocedural, postprocedural, and periprocedural change in Venous Clinical Severity Score (VCSS) and total symptom score by gender. Rates of complications including deep vein thrombosis, endovenous heat-induced thrombosis, leg pigmentation, blistering, paresthesia, incisional infection, and any postprocedural complications were reported by gender. Multivariable analysis leveraged linear regression to examine how gender affected the relationships between patient characteristics, complication rates, and periprocedural change in VCSS score and total symptom score. RESULTS: Of 9743 patients who met the inclusion criteria, 3090 (31.7%) were men and 6653 (68.2%) were women. The perioperative change in VCSS score was greater for men than women (average -4.46 for men vs -4.13 for women; P < .0001). Perioperative change in total symptom score was greater for women than for men (average -10.64 for women vs -9.64 for men; P < .0001). Women had lower incidence of any leg complication (6.1% vs 8.6%; P = .001) endovenous heat-induced thrombosis (1.1% vs 2.2%; P = .002), and infection (0.4% vs 0.7%; P = .001). In multivariable analysis, among patients with a body mass index of more than 40, presence of deep reflux, and preoperative Clinical, Etiologic, Anatomic, and Physiologic classification of 2, women had a greater periprocedural change in VCSS score than men. CONCLUSIONS: Women benefited from endovenous ablation similarly as men, with a lower incidence of postprocedural complications. Gender may be useful for patient selection and counseling for endovenous ablation, with particular usefulness among patients with a high body mass index, presence of deep reflux, and preoperative Clinical, Etiologic, Anatomic, and Physiologic classification of 2.