Efficacy and Safety of Botulinum Toxin Type A for the Prevention of Postoperative Atrial Fibrillation.

BACKGROUND: Postoperative atrial fibrillation (POAF) is associated with increased morbidity and mortality. Epicardial injection of botulinum toxin may suppress POAF. OBJECTIVES: This study sought to assess the safety and efficacy of AGN-151607 for the prevention of POAF after cardiac surgery. METHODS: This phase 2, randomized, placebo-controlled trial assessed the safety and efficacy of AGN-151607, 125 U and 250 U vs placebo (1:1:1), for the prevention of POAF after cardiac surgery. Randomization was stratified by age (<65, ≥65 years) and type of surgery (nonvalvular/valve surgery). The primary endpoint was the occurrence of continuous AF ≥30 seconds. RESULTS: Among 312 modified intention-to-treat participants (placebo, n = 102; 125 U, n = 104; and 250 U, n = 106), the mean age was 66.9 ± 6.8 years; 17% were female; and 64% had coronary artery bypass graft (CABG) only, 12% had CABG + valve, and 24% had valve surgery. The primary endpoint occurred in 46.1% of the placebo group, 36.5% of the 125-U group (relative risk [RR] vs placebo: 0.80; 95% CI: 0.58-1.10; P = 0.16), and 47.2% of the 250-U group (RR vs placebo: 1.04; 95% CI: 0.79-1.37; P = 0.78). The primary endpoint was reduced in the 125-U group in those ≥65 years of age (RR: 0.64; 95% CI: 0.43-0.94; P = 0.02) with a greater reduction in CABG-only participants ≥65 years of age (RR: 0.49; 95% CI: 0.27-0.87; P = 0.01). Rehospitalization and rates of adverse events were similar across the 3 groups. CONCLUSIONS: There were no significant differences in the rate of POAF with either dose compared with placebo; however, there was a lower rate of POAF in participants ≥65 years undergoing CABG only and receiving 125 U of AGN-151607. These hypothesis-generating findings require investigation in a larger, adequately powered randomized clinical trial. (Botulinum Toxin Type A [AGN-151607] for the Prevention of Post-operative Atrial Fibrillation in Adult Participants Undergoing Open-chest Cardiac Surgery [NOVA]; NCT03779841); A Phase 2, Multi-Center, Randomized, Double-Blind, Placebo-Controlled, Dose Ranging Study to Evaluate the Efficacy and Safety of Botulinum Toxin Type A [AGN 151607] Injections into the Epicardial Fat Pads to Prevent Post-Operative Atrial Fibrillation in Patients Undergoing Open-Chest Cardiac Surgery; 2017-004399-68).

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.

Outcomes After Successful Debridement, Antibiotic, and Implant Retention Therapy for Periprosthetic Joint Infection in Total Knee Arthroplasty.

BACKGROUND: Controversy surrounds debridement, antibiotic and implant retention (DAIR) for treatment of acute periprosthetic joint infection (PJI). Data regarding DAIR's rate of infection resolution is variable with little investigation of functional outcomes. METHODS: We identified 191 DAIR cases at a single institution from 2008 to 2020. Knee Injury and Osteoarthritis Outcome Score for Joint Replacement (KOOS-JR) and Patient Reported Outcome Measurement Information System-10 (PROMIS) scores were collected. Patient Reported Outcome Scores were obtained from 60 cases. Median follow-up (IQR) was 4.5 (2.1 to 7.6) versus 3.0 (1.2 to 5.3) years for the control group. Mean scores were compared to a cohort of uncomplicated total knee arthroplasties matched by age, body mass index, and sex using generalized linear models adjusted for follow-up duration. Kaplan-Meier survivorship curves for PJI were constructed. RESULTS: Mean Patient Reported Outcome Scores for the DAIR cohort were 57.2 ± 19.7 for KOOS-JR, 41.6 ± 7.1 for PROMIS physical health (PH), and 46.6 ± 8.7 for PROMIS mental health (MH). Mean control group values were 65.8 ± 21.0 for KOOS-JR, 44.6 ± 8.4 for PROMIS PH, and 49.2 ± 9.2 for PROMIS MH. No difference was observed in KOOS-JR (P = .83) or PROMIS MH (P = .11). PROMIS PH was lower in the DAIR cohort compared to the control group (P = .048). Median follow-up (years) for all 191 cases was 5.9 (range, 0.5 to 13.1). Survivorship (years) without subsequent operation for infection was 84% at 1, 82% at 2, and 79% at 5. CONCLUSION: Knee and MH outcomes in successful DAIR procedures were similar to uncomplicated total knee arthroplasty. DAIR's success rate was 79% in treating acute PJI at 5 years. LEVEL OF EVIDENCE: Level III.

Correlation between measured and predicted mismatch with valve hemodynamics in transcatheter aortic valve replacement: A sex-based analysis.

BACKGROUND: Data regarding the reliability of predicted effective orifice area indexed (pEOAi) is scarce in transcatheter aortic valve replacement (TAVR). AIMS: To assess the validity of the pEOAi in TAVR by correlating its value with echocardiography-derived hemodynamic data. METHODS: A single-center retrospective cohort study of TAVR patients from 2012 to 2021 with available echocardiograms was conducted. Patient-prosthesis mismatch (PPM) was defined based on the Valve Academic Research Consortium 3 criteria. The main endpoints were the congruence of measured effective orifice area indexed (EOAi) and pEOAi with the hemodynamic data obtained by echocardiography. The secondary endpoint included a correlation of predicted PPM (pPPM) and measured PPM (mPPM) with postoperative New York Heart Association (NYHA) status. RESULTS: A total of 318 patients were included. pPPM was more frequent than mPPM (54 [17%]; all moderate PPM vs. 39 [12.3%]: 32 moderate and 7 severe PPM). Predicted and measured EOAi were statistically correlated with postprocedural transvalvular mean gradient and Doppler velocity index (all p < 0.001), including in both sex-based subgroups. The positive predictive value and negative predictive value (NPV) of pPPM for postprocedural transvalvular mean gradient ≥ 20 mmHg were 16% and 97%, respectively. Only pPPM was significantly more prevalent in the group in which NYHA failed to improve than in those with symptom improvement (30.1% vs. 16%, p = 0.027). CONCLUSION: Predicted PPM has an excellent NPV for postprocedural transvalvular mean gradient ≥ 20 mmHg and seems to be a good predictor of NYHA status evolution as opposed to measured PPM. Predicted EOAi can be used in procedural planning to reduce the risk of PPM in both TAVR male and female patients.

NSAIDs use history: impact on the genome-wide DNA methylation profile and possible mechanisms of action.

BACKGROUND AND OBJECTIVE: NSAIDs inhibit cyclooxygenase, but their role in aging and other diseases is not well understood. Our group previously showed the potential benefit of NSAIDs in decreasing the risk of delirium and mortality. Concurrently, epigenetics signals have also been associated with delirium. Therefore, we sought to find differentially methylated genes and biological pathways related to exposure with NSAIDs by comparing the genome-wide DNA methylation profiles of patients with and without a history of NSAIDs use. METHODS: Whole blood samples were collected from 171 patients at the University of Iowa Hospital and Clinics from November 2017 to March 2020. History of NSAIDs use was assessed through a word-search function in the subjects' electronic medical records. DNA was extracted from the blood samples, processed with bisulfite conversion, and analyzed using Illumina's EPIC array. The analysis of top differentially methylated CpG sites and subsequent enrichment analysis were conducted using an established pipeline using R statistical software. RESULTS: Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genome (KEGG) showed several biological pathways relevant to NSAIDs' function. The identified GO terms included "arachidonic acid metabolic process," while KEGG results included "linoleic acid metabolism," "cellular senescence," and "circadian rhythm." Nonetheless, none of the top GO and KEGG pathways and the top differentially methylated CpG sites reached statistical significance. CONCLUSION: Our results suggest a potential role of epigenetics in the mechanisms of the action of NSAIDs. However, the results should be viewed with caution as exploratory and hypothesis-generating given the lack of statistically significant findings.

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.

Five-Year Hospital Readmission After Coronary Artery Bypass Surgery and the Association With Off-Pump Surgery and Sex.

Background Limited data exist on long-term readmission and its association with patient and procedural characteristics after coronary artery bypass grafting. We aimed to investigate 5-year readmission after coronary artery bypass grafting and specifically focus on the role of sex and off-pump surgery. Methods and Results We performed a post hoc analysis of the CORONARY (Coronary Artery Bypass Grafting [CABG] Off or On Pump Revascularization) trial, involving 4623 patients. The primary outcome was all-cause readmission, and the secondary outcome was cardiac readmission. Cox models were used to investigate the association of outcomes with sex and off-pump surgery. Hazard function for sex was studied over time using a flexible, fully parametric model, and time-segmented analyses were performed accordingly. Rho coefficient was calculated for the correlation between readmission and long-term mortality. Median follow-up was 4.4 years (interquartile range, 2.9-5.4 years). The cumulative incidence rates of all-cause and cardiac readmission were 29.4% and 8.2% at 5 years, respectively. Off-pump surgery was not associated with either all-cause or cardiac readmission. The hazard for all-cause readmission in women over time was constantly higher than the hazard for men (hazard ratio [HR], 1.21 [95% CI, 1.04-1.40]; P=0.011). Time-segmented analyses confirmed the higher risk for all-cause (HR, 1.21 [95% CI, 1.05-1.40]; P<0.001) and cardiac (HR, 1.26 [95% CI, 1.03-1.69]; P=0.033) readmission in women after the first 3 years of follow-up. All-cause readmission was strongly correlated with long-term all-cause mortality (Rho, 0.60 [95% CI, 0.48-0.66]), whereas cardiac readmission was strongly correlated with long-term cardiovascular mortality (Rho, 0.60 [95% CI, 0.13-0.86]). Conclusions Readmission rates are substantial at 5 years after coronary artery bypass grafting and are higher in women but not with off-pump surgery. Registration URL: http://www.clinicaltrials.gov/; Unique identifier: NCT00463294.

Anti-inflammatory medication use associated with reduced delirium risk and all-cause mortality: A retrospective cohort study.

OBJECTIVE: To investigate the relationship between history of anti-inflammatory medication use and delirium risk, as well as long-term mortality. METHODS: In this retrospective cohort study, subjects recruited between January 2016 and March 2020 were analyzed. Information about anti-inflammatory medication use history including aspirin, NSAIDs, glucosamine, and other anti-inflammatory drugs, was collected. Logistic regression analysis investigated the relationship between anti-inflammatory medications and delirium. Log-rank analysis and cox proportional hazards model investigated the relationship between anti-inflammatory medications and one-year mortality. RESULTS: The data from 1274 subjects were analyzed. The prevalence of delirium was significantly lower in subjects with NSAIDs usage (23.0%) than in those without NSAIDs usage (35.0%) (p < 0.001). Logistic regression analysis controlling for age, sex, dementia status, and hospitalization department showed that the risk of delirium tended to be reduced by a history of NSAIDs use (OR, 0.76 [95% CI, 0.55 to 1.03]). The one-year mortality in the subjects with NSAIDs (survival rate, 0.879 [95% CI, 0.845 to 0.906]) was significantly lower than in the subjects without NSAIDs (survival rate, 0.776 [95% CI, 0.746 to 0.803]) (p < 0.001). A history of NSAIDs use associated with the decreased risk of one-year mortality even after adjustment for age, sex, Charlson Comorbidity Index, delirium status, and hospitalization department (HR, 0.70 [95% CI, 0.51 to 0.96]). CONCLUSION: This study suggested that NSAIDs usage was associated with decreased delirium prevalence and lower one-year mortality. The potential benefit of NSAIDs on delirium risk and mortality were shown.

The Use of Three-Dimensional Printing in Cardiac Structural Disease: A Review.

OBJECTIVE: Three-dimensional printing (3DP), or additive fabrication, is a process in which a physical 3D model is created using a multitude of 2-dimensional images. This process has been applied to numerous surgical subspecialties with growing interest for the use of 3DP in adult structural heart disease. This scoping review evaluates the use of 3DP in transcatheter and surgical aortic and mitral valve interventions as well as left atrial appendage occlusion in terms of its practical and clinical application. METHODS: Articles were identified through PubMed and Embase using MeSH search terms as well as independent searches. A total of 645 articles were screened, and 37 were retained for qualitative analysis. RESULTS: Operative planning was coded in 100% of articles, complication prevention in 43%, medical education in 5.4%, patient education in 0%, and simulation in 5.4%. CONCLUSIONS: The main uses of 3DP in acquired structural heart disease are centered around operative planning and complication prevention, with moderate use regarding surgical simulation and infrequent use regarding medical and/or patient education. Although patient anatomy varies greatly, deploying 3DP as a large-scale tool remains a possibility. The more 3D models are made, the more can be learned about demographic subsets of patient populations. Due to the lack of standard operating procedures for the creation of 3DP models, the cost-effectiveness of these models is hard to determine and likely center specific. More research into this facet could inform centers that wish to implement this tool.

Anterolateral territory coronary artery bypass grafting strategies: a non-inferiority randomized clinical trial: the AMI-PONT trial.

OBJECTIVES: The main objective was to assess whether a composite coronary artery bypass grafting strategy including a saphenous vein graft bridge to distribute left internal mammary artery outflow provides non-inferior patency rates compared to conventional grafting surgery with separated left internal mammary artery to left anterior descending coronary graft and aorto-coronary saphenous vein grafts to other anterolateral targets. METHODS: All patients underwent isolated grafting surgery with cardiopulmonary bypass and received ≥2 grafts/patients on the anterolateral territory. The graft patency (i.e. non-occluded) was assessed using multislice spiral computed tomography at 1 year. RESULTS: From 2012 to 2021, 208 patients were randomized to a bridge (n = 105) or conventional grafting strategy (n = 103). Patient characteristics were comparable between groups. The anterolateral graft patency was non-inferior in the composite bridge compared to conventional grafting strategy at 1 year [risk difference 0.7% (90% confidence interval -4.8 to 6.2%)]. The graft patency to the left anterior descending coronary was no different between groups (P = 0.175). Intraoperatively, the bridge group required shorter vein length for anterolateral targets (P < 0.001) and exhibited greater Doppler flow in the mammary artery pedicle (P = 0.004). The composite outcome of death, myocardial infarction or target vessel reintervention at 30 days was no different (P = 0.164). CONCLUSIONS: Anterolateral graft patency of the composite bridge grafting strategy is non-inferior to the conventional grafting strategy at 1 year. This novel grafting strategy is safe, efficient, associated with several advantages including better mammary artery flow and shorter vein requirement, and could be a valuable alternative to conventional grafting strategies. Ten-year clinical follow-up is underway. TRIAL REGISTRATION: ClinicalTrials.gov: NCT01585285.

What Is the Fate of Total Joint Arthroplasty Patients Who Are Asked to Quit Smoking Prior to Surgery?

Background: Smoking is a known risk factor for complications following primary total joint arthroplasty (TJA). Little is known regarding the fate of patients who are asked to quit smoking before surgery. The purpose of this study was to evaluate the success of smoking cessation prior to primary TJA and the impact of smoking cessation on perioperative outcomes. Methods: This is a retrospective review of patients who presented between 2008 and 2020 to a single academic medical center with a documented smoking history and were asked to quit smoking prior to receiving a date for primary TJA. The cohort was surveyed about smoking cessation, smoking history, use of quit aids, seeking surgery elsewhere due to the cessation policy, and postoperative complications. Descriptive statistics evaluated the relationship between demographics, smoking cessation, and postoperative complications. Results: A total of 101 patients completed the survey with an overall response rate of 48%. Sixty-two percent of patients quit smoking before surgery, and 51% of these patients reported remaining smoke-free at 6 months postoperatively. The average time to quit before TJA was 45 days (range: 1-365 days), and 62% quit without quit aids. The wound complication/infection rate was significantly higher for patients who did not stop smoking prior to TJA (4 of 16; 27%) than for those who did quit prior to surgery (3 of 63; 5%; P = .02). Conclusions: This study demonstrates that most patients (62%) will stop smoking, if required, prior to primary TJA. Furthermore, 51% of patients reported abstinence from smoking at 6 months following TJA. TJA appears to be an effective motivator for smoking cessation. Level of Evidence: III (retrospective cohort study).

Conduit selection and early graft failure in coronary artery bypass surgery: A post hoc analysis of the Cardiovascular Outcomes for People Using Anticoagulation Strategies (COMPASS) coronary artery bypass grafting study.

OBJECTIVES: Relative rates of early graft failure and conduit selection in coronary artery bypass grafting (CABG) surgery remain controversial. Therefore, we sought to determine the incidence and determinants of graft failure of the left internal mammary artery (LIMA), radial artery, saphenous vein, and right internal mammary artery (RIMA) 1 year after CABG surgery. METHODS: A post hoc analysis of the Cardiovascular Outcomes for People Using Anticoagulation Strategies (COMPASS) CABG study, involving patients from 83 centers in 22 countries. We completed an analysis of 3480 grafts from 1068 patients who underwent CABG surgery with complete computed tomography angiography data. The primary outcome was graft failure as diagnosed by computed tomography angiography 1 year after surgery. RESULTS: Graft failure occurred in 6.4% (68/1068) for LIMA, 9.9% (9/91) for radial artery, 10.4% (232/2239) for saphenous vein, and 26.8% (22/82) for RIMA grafts. The RIMA had a greater rate of graft failure (26.8%) than radial artery (9.9%) and veins (10.4%) (adjusted odds ratio, 2.69; 95% confidence interval, 1.30-5.57; P = .008 and adjusted odds ratio, 2.07; 95% confidence interval, 1.33-3.21; P = .001, respectively). CONCLUSIONS: In this international trial dataset, LIMA and radial artery performed as expected, whereas vein grafts performed better. However, high rates of RIMA failure are worrisome and highlight the need for a thorough evaluation of the patency and safety of the RIMA in CABG surgery.

Presence of a Lateral Trochlear Osteophyte Predicts Medial Unicompartmental Arthroplasty Failure at Midterm Follow-up.

Background: Specific clinical and radiographic risk factors for medial unicompartmental knee arthroplasty (UKA) failure are incompletely understood. The purpose of this study was to perform a midterm survivorship analysis of medial UKA from a single, nondesigner surgeon. Based on observations from clinical practice, we hypothesized that the presence of a lateral trochlear osteophyte on preoperative Merchant radiographs may be predictive of medial UKA failure secondary to progressive osteoarthritis (OA). Methods: Patients who underwent a mobile-bearing medial UKA by a single surgeon with minimum 24 months of clinical follow-up from 2008 to 2019 were retrospectively identified. Radiographic parameters, including the presence of a lateral trochlear osteophyte, were measured. Kaplan-Meier survivorship analyses were performed. Cox proportional hazards models were used to evaluate variables as risk factors for UKA failure, defined as reoperation or component revision. Results: A total of 233 UKAs were included. The mean age was 60 years, mean BMI 32 kg/m2, and 53% of patients were male. The mean follow-up duration was 5.7 years (range, 2.0-13.1 years). Using any reoperation as an endpoint, the 10-year survival was 91%. Using any component revision as an endpoint, the 10-year survival was 93%. Using revision due to progressive OA as an endpoint, the 10-year survival was 95%. The presence of a lateral trochlear osteophyte was associated with an increased risk of any reoperation (hazard ratio 3.6; 95% confidence interval 1.3-9.5) and increased risk of revision due to progressive OA (hazard ratio 9.8; 95% confidence interval 2.9-32.7). Conclusions: The presence of a lateral trochlear osteophyte on preoperative Merchant view radiographs was associated with an increased risk of medial UKA failure.

Correlation between Neutrophil Extracellular Traps (NETs) Expression and Primary Graft Dysfunction Following Human Lung Transplantation.

Primary graft dysfunction (PGD) is characterized by alveolar epithelial and vascular endothelial damage and inflammation, lung edema and hypoxemia. Up to one-third of recipients develop the most severe form of PGD (Grade 3; PGD3). Animal studies suggest that neutrophils contribute to the inflammatory process through neutrophil extracellular traps (NETs) release (NETosis). NETs are composed of DNA filaments decorated with granular proteins contributing to vascular occlusion associated with PGD. The main objective was to correlate NETosis in PGD3 (n = 9) versus non-PGD3 (n = 27) recipients in an exploratory study. Clinical data and blood samples were collected from donors and recipients pre-, intra- and postoperatively (up to 72 h). Inflammatory inducers of NETs' release (IL-8, IL-6 and C-reactive protein [CRP]) and components (myeloperoxidase [MPO], MPO-DNA complexes and cell-free DNA [cfDNA]) were quantified by ELISA. When available, histology, immunohistochemistry and immunofluorescence techniques were performed on lung biopsies from donor grafts collected during the surgery to evaluate the presence of activated neutrophils and NETs. Lung biopsies from donor grafts collected during transplantation presented various degrees of vascular occlusion including neutrophils undergoing NETosis. Additionally, in recipients intra- and postoperatively, circulating inflammatory (IL-6, IL-8) and NETosis biomarkers (MPO-DNA, MPO, cfDNA) were up to 4-fold higher in PGD3 recipients compared to non-PGD3 (p = 0.041 to 0.001). In summary, perioperative elevation of NETosis biomarkers is associated with PGD3 following human lung transplantation and these biomarkers might serve to identify recipients at risk of PGD3 and initiate preventive therapies.

Perioperative Opioid Counseling Reduces Opioid Use Following Primary Total Joint Arthroplasty.

Background: Preoperative counseling may reduce postoperative opioid requirements; however, there is a paucity of randomized controlled trials (RCTs) demonstrating efficacy. The purpose of this study was to perform an interventional, telehealth-based RCT evaluating the effect of peri-operative counseling on quantity and duration of opioid consumption following primary total joint arthroplasty (TJA). Methods: Participants were randomized into three groups: 1. Control group, no perioperative counseling; 2. Intervention group, preoperative educational video; 3. Intervention group, preoperative educational video and postoperative acceptance and commitment therapy (ACT). Opioid consumption was evaluated daily for 14 days and at 6 weeks postoperatively. Best-case and worse-case intention to treat analyses were performed to account for non-responses. Bonferroni corrections were applied. Results: 183 participants were analyzed (63 in Group 1, 55 in Group 2, and 65 in Group 3). At 2 weeks postoperatively, there was no difference in opioid consumption between Groups 1, 2, and 3 (p>0.05 for all). At 6 weeks postoperatively, Groups 2 and 3 had consumed significantly less opioids than Group 1 (p=0.04, p<0.001) (Table 1). Group 3 participants were less likely to obtain an opioid refill relative to Group 1 participants (p=0.04). Participants in groups 2 and 3 ceased opioid consumption a median of 6 days and 2 days sooner than Group 1, respectively (p<0.001, p=0.03) (Table 2). Conclusion: Perioperative opioid counseling significantly decreases the quantity and duration of opioid consumption at 6 weeks following primary TJA. Level of Evidence: I.

Percutaneous Mechanical Circulatory Support in Post-Myocardial Infarction Cardiogenic Shock: A Systematic Review and Meta-analysis.

BACKGROUND: Cardiogenic shock (CS) complicates 5%-10% of acute myocardial infarction (AMI) and is the leading cause of early mortality. It remains unclear whether percutaneous mechanical support (pMCS) devices improve post-AMI CS outcome. METHODS: A systematic review of original studies comparing the effect of pMCS on AMI-CS mortality was conducted with the use of Medline, Embase, Google Scholar, and the Cochrane Library databases. RESULTS: Of 8672 records, 50 were retained for quantitative analysis. Four additional references were added from other sources. Four references reported a significant mortality reduction with intra-aortic balloon pump (IABP) in patients with failed primary percutaneous coronary intervention (pPCI) or managed with thrombolysis. Meta-analyses showed no advantage of Impella over conventional therapy (pooled OR 0.55, 95% CI 0.20-1.46; I2 = 0.85) and increased mortality compared with IABP (pooled OR 1.32; 95% CI 1.08-1.62; I2 = 0.85). No study reported a mortality advantage for extracorporeal membrane oxygenation (ECMO) over conventional therapy, IABP, or Impella support. Early mortality might be improved with the addition of IABP or Impella to ECMO. Bleeding Academic Research Consortium ≥ 3 bleeding was increased with every pMCS strategy. CONCLUSIONS: The current evidence is of poor to moderate quality, with only 1 in 5 included articles reporting randomised data and several reporting unadjusted outcomes. Yet, there is some evidence to favour IABP use in the setting of thrombolysis or with failed pPCI, and adding IABP or Impella should be considered for patients requiring ECMO.

Large-Animal Model of Donation after Circulatory Death and Normothermic Regional Perfusion for Cardiac Assessment.

The increase in demand for cardiac transplantation throughout the years has fueled interest in donation after circulatory death (DCD) to expand the organ donor pool. However, the DCD process is associated with the risk of cardiac tissue injury due to the inevitable period of warm ischemia. Normothermic regional perfusion (NRP) allows for an in situ organ assessment, allowing the procurement of hearts determined to be viable. Here, we describe a clinically relevant large-animal model of DCD followed by NRP. Circulatory death is established in anesthetized pigs by stopping mechanical ventilation. After a preset warm ischemia period, an extracorporeal membrane oxygenator (ECMO) is used for a NRP period lasting at least 30 min. During this reperfusion period, the model allows the collection of various myocardial biopsies and blood samples for initial cardiac evaluation. Once NRP is weaned, biochemical, hemodynamic, and echocardiographic assessments of cardiac function and metabolism can be performed before organ procurement. This protocol closely simulates the clinical scenario previously described for DCD and NRP in heart transplantation and has the potential to facilitate studies aimed at decreasing ischemia-reperfusion injury and enhance cardiac functional preservation and recovery.

Novel heat shock protein 90 inhibitor improves cardiac recovery in a rodent model of donation after circulatory death.

OBJECTIVE: Organ donation after circulatory death (DCD) is a potential solution for the shortage of suitable organs for transplant. Heart transplantation using DCD donors is not frequently performed due to the potential myocardial damage following warm ischemia. Heat shock protein (HSP) 90 has recently been investigated as a novel target to reduce ischemia/reperfusion injury. The objective of this study is to evaluate an innovative HSP90 inhibitor (HSP90i) as a cardioprotective agent in a model of DCD heart. METHODS: A DCD protocol was initiated in anesthetized Lewis rats by discontinuation of ventilation and confirmation of circulatory death by invasive monitoring. Following 15 minutes of warm ischemia, cardioplegia was perfused for 5 minutes at physiological pressure. DCD hearts were mounted on a Langendorff ex vivo heart perfusion system for reconditioning and functional assessment (60 minutes). HSP90i (0.01 µmol/L) or vehicle was perfused in the cardioplegia and during the first 10 minutes of ex vivo heart perfusion reperfusion. Following assessment, pro-survival pathway signaling was evaluated by western blot or polymerase chain reaction. RESULTS: Treatment with HSP90i preserved left ventricular contractility (maximum + dP/dt, 2385 ± 249 vs 1745 ± 150 mm Hg/s), relaxation (minimum -dP/dt, -1437 ± 97 vs 1125 ± 85 mm Hg/s), and developed pressure (60.7 ± 5.6 vs 43.9 ± 4.0 mm Hg), when compared with control DCD hearts (All P = .001). Treatment abrogates ischemic injury as demonstrated by a significant reduction of infarct size (2,3,5-triphenyl-tetrazolium chloride staining) of 7 ± 3% versus 19 ± 4% (P = .03), troponin T release, and mRNA expression of Bax/Bcl-2 (P < .05). CONCLUSIONS: The cardioprotective effects of HSP90i when used following circulatory death might improve transplant organ availability by expanding the use of DCD hearts.