Chronic total occlusions and coronary artery bypass grafting outcomes.

OBJECTIVE: To investigate the association between the presence and grafting of chronic total occlusions (CTOs) and coronary artery bypass grafting (CABG) outcomes. METHODS: This was a post hoc analysis of the Randomized Endograft vs Open Prospective (REGROUP) trial, which randomized veterans undergoing isolated on-pump CABG to endoscopic versus open vein harvest (2014-2017). Patients were stratified on the basis of the presence of at least 1 CTO vessel (a 100% occluded coronary lesion for greater than or equal to 3 months) and according to whether all CTO vessels were bypassed. Rates of major cardiac adverse events (MACE) were compared. RESULTS: At least 1 CTO was present in 453 of 1149 patients (39.4%). Over a median follow-up of 4.7 years (interquartile range, 3.84-5.45), MACE rates were 23.4% versus 22.2% for the CTO versus no CTO group, respectively (adjusted hazard ratio [aHR], 0.92; 95% confidence interval [CI], 0.70-1.20). MACE rates for patients with complete CTO grafting versus not were 23.1% versus 25.0%, respectively (aHR, 0.95; 95% CI, 0.57-1.57). In patients with right coronary dominance undergoing left anterior descending artery grafting, bypassing a right coronary artery CTO was associated with significantly lower rates of all-cause mortality (aHR, 0.38; 95% CI, 0.17-0.83). CONCLUSIONS: In this REGROUP trial subanalysis, neither CTO presence or complete grafting of CTO vessels was associated with significantly different rates of MACE. However, the finding of possible survival benefit among a subgroup of patients undergoing grafting of a dominant RCA CTO vessel alongside left anterior descending artery grafting warrants additional study.

Non-Muscle Invasive Bladder Cancer: Many More Patients Die With It Than Of It.

BACKGROUND: The National Cancer Institute SEER Program regularly publishes bladder-cancer specific survival statistics. However, this data is for all bladder cancers, and information for non-muscle invasive bladder cancer (NMIBC) is difficult to obtain. OBJECTIVE: To quantify 5-year overall and bladder cancer-specific survival in a cohort of Department of Veterans Affairs (VA) patients diagnosed with NMIBC. METHODS: We identified VA patients diagnosed with NMIBC who underwent a transurethral resection from 2003-2013. The patient demographics and Charlson Comorbidity Index were categorized. We acquired the patients' date of death from the Veterans Health Administration's Death Ascertainment File and their cause of death from the Mortality Data Repository. We calculated Kaplan Meier estimates of survival. RESULTS: A total of 27,008 patients were included; median age was 69 and almost all were male (99%). The median comorbidity score was 4. The most prevalent comorbidity indicators included Chronic Pulmonary Disease (48%), cancer other than Bladder (41%), and diabetes (40%). This cohort was found to have a 5-year overall survival of 68% (99% CI 67% -69%) and a 5-year bladder cancer-specific survival of 93% (99% CI 92% -94%). CONCLUSIONS: The 5-year bladder cancer-specific survival in patients diagnosed with non-muscle invasive bladder cancer is substantially higher than the 5-year overall survival. This difference may be related to the severity and number of comorbidities that patients in this population must manage. This warrants further research into the necessity of currently recommended high-intensity cancer surveillance for individuals with NMIBC.

Superior Outcomes of Dual-Arterial Coronary Artery Bypass Grafting Are Maintained in the Veterans Health Administration.

INTRODUCTION: Controversy surrounds the long-term clinical benefit of coronary artery bypass grafting (CABG) using dual arterial grafts (DAGs) compared to single arterial grafts (SAGs). We investigated outcomes of DAG, using single internal thoracic artery and radial artery (DAG-RA) or bilateral internal thoracic artery grafts (DAG-BITA), compared to SAG, using the left internal thoracic artery and saphenous vein grafts, in the U.S. Veterans Health Administration (VA). METHODS: We conducted a cross-sectional study of U.S. Veterans undergoing isolated on-pump CABG between 2005 and 2015 at 44 VA medical centers. The primary composite outcome was first occurrence of a major adverse cardiac and cerebrovascular event (MACCE), comprised of death from any cause, myocardial infarction, stroke, or repeat revascularization. RESULTS: Among 25,969 Veterans undergoing isolated CABG, 1261 (4.9%) underwent DAG (66.8% DAG-RA and 33.2% DAG-BITA). Over a 5-y follow-up, DAG was associated with lower rates of all-cause death (adjusted hazard ratio [AHR] 0.70, 95% confidence interval [CI] 0.58-0.85), MACCE (AHR 0.80, 95% CI 0.71-0.91), and stroke (AHR 0.74, 95% CI 0.57-0.96) versus SAG. DAG-BITA was associated with lower rates of all-cause death (AHR 0.52, 95% CI 0.35-0.77) and MACCE (AHR 0.66, 95% CI 0.51-0.84) than SAG, while DAG-RA was associated with lower rates of all-cause death (AHR 0.79, 95% CI 0.64-0.99). CONCLUSIONS: In the VA, DAG was associated with improved long-term MACCE outcomes compared to SAG. These results suggest that the practice of DAG in the VA benefits Veterans and should be promoted further.

Performance of left internal thoracic artery-left anterior descending artery anastomosis by residents versus attendings and coronary artery bypass grafting outcomes.

OBJECTIVES: Performance of a technically sound left internal thoracic artery to left anterior descending artery (LITA-LAD) anastomosis during coronary artery bypass grafting (CABG) is critically important. We used prospectively collected data from the multicentre, randomized REGROUP (Randomized Endograft Vein Perspective) trial to investigate CABG outcomes based on whether a resident or an attending surgeon performed the LITA-LAD anastomosis. METHODS: This was a post hoc subanalysis of the REGROUP trial, which randomized veterans undergoing isolated on-pump CABG to endoscopic versus open vein harvest from 2014 through 2017. The primary end point was major cardiac adverse events, defined as the composite of all-cause deaths, nonfatal myocardial infarctions or repeat revascularizations. RESULTS: Among 1,084 patients, 344 (31.8%) LITA-LAD anastomoses were performed by residents and 740 (68.2%), by attending surgeons. Residents (compared to attendings) operated on fewer patients with high tercile SYNTAX scores (22.1% vs 37.4%, P < 0.001), performed fewer multiarterial CABGs (5.2% vs 14.6%, P < 0.001) and performed more anastomoses to distal targets with diameters > 2.0 mm (19.0% vs 10.9%, P < 0.001) and non-calcified landing zones (25.1% vs 21.6%, P < 0.001). During a median observation time of 4.7 years (interquartile range 3.84-5.45), major cardiac adverse events occurred in 77 patients (22.4%) in the group treated by residents and 169 patients (22.8%) in the group treated by attendings (unadjusted HR 1.00; 95% confidence interval, 0.76-1.33; P = 0.99). Outcomes persisted on adjusted analyses. CONCLUSIONS: Based on this REGROUP trial subanalysis, under careful supervision and with appropriate patient selection, LITA-LAD anastomoses performed by the residents yielded clinical outcomes similar to those of the attendings.

Hormonal intervention for the treatment of veterans with COVID-19 requiring hospitalization (HITCH): a multicenter, phase 2 randomized controlled trial of best supportive care vs best supportive care plus degarelix: study protocol for a randomized controlled trial.

BACKGROUND: Therapeutic targeting of host-cell factors required for SARS-CoV-2 entry is an alternative strategy to ameliorate COVID-19 severity. SARS-CoV-2 entry into lung epithelium requires the TMPRSS2 cell surface protease. Pre-clinical and correlative data in humans suggest that anti-androgenic therapies can reduce the expression of TMPRSS2 on lung epithelium. Accordingly, we hypothesize that therapeutic targeting of androgen receptor signaling via degarelix, a luteinizing hormone-releasing hormone (LHRH) antagonist, will suppress COVID-19 infection and ameliorate symptom severity. METHODS: This is a randomized phase 2, placebo-controlled, double-blind clinical trial in 198 patients to compare efficacy of degarelix plus best supportive care versus placebo plus best supportive care on improving the clinical outcomes of male Veterans who have been hospitalized due to COVID-19. Enrolled patients must have documented infection with SARS-CoV-2 based on a positive reverse transcriptase polymerase chain reaction result performed on a nasopharyngeal swab and have a severity of illness of level 3-5 (hospitalized but not requiring invasive mechanical ventilation). Patients stratified by age, history of hypertension, and severity are centrally randomized 2:1 (degarelix: placebo). The composite primary endpoint is mortality, ongoing need for hospitalization, or requirement for mechanical ventilation at 15 after randomization. Important secondary endpoints include time to clinical improvement, inpatient mortality, length of hospitalization, duration of mechanical ventilation, time to achieve a normal temperature, and the maximum severity of COVID-19 illness. Exploratory analyses aim to assess the association of cytokines, viral load, and various comorbidities with outcome. In addition, TMPRSS2 expression in target tissue and development of anti-viral antibodies will also be investigated. DISCUSSION: In this trial, we repurpose the FDA approved LHRH antagonist degarelix, commonly used for prostate cancer, to suppress TMPRSS2, a host cell surface protease required for SARS-CoV-2 cell entry. The objective is to determine if temporary androgen suppression with a single dose of degarelix improves the clinical outcomes of patients hospitalized due to COVID-19. TRIAL REGISTRATION: ClinicalTrials.gov NCT04397718. Registered on May 21, 2020.

Randomized Trial of Endoscopic or Open Vein-Graft Harvesting for Coronary-Artery Bypass.

BACKGROUND: The saphenous-vein graft is the most common conduit for coronary-artery bypass grafting (CABG). The influence of the vein-graft harvesting technique on long-term clinical outcomes has not been well characterized. METHODS: We randomly assigned patients undergoing CABG at 16 Veterans Affairs cardiac surgery centers to either open or endoscopic vein-graft harvesting. The primary outcome was a composite of major adverse cardiac events, including death from any cause, nonfatal myocardial infarction, and repeat revascularization. Leg-wound complications were also evaluated. RESULTS: A total of 1150 patients underwent randomization. Over a median follow-up of 2.78 years, the primary outcome occurred in 89 patients (15.5%) in the open-harvest group and 80 patients (13.9%) in the endoscopic-harvest group (hazard ratio, 1.12; 95% confidence interval [CI], 0.83 to 1.51; P=0.47). A total of 46 patients (8.0%) in the open-harvest group and 37 patients (6.4%) in the endoscopic-harvest group died (hazard ratio, 1.25; 95% CI, 0.81 to 1.92); myocardial infarctions occurred in 34 patients (5.9%) in the open-harvest group and 27 patients (4.7%) in the endoscopic-harvest group (hazard ratio, 1.27; 95% CI, 0.77 to 2.11), and revascularization occurred in 35 patients (6.1%) in the open-harvest group and 31 patients (5.4%) in the endoscopic-harvest group (hazard ratio, 1.14; 95% CI, 0.70 to 1.85). Leg-wound infections occurred in 18 patients (3.1%) in the open-harvest group and in 8 patients (1.4%) in the endoscopic-harvest group (relative risk, 2.26; 95% CI, 0.99 to 5.15). CONCLUSIONS: Among patients undergoing CABG, we did not find a significant difference between open vein-graft harvesting and endoscopic vein-graft harvesting in the risk of major adverse cardiac events. (Funded by the Cooperative Studies Program, Office of Research and Development, Department of Veterans Affairs; REGROUP ClinicalTrials.gov number, NCT01850082 .).

Predictors of outcome following acquired brain injury in children.

Acquired brain injury (ABI) in children and adolescents can result from multiple causes, including trauma, central nervous system infections, noninfectious disorders (epilepsy, hypoxia/ischemia, genetic/metabolic disorders), tumors, and vascular abnormalities. Prediction of outcomes is important, to target interventions, allocate resources, provide education to family or caregivers, and begin appropriate planning for the future. Researchers have identified several factors associated with better or worse outcomes after ABI, including variables related to the injury itself, postinjury factors related to intervention or trajectory of recovery, and preinjury or demographic factors. When examining the scientific literature, it is important to identify how "outcome" is defined, as the predictors may change depending on the outcome studied. In addition, key variables may be specific to the etiology of injury. Therefore, predictors of outcome cannot be generalized across the various etiologies of ABI, and this review will discuss predictors within the context of multiple etiologies of ABI. This article reviews the current literature on predicting outcomes after pediatric ABI, and areas in need of further research are discussed.