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BACKGROUND: Lung ischemia-reperfusion injury (IRI), involving severe inflammation and edema, is a major cause of primary graft dysfunction following transplant. Activation of transient receptor potential vanilloid 4 (TRPV4) channels modulates vascular permeability. Thus, this study tests the hypothesis that endothelial TRPV4 channels mediate lung IRI. METHODS: C57BL/6 wild-type (WT), TRPV4(−/−), tamoxifen-inducible endothelial TRPV4 knockout (TRPV4(EC)(−/−)), and tamoxifen-treated control (TRPV4(fl/fl)) mice underwent lung IR using a left lung hilarligation model (n≥6 mice/group). WT mice were also treated with a TRPV4-specific inhibitor (GSK2193874; 1mg/kg) (WT+GSK219). Partial pressure of oxygen (PaO(2)), edema (wet-to-dry weight ratio), compliance, neutrophil infiltration, and cytokine concentrations in bronchioalveolar lavage fluid were assessed. Pulmonary microvascular endothelial cells (PMVECs) were characterized in vitro following exposure to hypoxia-reoxygenation. RESULTS: Compared to WT, PaO(2) following IR was significantly improved in TRPV4(−/−) mice (133.1±43.9 vs 427.8±83.1 mmHg, p

Sepsis is the leading cause of acute respiratory distress syndrome (ARDS) in adults and carries a high mortality. Utilizing a previously validated porcine model of sepsis-induced ARDS, we sought to refine our novel therapeutic technique of in vivo lung perfusion (IVLP). We hypothesized that 2 hours of IVLP would provide non-inferior lung rehabilitation compared to 4 hours of treatment. Adult swine (n = 8) received lipopolysaccharide to develop ARDS and were placed on central venoarterial extracorporeal membrane oxygenation. Animals were randomized to 2 vs 4 hours of IVLP. The left pulmonary vessels were cannulated to IVLP using antegrade Steen solution. After IVLP treatment, the left lung was decannulated and reperfused for 4 hours. Total lung compliance and pulmonary venous gases from the right lung (control) and left lung (treatment) were sampled hourly. Biochemical analysis of tissue and bronchioalveolar lavage was performed along with tissue histologic assessment. Throughout IVLP and reperfusion, treated left lung PaO2/FiO2 ratio was significantly higher than the right lung control in the 2-hour group (332.2 ± 58.9 vs 264.4 ± 46.5, P = 0.01). In the 4-hour group, there was no difference between treatment and control lung PaO2/FiO2 ratio (258.5 ± 72.4 vs 253.2 ± 90.3, P = 0.58). Wet-to-dry weight ratios demonstrated reduced edema in the treated left lungs of the 2-hour group (6.23 ± 0.73 vs 7.28 ± 0.61, P = 0.03). Total lung compliance was also significantly improved in the 2-hour group. Two hours of IVLP demonstrated superior lung function in this preclinical model of sepsis-induced ARDS. Clinical translation of IVLP may shorten duration of mechanical support and improve outcomes.

Background There is a strong association between socioeconomic status and surgical outcomes; however, the optimal method for socioeconomic risk-stratification remains elusive. We aimed to compare 2 metrics of socioeconomic ranking by ZIP code, the Distressed Communities Index, and the Area Deprivation Index and their association with surgical outcomes. Methods This retrospective study included all general surgery cases performed at a single institution from 2005 to 2015. Each patient was assigned Distressed Communities Index and Area Deprivation Index scores based on ZIP code. Both indices are normalized composite measures of socioeconomic status derived from census data. Primary outcome was 30-day morbidity; secondary outcomes included long-term mortality and cost, stratified by socioeconomic status. The utility of the addition of each metric to the American College of Surgeons National Surgical Quality Improvement Program risk calculator was assessed. Results The 9,843 patients had normally distributed Distressed Communities Index (47.3 ± 22.4) and Area Deprivation Index (35.4 ± 19.0). Patients who experienced any complication or readmission had significantly higher Distressed Communities Index (48.6 vs 47.1, P = .04) and Area Deprivation Index (37.2 vs 35.1, P = .002). Risk-adjusted models demonstrated that only Area Deprivation Index independently predicted postoperative complications (odds ratio 1.11, P = .02), improved the discrimination of risk-stratification when added to the American College of Surgeons National Surgical Quality Improvement Program risk calculator (area under curve 0.758−0.790, P = .02), and was associated with hospitalization cost ($1,811 ± 856/quartile, P = .03). Conclusion Area Deprivation Index provides improved socioeconomic risk-adjustment in this surgical population. The addition of Area Deprivation Index to risk-stratification tools would allow us to better inform our patients of their expected postoperative courses, more accurately account for the increased cost of providing their care, and identify patients and regions that are most in need of improvements in health and healthcare.

Background Limited multi-institutional data evaluating minimally invasive cardiac surgery (MICS) coronary artery bypass surgery (CABG) outcomes have raised concern for increased resource utilization compared with standard sternotomy. The purpose of this study was to assess short-term outcomes and resource utilization with MICS CABG in a propensity-matched regional cohort. Methods Isolated CABG patients (2012-2019) were extracted from a regional Society of Thoracic Surgeons database. Patients were stratified by MICS CABG vs open CABG via sternotomy, propensity-score matched 1:2 to balance baseline differences, and compared by univariate analysis. Results Of 26,255 isolated coronary artery bypass graft patients, 139 MICS CABG and 278 open CABG patients were well balanced after matching. There was no difference in the operative mortality rate (2.2% open vs 0.7% MICS CABG, P = .383) or major morbidity (7.9% open vs 7.2% MICS CABG, P = .795). However, open CABG patients received more blood products (22.2% vs 12.2%, P = .013), and had longer intensive care unit (45 vs 30 hours, P = .049) as well as hospital lengths of stay (7 vs 6 days, P = .005). Finally, median hospital cost was significantly higher in the open CABG group ($35,011 vs $27,906, P Conclusions Open CABG via sternotomy and MICS CABG approaches are associated with similar, excellent perioperative outcomes. However, MICS CABG was associated with fewer transfusions, shorter length of stay, and ∼$7000 lower hospital cost, a superior resource utilization profile that improves patient care and lowers cost.

Objective Acute hyperglycemia during myocardial infarction worsens outcomes in part by inflammatory mechanisms. Pulsed ultrasound has anti-inflammatory potential in bone healing and neuromodulation. We hypothesized that pulsed ultrasound would attenuate the hyperglycemic exacerbation of myocardial ischemia–reperfusion injury via the cholinergic anti-inflammatory pathway. Methods Acute hyperglycemia was induced in wild-type C57BL6 or acetylcholine-receptor knockout (α7nAChR-/-) mice by intraperitoneal injection of glucose. Pulsed ultrasound (frequency 7 MHz, bursting mechanical index 1.2, duration 1 second, repeated every 6 seconds for 2 minutes, 20-second total exposure) was performed at the spleen or neck after glucose injection. Separate mice underwent vagotomy before treatment. The left coronary artery was occluded for 20 minutes, followed by 60 minutes of reperfusion. The primary end point was infarct size in explanted hearts. Results Splenic pulsed ultrasound significantly decreased infarct size in wild-type C57BL6 mice exposed to acute hyperglycemia and myocardial ischemia–reperfusion injury (5.2% ± 4.4% vs 16.9% ± 12.5% of risk region, P = .013). Knockout of α7nAChR abrogated the beneficial effect of splenic pulsed ultrasound (22.2% ± 12.1%, P = .79 vs control). Neck pulsed ultrasound attenuated the hyperglycemic exacerbation of myocardial infarct size (3.5% ± 4.8%, P = .004 vs control); however, the cardioprotective effect disappeared in mice that underwent vagotomy. Plasma acetylcholine, β2 adrenergic receptor, and phosphorylated Akt levels were increased after splenic pulsed ultrasound treatment. Conclusions Pulsed ultrasound treatment of the spleen or neck attenuated the hyperglycemic exacerbation of myocardial ischemia–reperfusion injury leading to a 3-fold decrease in infarct size. Pulsed ultrasound may provide cardioprotection via the cholinergic anti-inflammatory pathway and could be a promising new nonpharmacologic, noninvasive therapy to reduce infarct size during acute myocardial infarction and improve patient outcomes.

BACKGROUND: A significant percentage of patients that acutely develop high-grade atrioventricular block following valve surgery will ultimately recover, yet the ability to predict recovery is limited. OBJECTIVES: The purpose of this analysis was to evaluate the cost effectiveness of two different management strategies for the timing of permanent pacemaker implantation for new heart block following valve surgery. METHODS: A cost effectiveness model was developed using costs and probabilities of short and long-term complications of pacemaker placement, short-term atrioventricular node recovery, intensive care unit stays, and long-term follow up. We aggregated the total expected cost and utility of each option over a 20 year time period. Quality-adjusted survival with a pacemaker was estimated from the literature and institutional patient-reported outcomes. Primary decision analysis was based on an expected recovery rate of 36.7% at 12 days with timing of pacemaker implantation: early placement (5 days) versus watchful waiting for 12 days. RESULTS: A strategy of watchful waiting was more costly ($171,798 ± $45,695 vs $165,436 ± $52,923, p

Background The coronavirus disease 2019 (COVID-19) pandemic has resulted in >72 million cases and 1.6 million deaths. End-stage lung disease from COVID-19 is a new and growing entity that may benefit from lung transplant; however, there are limited data on the patient selection, perioperative management, and expected outcomes of transplantation for this indication. Methods A systematic review of the literature was performed with searches of MEDLINE and Web of Science databases as well as the gray literature. All manuscripts, editorials, commentaries, and gray literature reports of lung transplantation for COVID-related respiratory failure were included. A case from the University of Virginia is described and included in the review. Results A total of 27 studies were included: 11 manuscripts, 5 commentaries, and 11 gray literature reports. The total number of transplantations for COVID-related lung disease was 21. The mean age was 55±12 years, 16 (76%) were male individuals, and the acuity was high, with 85% on extracorporeal membrane oxygenation preoperatively. There was a 95% early survival rate, with 1 additional late death. There is growing histopathologic evidence for permanent structural damage with no replicating virus at the time of transplantation. Conclusions Bilateral lung transplantation is an effective treatment option with reasonable short-term outcomes for patients with end-stage lung failure secondary to COVID-19. However, specific considerations in this new population require a multidisciplinary approach. As we move into the second wave of the COVID-19 global pandemic, lung transplantation will likely have a growing role in management of these complex patients.

Background Concomitant surgical ablation for atrial fibrillation (AF) at the time of mitral valve surgery is a Society of Thoracic Surgeons Class IA recommendation with evidence from randomized trial data. We hypothesized that concomitant AF ablation rates have increased over time with implementation of this evidence-based practice. Methods All patients (N = 7261) undergoing mitral valve operations (2011-2018) were queried from a regional Society of Thoracic Surgeons database. Patients with preoperative AF were stratified by concomitant AF ablation. Trends in concomitant ablation were evaluated over time as well as by center and surgeon mitral surgical volume. The associations between patient and center factors on implementation of concomitant ablation were assessed with multivariate regression. Results A total of 1675 patients with preoperative AF underwent isolated mitral valve operations, with 1044 (64.6%) undergoing concomitant ablation. The utilization of concomitant ablation decreased over the study period (-2.82%/year), and was strongly associated with surgeon mitral valve volume (high 78.2% vs medium 62.5% vs low 59.0%; P Conclusions Despite increasing evidence and societal recommendations, we demonstrate a persistent underutilization of concomitant AF ablation during isolated mitral surgery across a large number of low-volume and high-volume centers. These data suggest significant variability and may represent an opportunity for improvement.

Infective endocarditis affects patients of all socioeconomic status. We hypothesized that the Distressed Communities Index (DCI), a comprehensive assessment of socioeconomic status, would be associated with risk-adjusted mortality for patients with endocarditis. All patients with endocarditis (2001-2017) in a regional Society of Thoracic Surgeons database were analyzed. DCI scores range from 0 (no socioeconomic distress) to 100 (severe distress) and account for unemployment, poverty rate, median income, housing vacancies, education level, and business growth by zip code. The most distressed patients (top quartile, DCI75) were compared to all other patients. Hierarchical logistic regression modeled the association between DCI and mortality. A total of 2,075 patients were included (median age 55 years, 65.2% urgent/emergent cases, 42.7% self-pay). Major morbidity was 32.8% and operative mortality was 9.5%. Tricuspid/pulmonic valve endocarditis was present in 12.5% of cases, with significantly worse mean DCI compared to patients with left-sided endocarditis (median 55.3, IQR 20.3-77.6 vs 46.8, IQR 17.3-74.2, P = 0.016). High socioeconomic distress (DCI75) was associated with higher rates of major morbidity, operative mortality, increased length of stay, and higher total cost. After risk-adjustment, DCI was independently predictive of higher operative mortality for patients with endocarditis (OR 1.24 per DCI quartile increase, 95% CI 1.06-1.45, P0.001). Increasing DCI, an indicator of poor socioeconomic status, independently predicts increased risk-adjusted mortality and resource utilization for patients with endocarditis. Accounting for socioeconomic status allows for more accurate risk prediction and resource allocation for patients with endocarditis.

OBJECTIVE We hypothesize the Distressed Communities Index (DCI), a composite socioeconomic ranking by ZIP code, will predict risk-adjusted outcomes after surgery. SUMMARY OF BACKGROUND DATA Socioeconomic status affects surgical outcomes; however, the American College of Surgeons National Surgery Quality Improvement Program (ACS NSQIP) database does not account for these factors. METHODS All ACS NSQIP patients (17,228) undergoing surgery (2005 to 2015) at a large academic institution were paired with the DCI, which accounts for unemployment, education level, poverty rate, median income, business growth, and housing vacancies. Developed by the Economic Innovation Group, DCI scores range from 0 (no distress) to 100 (severe distress). Multivariable regressions were used to evaluate ACS NSQIP predicted risk-adjusted effect of DCI on outcomes and inflation-adjusted hospital cost. RESULTS A total of 4522 (26.2%) patients came from severely distressed communities (top quartile). These patients had higher rates of medical comorbidities, transfer from outside hospital, emergency status, and higher ACS NSQIP predicted risk scores (all P < 0.05). In addition, these patients had greater resource utilization, increased postoperative complications, and higher short- and long-term mortality (all P < 0.05). Risk-adjustment with multivariate regression demonstrated that DCI independently predicts postoperative complications (odds ratio 1.1, P = 0.01) even after accounting for ACS NSQIP predicted risk score. Furthermore, DCI independently predicted inflation-adjusted cost (+$978/quartile, P < 0.0001) after risk adjustment. CONCLUSIONS The DCI, an established metric for socioeconomic distress, improves ACS NSQIP risk-adjustment to predict outcomes and hospital cost. These findings highlight the impact of socioeconomic status on surgical outcomes and should be integrated into ACS NSQIP risk models.

BACKGROUND: As robotic surgery becomes more ubiquitous, determining clinical benefit is necessary in order to justify the cost and time investment required to become proficient. We hypothesized that robotic cholecystectomy would be associated with improved clinical outcomes but also increased cost as compared with standard laparoscopic cholecystectomy. MATERIALS AND METHODS: All patients undergoing robotic or laparoscopic cholecystectomy at a single academic hospital between 2007-2017 were identified using an institutional clinical data repository. Patients were stratified by operative approach (robotic vs. laparoscopic) for comparison and propensity score-matched 1:10 based on relevant comorbidities and demographics. Categorical variables were analyzed by Chi-square test and continuous variables using Mann-Whitney U test. RESULTS: 3,255 patients underwent cholecystectomy during the study period. There were no differences in demographics or BMI, but greater rates of diabetes mellitus, hypertension, and gastroesophageal reflux disease were present in the laparoscopic group. After matching (n=106 robotic, n=1060 laparoscopic), there were no differences in preoperative comorbidities. Patients who underwent robotic cholecystectomy had lesser durations of stay (Robot: 0.1±0.7 vs. Lap: 0.8±1.9, p < 0.0001) and lesser 90-day readmission rates (Robot: 0% [0], Lap: 4.1% [43], p = 0.035); however, both operative and hospital costs were greater compared with laparoscopic cholecystectomy. CONCLUSIONS: Robotic cholecystectomy is associated with lesser duration of stay and lesser readmission rate within 90-days of the index operation, but also greater operative duration and hospital cost compared with laparoscopic cholecystectomy. Hospitals and surgeons need to consider the improved clinical outcomes but also the monetary and time investment required prior to pursuing robotic cholecystectomy.

Optimal energy goals for adult, obese critically ill surgical patients are unclear. To date, there has been little data comparing feeding regimens for obese and non-obese critically ill surgical patients and the effect on outcomes. The objective was to compare the effect of hypoenergetic and euenergetic feeding goals in critically ill obese patients on outcomes, including infection, intensive care unit length of stay, and mortality. We hypothesized that hypoenergetic feeding of patients with premorbid obesity (body mass index ≥ 30 kg•m-2) during critical illness does not affect clinical outcomes. Post hoc analyses were performed on critically ill surgical patients enrolled in a randomized controlled trial. Patients were randomized to receive 25-30 kcal•kg-1•d-1 (105-126 kJ.kg-1•d-1, euenergetic) or 12.5-15 kcal•kg-1•d-1 (52-63 kJ.kg-1 •d-1, hypoenergetic), with equal protein allocation (1.5 g•kg-1•d-1). The effect of feeding regimen on outcomes in obese and nonobese patients were assessed. Of the 83 patients, 30 (36.1%) were obese (body mass index ≥ 30 kg•m-2). Average energy intake differed based on feeding regimen (hypoenergetic: 982±61 vs euenergetic: 1338±92 kcal•d-1, P = .02). Comparing obese and nonobese patients, there was no difference in the percentage acquiring an infection (66.7% [20/30] vs 77.4% [41/53], P = .29), intensive care unit length of stay (16.4±3.7 vs 14.3±0.9 days, P = .39), or mortality (10% [3/30] vs 7.6% [4/53], P = .7). Within the subset of obese patients, the percentage acquiring an infection (hypoenergetic: 78.9% [15/19] vs euenergetic: 45.5% [5/11], P = .11) was not affected by the feeding regimen. Within the subset of nonobese patients, there was a trend toward more infections in the euenergetic group (hypoenergetic: 63.6% [14/22] vs euenergetic: 87.1% [27/31], P = .05). Hypoenergetic feeding does not appear to affect clinical outcomes positively or negatively in critically ill patients with premorbid obesity.

Primary graft dysfunction after lung transplantation, a consequence of ischemia-reperfusion injury (IRI), is a major cause of morbidity and mortality. IRI involves acute inflammation and innate immune cell activation, leading to rapid infiltration of neutrophils. Formyl peptide receptor 1 (FPR1) expressed by phagocytic leukocytes plays an important role in neutrophil function. The cell surface expression of FPR1 is rapidly and robustly upregulated on neutrophils in response to inflammatory stimuli. Thus, we hypothesized that use of [99mTc]cFLFLF, a selective FPR1 peptide ligand, would permit in vivo neutrophil labeling and noninvasive imaging of IRI using single-photon emission computed tomography (SPECT). A murine model of left lung IRI was utilized. Lung function, neutrophil infiltration, and SPECT imaging were assessed after 1 h of ischemia and 2, 12, or 24 h of reperfusion. [99mTc]cFLFLF was injected 2 h before SPECT. Signal intensity by SPECT and total probe uptake by gamma counts were 3.9- and 2.3-fold higher, respectively, in left lungs after ischemia and 2 h of reperfusion versus sham. These values significantly decreased with longer reperfusion times, correlating with resolution of IRI as shown by improved lung function and decreased neutrophil infiltration. SPECT results were confirmed using Cy7-cFLFLF-based fluorescence imaging of lungs. Immunofluorescence microscopy confirmed cFLFLF binding primarily to activated neutrophils. These results demonstrate that [99mTc]cFLFLF SPECT enables noninvasive detection of lung IRI and permits monitoring of resolution of injury over time. Clinical application of [99mTc]cFLFLF SPECT may permit diagnosis of lung IRI for timely intervention to improve outcomes after transplantation.

Current reporting on cardiac surgical outcomes focuses on a patient's status at 30 days and lacks long-term meaningful data. The purpose of this study was to determine the impact of complications after cardiac operation on patient-reported outcomes (PROs) at 1 year after surgery.All patients undergoing cardiac operation at an academic institution (2014-2015) were contacted 1 year after surgery to obtain vital status, location, and PROs using the validated National Institutes of Health Patient-Reported Outcomes Measurement Information System (NIH-PROMIS). Records were merged with Society of Thoracic Surgeons (STS) data, and multivariate linear regression evaluated the risk-adjusted effects of complications on 1-year PROs.A total of 782 eligible patients underwent cardiac operation, with PROs data available for 91% of patients alive at 1 year (648 of 716). Mean NIH-PROMIS scores were global physical health (GPH), 48.8 ± 10.2; global mental health (GMH), 51.3 ± 9.5; and physical functioning (PF), 45.5 ± 10.2 (reference score for general adult population, 50 ± 10). Occurrence of an STS Major Morbidity (prolonged ventilation, renal failure, reoperation, stroke, or deep sternal wound infection) significantly reduced 1-year PROs (GPH, 45.4 ± 8.9 [P.001]; GMH, 48.6 ± 9.5 [P = .01]; PF, 40.9 ± 10.2 [P.001]). After risk adjustment, incidence of a STS Major Morbidity, prolonged ventilation, or renal failure had a significant adverse effect on 1 or more PRO domains.Although cardiac surgical patients have PROs scores similar to the general population, complications after cardiac operation continue to negatively influence patient quality of life 1 year after surgery. Use of NIH-PROMIS shows that prolonged ventilation and renal failure have the largest impact on 1-year patient-reported outcomes.

Annular enlargement (AE) is a critical technique to avoid patient-prosthesis mismatch and may help facilitate future valve-in-valve (ViV) transcatheter replacement. We hypothesized that the addition of annular enlargement would increase risk of morbidity and mortality and that the number of annular enlargement procedures is increasing to accommodate future ViV procedures.Patients undergoing aortic valve replacement ± coronary surgery (2012 to 2017) were extracted from a regional Society of Thoracic Surgeons database. Patients were stratified by annular enlargement and era, pre-ViV (2012 to 2014) vs ViV (2015 to 2017) for univariate analysis. Risk-adjusted outcomes were assessed by hierarchical regression modeling adjusting for predicted risk of mortality.Of 6045 patients, the 300 (5.0%) who received an annular enlargement were younger and more commonly female. Patients receiving an annular enlargement had higher complication rates including operative mortality (4.7% vs 2.5%, P = .024). After risk adjustment, AE was independently associated with increased mortality (odds ratio, 2.06, P = .016) and major morbidity (odds ratio, 1.41, P = .042). The rate of enlargement increased from 3.9% pre-ViV to 6.3% ViV (P .001). The use of ViV capable valves (bioprosthetic ≥23 mm) from 61% to 67% (P = .001), and more in AE patients (30% vs 11% non-AE). Alternatively, the rate of patient prosthesis mismatch declined from 23% to 16%.Increasing utilization of AE coincides with a decline in patient prosthesis mismatch and may facilitate future ViV transcatheter aortic valve replacement. However, AE was independently associated with increased morbidity and mortality. High variability in AE volume may be increasing risk and deserves further investigation.

BACKGROUND: Sternal wound infections (SWI) can be a devastating long-term complication with significant morbidity and health care cost. The purpose of this analysis was to evaluate the cost-effectiveness of negative pressure incision management systems (NPIMS) in cardiac surgery. MATERIALS AND METHODS: All cardiac surgery cases at an academic hospital with risk scores available (2009–2017) were extracted from an institutional database (n=4,455). Patients were stratified by utilization of NPIMS and high-risk was defined as above the median. Costs included infection related readmissions and were adjusted for inflation. Multivariable regression models assessed the risk-adjusted cost of SWI and efficacy of NPIMS use. Cost-effectiveness was modeled using TreeAge Pro using institutional results. RESULTS: The rate of deep SWI was 0.9% with an estimated cost of $111,175 (p

Background The effects of socioeconomic factors other than insurance status and race on outcomes after cardiac operations are not well understood. We hypothesized that the Distressed Communities Index (DCI), a comprehensive socioeconomic ranking by zip code, would predict operative mortality after coronary artery bypass grafting (CABG). Methods All patients who underwent isolated CABG (2010 to 2017) in the Virginia Cardiac Services Quality Initiative database were analyzed. The DCI accounts for unemployment, education level, poverty rate, median income, business growth, and housing vacancies, with scores ranging from 0 (no distress) to 100 (severe distress). Patients were stratified by DCI quartiles (I: 0 to 24.9, II: 25 to 49.9, III: 50 to 74.9, IV: 75 to 100) and compared. Hierarchical linear regression modeled the association between the DCI and mortality. Results A total of 19,756 CABG patients were analyzed, with mean predicted risk of mortality of 2.0% ± 3.5%. Higher DCI scores were associated with increasing predicted risk of mortality. Overall operative mortality was 2.1% (n = 424) and increased with increasing DCI quartile (I: 1.6% [n = 95], II: 2.1% [n = 77], III: 2.4% [n = 114], IV: 2.6% [n = 138]; p = 0.0009). The observed-to-expected ratio for mortality increased as level of socioeconomic distress increased. After risk adjustment for The Society of Thoracic Surgeons predicted risk of mortality, year of surgical procedure, and hospital, the DCI remained predictive of operative mortality after CABG (odds ratio, 1.14 for each 25-point increase in DCI; 95% confidence interval 1.04 to 1.26; p = 0.007). Conclusions The DCI independently predicts risk-adjusted operative mortality after CABG. Socioeconomic status, although not part of traditional risk calculators, should be considered when building risk models, evaluating resource utilization, and comparing hospitals.

Global hypothermia prolongs survival in rats with intraabdominal feculent sepsis by inhibiting inflammatory responses. We hypothesized that topical neck cooling (TNC) has similar benefits. Septic shock was induced by cecal ligation and incision (CLI) in Sprague Dawley rats. Rats were randomized to sham laparotomy, control with CLI, CLI with TNC, or vagotomy at the gastroesophageal junction before CLI and TNC. Two more groups underwent peritoneal washout with and without TNC two hours after CLI. TNC significantly lowered neck skin temperature (16.7 ± 1.4 vs. 30.5 ± 0.6 °C, p &lt, 0.05) while maintaining core body normothermia. TNC rats recovered from anesthesia 70 min earlier than the control (p &lt, 0.05). Three hours following CLI, the control and vagotomy with TNC groups had significantly more splenic contraction, fewer circulating leukocytes and higher plasma IL-1β, IL-10 and TNF-α levels than TNC rats (p &lt, 0.05). TNC prolonged survival duration after CLI by a median of four hours vs. control (p &lt, 0.05), but no benefit was seen if vagotomy preceded TNC. Peritoneal washout alone increased survival by 3 h (9.2 (7.8–10.5) h). Survival duration increased dramatically with TNC preceding washout, to a 56% survival rate (&gt, 10 days). TNC significantly prolonged the survival of rats with severe intraabdominal sepsis by inhibiting systemic proinflammatory responses by activating vagal anti-inflammatory pathways.

Background We previously demonstrated that ischemically injured cardiomyocytes release cell‐free DNA and HMGB1 (high mobility group box 1 protein) into circulation during reperfusion, activating proinflammatory responses and ultimately exacerbating reperfusion injury. We hypothesize that cell‐free DNA and HMGB1 mediate myocardial ischemia‐reperfusion injury by stimulating plasmacytoid dendritic cells (pDCs) to secrete type I interferon (IFN‐I). Methods and Results C57BL/6 and interferon alpha receptor‐1 knockout mice underwent 40 minutes of left coronary artery occlusion followed by 60 minutes of reperfusion (40′/60′ IR) before infarct size was evaluated by 2,3,5‐Triphenyltetrazolium chloride–Blue staining. Cardiac perfusate was acquired in ischemic hearts without reperfusion by antegrade perfusion of the isolated heart. Flow cytometry in pDC‐depleted mice treated with multiple doses of plasmacytoid dendritic cell antigen‐1 antibody via intraperitoneal injection demonstrated plasmacytoid dendritic cell antigen‐1 antibody treatment had no effect on conventional splenic dendritic cells but significantly reduced splenic pDCs by 60%. pDC‐depleted mice had significantly smaller infarct size and decreased plasma interferon‐α and interferon‐β compared with control. Blockade of the type I interferon signaling pathway with cyclic GMP‐AMP synthase inhibitor, stimulator of interferon genes antibody, or interferon regulatory factor 3 antibody upon reperfusion similarly significantly attenuated infarct size by 45%. Plasma levels of interferon‐α and interferon‐β were significantly reduced in cyclic GMP‐AMP synthase inhibitor‐treated mice. Infarct size was significantly reduced by >30% in type I interferon receptor monoclonal antibody–treated mice and interferon alpha receptor‐1 knockout mice. In splenocyte culture, 40′/0′ cardiac perfusate treatment stimulated interferon‐α and interferon‐β production; however, this effect disappeared in the presence of cyclic GMP‐AMP synthase inhibitor. Conclusions Type I interferon production is stimulated following myocardial ischemia by cardiogenic cell‐free DNA/HMGB1 in a pDC‐dependent manner, and subsequently activates type I interferon receptors to exacerbate reperfusion injury. These results identify new potential therapeutic targets to attenuate myocardial ischemia‐reperfusion injury.

Racial disparities in outcomes after cardiac surgery are well reported. We sought to determine whether variation by race exists in controllable practices during coronary artery bypass graft surgery (CABG). We hypothesized that racial disparities exist in CABG quality metrics, but have improved over time.All patients undergoing isolated CABG (2000 to 2019) in a multiple state database were stratified into three eras by race. Analysis included propensity matched White Americans and Black Americans. Primary outcomes included left internal mammary artery use, multiple arterial grafting, revascularization completeness, and guideline-directed medication prescription.Of 72 248 patients undergoing CABG, Black American patients (n = 10 270, 15%) had higher rates of diabetes mellitus, hypertension, prior stroke, and myocardial infarction. After matching, 19 806 patients (n = 9903 per group) were well balanced. Left internal mammary artery use was significantly different early (era 1, Black Americans 84.7% vs White Americans 86.6%; P = .03), but equalized over time. Importantly, multiarterial grafting differed between Black Americans and White Americans over the entire study (9.1% vs 11.5%, P.001) and within each era. Black Americans had more incomplete revascularization during the study period (14% vs 12.8%, P = .02) driven by a large disparity in era 1 (9.5% vs 7.2%, P.001). Despite similar rates of preoperative use, Black Americans were more often discharged on a regimen of β-blockers (91.8% vs 89.6%, P.001).Coronary artery bypass graft surgery metrics of left internal mammary artery use and optimal medical therapy have improved over time and are similar despite patient race. Black Americans undergo less frequent multiarterial grafting and greater discharge β-blocker prescription. Identifying changes in controllable CABG quality practices across races supports a continued focus on standardizing such efforts.

The coronavirus disease 2019 (COVID-19) pandemic has resulted in72 million cases and 1.6 million deaths. End-stage lung disease from COVID-19 is a new and growing entity that may benefit from lung transplant; however, there are limited data on the patient selection, perioperative management, and expected outcomes of transplantation for this indication.A systematic review of the literature was performed with searches of MEDLINE and Web of Science databases as well as the gray literature. All manuscripts, editorials, commentaries, and gray literature reports of lung transplantation for COVID-related respiratory failure were included. A case from the University of Virginia is described and included in the review.A total of 27 studies were included: 11 manuscripts, 5 commentaries, and 11 gray literature reports. The total number of transplantations for COVID-related lung disease was 21. The mean age was 55±12 years, 16 (76%) were male individuals, and the acuity was high, with 85% on extracorporeal membrane oxygenation preoperatively. There was a 95% early survival rate, with 1 additional late death. There is growing histopathologic evidence for permanent structural damage with no replicating virus at the time of transplantation.Bilateral lung transplantation is an effective treatment option with reasonable short-term outcomes for patients with end-stage lung failure secondary to COVID-19. However, specific considerations in this new population require a multidisciplinary approach. As we move into the second wave of the COVID-19 global pandemic, lung transplantation will likely have a growing role in management of these complex patients.

Surgical mitral valve intervention for severe functional, or secondary mitral regurgitation is a viable option for patients deemed to be operative candidates and can be performed via traditional sternotomy or by minimally invasive techniques with similar outcomes. Transcatheter mitral valve replacement is an emerging technology with a potential role in the treatment of functional mitral valve regurgitation. A plethora of devices are currently in development and in various stages of clinical investigation. Operative approach to transcatheter mitral valve replacement varies from a percutaneous transseptal approach to a hybrid percutaneous/surgical apical approach. The Tendyne, Intrepid and Evoque systems show promising results from their early feasibility studies in treatment of patients with mitral regurgitation that were too high risk for surgery. In this review, we describe considerations for surgical and transcatheter mitral valve replacement for functional mitral valve regurgitation.

Objectives The United States has the highest number of Coronavirus Disease 2019 (COVID-19) in the world, with high variability in cases and mortality between communities. We aimed to quantify the associations between socioeconomic status and Coronavirus Disease 2019 (COVID-19) related cases and mortality in the U.S. Study Design: Nationwide COVID-19 data at the county level that was paired with the Distressed Communities Index (DCI) and its component metrics of socioeconomic status. Methods Severely distressed communities were classified by DCI>75 for univariate analyses. Adjusted rate ratios were calculated for cases and fatalities per 100,000 persons using hierarchical linear mixed models. Results This cohort included 1,089,999 cases and 62,298 deaths in 3,127 counties for a case-fatality rate of 5.7%. Severely distressed counties had significantly fewer deaths from COVID-19, but higher number of deaths/100,000. In risk-adjusted analysis, the two socioeconomic determinants of health with the strongest association with both higher cases/100,000 and higher fatalities/100,000 were percent of adults without a high school degree (cases: RR 1.10; fatalities: RR 1.08) and proportion of black residents (cases and fatalities: RR 1.03). The percentage of the population over 65 was also highly predictive for fatalities/100,000 (RR 1.07). Conclusion Lower education levels and greater percentages of black residents are strongly associated with higher rates of both COVID-19 cases and fatalities. Socioeconomic factors should be considered when implementing public health interventions in order to ameliorate the disparities in the impact of COVID-19 on distressed communities., Highlights • Socioeconomic factors play an important role in COVID-19 prevalence and mortality. • Lower education level was the strongest association with both cases and fatalities. • Higher proportion of black residents also associated with cases and fatalities. • The poverty rate and median income were also associated with COVID-19 cases. • Median income and change in employment were also associated with COVID-19 fatalities.

Background Postoperative glycemic control improves cardiac surgery outcomes but insulin protocols are limited by complexity and inflexibility. We sought to evaluate the effect of implementing an electronic glycemic management system (eGMS) in conjunction with a cardiac surgery endocrinology consult service on glycemic control and outcomes after cardiac surgery. Methods All patients with a calculated preoperative risk of mortality who underwent cardiac surgery before and after implementation of an eGMS and an endocrinology consult service were identified. Glycemic control and surgical outcomes were compared using univariate analysis, and multivariate regression was used to model the risk-adjusted effects of the interventions on glycemic control, surgical outcomes, and resource utilization. The health care–related value added by the interventions was calculated by dividing risk-adjusted outcomes by total hospital costs. Results A total of 2612 patients were identified, with 1263 patients in the preimplementation cohort and 1349 in the postimplementation cohort. Multivariate regression demonstrated fewer postoperative hyperglycemic events (odds ratio [OR] 0.8, 95% CI, 0.65-0.99) after protocol implementation without an increase in hypoglycemic events (OR 0.96, 95% CI, 0.71-1.3). Average day-weighted mean glucose decreased from 144 to 138 mg/dL ( P < .001). The improved glycemic control correlated with a risk-adjusted decrease in composite morbidity or mortality (OR 0.61, 95% CI, 0.47-0.79). Although hospital costs increased after implementation, the protocol increased health care–related value by 38%. Conclusion Implementation of a protocol consisting of an eGMS paired with a cardiac surgery–specific endocrinology consult service was associated with improved glycemic control and reduced morbidity. Despite higher costs health care–related value increased as a result of eGMS implementation.

Background Nearly 40% of patients with atrial fibrillation (AF) undergoing mitral valve surgery do not receive concomitant ablation despite societal guidelines. We assessed barriers to implementation of this evidence-based practice through a survey of cardiac surgeons in 2 statewide quality collaboratives. Methods Adult cardiac surgeons across 2 statewide collaboratives were surveyed on their knowledge and practice regarding AF ablation. Questions concerning experience, clinical practice, case scenarios, and barriers to implementation were included. Results Among 66 respondents (66 of 135; 48.9%), the majority reported “very comfortable/frequently use” cryoablation (53 of 66; 80.3%) and radiofrequency (55 of 66; 83.3%). Only 12.1% (8/66) were not aware of the recommendations. Approximately one-half of the respondents reported learning AF ablation in fellowship (50.0%; 33 of 66) or attending courses (47.0%; 31 of 66). Responses to clinical scenarios demonstrated wide variability in practice patterns. One-half of the respondents reported no barriers; others cited increased cross-clamp time, excessive patient risk, and arrhythmia incidence as obstacles. Desired interventions included cardiology/electrophysiology support, protocols, pacemaker rate information, and education in the form of site visits, videos and proctors. Conclusions Knowledge of evidence-based recommendations and practice patterns vary widely. These data identify several barriers to implementation of concomitant AF ablation and suggest specific interventions (mentorship/support, protocols, research, and education) to overcome these barriers.

BACKGROUND: The spleen is an important contributor to the uncontrolled, excessive release of pro-inflammatory signals during sepsis that leads to the development of tissue injury and diffuse end-organ dysfunction. Therapeutic pUS has been shown to inhibit splenic leukocyte release and reduce cytokine production in other inflammatory disease processes. We hypothesized that pulsed ultrasound (pUS) treatment inhibits spleen-derived inflammatory responses and increases survival duration in rats with severe intra-abdominal sepsis leading to septic shock. MATERIALS AND METHODS: Rats with intra-abdominal sepsis, induced by cecal ligation and incision, underwent abdominal washout, intra-peritoneal administration of cefazolin, and then either no further treatment (control), splenectomy, or pUS of the spleen. Animals were observed for the primary endpoint of survival duration. RESULTS: Survival curves were significantly different for all groups (p

Ischemia-reperfusion (I/R) injury (IRI), which involves inflammation, vascular permeability, and edema, remains a major challenge after lung transplantation. Pannexin-1 (Panx1) channels modulate cellular ATP release during inflammation. This study tests the hypothesis that endothelial Panx1 is a key mediator of vascular inflammation and edema after I/R and that IRI can be blocked by Panx1 antagonism. A murine hilar ligation model of IRI was used whereby left lungs underwent 1 h of ischemia and 2 h of reperfusion. Treatment of wild-type mice with Panx1 inhibitors (carbenoxolone or probenecid) significantly attenuated I/R-induced pulmonary dysfunction, edema, cytokine production, and neutrophil infiltration versus vehicle-treated mice. In addition, VE-Cad-CreERT2+/Panx1fl/fl mice (tamoxifen-inducible deletion of Panx1 in vascular endothelium) treated with tamoxifen were significantly protected from IRI (reduced dysfunction, endothelial permeability, edema, proinflammatory cytokines, and neutrophil infiltration) versus vehicle-treated mice. Furthermore, extracellular ATP levels in bronchoalveolar lavage fluid is Panx1-mediated after I/R as it was markedly attenuated by Panx1 antagonism in wild-type mice and by endothelial-specific Panx1 deficiency. Panx1 gene expression in lungs after I/R was also significantly elevated compared with sham. In vitro experiments demonstrated that TNF-α and/or hypoxia-reoxygenation induced ATP release from lung microvascular endothelial cells, which was attenuated by Panx1 inhibitors. This study is the first, to our knowledge, to demonstrate that endothelial Panx1 plays a key role in mediating vascular permeability, inflammation, edema, leukocyte infiltration, and lung dysfunction after I/R. Pharmacological antagonism of Panx1 activity may be a novel therapeutic strategy to prevent IRI and primary graft dysfunction after lung transplantation.

Background Frailty is an important predictor of outcomes after cardiac surgery, but utility is limited by difficult assessment and quantification. We hypothesize that sarcopenia defined as psoas muscle cross-sectional area is a useful predictor of surgical aortic valve replacement outcomes in moderate to high-risk patients. Methods Moderate to high risk patients (predicted risk of mortality greater than 3%) who underwent surgical aortic valve replacement with or without coronary artery bypass were extracted from an institutional database (2009 to 2016). Psoas index was calculated as the cross-sectional area of the psoas muscle at the L4 vertebral level normalized to body surface area. Patients were stratified by sarcopenia status, defined as less than 25th sex-specific percentile. Multivariable regression analysis identified risk-adjusted associations with psoas index using The Society of Thoracic Surgeons predicted risk scores. Results Of the 240 patients included, the median predicted risk of mortality was 6%, median age 80 years, and 40% were female. Patients with (33.3%) and without (66.7%) sarcopenia had equivalent baseline risk (median predicted risk of mortality 5.7% versus 6.0%, p = 0.29). Patients with sarcopenia had higher 1-year mortality (31.9% versus 16.9% p = 0.03). Psoas index significantly predicted risk-adjusted 1-year mortality (odds ratio 0.84, p = 0.02) and long-term mortality (hazard ratio 0.92, p = 0.04), as well as risk-adjusted major morbidity, prolonged ventilation, length of stay, discharge to a facility, and hospital cost. Finally, psoas index measurements were highly reproducible (Pearson correlation coefficient 0.944). Conclusions Psoas index is an easily obtained and reproducible measure of frailty that predicts risk-adjusted resource utilization, morbidity, and long-term mortality. Psoas index may improve procedural selection and risk adjustment in high-risk patients with aortic valve disease.

Background The Ruth L. Kirschstein Institutional National Research Service Award (T32) provides institutions with financial support to prepare trainees for careers in academic medicine. In 1990, the Cardiac Surgery Branch of the National Heart, Lung and Blood Institute (NHLBI) was replaced by T32 training grants, which became crucial sources of funding for cardiothoracic (CT) surgical research. We hypothesized that T32 grants would be valuable for CT surgery training and yield significant publications and subsequent funding. Methods Data on all trainees (past and present) supported by CT T32 grants at two institutions were obtained (T32), along with information on trainees from two similarly sized programs without CT T32 funding (Non-T32). Data collected were publicly available and included publications, funding, degrees, fellowships, and academic rank. Non-surgery residents and residents who did not pursue CT surgery were excluded. Results Out of 76 T32 trainees and 294 Non-T32 trainees, data on 62 current trainees or current CT surgeons (T32: 42 vs Control: 20) were included. Trainees who were supported by a CT T32 grant were more likely to pursue CT surgery after residency (T32: 40% [30/76] vs Non-T32: 7% [20/294], P P P = .02), and pursue advanced fellowships (T32: 41% [9/22] vs Non-T32: 10% [2/20], P = .02). Conclusions T32 training grants supporting CT surgery research are vital to develop academic surgeons. These results support continued funding by the NHLBI to effectively develop and train the next generation of academic CT surgeons.

Objective National Institutes of Health (NIH) funding for academic (noncardiac) thoracic surgeons at the top-140 NIH-funded institutes in the United States was assessed. We hypothesized that thoracic surgeons have difficulty in obtaining NIH funding in a difficult funding climate. Methods The top-140 NIH-funded institutes' faculty pages were searched for noncardiac thoracic surgeons. Surgeon data, including gender, academic rank, and postfellowship training were recorded. These surgeons were then queried in NIH Research Portfolio Online Reporting Tools Expenditures and Results for their funding history. Analysis of the resulting grants (1980-2019) included grant type, funding amount, project start/end dates, publications, and a citation-based Grant Impact Metric to evaluate productivity. Results A total of 395 general thoracic surgeons were evaluated with 63 (16%) receiving NIH funding. These 63 surgeons received 136 grants totaling $228 million, resulting in 1772 publications, and generating more than 50,000 citations. Thoracic surgeons have obtained NIH funding at an increasing rate (1980-2019); however, they have a low percentage of R01 renewal (17.3%). NIH-funded thoracic surgeons were more likely to have a higher professorship level. Thoracic surgeons perform similarly to other physician-scientists in converting K-Awards into R01 funding. Conclusions Contrary to our hypothesis, thoracic surgeons have received more NIH funding over time. Thoracic surgeons are able to fill the roles of modern surgeon-scientists by obtaining NIH funding during an era of increasing clinical demands. The NIH should continue to support this mission.

The most common mechanism of traumatic injury is ground-level fall. The objective of this study was to understand how patients sustaining falls and their outcomes have evolved. An institutional trauma database was used to identify adult patients who suffered a fall and were admitted to a Level I trauma center during two distinct time periods: 1998 to 2003 (past) and 2008 to 2013 (current). Data on anticoagulant use and comorbidities was gathered by retrospective chart review of patients treated during 2003 and 2013. Univariable analyses and multivariable regression were used to evaluate demographics and outcomes. A total of 6116 patients were identified, with a 24 per cent increase in number of falls between groups. Current fall patients are older (70 vs 66 years, P < 0.001), more often admitted to intensive care (28 vs 12%, P < 0.001), have longer lengths of stay (5 vs 4 days, P < 0.001), are frequently discharged to skilled nursing facilities (24 vs 8%, P < 0.001), and have higher mortality (5 vs 3%, P = 0.002). The adjusted odds of mortality for patients treated during 2003 and 2013 was associated with age, gender, injury severity score, and Glasgow Coma Scale score. Current fall patients use more health care resources and have worse outcomes, despite advances in trauma and geriatric care.

Background Bariatric surgery provides durable weight loss and decreases the incidence of co-morbid conditions for people with obesity. Most patients benefit from resultant weight loss, but some are at risk for postoperative refractory malnutrition, a serious but poorly understood complication. Objective To evaluate differences in bariatric surgery patients who received a feeding tube postoperatively for malnutrition compared with other indications. Setting Retrospective cohort study at an academic bariatric surgery center (1985-2015). Methods All bariatric surgery patients that received a feeding tube postoperatively over a 30-year period were identified. Data abstraction from the medical record was performed to assess demographic characteristics, operative details, tube indication, and resultant body mass index (BMI) changes. Results From a total of 3487 patients who underwent bariatric surgery during the study period, 139 (3.9%) required placement of a feeding tube postoperatively. Refractory malnutrition was the indication in 24 patients, all after Roux-en-Y gastric bypass. There were no significant differences between these patients and other bariatric surgery patients in terms of mean age (40.6±9.9 versus 43.1±13.4 years, P = .4) and preoperative BMI (47.5±10.5 versus 51.0±9.6 kg/m2, P = .1). The median time from surgery to tube placement for malnutrition patients was 4 years. Compared with other feeding tube indications, malnutrition patients had higher percent excess BMI lost after surgery (126.2±31.9 versus 52.5±44.3%, P Conclusion Patients with refractory malnutrition benefit from feeding tube placement, which results in a significant increase in BMI.

To determine the frequency and risk factors for non-home discharge (NHD) and its association with clinical outcomes and quality of life (QOL) at 1 year following cardiac surgery in patients with ischemic mitral regurgitation (IMR).Discharge disposition was evaluated in 552 patients enrolled in trials of severe or moderate IMR. Patient and in-hospital factors associated with NHD were identified using logistic regression. Subsequently, association of NHD with 1-year mortality, serious adverse events (SAEs), and QOL was assessed.NHD was observed in 30% (154/522) with 25% (n = 71/289) in moderate and 36% (n = 83/233) in patients with severe IMR (unadjusted P = .006), a difference not significant after including age (5-year change: adjusted odds ratio [adjOR], 1.52; 95% confidence interval [CI], 1.35-1.72; P .001), diabetes (adjOR, 1.94; 95% CI, 1.27-2.94; P = .002), and previous heart failure (adjOR, 1.64; 95% CI, 1.06-2.52; P = .03). Odds of NHD were increased for patients with postoperative SAEs (adjOR, 1.85; 95% CI, 1.19-2.86; P = .01) but not based on type of cardiac surgery. Greater rates of death and SAEs were observed in NHD patients at 1 year: adjusted hazard ratio, 4.29 (95% CI, 2.14-8.59; P .001) and adjusted rate ratio, 1.45 (95% CI, 1.03-2.02; P = .03), respectively. QOL did not differ significantly between groups.NHD is common following surgery for IMR, influenced by older age, diabetes, previous heart failure, and postoperative SAEs. These patients may be at greater risk of death and subsequent SAEs after discharge. Discussion of NHD with patients may have important implications for decision-making and guiding expectations following cardiac surgery.

Objective The current supply of acceptable donor lungs is not sufficient for the number of patients awaiting transplantation. We hypothesized that ex vivo lung perfusion (EVLP) with targeted drug therapy would allow successful rehabilitation and transplantation of donation after circulatory death lungs exposed to 2 hours of warm ischemia. Methods Donor porcine lungs were procured after 2 hours of warm ischemia postcardiac arrest and subjected to 4 hours of cold preservation or EVLP. ATL802, an adenosine A 2B receptor antagonist, was administered to select groups. Four groups (n = 4/group) were randomized: cold preservation (Cold), cold preservation with ATL802 during reperfusion (Cold + ATL802), EVLP (EVLP), and EVLP with ATL802 during ex vivo perfusion (EVLP + ATL802). Lungs subsequently were transplanted, reperfused, and assessed by measuring dynamic lung compliance and oxygenation capacity. Results EVLP + ATL802 significantly improved dynamic lung compliance compared with EVLP (25.0 ± 1.8 vs 17.0 ± 2.4 mL/cmH 2 O, P = .04), and compared with cold preservation (Cold: 12.2 ± 1.3, P = .004; Cold + ATL802: 10.6 ± 2.0 mL/cmH 2 O, P = .002). Oxygenation capacity was highest in EVLP (440.4 ± 37.0 vs Cold: 174.0 ± 61.3 mm Hg, P = .037). No differences in oxygenation or pulmonary edema were observed between EVLP and EVLP + ATL802. A significant decrease in interleukin-12 expression in tissue and bronchoalveolar lavage was identified between groups EVLP and EVLP + ATL802, along with less neutrophil infiltration. Conclusions Severely injured donation after circulatory death lungs subjected to 2 hours of warm ischemia are transplanted successfully after enhanced EVLP with targeted drug therapy. Increased use of lungs after uncontrolled donor cardiac death and prolonged warm ischemia may be possible and may improve transplant wait list times and mortality.

The number of robotic surgical procedures performed yearly is constantly rising, due to improved dexterity and visualization capabilities compared with conventional methods. We hypothesized that outcomes after robotic-assisted inguinal hernia repair would not be significantly different from outcomes after laparoscopic or open repair. All patients undergoing inguinal hernia repair between 2012 and 2016 were identified using institutional American College of Surgeons National Surgical Quality Improvement Program data. Demographics; preoperative, intraoperative, and postoperative characteristics; and outcomes were evaluated based on method of repair (Robot, Lap, or Open). Categorical variables were analyzed by Chi-square test and continuous variables using Mann–Whitney U. A total of 510 patients were identified who underwent unilateral inguinal hernia repair (Robot: 13.8% [n = 69], Lap: 48.1% [n = 241], Open: 38.1% [n = 191]). There were no demographic differences between groups other than age (Robot: 52 [39–62], Lap: 57 [45–67], and Open: 56 [48–67] years, p = 0.03). Operative duration was also different (Robot: 105 [76–146] vs. Lap: 81 [61–103] vs. Open: 71 [56–88] min, p

Degenerative mitral valve disease causing mitral regurgitation is the most common organic valve pathology and is classified based on leaflet motion. The "French correction" mitral valve repair method restores normal valvular anatomy with extensive leaflet resection, chordal manipulation, and rigid annuloplasty. The American correction attempts to restore normal valve function through minimal leaflet resection, flexible annuloplasty, and use of artificial chordae. These differing methods of mitral valve repair reflect an evolution in principles, but both require understanding of the valve pathology and correction of leaflet prolapse and annular dilatation. Adhering to those unifying principles and ensuring that no patient leaves the operating room with significant persistent mitral regurgitation produces durable results and satisfactory patient outcomes.

Therapeutic hypothermia (HT) in severe septic shock is associated with prolonged survival. We hypothesized that moderate HT would prolong survival and modulate the inflammatory response in rats with septic shock by exerting its therapeutic effect on splenic leukocytes.Severe septic shock was created in rats by cecal ligation and incision (CLI). One hour after CLI or laparotomy, rats were randomized to sham, normothermia (NT), or 4 h of HT followed by 2 h of rewarming. HT (31 ± 1°C) was induced using a cooling blanket and monitored via a rectal temperature probe.Survival duration was 2.78 ± 1.0 h in NT rats and 8.33 ± 0.32 h in HT rats (n = 8/group, P 0.0001). In separate groups, 3 h after CLI, the spleen weight was significantly smaller in NT rats (769 ± 100 mg) than in HT rats (947 ± 157 mg, P = 0.04). Fluorescent immunostaining of formyl peptide receptors on leukocytes in spleen tissue showed considerably higher formyl peptide receptor expression in HT rats than in NT rats. Significantly elevated proinflammatory cytokines and myeloperoxidase enzyme in plasma were found in NT rats compared with HT rats. Anti-inflammatory cytokine, interleukin-10, was significantly higher in HT rats. Both proinflammatory cytokines and plasma myeloperoxidase were significantly reduced in splenectomized NT rats.Moderate hypothermic therapy significantly prolongs the survival duration of rats with severe septic shock. HT dampens the inflammatory response during septic shock by modulating the spleen to an anti-inflammatory mode and preventing the spleen from releasing activated splenic leukocytes into the blood.

Background Vasoplegic syndrome, defined by hypotension despite normal or increased cardiac output, is associated with high mortality rate after cardiopulmonary bypass. Methylene blue (MB) is reported to ameliorate vasoplegic syndrome through the nitric oxide pathway. We hypothesized that early administration of MB would improve outcomes in patients with vasoplegic syndrome after cardiopulmonary bypass. Methods All patients that underwent cardiopulmonary bypass at our institution (Jan 1, 2011 to Jun 30, 2016) were identified through our Society of Thoracic Surgery database. Pharmacy records identified patients receiving MB within 72 hours of cardiopulmonary bypass. Multivariate logistic regression identified predictors of major adverse events among patients receiving MB. Results A total of 118 cardiopulmonary bypass patients (3.3%) received MB for vasoplegic syndrome. These patients had a higher incidence of comorbidities, and these cases were more commonly reoperative (76.1% versus 41.2%, p Conclusions Operative mortality rate is high in patients receiving MB for the treatment of vasoplegia after cardiopulmonary bypass. Early administration of MB improves survival and reduces the risk-adjusted rate of major adverse events in these patients.

Background Sepsis is the number one cause of lung injury in adults. Ex vivo lung perfusion (EVLP) is gaining clinical acceptance for donor lung evaluation and rehabilitation and may expand the use of marginal organs for transplantation. We hypothesized that 4 hours of normothermic EVLP would improve compliance and oxygenation in a porcine model of sepsis-induced lung injury. Methods We used intravenous lipopolysaccharide (LPS) to induce a systemic inflammatory response in a porcine model of lung injury. Two groups of 4 animals each received a 2-hour infusion of LPS through the external jugular vein. Serial measurements of blood gases were performed every 30 minutes until the partial pressure of oxygen/fraction of inspired oxygen ratio dropped below 150 on two consecutive readings. Lungs were then randomized to treatment with 4 hours of normothermic EVLP with STEEN Solution (XVIVO Perfusion Inc, Englewood, CO) or 4 additional hours of in vivo perfusion (control). Airway pressures and blood gases were recorded for calculation of dynamic lung compliance and partial pressure of oxygen/fraction of inspired oxygen ratios. EVLP was performed with hourly recruitment maneuvers and oxygen challenge. Results All animals reached a partial pressure of oxygen/fraction of inspired oxygen ratio of less than 150 mm Hg within 3 hours after start of the LPS infusion. Oxygenation and compliance in the control animals continued to decline during the 4-hour in vivo perfusion period, and 3 of the 4 animals died of severe hypoxia within 4 hours. The EVLP group demonstrated significant improvements hour 1 to hour 4 in oxygenation (365.8 ± 53.0 vs 584.4 ± 21.0 mm Hg, p = 0.02) and dynamic compliance (9.0 ± 2.8 vs 15.0 ± 3.6, p = 0.02 mL/cm H 2 O). Conclusions EVLP successfully rehabilitated LPS-induced lung injury in this preclinical porcine model and may thus provide a means to rehabilitate many types of acute lung injury.

BACKGROUND. Current cardiac surgery risk algorithms and quality measures focus on perioperative outcomes. However, delivering high-value, patient-centered cardiac care will require a better understanding of long-term patient-reported quality of life after surgery. Our objective was to prospectively assess the effect of cardiac surgery on long-term patient-reported outcomes. METHODS. Patients undergoing cardiac surgery at an academic medical center (2016 to 2017) were eligible for enrollment. Patient-reported outcomes were measured using the National Institutes of Health Patient-Reported Outcomes Measurement Information System preoperatively and 1 year postoperatively across five domains: mental health, physical health, physical functioning, social satisfaction, and applied cognition. Baseline data and perioperative outcomes were obtained from The Society of Thoracic Surgeons Database. The effect of cardiac surgery on long-term patient-reported quality of life was assessed. RESULTS. Ninety-eight patients were enrolled and underwent cardiac surgery, with 92.9% (91 of 98) successful follow-up. The most common operation was coronary artery bypass graft surgery at 63.3% (62 of 98), with 60.2% (59 of 98) undergoing an elective operation. One-year all-cause mortality was 5.1% (5 of 98). Rate of major morbidity was 11.2% (11 of 98). Cardiac surgery significantly improved patient-reported outcomes at 1 year across four domains: mental health (preoperative 47.3 ± 7.7 vs postoperative 51.1 ± 8.9, P < .001), physical health(41.2 ± 8.2 vs 46.3 ± 9.3, P < .001), physical functioning(39.8 ± 8.6 vs 44.8 ± 8.5, P < .001), and social satisfaction(46.8 ± 10.9 vs 50.7 ± 10.8, P = .023). Hospital discharge to a facility did not affect 1-year patient-reported outcomes. CONCLUSIONS. Cardiac surgery improves long-term patient-reported quality of life. Mental, physical, and social well-being scores were significantly higher 1 year postoperatively. Data collection with the National Institutes of Health Patient-Reported Outcomes Measurement Information System provides meaningful, quantifiable results that may improve delivery of patient-centered care.

BACKGROUND Currently, there are no clinically approved treatments for ischemia-reperfusion injury after lung transplantation. Pre-clinical animal models have demonstrated a promising efficacy of adenosine 2A receptor (A2AR) agonists as a treatment option for reducing ischemia-reperfusion injury. The purpose of this human study, is to conduct a Phase I clinical trial for evaluating the safety of continuous infusion of an A2AR agonist in lung transplant recipients. METHODS An adaptive, two-stage continual reassessment trial was designed to evaluate the safety of regadenoson (A2AR agonist) in the setting of lung transplantation. Continuous infusion of regadenoson was administered to lung transplant recipients that was started at the time of skin incision. Adverse events and dose-limiting toxicities, as pre-determined by a study team and assessed by a clinical team and an independent safety monitor, were the primary end-points for safety in this trial. RESULTS Between January 2018 and March 2019, 14 recipients were enrolled in the trial. Of these, 10 received the maximum infused dose of 1.44 µg/kg/min for 12 hours. No dose-limiting toxicities were observed. The steady-state plasma regadenoson levels sampled before the reperfusion of the first lung were 0.98 ± 0.46 ng/ml. There were no mortalities within 30 days. CONCLUSIONS Regadenoson, an A2AR agonist, can be safely infused in the setting of lung transplantation with no dose-limiting toxicities or drug-related mortality. Although not powered for the evaluation of secondary end-points, the results of this trial and the outcome of pre-clinical studies warrant further investigation with a Phase II randomized controlled trial.