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Objective: Transient receptor potential vanilloid 4 (TRPV4) is a nonselective cation channel important in many physiological and pathophysiological processes, including pulmonary disease. Using a murine model, we previously demonstrated that TRPV4 mediates lung ischemia-reperfusion injury, the major cause of primary graft dysfunction after transplant. The current study tests the hypothesis that treatment with a TRPV4 inhibitor will attenuate lung ischemia-reperfusion injury in a clinically relevant porcine lung transplant model., Methods: A porcine left-lung transplant model was used. Animals were randomized to 2 treatment groups (n = 5/group): vehicle or GSK2193874 (selective TRPV4 inhibitor). Donor lungs underwent 30 minutes of warm ischemia and 24 hours of cold preservation before left lung allotransplantation and 4 hours of reperfusion. Vehicle or GSK2193874 (1 mg/kg) was administered to the recipient as a systemic infusion after recipient lung explant. Lung function, injury, and inflammatory biomarkers were compared., Results: After transplant, left lung oxygenation was significantly improved in the TRPV4 inhibitor group after 3 and 4 hours of reperfusion. Lung histology scores and edema were significantly improved, and neutrophil infiltration was significantly reduced in the TRPV4 inhibitor group. TRPV4 inhibitor-treated recipients had significantly reduced expression of interleukin-8, high mobility group box 1, P-selectin, and tight junction proteins (occludin, claudin-5, and zonula occludens-1) in bronchoalveolar lavage fluid as well as reduced angiopoietin-2 in plasma, all indicative of preservation of endothelial barrier function., Conclusions: Treatment of lung transplant recipients with TRPV4 inhibitor significantly improves lung function and attenuates ischemia-reperfusion injury. Thus, selective TRPV4 inhibition may be a promising therapeutic strategy to prevent primary graft dysfunction after transplant., Competing Interests: Conflict of Interest Statement The authors reported no conflicts of interest. The Journal policy requires editors and reviewers to disclose conflicts of interest and to decline handling or reviewing manuscripts for which they may have a conflict of interest. The editors and reviewers of this article have no conflicts of interest., (Copyright © 2024 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.)

Objective: Literature describing outcomes of myocardial ischemia after coronary artery bypass grafting is sparse. We hypothesized these patients had more complications and incurred higher costs of care., Methods: Using adult cardiac surgery data and cardiac catheterization (CathPCI) data from the Virginia Cardiac Services Quality Initiative, we identified patients who underwent unplanned cardiac catheterization after coronary artery bypass grafting from 2018 to 2021. Adult cardiac surgery data were matched to CathPCI data examining earliest in-hospital catheterization. Patients not requiring catheterization served as the control group., Results: We identified 10,597 patients who underwent isolated coronary artery bypass grafting, of whom 41 of 10,597 underwent unplanned cardiac catheterization. A total of 21 of 41 patients (51%) received percutaneous coronary intervention, most commonly for non-ST-elevation myocardial infarction (n = 7, 33%) and ST-elevation myocardial infarction (n = 6, 29%). Postoperative cardiac arrest occurred in 14 patients (40%). In patients who underwent percutaneous coronary intervention, 14 (67%) had a single lesion, 4 (19%) had 2 lesions, and 3 (14%) had 3 lesions. The left anterior descending artery (38%) was the most frequently intervened upon vessel. Patients who underwent catheterization were more likely to require balloon pump support (26% vs 11%), to have prolonged ventilation (57% vs 20%), to have renal failure (17% vs 7.1%), and to undergo reintubation (37% vs 3.8%, all P < .04). There was no statistical difference in operative mortality (4.9% vs 2.3%, P = .2) or failure to rescue (4.9% vs 1.6%, P = .14). Total costs were higher in patients who underwent unplanned catheterization ($81,293 vs $37,011, P < .001)., Conclusions: Unplanned catheterization after coronary artery bypass grafting is infrequent but associated with more complications and a higher cost of care. Therefore, determination of an association with operative mortality in patients with suspected ischemia after coronary artery bypass grafting requires additional study., (Copyright © 2023 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.)

Objectives: Acute respiratory distress syndrome represents the devastating result of acute lung injury, with high mortality. Limited methods are available for rehabilitation of lungs affected by acute respiratory distress syndrome. Our laboratory has demonstrated rehabilitation of sepsis-injured lungs via normothermic ex vivo and in vivo perfusion with Steen solution (Steen). However, mechanisms responsible for the protective effects of Steen remain unclear. This study tests the hypothesis that Steen directly attenuates pulmonary endothelial barrier dysfunction and inflammation induced by lipopolysaccharide., Methods: Primary pulmonary microvascular endothelial cells were exposed to lipopolysaccharide for 4 hours and then recovered for 8 hours in complete media (Media), Steen, or Steen followed by complete media (Steen/Media). Oxidative stress, chemokines, permeability, interendothelial junction proteins, and toll-like receptor 4-mediated pathways were assessed in pulmonary microvascular endothelial cells using standard methods., Results: Lipopolysaccharide treatment of pulmonary microvascular endothelial cells and recovery in Media significantly induced reactive oxygen species, lipid peroxidation, expression of chemokines (eg, chemokine [C-X-C motif] ligand 1 and C-C motif chemokine ligand 2) and cell adhesion molecules (P-selectin, E-selectin, and vascular cell adhesion molecule 1), permeability, neutrophil transmigration, p38 mitogen-activated protein kinase and nuclear factor kappa B signaling, and decreased expression of tight and adherens junction proteins (zonula occludens-1, zonula occludens-2, and vascular endothelial-cadherin). All of these inflammatory pathways were significantly attenuated after recovery of pulmonary microvascular endothelial cells in Steen or Steen/Media., Conclusions: Steen solution preserves pulmonary endothelial barrier function after lipopolysaccharide exposure by promoting an anti-inflammatory environment via attenuation of oxidative stress, toll-like receptor 4-mediated signaling, and conservation of interendothelial junctions. These protective mechanisms offer insight into the advancement of methods for in vivo lung perfusion with Steen for the treatment of severe acute respiratory distress syndrome., (Copyright © 2022 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.)

Objectives: Obtaining National Institutes of Health funding for heart transplant research is becoming increasingly difficult, especially for surgeons. We sought to determine the impact of National Institutes of Health-funded cardiac transplantation research over the past 30 years., Methods: National Institutes of Health Research Portfolio Online Reporting Tools Expenditures and Results was queried for R01s using 10 heart transplant-related terms. Principal Investigator, total grant funding amount, number of publications, and citations of manuscripts were collected. A citation-based Grant Impact Metric was assigned to each grant: sum of citations for each manuscript normalized by the funding of the respective grant (per $100K). The department and background degree(s) (MD, PhD, MD/PhD) for each funded Principal Investigator were identified from institutional faculty profiles., Results: A total of 321 cardiac transplantation R01s totaling $723 million and resulting in 6513 publications were analyzed. Surgery departments received more grants and more funding dollars to study cardiac transplantation than any other department (n = 115, $249 million; Medicine: n = 93, $208 million; Pathology: 26, $55 million). Surgeons performed equally well compared with all other Principal Investigators with respect to Grant Impact Metric (15.1 vs 20.6; P = .19) and publications per $1 million (7.5 vs 6.8; P = .75). Finally, all physician-scientists (MDs) have a significantly higher Grant Impact Metric compared with nonclinician researchers (non-MDs) (22.3 vs 16.3; P = .028)., Conclusions: Surgeon-scientists are equally productive and impactful compared with nonsurgeons despite decreasing funding rates at the National Institutes of Health and greater pressure from administrators to increase clinical productivity., (Copyright © 2020 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.)

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., (Copyright © 2019 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.)

Objective: To determine trends in National Institutes of Health (NIH) funding for cardiac surgeons, hypothesizing they are at a disadvantage in obtaining funding owing to intensive clinical demands., Methods: Cardiac surgeons (adult/congenital) currently at the top 141 NIH-funded institutions were identified using institutional websites. The NIH funding history for each cardiac surgeon was queried using the NIH Research Portfolio Online Reporting Tools Expenditures and Results (RePORTER). Total grant funding, publications, and type was collected. Academic rank, secondary degrees, and fellowship information was collected from faculty pages. Grant productivity was calculated using a validated grant impact metric., Results: A total of 818 academic cardiac surgeons were identified, of whom 144 obtained 293 NIH grants totaling $458 million and resulting in 6694 publications. We identified strong associations between an institution's overall NIH funding rank and the number of cardiac surgeons, NIH grants to cardiac surgeons, and amount of NIH funding to cardiac surgeons (P < .0001 for all). The majority of NIH funding to cardiac surgeons is concentrated in the top quartile of institutions. Cardiac surgeons had a high conversion rates from K awards (mentored development awards) to R01s (6 of 14; 42.9%). Finally, we demonstrate that the rate of all NIH grants awarded to cardiac surgeons has increased, driven primarily by P and U (collaborative project) grants., Conclusions: NIH-funded cardiac surgical research has had a significant impact over the last 3 decades. Aspiring cardiac surgeon-scientists may be more successful at top quartile institutions owing to better infrastructure and mentorship., (Copyright © 2019 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.)

Objective: Acute kidney injury (AKI) occurs in 20% of patients following cardiac surgery. To reduce AKI in our institution, we instituted a quality improvement (QI) initiative using a goal-directed volume resuscitation protocol. Our protocol was designed to achieve quantifiable physiologic goals (eg, cardiac index > 2.5 L/min/m 2 , mean arterial pressure > 65 mm Hg) using fluid and vasoactive agents. The objective of this study was to evaluate AKI in the pre- and post-QI eras, hypothesizing that AKI incidence would decrease in the post-QI era., Methods: In this observational retrospective cohort study, we identified patients who underwent cardiac operations from July 2011 to July 2015 with a risk score available. Kidney injury was determined using the lowest postoperative GFR within 7 days of surgery and standard Risk, Injury, Failure, Loss of Kidney Function, and End-Stage Kidney Disease (RIFLE) classification criteria. The primary outcome was the rate of AKI, as defined by glomerular filtration rate-based RIFLE classification criteria injury, in the post- versus pre-QI eras., Results: A total of 1979 patients were included, of whom 725 were in the pre-QI cohort, and 1254 in the post-QI cohort. Overall, rates of RIFLE classification criteria risk, injury and failure were 27.5%, 5.9%, and 3.6%, respectively. RIFLE classification criteria injury saw the largest decrease in the post-QI cohort (8.1% vs 4.6%; P = .001). Multivariable analysis demonstrated a 37% reduction in the odds of AKI in the post-QI cohort (adjusted odds ratio, 0.63; 95% confidence interval, 0.43-0.90)., Conclusions: A goal-directed volume resuscitation protocol centered on patient fluid responsiveness is associated with significantly reduced risk for AKI after cardiac surgery. Protocol-driven approaches should be employed in intensive care units to improve outcomes., (Copyright © 2019 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.)

Objectives: β-Blocker use is associated with fewer cardiac complications in patients undergoing noncardiac surgery and is a quality metric for coronary artery bypass grafting. We sought to determine the influence of preoperative β-blocker administration before aortic valve replacement (AVR)., Methods: All patients undergoing isolated AVR from 2002 to 2016 were extracted from a multi-institutional, statewide database composed of Society of Thoracic Surgeons data. Patients were propensity score matched by preoperative and operative variables, and the effects of preoperative β-blockers on outcomes were assessed., Results: Of 7380 eligible patients, 53% received a preoperative β-blocker. After propensity matching, a total of 4592 patients were well matched (1:1) with minimal baseline differences between groups. Within the matched cohort, the operative mortality rate (β-blocker: 2.8% vs no β-blocker: 2.4%; P = .454) and rate of major morbidity (14.4% vs 12.7%; P = .101) were similar between groups. The rates of cardiac arrest (2.1% vs 1.3%; P = .034), renal failure requiring dialysis (1.7% vs 0.9%; P = .007), and postoperative transfusion (38.2% vs 33.8%; P = .002) after AVR were significantly greater in the cohort receiving preoperative β-blockade. Postoperative atrial fibrillation was also more prevalent in patients receiving a preoperative β-blocker (26.9% vs 23.4%; P = .007). Finally, preoperative β-blocker use was associated with longer postoperative intensive care unit stays (45.2 vs 47.0 hours; P = .001), but clinically similar hospital length of stay., Conclusions: Preoperative β-blocker administration is not associated with improved outcomes after AVR but instead is associated with increased postoperative morbidity. Routinely initiating preoperative β-blockade is not supported in patients undergoing AVR., (Copyright © 2019. Published by Elsevier Inc.)

Background: Prompt revascularization is often required in acute coronary syndromes (ACS), whereas stable ischemic heart disease (SIHD) may allow for more measured procedural planning. Whether the acuity of presentation preferentially affects outcomes after coronary artery bypass grafting (CABG) versus percutaneous coronary intervention (PCI) in patients with left main coronary artery disease (LMCAD) is unknown. We investigated whether the acuity of presentation discriminated patients who derived a differential benefit from PCI versus CABG in the randomized Evaluation of XIENCE versus Coronary Artery Bypass Surgery for Effectiveness of Left Main Revascularization (EXCEL) trial., Methods: We used multivariable Cox models to assess the interaction between the acuity of presentation, type of revascularization and outcomes in patients with low or intermediate SYNTAX scores enrolled in EXCEL., Results: At baseline, 1151 patients (60.7%) presented with SIHD and 746 patients (39.3%) presented with an ACS. The acuity of presentation was not associated with the primary endpoint of all-cause death, MI, or stroke at 3 years (multivariable adjusted hazard ratio [HR] 0.94; 95% CI 0.70-1.26, P = .64). The primary endpoint rate was similar in patients assigned to PCI versus CABG whether they presented with SIHD (adjusted HR 1.04; 95% CI 0.73-1.48]) or with ACS (HR 0.82; 95% CI 0.54-1.26) (P interaction  = .34)., Conclusions: The acuity of presentation did not predict outcomes in patients with LMCAD undergoing revascularization, nor did it discriminate patients who derive greater event-free survival from PCI versus CABG., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Introduction: Damage-associated molecular patterns, such as high-mobility group box 1 (HMGB1) and cell-free DNA (cfDNA), play critical roles in mediating ischemia-reperfusion injury (IRI). HMGB1 activates RAGE to exacerbate IRI, but the mechanism underlying cfDNA-induced myocardial IRI remains unknown. We hypothesized that the infarct-exacerbating effect of cfDNA is mediated by HMGB1 and receptor for advanced glycation end products (RAGE)., Methods: C57BL/6 wild type mice, RAGE knockout (KO), and Toll-like receptor 9 KO mice underwent 20- or 40-minute occlusions of the left coronary artery followed by up to 60 minutes of reperfusion. Cardiac coronary perfusate was acquired from ischemic hearts without reperfusion. Exogenous mitochondrial DNA was acquired from livers of normal C57BL/6 mice. Myocardial infarct size (IS) was reported as percent risk region, as measured by 2,3,5-triphenyltetrazolium chloride and Phthalo blue (Heucotech, Fairless Hill, Pa) staining. cfDNA levels were measured by Sytox Green assay (Thermo Fisher Scientific, Waltham, Mass) and/or spectrophotometer., Results: Free HMGB1 and cfDNA levels were increased in the ischemic myocardium during prolonged ischemia and subsequently in the plasma during reperfusion. In C57BL/6 mice undergoing 40'/60' IRI, deoxyribonuclease I, or anti-HMGB1 monoclonal antibody reduced IS by approximately half to 29.0% ± 5.2% and 24.3% ± 3.5% (P < .05 vs control 54.3% ± 3.4%). However, combined treatment with deoxyribonuclease I + anti-HMGB1 monoclonal antibody did not further attenuate IS (29.3% ± 4.9%). In C57BL/6 mice undergoing 20'/60' IRI, injection of 40'/5' plasma upon reperfusion increased IS by more than 3-fold (to 19.9 ± 4.3; P < .05). This IS exacerbation was abolished by pretreating the plasma with deoxyribonuclease I or by depleting the HMGB1 by immunoprecipitation, or by splenectomy. The infarct-exacerbating effect also disappeared in RAGE KO mice and Toll-like receptor 9 KO mice. Injection of 40'/0' coronary perfusate upon reperfusion similarly increased IS. The levels of HMGB1 and cfDNA were significantly elevated in the 40'/0' coronary perfusate and 40'/reperfusion (min) plasma but not in those with 10' ischemia. In C57BL/6 mice without IRI, 40'/5' plasma significantly increased the interleukin-1β protein and messenger RNA expression in the spleen by 30 minutes after injection. Intravenous bolus injection of recombinant HMGB1 (0.1 μg/g) or mitochondrial DNA (0.5 μg/g) 5 minutes before reperfusion did not exacerbate IS (P = not significant vs control). However, combined administration of recombinant HMGB1 + mitochondrial DNA significantly increased IS (P < .05 vs individual treated groups) and this infarct-exacerbating effect disappeared in RAGE KO mice and splenectomized C57BL/6 mice. The accumulation of cfDNA in the spleen after combined recombinant HMGB1 + mitochondrial DNA treatment was significantly more elevated in C57BL/6 mice than in RAGE KO mice., Conclusions: Both HMGB1 and cfDNA are released from the heart upon reperfusion after prolonged ischemia and both contribute importantly and interdependently to post-IRI by a common RAGE-Toll-like receptor 9-dependent mechanism. Depleting either of these 2 damage-associated molecular patterns suffices to significantly reduce IS by approximately 50%., (Copyright © 2018 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.)

Background: Sphingosine-1-phosphate regulates endothelial barrier integrity and promotes cell survival and proliferation. We hypothesized that upregulation of sphingosine-1-phosphate during ex vivo lung perfusion would attenuate acute lung injury and improve graft function., Methods: C57BL/6 mice (n = 4-8/group) were euthanized, followed by 1 hour of warm ischemia and 1 hour of cold preservation in a model of donation after cardiac death. Subsequently, mice underwent 1 hour of ex vivo lung perfusion with 1 of 4 different perfusion solutions: Steen solution (Steen, control arm), Steen with added sphingosine-1-phosphate (Steen + sphingosine-1-phosphate), Steen plus a selective sphingosine kinase 2 inhibitor (Steen + sphingosine kinase inhibitor), or Steen plus both additives (Steen + sphingosine-1-phosphate + sphingosine kinase inhibitor). During ex vivo lung perfusion, lung compliance and pulmonary artery pressure were continuously measured. Pulmonary vascular permeability was assessed with injection of Evans Blue dye., Results: The combination of 1 hour of warm ischemia, followed by 1 hour of cold ischemia created significant lung injury compared with lungs that were immediately harvested after circulatory death and put on ex vivo lung perfusion. Addition of sphingosine-1-phosphate or sphingosine kinase inhibitor alone did not significantly improve lung function during ex vivo lung perfusion compared with Steen without additives. However, group Steen + sphingosine-1-phosphate + sphingosine kinase inhibitor resulted in significantly increased compliance (110% ± 13.9% vs 57.7% ± 6.6%, P < .0001) and decreased pulmonary vascular permeability (33.1 ± 11.9 μg/g vs 75.8 ± 11.4 μg/g tissue, P = .04) compared with Steen alone., Conclusions: Targeted drug therapy with a combination of sphingosine-1-phosphate + sphingosine kinase inhibitor during ex vivo lung perfusion improves lung function in a murine donation after cardiac death model. Elevation of circulating sphingosine-1-phosphate via specific pharmacologic modalities during ex vivo lung perfusion may provide endothelial protection in marginal donor lungs leading to successful lung rehabilitation for transplantation., (Copyright © 2018 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.)

Objectives: Minimally invasive mitral valve surgery (mini-MVR) has numerous associated benefits. However, many studies fail to include greater-risk patients. We hypothesized that a minimally invasive approach in a representative cohort provides excellent outcomes with reduced resource utilization., Methods: Mitral valve surgical records from 2011 to 2016 were paired with institutional financial records. Patients were stratified by approach and propensity-score matched to balance preoperative difference. The primary outcomes of interest were resource utilization including cost, discharge to a facility, and readmission., Results: A total of 478 patients underwent mitral surgery (21% mini-MVR) and were balanced after matching (n = 74 per group), with 18% of patients having nondegenerative mitral disease. Outcomes were excellent with similar rates of major morbidity (9.5% mini-MVR vs 10.8% conventional, P = .78). Mini-MVR cases had lower rates of transfusion (11% vs 27%, P = .01) and shorter ventilator times (3.7 vs 6.0 hours, P < .0001). Mean total hospital cost was equivalent ($49,703 vs $54,970, P = .235) with mini-MVR having lower ancillary ($1645 vs $2652, P = .001) and blood costs ($383 vs $1058, P = .001). These savings were offset by longer surgical times (291 vs 234 minutes, P < .0001) with greater surgical ($7645 vs $7293, P = .0001) and implant costs ($1148 vs $748, P = .03). Rates of discharge to a facility (9.6% vs 16.2%) and readmission (9.6% vs 4.1%) were not statistically different., Conclusions: In a real-world cohort, mini-MVR continues to demonstrate excellent results with a favorable resource utilization profile. Greater surgical and implant costs with mini-MVR are offset by decreased transfusions and ancillary needs leading to equivalent overall hospital cost., (Copyright © 2018 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.)

Background: Reducing blood product utilization after cardiac surgery has become a focus of perioperative care as studies have suggested improved outcomes. The relative impact of preoperative anemia versus packed red blood cells (PRBC) transfusion on outcomes remains poorly understood, however. In this study, we investigated the relative association between preoperative hematocrit (Hct) level and PRBC transfusion on postoperative outcomes after coronary artery bypass grafting (CABG) surgery., Methods: Patient records for primary, isolated CABG operations performed between January 2007 and December 2017 at 19 cardiac surgery centers were evaluated. Hierarchical logistic regression modeling was used to estimate the relationship between baseline preoperative Hct level as well as PRBC transfusion and the likelihoods of postoperative mortality and morbidity, adjusted for baseline patient risk. Variable and model performance characteristics were compared to determine the relative strength of association between Hct level and PRBC transfusion and primary outcomes., Results: A total of 33,411 patients (median patient age, 65 years; interquartile range [IQR], 57-72 years; 26% females) were evaluated. The median preoperative Hct value was 39% (IQR, 36%-42%), and the mean Society of Thoracic Surgeons (STS) predicted risk of mortality was 1.8 ± 3.1%. Complications included PRBC transfusion in 31% of patients, renal failure in 2.8%, stroke in 1.3%, and operative mortality in 2.0%. A strong association was observed between preoperative Hct value and the likelihood of PRBC transfusion (P < .001). After risk adjustment, PRBC transfusion, but not Hct value, demonstrated stronger associations with postoperative mortality (odds ratio [OR], 4.3; P < .0001), renal failure (OR 6.3; P < .0001), and stroke (OR, 2.4; P < .0001). A 1-point increase in preoperative Hct was associated with decreased probabilities of mortality (OR, 0.97; P = .0001) and renal failure (OR, 0.94; P < .0001). The models with PRBC had superior predictive power, with a larger area under the curve, compared with Hct for all outcomes (all P < .01). Preoperative anemia was associated with up to a 4-fold increase in the probability of PRBC transfusion, a 3-fold increase in renal failure, and almost double the mortality., Conclusions: PRBC transfusion appears to be more closely associated with risk-adjusted morbidity and mortality compared with preoperative Hct level alone, supporting efforts to reduce unnecessary PRBC transfusions. Preoperative anemia independently increases the risk of postoperative morbidity and mortality. These data suggest that preoperative Hct should be included in the STS risk calculators. Finally, efforts to optimize preoperative hematocrit should be investigated as a potentially modifiable risk factor for mortality and morbidity., (Copyright © 2018 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.)

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 < .0001), publish manuscripts during residency years (P < .0001), obtain subsequent NIH funding (T32: 33% [7/21] vs Non-T32: 5% [1/20], 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., (Copyright © 2017 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.)

Objectives: The Centers for Medicare and Medicaid Services plans to institute a 5-year trial of bundled payments for coronary artery bypass grafting through 90 days after discharge. To investigate the impact, we reviewed actual inpatient costs for patients undergoing bypass surgery relative to the target price., Methods: A total of 13,276 Medicare patients with estimated cost data underwent isolated coronary artery bypass grafting from 2008 to 2015 in 18 hospitals over 8 Medicare-defined regions within the Commonwealth of Virginia. Actual 2015 inpatient costs were compared with estimated target prices for each year of the pilot, based on the previous 3 years and stratified by Diagnosis-Related Group., Results: The mean 2015 cost per patient was $50,394 with high variation (range, $27,862-$74,169). On average, hospitals would receive a refund of $17,682 in year 1, but then owe Medicare increasing amounts up to $367,985 in year 5. If 2015 were the final year of the pilot, 13 of the 18 hospitals (72%) would have owed Medicare for cost overruns averaging $614,270 (range, $67,404-$2,102,292). Costs were below the target price at 5 of 18 hospitals, and the Centers for Medicare and Medicaid Services would have paid them an extra $272,355 on average (range, $88,628-$567,429)., Conclusions: Hospitals will face immediate financial pressure due to average cost increases of 3.6% per year and an automatic reduction in payment. As regional pricing is phased in, hospitals can expect to owe Medicare increasing amounts. The net effect is shifting of financial risks to hospitals, which could restrict access to care for higher-risk patients., (Copyright © 2017 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.)

Background: Sepsis is the leading cause of lung injury in adults and can lead to acute respiratory distress syndrome (ARDS). Using a novel technique of isolated in vivo lung perfusion (IVLP), we hypothesized that normothermic IVLP will improve oxygenation and compliance in a porcine model of sepsis-induced lung injury., Methods: Mature adult swine (n = 8) were administered lipopolysaccharide (LPS; 50 μg/kg over 2 hours) via the external jugular vein, followed by sternotomy and central extracorporeal membrane oxygenation (ECMO) cannulation (right atrium to ascending aorta). The left pulmonary artery (inflow) and left superior and inferior pulmonary veins (outflow) were dissected out and cannulated to deliver isolated perfusion to the left lung. After 4 hours of normothermic IVLP with Steen solution, the left lung then underwent 4 hours of reperfusion after IVLP decannulation. Airway pressures and lung-specific pulmonary vein blood gases from the right lung (LPS control) and left lung (LPS + IVLP) of the same animal were compared., Results: All animals demonstrated a significant reduction in the ratio of partial pressure of oxygen in arterial blood (PaO 2 )/fraction of inspired oxygen (FiO 2 ) (P/F ratio) and total lung compliance at 2 hours after the start of LPS infusion (mean, 469 ± 19.7 mm Hg vs 222.2 ± 21.4 mm Hg; P < .0001). After reperfusion, 6 animals (75%) exhibited improved lung function, allowing for ECMO decannulation. Lung-specific oxygenation was superior in the left lung after 4 hours of reperfusion (mean, 310.5 ± 54.7 mm Hg vs 201.1 ± 21.7 mm Hg; P = .01). Similarly, total lung compliance improved after IVLP of the left lung. The lung wet weight to dry weight ratio demonstrated reduced edema in rehabilitated left lungs (mean, 6.5 ± 0.3 vs 7.5 ± 0.4; P = .04)., Conclusions: IVLP successfully rehabilitated LPS-injured lungs compared to ECMO support alone in this preclinical porcine model., (Copyright © 2017 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.)

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., (Copyright © 2017 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.)

Background: While it is anticipated that decubitus ulcers are detrimental to outcomes after vascular operations, the contemporary influence of perioperative decubitus ulcers in vascular surgery remains unknown., Methods: Using the National Impatient Survey, all adult patients who underwent vascular operation were selected. Patients were stratified by the presence or absence (non-decubitus ulcers) of decubitus ulcer. Case-mix adjusted hierarchical mixed-models examined in-hospital mortality, the occurrence of any complication, and discharge disposition., Results: A total of 538,808 cases were analyzed. Decubitus ulcers were most prevalent among Caucasian male Medicare beneficiaries (P < .001). Decubitus ulcer patients also underwent more nonelective vascular operations (P < .001). Wound, infectious, and procedural complications were more common in patients with decubitus ulcers (P < .001). Failure to rescue, defined as mortality after any complication, was more than doubled in decubitus ulcers (non-decubitus ulcers: 1.5%, decubitus ulcers: 3.2%, P < .001). Similarly, unadjusted mortality was also doubled in patients undergoing vascular operation with decubitus ulcers (non-decubitus ulcers: 3%, decubitus ulcers: 6%, P < .001). After risk adjustment among all patients, neither the presence of a decubitus ulcer nor specific ulcer staging increased the adjusted odds of death. Having a decubitus ulcer increased the adjusted odds of discharge to an intermediate care facility (odds ratio 2.9, P < .001). These patients also had 1.6 times the total charges compared to their non-decubitus ulcer cohort (non-decubitus ulcers: $49,460 ± $281 vs decubitus ulcers: $81,149 ± $5,855, P < .001)., Conclusion: Contrary to common perception, perioperative decubitus ulcer does not adversely affect mortality after vascular operation in patients proceeding to operative intervention. Patients with decubitus ulcers are, however, at higher risk for complications and incur sizeable additional charges., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Objective: Critical organ shortages have resulted in ex vivo lung perfusion gaining clinical acceptance for lung evaluation and rehabilitation to expand the use of donation after circulatory death organs for lung transplantation. We hypothesized that an innovative use of airway pressure release ventilation during ex vivo lung perfusion improves lung function after transplantation., Methods: Two groups (n = 4 animals/group) of porcine donation after circulatory death donor lungs were procured after hypoxic cardiac arrest and a 2-hour period of warm ischemia, followed by a 4-hour period of ex vivo lung perfusion rehabilitation with standard conventional volume-based ventilation or pressure-based airway pressure release ventilation. Left lungs were subsequently transplanted into recipient animals and reperfused for 4 hours. Blood gases for partial pressure of oxygen/inspired oxygen fraction ratios, airway pressures for calculation of compliance, and percent wet weight gain during ex vivo lung perfusion and reperfusion were measured., Results: Airway pressure release ventilation during ex vivo lung perfusion significantly improved left lung oxygenation at 2 hours (561.5 ± 83.9 mm Hg vs 341.1 ± 136.1 mm Hg) and 4 hours (569.1 ± 18.3 mm Hg vs 463.5 ± 78.4 mm Hg). Likewise, compliance was significantly higher at 2 hours (26.0 ± 5.2 mL/cm H 2 O vs 15.0 ± 4.6 mL/cm H 2 O) and 4 hours (30.6 ± 1.3 mL/cm H 2 O vs 17.7 ± 5.9 mL/cm H 2 O) after transplantation. Finally, airway pressure release ventilation significantly reduced lung edema development on ex vivo lung perfusion on the basis of percentage of weight gain (36.9% ± 14.6% vs 73.9% ± 4.9%). There was no difference in additional edema accumulation 4 hours after reperfusion., Conclusions: Pressure-directed airway pressure release ventilation strategy during ex vivo lung perfusion improves the rehabilitation of severely injured donation after circulatory death lungs. After transplant, these lungs demonstrate superior lung-specific oxygenation and dynamic compliance compared with lungs ventilated with standard conventional ventilation. This strategy, if implemented into clinical ex vivo lung perfusion protocols, could advance the field of donation after circulatory death lung rehabilitation to expand the lung donor pool., Competing Interests: There are no financial disclosures or conflicts of interest from any of the authors., (Copyright © 2016 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.)

Objectives: The long-term evolution of coexistent mitral regurgitation (MR) after aortic valve replacement (AVR) for aortic stenosis remains poorly defined. Prior studies have demonstrated that acute improvement in MR after AVR is modest, and more aggressive approaches have been advocated. This study examines the evolution of MR after AVR and identifies prognostic indicators for MR improvement., Methods: We retrospectively evaluated demographic and echocardiographic data of 423 patients who underwent primary isolated AVR for aortic stenosis with coexistent mild (n = 314) or moderate (n = 109) MR at our institution, from 2004 to 2013. For each patient, preoperative and postoperative MR was extracted from 903 echocardiograms and graded on a 0 to 4+ scale. Hierarchic linear models were used to estimate postoperative residual MR over a 5-year follow-up period. Patients were then stratified by improvement in MR, and preoperative risk factors and survival were compared between groups. Cox proportional hazards regression was used to assess the association between survival and preoperative and postoperative MR., Results: The overall acute reduction in MR was -0.23 degrees per patient. Patients with moderate MR had a -0.53 degree reduction in MR, whereas patients with mild MR had only a -0.13 degree reduction in MR (P < .001). Residual MR, however, worsened over time and regressed back to baseline, particularly in patients with preoperative moderate MR. At last follow-up, 70 (17%) patients returned to 2+ or worse MR. Residual MR at last echocardiographic follow-up was not affected by left ventricular ejection fraction, severity of preoperative aortic valve gradient (AVG), magnitude of reduction of AVG, or other comorbidities. Degree of preoperative MR did not affect midterm survival. Patients whose MR improved after AVR demonstrated a trend toward improved survival (75% vs 65% 5-year survival; P = .06), compared with those without MR whose survival remained unchanged or worsened., Conclusions: Coexistent MR modestly improves after AVR, but eventually regresses back to baseline or worsens over time in many patients. Preoperative AVG, reduction of AVG, heart failure, or atrial fibrillation was not predictive of residual MR. Moderate preoperative MR did not adversely affect 5-year survival. Patients with improvement in MR, however, demonstrated a trend toward improved survival at 5 years. More aggressive approaches for coexistent moderate MR should be considered in patients who need AVR for aortic stenosis., (Copyright © 2016 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.)

Objective: B lymphocytes are generally considered to be activators of the immune response; however, recent findings have shown that a subtype of B lymphocytes, regulatory B lymphocytes, play a role in attenuating the immune response. Bronchiolitis obliterans remains the major limitation to modern-day lung transplantation. The role of regulatory B lymphocytes in bronchiolitis obliterans has not been elucidated. We hypothesized that regulatory B lymphocytes play a role in the attenuation of bronchiolitis obliterans., Methods: We performed a standard heterotopic tracheal transplant model. Tracheas from Balb/c mice were transplanted into C57BL/6 recipients. Rapamycin treatment and dimethyl sulfoxide control groups were each treated for the first 14 days after the transplant. Tracheas were collected on days 7, 14, and 28 post-transplantation. Luminal obliteration was evaluated by hematoxylin-eosin staining and Picrosirius red staining. Immune cell infiltration and characteristics, and secretion of interleukin-10 and transforming growth factor-β1 were accessed by immunohistochemistry. Cytokines and transforming growth factor-β1 were measured using the Luminex assay (Bio-Rad, Hercules, Calif)., Results: The results revealed that intraperitoneal injection of rapamycin for 14 days after tracheal transplantation significantly reduced luminal obliteration on day 28 when compared with the dimethyl sulfoxide control group (97.78% ± 3.63% vs 3.02% ± 2.14%, P < .001). Rapamycin treatment markedly induced regulatory B lymphocytes (B220(+)IgM(+)IgG(-)IL-10(+)TGF-β1(+)) cells when compared with dimethyl sulfoxide controls. Rapamycin treatment inhibited interleukin-1β, 6, 13, and 17 on days 7 and 14. Rapamycin also greatly increased interleukin-10 and transforming growth factor-β1 production in B cells and regulatory T lymphocytes infiltration on day 28., Conclusions: Mammalian target of rapamycin inhibition decreases the development of bronchiolitis obliterans via inhibition of proinflammatory cytokines and increasing regulatory B lymphocytes cell infiltration, which subsequently produces anti-inflammatory cytokines and upregulates regulatory T lymphocyte cells., (Published by Elsevier Inc.)

Objective: Ex vivo lung perfusion has been successful in the assessment of marginal donor lungs, including donation after cardiac death (DCD) donor lungs. Ex vivo lung perfusion also represents a unique platform for targeted drug delivery. We sought to determine whether ischemia-reperfusion injury would be decreased after transplantation of DCD donor lungs subjected to prolonged cold preservation and treated with an adenosine A2A receptor agonist during ex vivo lung perfusion., Methods: Porcine DCD donor lungs were preserved at 4°C for 12 hours and underwent ex vivo lung perfusion for 4 hours. Left lungs were then transplanted and reperfused for 4 hours. Three groups (n = 4/group) were randomized according to treatment with the adenosine A2A receptor agonist ATL-1223 or the dimethyl sulfoxide vehicle: Infusion of dimethyl sulfoxide during ex vivo lung perfusion and reperfusion (DMSO), infusion of ATL-1223 during ex vivo lung perfusion and dimethyl sulfoxide during reperfusion (ATL-E), and infusion of ATL-1223 during ex vivo lung perfusion and reperfusion (ATL-E/R). Final Pao2/Fio2 ratios (arterial oxygen partial pressure/fraction of inspired oxygen) were determined from samples obtained from the left superior and inferior pulmonary veins., Results: Final Pao2/Fio2 ratios in the ATL-E/R group (430.1 ± 26.4 mm Hg) were similar to final Pao2/Fio2 ratios in the ATL-E group (413.6 ± 18.8 mm Hg), but both treated groups had significantly higher final Pao2/Fio2 ratios compared with the dimethyl sulfoxide group (84.8 ± 17.7 mm Hg). Low oxygenation gradients during ex vivo lung perfusion did not preclude superior oxygenation capacity during reperfusion., Conclusions: After prolonged cold preservation, treatment of DCD donor lungs with an adenosine A2A receptor agonist during ex vivo lung perfusion enabled Pao2/Fio2 ratios greater than 400 mm Hg after transplantation in a preclinical porcine model. Pulmonary function during ex vivo lung perfusion was not predictive of outcomes after transplantation., (Copyright © 2016 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.)

Background: Several single-center studies have reported excellent outcomes with minimally invasive aortic valve replacement (mini-AVR). Although criticized as requiring more operative time and complexity, mini-AVR is increasingly performed. We compared contemporary outcomes and cost of mini-AVR versus conventional AVR in a multi-institutional regional cohort. We hypothesized that mini-AVR provides equivalent outcomes to conventional AVR without increased cost., Methods: Patient records for primary isolated AVR (2011-2013) were extracted from a regional, multi-institutional Society of Thoracic Surgeons database and stratified by conventional versus mini-AVR, performed by either partial sternotomy or right thoracotomy. To compare similar patients, a 1:1 propensity-matched cohort was performed after adjusting for surgeon; operative year; and Society of Thoracic Surgeons risk score, including age and risk factors (n = 289 in each group). Differences in outcomes and cost were analyzed., Results: A total of 1341 patients underwent primary isolated AVR, of which 442 (33%) underwent mini-AVR at 17 hospitals. Mortality, stroke, renal failure, and other major complications were equivalent between groups. Mini-AVR was associated with decreased ventilator time (5 vs 6 hours; P = .04) and decreased blood product transfusion (25% vs 32%; P = .04). A greater percentage of mini-AVR patients were discharged within 4 days of the operation (15.2% vs 4.8%; P < .001). Consequently, total hospital costs were lower in the mini-AVR group ($36,348 vs $38,239; P = .02)., Conclusions: Mortality and morbidity outcomes of mini-AVR are equivalent to conventional AVR. Mini-AVR is associated with decreased ventilator time, blood product use, early discharge, and reduced total hospital cost. In contemporary clinical practice, mini-AVR is safe and cost-effective., (Copyright © 2015 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.)

Objectives: The Cardiothoracic Surgical Trials Network recently reported no difference in the primary end point of left ventricular end-systolic volume index at 1 year postsurgery in patients randomized to repair (n = 126) or replacement (n = 125) for severe ischemic mitral regurgitation. However, patients undergoing repair experienced significantly more recurrent mitral regurgitation than patients undergoing replacement (32.6% vs 2.3%). We examined whether baseline echocardiographic and clinical characteristics could identify those who will develop moderate/severe recurrent mitral regurgitation or die., Methods: Our analysis includes 116 patients who were randomized to and received mitral valve repair. Logistic regression was used to estimate a model-based probability of recurrence or death from baseline factors. Receiver operating characteristic curves were constructed from these estimated probabilities to determine classification cut-points maximizing accuracy of prediction based on sensitivity and specificity., Results: Of the 116 patients, 6 received a replacement before leaving the operating room; all other patients had mild or less mitral regurgitation on intraoperative echocardiogram after repair. During the 2-year follow-up period, 76 patients developed moderate/severe mitral regurgitation or died (53 mitral regurgitation recurrences, 13 mitral regurgitation recurrences and death, and 10 deaths). The mechanism for recurrent mitral regurgitation was largely mitral valve leaflet tethering. Our model (including age, body mass index, sex, race, effective regurgitant orifice area, basal aneurysm/dyskinesis, New York Heart Association class, history of coronary artery bypass grafting, percutaneous coronary intervention, or ventricular arrhythmias) yielded an area under the receiver operating characteristic curve of 0.82., Conclusions: The model demonstrated good discrimination in identifying patients who will survive 2 years without recurrent mitral regurgitation after mitral valve repair. Although our results require validation, they offer a clinically relevant risk score for selection of surgical candidates for this procedure., (Copyright © 2015 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.)

Objectives: Cardiothoracic surgical leadership recently challenged the surgical community to achieve an operative mortality rate of 1.0% for the performance of isolated coronary artery bypass grafting (CABG). The possibility of achieving this goal remains unknown due to the increasing number of high-risk patients being referred for CABG. The purpose of our study was to identify a patient population in which this operative mortality goal is achievable relative to the estimated operative risk., Methods: Patient records from a multi-institution (17 centers) Society of Thoracic Surgeons (STS) database for primary, isolated CABG operations (2001-2012) were analyzed. Multiple logistic regression modeling with spline functions for calculated STS predicted risk of mortality (PROM) was used to rigorously assess the relationship between estimated patient risk and operative mortality, adjusted for operative year and surgeon volume., Results: A total of 34,416 patients (average patient age, 63.9 ± 10.7 years; 27% [n = 9190] women) incurred an operative mortality rate of 1.87%. Median STS predicted risk of mortality was 1.06% (interquartile range, 0.60%-2.13%) and median surgeon CABG volume was 544 (interquartile range, 303-930) operations over the study period. After risk adjustment for the confounding influence of surgeon volume and operative year, the association between STS PROM and operative mortality was highly significant (P < .0001). More importantly, the adjusted spline function revealed that an STS PROM threshold value of 1.27% correlated with a 1.0% probability of death, accounting for 57.3% (n = 19,720) of the total study population. Further, the STS PROM demonstrated a limited predictive capacity for operative mortality for STS PROM > 25% as observed to expected mortality began to diverge., Conclusions: Achieving the goal of 1.0% operative mortality for primary, isolated CABG is feasible in appropriately selected patients in the modern surgical era. However, this goal may be achieved in only 60% of CABG patients without other improvements in processes of care. Calculated STS PROM can be used to strongly identify patients with estimated mortality risk <1.27% to achieve this goal, but it appears limited in its predictive capacity for those patients with estimated risk >25.0%. These data provide a foundation for further study to determine if 1.0% mortality for CABG is achievable nationwide., (Copyright © 2014. Published by Elsevier Inc.)

Objectives: Mitral valve (MV) repair rates have lagged despite reported superior outcomes in patients with mitral regurgitation. The purpose of the present study was to evaluate the relationship between procedure volume and the propensity for MV repair in a multi-institution, regional patient cohort., Methods: Society of Thoracic Surgeons-certified patient records of those undergoing MV repair or MV replacement (MVR) for moderate or severe mitral regurgitation were evaluated from 17 different centers (2001-2011). The relationship between the annual hospital and surgeon volume and the propensity for MV repair over MVR was analyzed using multivariable, mortality risk-adjusted models with restricted cubic splines., Results: A total of 4194 patients were evaluated (MV repair, 2516; MVR, 1662). The median annual mitral procedure volume was 54 operations for hospitals and 13 operations for surgeons. The overall MV repair rate was 60%, with significant variations among hospitals (range, 35%-70%) and surgeons (range, 0%-90%). The MVR patients presented with higher Society of Thoracic Surgeons Predicted Risk of Mortality scores (6% vs 2%, P < .001). After adjustment for Predicted Risk of Mortality score, both annual hospital (P = .04) and surgeon (P < .0001) procedure volume were associated with the probability of MV repair. The likelihood for MV repair correlated with an operative volume of ≥ 20 procedures annually. Among surgeons and hospitals performing ≥ 20 mitral operations annually, MV repair rates were greater (73% vs 26% and 62% vs 37%, respectively, P < .001 for both)., Conclusions: Significant variation in the performance of MV repair over MVR for mitral regurgitation persists in the modern surgical era. Average annual surgeon volume was more significantly associated with MV repair rate than institutional volume, with an increased likelihood for performance of MV repair among surgeons performing >20 procedures annually. In the upcoming era of percutaneous MV repair, surgeon volume and expertise as a gatekeeper should dictate access to this technology and the decisions for the best approach to MV repair., (Copyright © 2014 The American Association for Thoracic Surgery. Published by Mosby, Inc. All rights reserved.)

Objective: Bone marrow-derived mesenchymal stem cells (MSCs) have shown therapeutic potential in acute lung injury. Recently, placenta-derived human mesenchymal stem cells (PMSCs) have shown similarities with bone marrow-derived MSCs in terms of regenerative capabilities and immunogenicity. This study investigates the hypothesis that treatment with PMSCs reduces the development of bronchiolitis obliterans in a murine heterotopic tracheal transplant model., Methods: A murine heterotopic tracheal transplant model was used to study the continuum from acute to chronic rejection. In the treatment groups, PMSCs or PMSC-conditioned medium (PMSCCM) were injected either locally or intratracheally into the allograft. Phosphate-buffered saline (PBS) or blank medium was injected in the control groups. Tracheal luminal obliteration was assessed on sections stained with hematoxylin and eosin. Infiltration of inflammatory and immune cells and epithelial progenitor cells was assessed using immunohistochemistry and densitometric analysis., Results: Compared with injection of PBS, local injection of PMSCs significantly reduced luminal obliteration at 28 days after transplantation (P = .015). Intratracheal injection of PMSCs showed similar results to local injection of PMSCs compared with injection of PBS and blank medium (P = .022). Tracheas treated with PMSC/PMSCCM showed protection against the loss of epithelium on day 14, with an increase in P63+CK14+ epithelial progenitor cells and Foxp3+ regulatory T cells. In addition, injection of PMSCs and PMSCCM significantly reduced the number of neutrophils and CD3+ T cells on day 14., Conclusions: This study demonstrates that treatment with PMSCs is protective against the development of bronchiolitis obliterans in an heterotopic tracheal transplant model. These results indicate that PMSCs could provide a novel therapeutic option to reduce chronic rejection after lung transplant., (Published by Mosby, Inc.)

Objective: The current Surgical Care Improvement Project (SCIP) measure for controlled postoperative 6-am glycemic control after cardiac surgery identifies those with blood glucose levels of ≤200 mg/dL. The purpose of the present study was to evaluate the effect of achieving this SCIP measure on risk-adjusted postoperative cardiac surgical outcomes., Methods: The data were analyzed for all cardiac surgery patients from a single institution (June 2010 to August 2012). The patients were categorized by the postoperative 6-am glucose levels into 2 SCIP measure cohorts: SCIP (≤200 mg/dL) versus non-SCIP (>200 mg/dL). Propensity-matched cohort comparisons and multiple regression analyses assessed the associations between SCIP measure compliance and the risk-adjusted outcomes., Results: Of 1703 patients, 1527 (90%) achieved SCIP measure glycemic control. Preoperative diabetes was more common among the non-SCIP patients (P < .001); the median Society of Thoracic Surgeons-predicted mortality (P = .14) was similar between the 2 groups. No significant differences were observed in major morbidity, mortality, or resource usage among the propensity-matched cohorts. After adjustment for Society of Thoracic Surgeons-predicted risk, non-SCIP status was not associated with increased mortality (P = .44), composite major morbidity (P = .16), major sternal complications (P = .68), total intensive care unit duration (P = .70), or postoperative length of stay (P = .27). Similar risk-adjusted results were estimated for patients undergoing isolated coronary artery bypass grafting., Conclusions: Achieving the SCIP measure for controlled postoperative 6-am blood glucose levels ≤200 mg/dL after cardiac surgery was not associated with improved risk-adjusted mortality, morbidity, or hospital resource usage. These data suggest that this metric might not be a valid measure of postoperative cardiac surgical quality., (Copyright © 2014 The American Association for Thoracic Surgery. Published by Mosby, Inc. All rights reserved.)

Objective: This study assessed the impact of pulmonary hypertension (PH) on morbidity and mortality after the most common cardiac operations and evaluated the accuracy of the Society of Thoracic Surgeons (STS) risk model for patients with PH., Methods: At a single center between 1994 and 2010, all adult cardiac operations performed with recorded preoperative mean pulmonary arterial pressure (MPAP) and STS predicted mortality were reviewed. MPAP was defined as normal (<25 mm Hg) or as mild (25-34 mm Hg), moderate (35-44 mm Hg), or severe (≥ 45 mm Hg) PH. Multivariate analysis was performed to elucidate the contribution of PH to morbidity and mortality., Results: In all, 3343 patient records were reviewed. Coronary artery bypass grafting (CABG) was the most common procedure (67.5%), followed by aortic valve replacement (24.9%) and mitral valve procedures (6.3%). Postoperative complications and mortality increased with increasing MPAP. Multivariable analysis found that both moderate (odds ratio, 7.17; P < .001) and severe (odds ratio, 13.73; P < .001) PH were significantly associated with increased mortality, even after accounting for STS risk. A subset analysis of isolated CABG cases revealed markedly increased mortality for all categories of PH (mild odds ratio, 1.99; moderate odds ratio, 11.5; severe odds ratio, 38.9; P < .001)., Conclusions: Morbidity and mortality were independently associated with PH. Observed mortality was significantly higher than predicted by the STS model for patients with moderate and severe PH, particularly in isolated CABG. Addition of PH to the STS risk model should be considered, or alternative tools should be used to assess risk in these patients., (Copyright © 2013 The American Association for Thoracic Surgery. Published by Mosby, Inc. All rights reserved.)