Early immune responses are important in shaping long-term outcomes of human lung transplants. To examine the role of early immune responses in lung rejection and acceptance we developed a method to retransplant mouse lungs. Retransplantation into T cell-deficient hosts showed that for lungs and hearts alloimmune responses occurring within 72 hours of transplantation are reversible. In contrast to hearts, a 72-hour period of immunosuppression with costimulation blockade in primary allogeneic recipients suffices to prevent rejection of lungs upon retransplantation into untreated allogeneic hosts. Long-term lung acceptance is associated with induction of bronchus-associated lymphoid tissue, where Foxp3+ cells accumulate and recipient T cells interact with CD11c+ dendritic cells. Acceptance of retransplanted lung allografts is abrogated by treatment of immunosuppressed primary recipients with anti-CD25 antibodies. Thus, events contributing to lung transplant acceptance are established early in the graft and induction of bronchus-associated lymphoid tissue can be associated with an immune quiescent state.

Background-Opioid dependence, misuse, and abuse in the United States continue to rise. Prior studies indicate an important risk factor for persistent opioid use includes elective surgical procedures, though the probability following thoracic procedures remains unknown. We analyzed the incidence and factors associated with new persistent opioid use after lung resection Methods-We evaluated data from opioid-naïve cancer patients undergoing lung resection between 2010 and 2014 using insurance claims from the Truven Health MarketScan Databases. New persistent opioid usage was defined as continued opioid prescription fills between 90 and 180 days following surgery. Variables with p<0.10 by univariate analysis were included in a multivariable logistic regression performed for risk adjustment. Multivariable results were each reported with odds ratio (OR) and confidence interval (CI) Results-3,026 patients (44.8% male; 55.2% female) were identified as opioid-naïve undergoing lung resection. Mean age was 64 ± 11 years and mean postoperative length of stay (LOS) was 5.2±3.3 days. 6.5% underwent neoadjuvant therapy, while 21.7% underwent adjuvant therapy. Among opioid-naïve patients, 14% continued to fill opioid prescriptions following lung resection. Multivariable analysis showed that age ≤ 64 (OR 1.28 [CI 1.03-1.59], p=0.028), male sex (1.40 [1.13-1.73], p=0.002), postoperative LOS (1.32 [1.05-1.65], p=0.016), thoracotomy (1.58 [1.24-2.02], p<0.001), and adjuvant therapy (2.19 [1.75-2.75], p<0.001) were independent risk factors for persistent opioid usage Conclusions-The greatest risk factors for persistent opioid use (14%) following lung resection were adjuvant therapy and thoracotomy. Future studies should focus on reducing excess prescribing, perioperative patient education, and safe opioid disposal.

Background. New persistent opioid use occurs in 3% to 14% of patients after elective surgery, but is poorly described after cardiothoracic surgery. We examined the association of prescription size with new persistent opioid use after cardiothoracic surgery. Methods. Opioid-naive Medicare patients undergoing cardiothoracic surgery between 2009 and 2015 were identified. Patients who filled an opioid prescription between 30 days before surgery and 14 days after discharge and with continuous Medicare enrollment 12 months before and 6 months after surgery were selected (n [ 24,549). New persistent use was defined as continued prescription fills 91 to 180 days after surgery. Prescription size was reported in oral morphine equivalents. Multivariable regression was performed for risk adjustment, and new persistent use rate was estimated. Results. Patient age was 71 ± 8 years, 9222 (38%) were female, and 20,898 (85%) were white. Overall new persistent use was 12.8% (3153 of 24,549), and declined yearly from 17% in 2009 to 7.1% in 2015 (P < .001). Prescription size, preoperative prescription fills, black race, gastrointestinal complications, disability status, open lung resection, dual eligibility (Medicare and Medicaid), drug and substance abuse, female sex, tobacco use, high comorbidity, pain disorders, longer hospital stay, and younger age were associated with new persistent use. Adjusted new persistent use was 19.6% (95% confidence interval, 18.7% to 20.4%) among patients prescribed more than 450 oral morphine equivalents, compared with 10.4% (95% confidence interval, 9.9% to 10.8%) among those prescribed 200 oral morphine equivalents or less (P < .001). Conclusions. Size and timing of perioperative opioid prescriptions were the strongest predictors of new persistent opioid use after cardiothoracic surgery. Modifiable risk factors such as prescription size should be targeted to reduce new persistent use.

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Background. The benefit of adjuvant treatment for esophageal cancer patients with positive lymph nodes after induction therapy and esophagectomy is uncertain. This in-depth multicenter study assessed the benefit of adjuvant therapy in this population.Methods. A retrospective cohort study from 9 institutions included patients who received neoadjuvant treatment, underwent esophagectomy from 2000 to 2014, and had positive lymph nodes on pathology. Factors associated with administration of adjuvant therapy were assessed using multilevel random-intercept modeling to account for institutional variation in practice. Kaplan-Meier analyses were performed based on adjuvant treatment status. Variables associated with survival were identified using Cox proportional hazards modeling.Results. The study analyzed 1082 patients with node-positive cancer after induction therapy and esophagectomy: 209 (19.3%) received adjuvant therapy and 873 (80.7%) did not. Administration of adjuvant treatment varied significantly from 3.2% to 50.0% between sites (P < .001). Accounting for institution effect, factors associated with administration of adjuvant therapy included clinically positive and negative prognostic characteristics: younger age, higher pathologic stage, pathologic grade, no neoadjuvant radiotherapy nonsmoking status, and absence of postoperative infection. Kaplan-Meier analysis showed patients receiving adjuvant therapy had a longer median survival of 2.6 years vs 2.3 years (P [ .02). Cox modeling identified adjuvant treatment as independently associated with improved survival, with a 24% reduction in mortality (hazard ratio, 0.76; P [ .005).Conclusions. Adjuvant therapy was associated with improved overall survival. Therefore, consideration should be given to administration of adjuvant therapy to esophageal cancer patients who have persistent nodepositive disease after induction therapy and esophagectomy and are able to tolerate additional treatment.