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The article discusses the American College of Chest Physicians Evidence-Based Clinical Practice Guidelines update that addresses patients with non-small cell lung cancer including the Pancoast tumors, T4 NO, 1 MO tumors and additional nodules in the same lobe(T3). Topics mentioned include the use of the MEDLINE computerized database, the use of multimodality approach in patients with a Pancoast tumor and T4 tumors with no mediastinal node involvement are treated by surgical resection.

Background: The University HealthSystem Consortium (UHC) mortality risk adjustment models are increasingly being used as benchmarks for quality assessment. But these administrative database models may include postoperative complications in their adjustments for preoperative risk. The purpose of this study was to compare the performance of the UHC with the Society of Thoracic Surgeons (STS) risk-adjusted mortality models for adult cardiac surgery and evaluate the contribution of postoperative complications on model performance. Study Design: We identified adult cardiac surgery patients with mortality risk estimates in both the UHC and Society of Thoracic Surgeons databases. We compared the predictive performance and calibration of estimates from both models. We then reestimated both models using only patients without any postoperative complications to determine the relative contribution of adjustments for postoperative events on model performance. Results: In the study population of 2,171 patients, the UHC model explained more variability (27% versus 13%, p < 0.001) and achieved better discrimination (C statistic = 0.88 versus 0.81, p < 0.001). But when applied in the population of patients without complications, the UHC model performance declined severely. The C statistic decreased from 0.88 to 0.49, a level of discrimination equivalent to random chance. The discrimination of the Society of Thoracic Surgeons model was unchanged (C statistic of 0.79 versus 0.81). Conclusions: Although the UHC model demonstrated better performance in the total study population, this difference in performance reflects adjustments for conditions that are postoperative complications. The current UHC models should not be used for quality benchmarks. [Copyright &y& Elsevier]

Vascular immunotargeting may facilitate the rapid and specific delivery of therapeutic agents to endothelial cells. We investigated whether targeting of an antioxidant enzyme, catalase, to the pulmonary endothelium alleviates oxidative stress in an in vivo model of lung transplantation. Intravenously injected enzymes, conjugated with an antibody to platelet-endothelial cell adhesion molecule-1, accumulate in the pulmonary vasculature and retain their activity during prolonged cold storage and transplantation. Immunotargeting of catalase to donor rats augments the antioxidant capacity of the pulmonary endothelium, reduces oxidative stress, ameliorates ischemia-reperfusion injury, prolongs the acceptable cold ischemia period of lung grafts, and improves the function of transplanted lung grafts. These findings validate the therapeutic potential of vascular immunotargeting as a drug delivery strategy to reduce endothelial injury. Potential applications of this strategy include improving the outcome of clinical lung transplantation and treating a wide variety of endothelial disorders. [ABSTRACT FROM AUTHOR]

BACKGROUND: The preoperative period is an important target for interventions (eg Surgical Prehabilitation and Readiness [SPAR]) that can improve postoperative outcomes for older patients with comorbidities. STUDY DESIGN: To determine whether a preoperative multidisciplinary prehabilitation program (SPAR) reduces postoperative 30-day mortality and the need for non-home discharge in high-risk surgical patients, surgical patients enrolled in a prehabilitation program targeting physical activity, pulmonary function, nutrition, and mindfulness were compared with historical control patients from 1 institution's American College of Surgeons (ACS) NSQIP database. SPAR patients were propensity score-matched 1:3 to pre-SPAR NSQIP patients, and their outcomes were compared. The ACS NSQIP Surgical Risk Calculator was used to compare observed-to-expected ratios for postoperative outcomes. RESULTS: A total of 246 patients were enrolled in SPAR. A 6-month compliance audit revealed that overall patient adherence to the SPAR program was 89%. At the time of analysis, 118 SPAR patients underwent surgery with 30 days of follow-up. Compared with pre-SPAR NSQIP patients (n = 4,028), SPAR patients were significantly older with worse functional status and more comorbidities. Compared with propensity score-matched pre-SPAR NSQIP patients, SPAR patients had significantly decreased 30-day mortality (0% vs 4.1%, p = 0.036) and decreased need for discharge to postacute care facilities (6.5% vs 15.9%, p = 0.014). Similarly, SPAR patients exhibited decreased observed 30-day mortality (observed-to-expected ratio 0.41) and need for discharge to a facility (observed-to-expected ratio 0.56) compared with their expected outcomes using the ACS NSQIP Surgical Risk Calculator. CONCLUSIONS: The SPAR program is safe and feasible and may reduce postoperative mortality and the need for discharge to postacute care facilities in high-risk surgical patients. [ABSTRACT FROM AUTHOR]

Background This guideline updates the second edition and addresses patients with particular forms of non-small cell lung cancer that require special considerations, including Pancoast tumors, T4 N0,1 M0 tumors, additional nodules in the same lobe (T3), ipsilateral different lobe (T4) or contralateral lung (M1a), synchronous and metachronous second primary lung cancers, solitary brain and adrenal metastases, and chest wall involvement. Methods The nature of these special clinical cases is such that in most cases, meta-analyses or large prospective studies of patients are not available. To ensure that these guidelines were supported by the most current data available, publications appropriate to the topics covered in this article were obtained by performing a literature search of the MEDLINE computerized database. Where possible, we also reference other consensus opinion statements. Recommendations were developed by the writing committee, graded by a standardized method, and reviewed by all members of the Lung Cancer Guidelines panel prior to approval by the Thoracic Oncology NetWork, Guidelines Oversight Committee, and the Board of Regents of the American College of Chest Physicians. Results In patients with a Pancoast tumor, a multimodality approach appears to be optimal, involving chemoradiotherapy and surgical resection, provided that appropriate staging has been carried out. Carefully selected patients with central T4 tumors that do not have mediastinal node involvement are uncommon, but surgical resection appears to be beneficial as part of their treatment rather than definitive chemoradiotherapy alone. Patients with lung cancer and an additional malignant nodule are difficult to categorize, and the current stage classification rules are ambiguous. Such patients should be evaluated by an experienced multidisciplinary team to determine whether the additional lesion represents a second primary lung cancer or an additional tumor nodule corresponding to the dominant cancer. Highly selected patients with a solitary focus of metastatic disease in the brain or adrenal gland appear to benefit from resection or stereotactic radiosurgery. This is particularly true in patients with a long disease-free interval. Finally, in patients with chest wall involvement, provided that the tumor can be completely resected and N2 nodal disease is absent, primary surgical resection should be considered. Conclusions Carefully selected patients with more uncommon presentations of lung cancer may benefit from an aggressive surgical approach. [ABSTRACT FROM AUTHOR]

Background: This guideline updates the second edition and addresses patients with particular forms of non-small cell lung cancer that require special considerations, including Pancoast tumors, T4 N0,1 M0 tumors, additional nodules in the same lobe (T3), ipsilateral different lobe (T4) or contralateral lung (M1a), synchronous and metachronous second primary lung cancers, solitary brain and adrenal metastases, and chest wall involvement.Methods: The nature of these special clinical cases is such that in most cases, meta-analyses or large prospective studies of patients are not available. To ensure that these guidelines were supported by the most current data available, publications appropriate to the topics covered in this article were obtained by performing a literature search of the MEDLINE computerized database. Where possible, we also reference other consensus opinion statements. Recommendations were developed by the writing committee, graded by a standardized method, and reviewed by all members of the Lung Cancer Guidelines panel prior to approval by the Thoracic Oncology NetWork, Guidelines Oversight Committee, and the Board of Regents of the American College of Chest Physicians.Results: In patients with a Pancoast tumor, a multimodality approach appears to be optimal, involving chemoradiotherapy and surgical resection, provided that appropriate staging has been carried out. Carefully selected patients with central T4 tumors that do not have mediastinal node involvement are uncommon, but surgical resection appears to be beneficial as part of their treatment rather than definitive chemoradiotherapy alone. Patients with lung cancer and an additional malignant nodule are difficult to categorize, and the current stage classification rules are ambiguous. Such patients should be evaluated by an experienced multidisciplinary team to determine whether the additional lesion represents a second primary lung cancer or an additional tumor nodule corresponding to the dominant cancer. Highly selected patients with a solitary focus of metastatic disease in the brain or adrenal gland appear to benefit from resection or stereotactic radiosurgery. This is particularly true in patients with a long disease-free interval. Finally, in patients with chest wall involvement, provided that the tumor can be completely resected and N2 nodal disease is absent, primary surgical resection should be considered.Conclusions: Carefully selected patients with more uncommon presentations of lung cancer may benefit from an aggressive surgical approach. [ABSTRACT FROM AUTHOR]

Background: Recent studies have suggested that more frequent post-operative surveillance imaging via computed tomography (CT) following lung cancer resection may not improve outcomes. We sought to validate these findings using a uniquely compiled dataset from the Veterans Health Administration, the largest integrated healthcare system in the United States.Methods: We performed a retrospective cohort study of Veterans with pathologic stage I non-small cell lung cancer (NSCLC) receiving surgery (2006-2016). We assessed the relationship between surveillance frequency (chest CT scans within 2 years after surgery) and recurrence-free survival and overall survival.Results: Among 6171 patients, 3047 (49.4%) and 3124 (50.6%) underwent low-frequency (<2 scans/year; every 6-12 months) and high-frequency (≥2 scans/year; every 3-6 months) surveillance, respectively. Factors associated with high-frequency surveillance included being a former smoker (vs. current, adjusted odds ratio [aOR] 1.18, 95% CI 1.05-1.33), receiving a wedge resection (vs. lobectomy, aOR 1.21, 95% CI 1.05-1.39), and having follow-up with an oncologist (aOR 1.58, 95% CI 1.42-1.77), whereas African American race was associated with low-frequency surveillance (vs. White race, aOR 0.64, 95% CI 0.54-0.75). With a median (IQR) follow-up of 7.3 (3.4-12.5) years, recurrence was detected in 1360 (22.0%) patients. High-frequency surveillance was not associated with longer recurrence-free survival (adjusted hazard ratio [aHR], 0.93; 95% CI, 0.83-1.04, p = 0.22) or overall survival (aHR, 1.04; 95% CI, 0.96-1.12, p = 0.35).Conclusions: We found that high-frequency surveillance does not improve outcomes in surgically treated stage I NSCLC. Future lung cancer treatment guidelines should consider less frequent surveillance imaging in patients with stage I disease. [ABSTRACT FROM AUTHOR]

Introduction: The impact of induction chemoradiation therapy on esophageal cancer survival is controversial. The purpose of this study was to evaluate the comparative effectiveness of induction chemoradiation therapy on perioperative outcomes and long-term survival. Methods: A retrospective study of 347 consecutive patients undergoing esophagectomies between 1999-2010 at a high-volume institution was performed. Comparison cohorts were patients treated with induction chemoradiation followed by surgery and surgery only patients. Follow-up was complete in 97% of patients. Propensity score analysis controlled for potential allocation-to-treatment bias and created matched groups. Cox proportional hazards regression evaluated differences in survival. Multivariable logistic regression and the generalized linear model determined differences in perioperative outcomes. Results: The majority (86%, 298/347) of patients had pretreatment endoscopic ultrasonography and PET imaging. 170 (49%) patients received induction chemoradiation therapy and 44 (26%) achieved pathologic complete response. The propensity score model performed well to create matched groups (c-index=0.88). The Cox proportional hazards regression analysis demonstrated a survival difference by treatment group (p = 0.04). Controlling for treatment bias, clinical stage and comorbidity, surgery only patients had an increased risk of five-year mortality (HR = 2.6, CI: 1.05-6.50) compared to patients treated with induction therapy. Perioperative outcomes were similar between groups (Table 1). Conclusions: In a contemporary, propensity-matched cohort, induction chemoradiation therapy for appropriate esophageal cancer patients improves long-term survival without significant increases in perioperative morbidity or mortality. [Copyright &y& Elsevier]

With advancements in basic science and clinical medicine, lung transplantation (LT) has evolved rapidly over the last three decades. However, it is unclear if significant regional variations exist in long-term outcomes after LT. To investigate potential differences, we performed a retrospective, comparative cohort analysis of adult patients undergoing deceased donor single or double LT in North America (NA) or Europe between January 2006 and December 2016. Data up to April 2019 were abstracted from the International Society for Heart and Lung Transplantation (ISHLT) Thoracic Organ Registry. We compared overall survival (OS) between North American and European LT centers in a propensity score matched analysis. In 3,115 well-matched pairs, though 30-day survival was similar between groups (NA 96.2% vs Europe 95.4%, p = 0.116), 5-year survival was significantly higher in European patients (NA 60.1% vs Europe 70.3%, p < 0.001). This survival difference persisted in a sensitivity analysis excluding Canadian patients. Prior observations suggest that these disparities are at least partly related to better access to care via universal healthcare models prevalent in Europe. Future studies are warranted to confirm our findings and explore other causal mechanisms. It is likely that potential solutions will require concerted efforts from healthcare providers and policymakers. [ABSTRACT FROM AUTHOR]

Background: Guidelines for follow-up after locoregional breast cancer treatment recommend imaging for distant metastases only in the presence of patient signs and/or symptoms. However, guidelines have not been updated to reflect advances in imaging, systemic therapy, or the understanding of biological subtype. We assessed the association between mode of distant recurrence detection and survival.Methods: In this observational study, a stage-stratified random sample of women with stage II-III breast cancer in 2006-2007 and followed through 2016 was selected, including up to 10 women from each of 1217 Commission on Cancer facilities (n = 10 076). The explanatory variable was mode of recurrence detection (asymptomatic imaging vs signs and/or symptoms). The outcome was time from initial cancer diagnosis to death. Registrars abstracted scan type, intent (cancer-related vs not, asymptomatic surveillance vs not), and recurrence. Data were merged with each patient's National Cancer Database record.Results: Surveillance imaging detected 23.3% (284 of 1220) of distant recurrences (76.7%, 936 of 1220 by signs and/or symptoms). Based on propensity-weighted multivariable Cox proportional hazards models, patients with asymptomatic imaging compared with sign and/or symptom detected recurrences had a lower risk of death if estrogen receptor (ER) and progesterone receptor (PR) negative, HER2 negative (triple negative; hazard ratio [HR] = 0.73, 95% confidence interval [CI] = 0.54 to 0.99), or HER2 positive (HR = 0.51, 95% CI = 0.33 to 0.80). No association was observed for ER- or PR-positive, HER2-negative (HR = 1.14, 95% CI = 0.91 to 1.44) cancers.Conclusions: Recurrence detection by asymptomatic imaging compared with signs and/or symptoms was associated with lower risk of death for triple-negative and HER2-positive, but not ER- or PR-positive, HER2-negative cancers. A randomized trial is warranted to evaluate imaging surveillance for metastases results in these subgroups. [ABSTRACT FROM AUTHOR]

Background: Prior studies in the civilian population have reported racial disparities in lung cancer outcomes following surgical treatment, including inferior quality of care and worse survival. It is unclear if racial disparities exist in the Veterans Health Administration (VHA), the largest integrated health care system in the United States.Research Question: Do racial disparities affect early-stage non-small cell lung cancer (NSCLC) outcomes following surgical treatment within the VHA?Study Design and Methods: This retrospective cohort study was conducted in veterans with clinical stage I NSCLC undergoing surgical treatment in the VHA system. Demographic characteristics, access to care, surgical quality measures, and short- and long-term oncologic outcomes between White and Black veterans were evaluated.Results: From 2006 to 2016, a total of 18,800 veterans with clinical stage I NSCLC were included. The rates of definitive surgical treatment were similar between Black (57.3%) and White (58.1%) veterans (P = .42). The final study cohort included 9,842 patients receiving surgical treatment, of whom 8,356 (84.9%) were White and 1,486 (15.1%) were Black. Black patients were younger and more likely to smoke, although comorbidities were similar between the two groups. Black patients were somewhat less likely to receive adequate lymph node sampling (30.6% vs 33.3%; P = .050); however, other access-to-care metrics and surgical quality measures, including rates of anatomic lobectomy (71.9% vs 69.4%; P = .189) and positive margins (3.2% vs 3.1%; P = .955), were similar between the two groups. Although Black veterans were less likely to experience major postoperative complications, there was no difference in 30-day readmission, 30-day mortality, or disease-free survival between the two groups. Black patients had significantly better risk-adjusted overall survival (hazard ratio, 0.802; 95% CI, 0.729-0.883; P < .001).Interpretation: Among veterans with NSCLC undergoing surgical treatment through the VHA, Black patients received comparable care with equivalent if not superior outcomes compared with White patients. [ABSTRACT FROM AUTHOR]

Background Persistent postsurgical pain (PPSP) is a common complication that impacts quality of life, often necessitating long-term opioid treatment. Certain neurocognitive factors, including reduced performance on cognitive flexibility tasks, are associated with increased risk of PPSP. We examine the perceptions of surgical patients and clinicians with regard to perioperative pain management activities and needs; patient acceptance and use of a perioperative neurocognitive training intervention; and implementation feasibility. Methods We conducted both individual and focus group interviews with patients undergoing thoracic surgery and clinicians in an academic medical center. The Consolidated Framework for Intervention Research guided the development of interview questions related to the adoption and implementation of a neurocognitive intervention to mitigate PPSP. A thematic analysis was used to analyze the responses. Results Forty patients and 15 clinicians participated. Interviews revealed that there is minimal discussion between clinicians and patients about PPSP. Most participants were receptive to a neurocognitive intervention to prevent PPSP, if evidence demonstrating its effectiveness were available. Potential barriers to neurocognitive training program adoption included fatigue, cognitive overload, lack of familiarity with the technology used for delivering the intervention, and immediate postoperative pain and stress. Implementation facilitators would include patient education about the intervention, incentives for its use, and daily reminders. Conclusion The study identified several guiding principles for addressing patients' and clinicians' barriers to effectively implementing a neurocognitive training intervention to mitigate PPSP after surgery. To ensure the sustainability of neurocognitive interventions for preventing PPSP, such interventions would need to be adapted to meet patients' and clinicians' needs within the perioperative context. [ABSTRACT FROM AUTHOR]

Purpose/Objectives: To test the feasibility of a multidisciplinary, multicomponent, theory-based decision aid.Design: Prospective, one-group repeated measures.Setting: Thoracic surgery clinic in a university hospital cancer center in central Virginia.Sample: 8 dyads, consisting of 16 total participants.Methods: A multidisciplinary, multicomponent smoking cessation intervention incorporated a theory-based decision aid. Enrollment occurred preoperatively; four face-to-face visits and an exit interview were conducted during six months.Main Research Variables: Feasibility was evaluated based on four criteria: recruitment, retention, adherence, and acceptability.Findings: The recruitment rate was 44%, and the retention rate was 100%. Adherence to the intervention and the acceptability of the decision aid were greater for patients than family members. Patients had greater abstinence than family members before surgery and at six months. Exit interview themes included (a) preoperative timing was acceptable and (b) involving household members who smoke was important.Conclusions: Recruiting male patients and their female partners is feasible. Participants liked convenience, autonomy, and a family approach. Family members wanted more control over cessation timing and a more intensive approach to weight and mental health management. Successful dyads worked together to maintain abstinence.Implications for Nursing: Oncology nurses can assess patients' and family members' smoking status, facilitate understanding about specific benefits of smoking cessation and the obstacle posed by household smokers, and make referrals to expert resources. Encouraging smoke-free environments is an important step toward reducing secondhand smoke exposure and promoting cessation. [ABSTRACT FROM AUTHOR]

Background: Smoking at the time of surgical treatment for lung cancer increases the risk for perioperative morbidity and mortality. The prevalence of persistent smoking in the postoperative period and its association with long-term oncologic outcomes are poorly described.Research Question: What is the relationship between persistent smoking and long-term outcomes in early-stage lung cancer after surgical treatment?Study Design and Methods: We performed a retrospective cohort study using a uniquely compiled Veterans Health Administration dataset of patients with clinical stage I non-small cell lung cancer (NSCLC) undergoing surgical treatment between 2006 and 2016. We defined persistent smoking as individuals who continued smoking 1 year after surgery and characterized the relationship between persistent smoking and disease-free survival and overall survival.Results: This study included 7,489 patients undergoing surgical treatment for clinical stage I NSCLC. Of 4,562 patients (60.9%) who were smoking at the time of surgery, 2,648 patients (58.0%) continued to smoke at 1 year after surgery. Among 2,927 patients (39.1%) who were not smoking at the time of surgical treatment, 573 (19.6%) relapsed and were smoking at 1 year after surgery. Persistent smoking at 1 year after surgery was associated with significantly shorter overall survival (adjusted hazard ration [aHR], 1.291; 95% CI, 1.197-1.392; P < .001). However, persistent smoking was not associated with inferior disease-free survival (aHR, 0.989; 95% CI, 0.884-1.106; P = .84).Interpretation: Persistent smoking after surgery for stage I NSCLC is common and is associated with inferior overall survival. Providers should continue to assess smoking habits in the postoperative period given its disproportionate impact on long-term outcomes after potentially curative treatment for early-stage lung cancer. [ABSTRACT FROM AUTHOR]

Pulmonary carcinoid tumorlet (PCT) is defined as small proliferation of neuroendocrine cells that invade the adjacent basement membrane. It is often associated with chronic pulmonary inflammatory processes. However, the characteristics of PCT in end-stage lung diseases remain unclear. We conducted a retrospective cohort study of the explanted lungs after transplantation at our institution between January 1999 and October 2020. Patients who underwent re-transplantation were excluded. Pulmonary carcinoid tumorlet was incidentally discovered in the explanted lungs from 15 patients (1.1%) out of 1367 lung transplants performed during the study period. Nine patients (60.0 %) were women, with a median age of 59 years (IQR: 57-62) at transplant. Underlying pulmonary indications for lung transplantation were chronic obstructive pulmonary disease (9/15, 60.0%), interstitial lung disease (2/15, 13.0%), pulmonary vascular disease (2/15, 13.0%), alpha-1 antitrypsin deficiency (1/15, 7.0%), and bronchiectasis (1/15, 7.0%). Of the patients who underwent bilateral lung transplantation (13/15, 86.7%), PCT was found in the right lung in 10 patients (10/13, 76.9%). Thirteen patients had one lesion, 1 patient had 2 lesions and 1 patient had multiple lesions. Our study shows that PCT is generally uncommon, but when it occurs, it occurs more frequently on the right side and in female patients with end-stage pulmonary disease. Chronic obstructive pulmonary disease may be a predisposing factor for developing PCT. [ABSTRACT FROM AUTHOR]

Background: Combined pulmonary fibrosis and emphysema (CPFE) is recognized as a characteristic syndrome of smoking-related interstitial lung disease that has a worse prognosis than idiopathic pulmonary fibrosis (IPF). However, outcomes after lung transplantation for CPFE have not been reported. The aim of this study is to describe the clinical features and outcomes of CPFE after lung transplantation.Research Question: What are the clinical features and outcomes of CPFE after lung transplantation?Study Design and Methods: This is a single-center retrospective cohort study of patients with CPFE and IPF who underwent lung transplantation at our center between January 2011 and December 2016. We defined CPFE as ≥10% emphysema in the upper lung fields combined with fibrosis on high-resolution CT scan. We characterized the clinical features of patients with CPFE and compared their outcomes after lung transplantation with those with IPF.Results: Twenty-seven of 172 (16%) patients with IPF met criteria for CPFE. Severe pulmonary hypertension was present in 16 of 27 (59%) patients with CPFE. On logistic regression analysis, CPFE was significantly associated with primary graft dysfunction (PGD) grade 3 (OR, 3.14; 95% CI, 1.18-8.37; P = .02). On competing risk regression analysis, CPFE was associated with acute cellular rejection (ACR) grade ≥ A2, and chronic lung allograft dysfunction (CLAD) (hazard ratio [HR], 1.89; 95% CI, 1.10-3.25; P = .02; HR, 1.96; 95% CI, 1.02-3.77; P = .04, respectively). Five-year survival was 79.0% for the CPFE group and 75.4% for the IPF group (log-rank P = .684).Interpretation: After transplantation, patients with CPFE were more likely to develop PGD, ACR, and CLAD compared with those with IPF. However, survival was not significantly different between the two groups. [ABSTRACT FROM AUTHOR]

Background: Protective ventilation may improve outcomes after major surgery. However, in the context of one-lung ventilation, such a strategy is incompletely defined. The authors hypothesized that a putative one-lung protective ventilation regimen would be independently associated with decreased odds of pulmonary complications after thoracic surgery.Methods: The authors merged Society of Thoracic Surgeons Database and Multicenter Perioperative Outcomes Group intraoperative data for lung resection procedures using one-lung ventilation across five institutions from 2012 to 2016. They defined one-lung protective ventilation as the combination of both median tidal volume 5 ml/kg or lower predicted body weight and positive end-expiratory pressure 5 cm H2O or greater. The primary outcome was a composite of 30-day major postoperative pulmonary complications.Results: A total of 3,232 cases were available for analysis. Tidal volumes decreased modestly during the study period (6.7 to 6.0 ml/kg; P < 0.001), and positive end-expiratory pressure increased from 4 to 5 cm H2O (P < 0.001). Despite increasing adoption of a "protective ventilation" strategy (5.7% in 2012 vs. 17.9% in 2016), the prevalence of pulmonary complications did not change significantly (11.4 to 15.7%; P = 0.147). In a propensity score matched cohort (381 matched pairs), protective ventilation (mean tidal volume 6.4 vs. 4.4 ml/kg) was not associated with a reduction in pulmonary complications (adjusted odds ratio, 0.86; 95% CI, 0.56 to 1.32). In an unmatched cohort, the authors were unable to define a specific alternative combination of positive end-expiratory pressure and tidal volume that was associated with decreased risk of pulmonary complications.Conclusions: In this multicenter retrospective observational analysis of patients undergoing one-lung ventilation during thoracic surgery, the authors did not detect an independent association between a low tidal volume lung-protective ventilation regimen and a composite of postoperative pulmonary complications.Editor’s Perspective: [ABSTRACT FROM AUTHOR]

Drug overdoses have tripled in the United States over the last two decades. With the increasing demand for donor organs, one potential consequence of the opioid epidemic may be an increase in suitable donor organs. Unfortunately, organs from donors dying of drug overdose have poorer utilization rates than other groups of brain‐dead donors, largely due to physician and recipient concerns about viral disease transmission. During the study period of 2011 to 2016, drug overdose donors (DODs) account for an increasingly greater proportion of the national donor pool. We show that a novel model of donor care, known as specialized donor care facility (SDCF), is associated with an increase in organ utilization from DODs compared to the conventional model of hospital‐based donor care. This is likely related to the close relationship of the SDCF with the transplant centers, leading to improved communication and highly efficient donor care. [ABSTRACT FROM AUTHOR]

BACKGROUND Lung transplant (LTx) recipients have low long-term survival and a high incidence of bronchiolitis obliterans syndrome (BOS). However, few long-term, multicenter, and precise estimates of BOS-free survival (a composite outcome of death or BOS) incidence exist. METHODS This retrospective cohort study of primary LTx recipients (1994–2011) reported to the International Society of Heart and Lung Transplantation Thoracic Transplant Registry assessed outcomes through 2012. For the composite primary outcome of BOS-free survival, we used Kaplan-Meier survival and Cox proportional hazards regression, censoring for loss to follow-up, end of study, and re-LTx. Although standard Thoracic Transplant Registry analyses censor at the last consecutive annual complete BOS status report, our analyses allowed for partially missing BOS data. RESULTS Due to BOS reporting standards, 99.1% of the cohort received LTx in North America. During 79,896 person-years of follow-up, single LTx (6,599 of 15,268 [43%]) and bilateral LTx (8,699 of 15,268 [57%]) recipients had a median BOS-free survival of 3.16 years (95% confidence interval [CI], 2.99–3.30 years) and 3.58 years (95% CI, 3.53–3.72 years), respectively. Almost 90% of the single and bilateral LTx recipients developed the composite outcome within 10 years of transplantation. Standard Registry analyses "overestimated" median BOS-free survival by 0.42 years and "underestimated" the median survival after BOS by about a half-year for both single and bilateral LTx (p < 0.05). CONCLUSIONS Most LTx recipients die or develop BOS within 4 years, and very few remain alive and free from BOS at 10 years post-LTx. Less inclusive Thoracic Transplant Registry analytic methods tend to overestimate BOS-free survival. The Registry would benefit from improved international reporting of BOS and other chronic lung allograft dysfunction (CLAD) events. [ABSTRACT FROM AUTHOR]

Purpose: Accurate comorbidity measurement is critical for cancer research. We evaluated comorbidity assessment in the National Cancer Database (NCDB), which uses a code-based Charlson-Deyo Comorbidity Index (CCI), and compared its prognostic performance with a chart-based CCI and individual comorbidities in a national sample of patients with breast, colorectal, or lung cancer. Patients and Methods: Through an NCDB Special Study, cancer registrars re-abstracted perioperative comorbidities for 11,243 patients with stage II to III breast cancer, 10,880 with stage I to III colorectal cancer, and 9,640 with stage I to III lung cancer treated with definitive surgical resection in 2006-2007. For each cancer type, we compared the prognostic performance of the NCDB code-based CCI (categorical: 0 or missing data, 1, 2+), Special Study chart-based CCI (continuous), and 18 individual comorbidities in three separate Cox proportional hazards models for postoperative 5-year overall survival. Results: Comorbidity was highest among patients with lung cancer (13.2% NCDB CCI 2+) and lowest among patients with breast cancer (2.8% NCDB CCI 2+). Agreement between the NCDB and Special Study CCI was highest for breast cancer (rank correlation, 0.50) and lowest for lung cancer (rank correlation, 0.40). The NCDB CCI underestimated comorbidity for 19.1%, 29.3%, and 36.2% of patients with breast, colorectal, and lung cancer, respectively. Within each cancer type, the prognostic performance of the NCDB CCI, Special Study CCI, and individual comorbidities to predict postoperative 5-year overall survival was similar. Conclusion: The NCDB underestimated comorbidity in patients with surgically resected breast, colorectal, or lung cancer, partly because the NCDB codes missing data as CCI 0. However, despite underestimation of comorbidity, the NCDB CCI was similar to the more complete measures of comorbidity in the Special Study in predicting overall survival. [ABSTRACT FROM AUTHOR]

Importance: Surveillance testing is performed after primary treatment for colorectal cancer (CRC), but it is unclear if the intensity of testing decreases time to detection of recurrence or affects patient survival.Objective: To determine if intensity of posttreatment surveillance is associated with time to detection of CRC recurrence, rate of recurrence, resection for recurrence, or overall survival.Design, Setting, and Participants: A retrospective cohort study of patient data abstracted from the medical record as part of a Commission on Cancer Special Study merged with records from the National Cancer Database. A random sample of patients (n=8529) diagnosed with stage I, II, or III CRC treated at a Commission on Cancer-accredited facilities (2006-2007) with follow-up through December 31, 2014.Exposures: Intensity of imaging and carcinoembryonic antigen (CEA) surveillance testing derived empirically at the facility level using the observed to expected ratio for surveillance testing during a 3-year observation period.Main Outcomes and Measures: The primary outcome was time to detection of CRC recurrence; secondary outcomes included rates of resection for recurrent disease and overall survival.Results: A total of 8529 patients (49% men; median age, 67 years) at 1175 facilities underwent surveillance imaging and CEA testing within 3 years after their initial CRC treatment. The cohort was distributed by stage as follows: stage I, 25.0%; stage II, 35.2%; and stage III, 39.8%. Patients treated at high-intensity facilities-4188 patients (49.1%) for imaging and 4136 (48.5%) for CEA testing-underwent a mean of 2.9 (95% CI, 2.8-2.9) imaging scans and a mean of 4.3 (95% CI, 4.2-4.4) CEA tests. Patients treated at low-intensity facilities-4341 patients (50.8%) for imaging and 4393 (51.5%) for CEA testing-underwent a mean of 1.6 (95% CI, 1.6-1.7) imaging scans and a mean of 1.6 (95% CI, 1.6-1.7) CEA tests. Imaging and CEA surveillance intensity were not associated with a significant difference in time to detection of cancer recurrence. The median time to detection of recurrence was 15.1 months (IQR, 8.2-26.3) for patients treated at facilities with high-intensity imaging surveillance and 16.0 months (IQR, 7.9-27.2) with low-intensity imaging surveillance (difference, -0.95 months; 95% CI, -2.59 to 0.68; HR, 0.99; 95% CI, 0.90-1.09) and was 15.9 months (IQR, 8.5-27.5) for patients treated at facilities with high-intensity CEA testing and 15.3 months (IQR, 7.9-25.7) with low-intensity CEA testing (difference, 0.59 months; 95% CI, -1.33 to 2.51; HR, 1.00; 95% CI, 0.90-1.11). No significant difference existed in rates of resection for cancer recurrence (HR for imaging, 1.22; 95% CI, 0.99-1.51 and HR for CEA testing, 1.12; 95% CI, 0.91-1.39) or overall survival (HR for imaging, 1.01; 95% CI, 0.94-1.08 and HR for CEA testing, 0.96; 95% CI, 0.89-1.03) among patients treated at facilities with high- vs low-intensity imaging or CEA testing surveillance.Conclusions and Relevance: Among patients treated for stage I, II, or III CRC, there was no significant association between surveillance intensity and detection of recurrence.Trial Registration: clinicaltrials.gov Identifier: NCT02217865. [ABSTRACT FROM AUTHOR]

Purpose: Few studies have assessed patient-reported outcomes following colorectal surgery. The absence of this information makes it difficult to inform patients about the near-term effects of surgery, beyond outcomes assessed by traditional clinical measures. This study was designed to provide information about the effects of colorectal surgery on physical, mental, and social well-being outcomes.Methods: The NIH Patient-Reported Outcomes Measurement Information System (PROMIS®) Assessment Center was used to collect patient responses prior to surgery and at their routine postoperative visit. Four domains were selected based on patient consultation and clinical experience: depression, pain interference, ability to participate in social roles and activities, and interest in sexual activity. Multilevel random coefficient models were used to assess the change in scores during the follow-up period and to assess the statistical significance of differences in trends over time associated with key clinical measures.Results: In total, 142 patients were consented, with 107 patients completing pre- and postoperative assessments (75%). Preoperative assessments were typically completed 1 month prior to surgery (mean 29.5 days before, SD = 19.7) and postoperative assessments 1 month after surgery (mean 30.7 days after, SD = 9.2), with a mean of 60.3 days between assessment dates. Patients demonstrated no statistically significant changes in scores for pain interference (-0.18 points, p = 0.80) or the ability to participate in social roles and activities (0.44 points, p = 0.55), but had significant decreases in depression scores between pre- and postoperative assessments (-1.6 points, p = 0.03) and near significant increases in scores for interest in sex (1.5 points, p = 0.06). Pain interference scores for patients with neoadjuvant chemotherapy significantly increased (3.5 points, p = 0.03). Scores for the interest in sex domain decreased (worsened) for patients with oncologic etiology (-3.7 points, p = 0.03). No other differences in score trends by patient characteristics were large enough to be statistically significant at the p < 0.05 threshold.Conclusion: These data suggest that the majority of patients quickly return to baseline physical, mental, and social function following colorectal surgery. This information can be used preoperatively to counsel patients about the typical impact of colorectal surgery on quality of life. [ABSTRACT FROM AUTHOR]

Background Primary graft dysfunction (PGD) is a major cause of early morbidity and mortality after lung transplantation. Statins reduce the risk of chronic rejection after lung transplantation, but their effects on PGD are unknown. We hypothesized that perioperative statin therapy decreases the risk for PGD after lung transplantation. Methods We retrospectively reviewed records of all patients undergoing lung transplantation between January 1999 and December 2014 at the University of Virginia Health System. The primary outcome was PGD (grades 1-3). Secondary outcomes included grade 3 PGD, length of intensive care unit and hospital stay, and mortality. Results Of 266 patients who met final inclusion criteria, 138 (52%) were diagnosed with PGD. In-hospital mortality among patients with PGD was 6.5%. There were no deaths in patients without PGD ( p < 0.001). PGD was diagnosed in 24 patients taking statins (34.8%) and in 114 patients (57.9%) who did not take statins ( p = 0.001). After propensity score adjustments, perioperative statin use was independently associated with a reduced risk for PGD (odds ratio [OR] 0.41, 95% confidence interval [CI] 0.20–0.84, p = 0.015) and reduced risk to develop grade 3 PGD (OR 0.42, 95% CI 0.18–0.94, p = 0.036). Other risk factors associated with PGD included intraoperative use of cardiopulmonary bypass (OR 3.74, 95% CI 1.75–8.02, p = 0.001) and positive donor smoking status (OR 2.27, 95% CI 1.18–4.35, p = 0.014). Conclusions The results demonstrate that perioperative use of statins is independently associated with reduced risk for PGD after lung transplantation. [ABSTRACT FROM AUTHOR]

Objective Older patients with non-small cell lung cancer (NSCLC) are less likely to receive guideline-recommended treatment at diagnosis, independent of comorbidity. However, national data on treatment of postoperative recurrence are limited. We evaluated the associations between age, comorbidity, and other patient factors and treatment of postoperative NSCLC recurrence in a national cohort. Materials and methods We randomly selected 9001 patients with surgically resected stage I–III NSCLC in 2006–2007 from the National Cancer Data Base. Patients were followed for 5 years or until first NSCLC recurrence, new primary cancer, or death, whichever came first. Perioperative comorbidities, first recurrence, treatment of recurrence, and survival were abstracted from medical records and merged with existing registry data. Factors associated with active treatment (chemotherapy, radiation, and/or surgery) versus supportive care only were analyzed using multivariable logistic regression. Results Median age at initial diagnosis was 67; 69.7% had >1 comorbidity. At 5-year follow-up, 12.3% developed locoregional and 21.5% developed distant recurrence. Among patients with locoregional recurrence, 79.5% received active treatment. Older patients (OR 0.49 for age >75 compared with <55; 95% CI 0.27–0.88) and those with substance abuse (OR 0.43; 95% CI 0.23–0.81) were less likely to receive active treatment. Women (OR 0.62; 95% CI 0.43–0.89) and patients with symptomatic recurrence (OR 0.69; 95% CI 0.47–0.99) were also less likely to receive active treatment. Among those with distant recurrence, 77.3% received active treatment. Older patients (OR 0.42 for age >75 compared with <55; 95% CI 0.26–0.68) and those with any documented comorbidities (OR 0.59; 95% CI 0.38–0.89) were less likely to receive active treatment. Conclusion Older patients independent of comorbidity, patients with substance abuse, and women were less likely to receive active treatment for postoperative NSCLC recurrence. Studies to further characterize these disparities in treatment of NSCLC recurrence are needed to identify barriers to treatment. [ABSTRACT FROM AUTHOR]

Background: The Hospital Value-Based Purchasing Program measures value of care provided by participating Medicare hospitals and creates financial incentives for quality improvement and fosters increased transparency. Limited information is available comparing hospital performance across health care business models.Study Design: The 2015 Hospital Value-Based Purchasing Program results were used to examine hospital performance by business model. General linear modeling assessed differences in mean total performance score, hospital case mix index, and differences after adjustment for differences in hospital case mix index.Results: Of 3,089 hospitals with total performance scores, categories of representative health care business models included 104 physician-owned surgical hospitals, 111 University HealthSystem Consortium, 14 US News & World Report Honor Roll hospitals, 33 Kaiser Permanente, and 124 Pioneer accountable care organization affiliated hospitals. Estimated mean total performance scores for physician-owned surgical hospitals (64.4; 95% CI, 61.83-66.38) and Kaiser Permanente (60.79; 95% CI, 56.56-65.03) were significantly higher compared with all remaining hospitals, and University HealthSystem Consortium members (36.8; 95% CI, 34.51-39.17) performed below the mean (p < 0.0001). Significant differences in mean hospital case mix index included physician-owned surgical hospitals (mean 2.32; p < 0.0001), US News & World Report honorees (mean 2.24; p = 0.0140), and University HealthSystem Consortium members (mean 1.99; p < 0.0001), and Kaiser Permanente hospitals had lower case mix value (mean 1.54; p < 0.0001). Re-estimation of total performance scores did not change the original results after adjustment for differences in hospital case mix index.Conclusions: The Hospital Value-Based Purchasing Program revealed superior hospital performance associated with business model. Closer inspection of high-value hospitals can guide value improvement and policy-making decisions for all Medicare Value-Based Purchasing Program Hospitals. [ABSTRACT FROM AUTHOR]

Background: The use of lung-protective ventilation (LPV) strategies may minimize iatrogenic lung injury in surgical patients. However, the identification of an ideal LPV strategy, particularly during one-lung ventilation (OLV), remains elusive. This study examines the role of ventilator management during OLV and its impact on clinical outcomes.Methods: Data were retrospectively collected from the hospital electronic medical record and the Society of Thoracic Surgery database for subjects undergoing thoracic surgery with OLV between 2012 and 2014. Mean tidal volume (VT) during two-lung ventilation and OLV and ventilator driving pressure (ΔP) (plateau pressure - positive end-expiratory pressure [PEEP]) were analyzed for the 1,019 cases that met the inclusion criteria. Associations between ventilator parameters and clinical outcomes were examined by multivariate linear regression.Results: After the initiation of OLV, 73.3, 43.3, 18.8, and 7.2% of patients received VT greater than 5, 6, 7, and 8 ml/kg predicted body weight, respectively. One hundred and eighty-four primary and 288 secondary outcome events were recorded. In multivariate logistic regression modeling, VT was inversely related to the incidence of respiratory complications (odds ratio, 0.837; 95% CI, 0.729 to 0.958), while ΔP predicted the development of major morbidity when modeled with VT (odds ratio, 1.034; 95% CI, 1.001 to 1.068).Conclusions: Low VT per se (i.e., in the absence of sufficient PEEP) has not been unambiguously demonstrated to be beneficial. The authors found that a large proportion of patients continue to receive high VT during OLV and that VT was inversely related to the incidence of respiratory complications and major postoperative morbidity. While low (physiologically appropriate) VT is an important component of an LPV strategy for surgical patients during OLV, current evidence suggests that, without adequate PEEP, low VT does not prevent postoperative respiratory complications. Thus, use of physiologic VT may represent a necessary, but not independently sufficient, component of LPV. [ABSTRACT FROM AUTHOR]

Compelling evidence exists that continued smoking after a diagnosis of lung cancer adversely affects treatment effectiveness, survival, risk of recurrence, second malignancy, and health-related quality of life (HRQOL). The importance of HRQOL to patients with cancer and their families has been well documented. Because of increasing evidence of the benefits of smoking cessation, more research has focused on the impact of smoking on HRQOL. Smoking is a behavior that clusters in families; patients who smoke are likely to have family members who smoke, and together they experience impaired HRQOL. This article describes the evidence regarding HRQOL measurement in individuals diagnosed with lung cancer and their family members who smoke and explores the implications for nursing practice. Oncology nurses are in a critical position to advocate for the integration of HRQOL assessment into clinical settings, monitor patient and family member smoking status and environmental tobacco smoke exposure, and support development of smoking cessation interventions to enhance HRQOL. [ABSTRACT FROM AUTHOR]

Failure to anticipate the need to discharge patients to rehabilitation centers and skilled nursing facilities results in expensive delays in the discharge of patients after surgery. Early identification of patients at high risk for discharge to these extended care facilities could mitigate these delays and expenditures. The purpose of this study was to identify preoperative patient factors associated with discharge to extended care facilities after major general thoracic surgery. Discharge records were identified for all patients undergoing major general thoracic surgery admitted to a university hospital between January 2006 and May 2009 who had a stay of longer than one day. The following risk factors were selected a priori based on clinical judgment: age, preoperative albumin, preoperative Zubrod score, history of peripheral vascular disease, and use of home oxygen. Multiple logistic regression analysis was used to estimate the statistical significance and magnitude of risk associated with each predictor of patient discharge to extended care facilities. Of the 1646 patients identified, 68 (4.1%) were discharged to extended care facilities. Hospital length of stay was on average six days longer for patients discharged to these facilities than for patients discharged home (P < 0.0001). Multivariate analysis demonstrated that advanced age, lower preoperative albumin, and increased preoperative Zubrod score were statistically significant predictors of discharge to extended care facilities. Age, preoperative nutritional status, and functional status are strong predictors of patient discharge to extended care facilities. Early identification of these patients may improve patient discharge planning and reduce hospital length of stay after major thoracic surgery. [ABSTRACT FROM AUTHOR]

Abstract: Background: Chronic renal failure after lung transplantation is associated with significant morbidity. However, the significance of acute kidney injury (AKI) after lung transplantation remains unclear and poorly studied. We hypothesized that hemodialysis (HD)-dependent AKI after lung transplantation is associated with significant mortality. Materials and methods: We performed a retrospective review of all patients undergoing lung transplantation from July 1991 to July 2009 at our institution. Recipients with AKI (creatinine > 3 mg/dL) were identified. We compared recipients without AKI versus recipients with and without HD-dependent AKI. Kaplan-Meier survival curves were compared by log rank test. Results: Of 352 lung transplant recipients reviewed at our institution, 17 developed non–HD-dependent AKI (5%) and 16 developed HD-dependent AKI (4.6%). Cardiopulmonary bypass was significantly higher in patients with HD-dependent AKI. None of the recipients who required HD had recovery of renal function. The 30-day mortality was significantly greater in recipients requiring HD (63% versus 0%; P < 0.0001). One-year mortality after transplantation was significantly increased in recipients with HD-dependent AKI compared with those with non–HD-dependent AKI (87.5% versus 17.6%; P < 0.001). Conclusions: Hemodialysis is associated with mortality after lung transplantation. Fortunately, AKI that does not progress to HD commonly resolves and has a better overall survival. Avoidance, if possible, of cardiopulmonary bypass may attenuate the incidence of AKI. Aggressive measures to identify and treat early postoperative renal dysfunction and prevent progression to HD may improve outcomes after lung transplantation. [Copyright &y& Elsevier]

Abstract: Objective: The effect of seasonal variation on postoperative outcomes following lung cancer resections is unknown. We hypothesized that postoperative outcomes following surgical resection for lung cancer within the United States would not be impacted by operative season. Methods: From 2002 to 2007, 182507 isolated lung cancer resections (lobectomy (n =147 937), sublobar resection (n =21650), and pneumonectomy (n =13916)) were evaluated using the Nationwide Inpatient Sample (NIS) database. Patients were stratified according to operative season: spring (n =47382), summer (n =46131), fall (n =45370) and winter (n =43624). Multivariate regression models were applied to assess the effect of operative season on adjusted postoperative outcomes. Results: Patient co-morbidities and risk factors were similar despite the operative season. Lobectomy was the most common operation performed: spring (80.0%), summer (81.3%), fall (81.8%), and winter (81.1%). Lung cancer resections were more commonly performed at large, high-volume (>75th percentile operative volume) centers (P <0.001). Unadjusted mortality was lowest during the spring (2.6%, P <0.001) season compared with summer (3.1%), fall (3.0%) and winter (3.2%), while complications were most common in the fall (31.7%, P <0.001). Hospital length of stay was longest for operations performed in the winter season (8.92±0.11 days, P <0.001). Importantly, multivariable logistic regression revealed that operative season was an independent predictor of in-hospital mortality (P <0.001) and of postoperative complications (P <0.001). Risk-adjusted odds of in-hospital mortality were increased for lung cancer resections occurring during all other seasons compared with those occurring in the spring. Conclusions: Outcomes following surgical resection for lung cancer are independently influenced by time of year. Risk-adjusted in-hospital mortality and hospital length of stay were lowest during the spring season. [Copyright &y& Elsevier]

Abstract: Objective: Esophageal cancer tumor biology is best assessed clinically by 2-[18F]fluoro-2-deoxy-d-glucose (FDG)-PET. Both FDG-PET maximal positron emission tomography (PET) standardized uptake values (SUVmax) and selected tumor markers have been shown to correlate with stage, nodal disease, and survival in esophageal cancer. Interestingly, there is limited data examining the relationship between FDG-PET SUVmax and expression of these tumor markers in esophageal cancer. The purpose of this study was to determine the correlation of tumor markers with FDG-PET SUVmax in esophageal cancer. Methods: FDG-PET SUVmax was calculated in 67 patients with esophageal cancer of which 59 (88%) had adenocarcinoma. Neoadjuvant radiotherapy and/or chemotherapy were administered to 42% (28/67) of patients. Esophageal tumor tissue and surrounding normal tissue was obtained and tissue microarrays were created. Immunohistochemical analysis was performed for five known esophageal cancer tumor markers (GLUT-1, p53, cyclin D1, epidermal growth factor receptor (EGFR), and vascular endothelial growth factor (VEGF)). Assessment of each tumor marker was made by two independent, blinded pathologists using common grading criteria of intensity and percentage of cells stained. A p value <0.05 was considered significant. Results: There were 55 men (82%) and 12 women (18%) with a median age of 63 years (range 40–83). Pathologic staging included stage I (n =29, 43%), stage II (n =19, 28%), stage III disease (n =18, 27%), and stage IV disease (n =1, 2%). PET SUVmax correlated with T stage (p =0.001). In patients undergoing surgery without induction therapy, increasing SUVmax values correlated with increased expression of GLUT-1 transporter (p =0.01). There was no correlation between SUVmax and EGFR, cyclin D1, VEGF, or p53 expression in primary tumor. Conclusions: FDG-PET SUVmax correlates with an increased expression of GLUT-1 transporter in esophageal cancer specimens not subjected to induction therapy. No significant difference in tumor marker expression was noted between patients undergoing induction therapy or surgery alone except p53 expression decreased in primary tumors following induction therapy. Failure of SUVmax values to correlate with known prognostic esophageal cancer tumor markers suggests that FDG-PET may have limited clinical utility in assessing response to therapies targeting these markers. [Copyright &y& Elsevier]

: BackgroundGene therapy may be an effective strategy for modulating lung graft ischemia–reperfusion injury. We investigated whether recipient intramuscular (IM) naked plasmid gene transfer of transforming growth factor β1–active (TGF-β1–active) ameliorates lung graft ischemia–reperfusion injury.: MethodsPreliminary studies in F344 rats demonstrated that gastrocnemius muscle transfection of TGF-β1–active produced muscle and plasma protein expression at 24 and 48 hours after transfection. Recipients (n = 8) received IM injection of naked plasmid-encoding chloramphenicol acetyl transferase (CAT), TGF-β1–latent or TGF-β1–active, respectively, at 24 or at 48 hours before left lung transplantation. We did not treat the control group before transplantation (18-hour cold ischemia). Donor lungs were flushed with low-potassium dextran–1% glucose and stored for 18 hours at 4°C. All groups were killed at 24 hours after transplantation. Immediately before killing the animals, we clamped the contralateral right hilum and assessed graft function. We measured wet-to-dry ratio (W/D), myeloperoxidase, pro-inflammatory cytokines (interleukin 1 [IL-1], tumor necrosis factor α [TNF-α], interferon-γ [INF-γ], and IL-2) and performed immunohistochemistry.: ResultsArterial oxygenation was greatest in the recipient group transfected with TGF-β1–active at 24 hours before transplantation compared with CAT, TGF-β1–latent, and 18-hour cold ischemia groups (p < 0.01). The W/D ratio and myeloperoxidase decreased in both 24- and 48-hour groups, with TGF-β1–active compared with CAT, and 18-hour cold ischemia groups (W/D, p < 0.02 and p < 0.004, respectively; myeloperoxidase, p < 0.05 and p < 0.01, respectively). All pro-inflammatory cytokines decreased in the 24-hour TGF-β1–active group compared with CAT, TGF-β1–latent, 18-hour and 1-hour cold ischemia, and non-treated lung groups (IL-1β, p < 0.03; TNF-α, p < 0.02; IFN-γ, p < 0.001; IL-2, p < 0.0001). In 24- and 48-hour groups with TGF-β1–active, immunohistochemistry showed marked staining of Type I and Type II alveolar cells and of macrophages from the apical to the caudal sections of the lung grafts.: ConclusionsRecipient IM administration of naked plasmid encoding TGF-β1–active before transplantation ameliorates lung isograft reperfusion injury after prolonged ischemia. [Copyright &y& Elsevier]

Lung transplant recipients are at increased risk for Mycobacterium tuberculosis infection secondary to the intense immunosuppressive regimen after transplantation. We report a case of fatal M tuberculosis infection that presented as a pericardial abscess in a lung transplant recipient and review the literature. [Copyright &y& Elsevier]