Donor management using a specialized donor care facility is associated with higher organ utilization from drug overdose donors.

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.

Comparison of outcomes in lung and heart transplant recipients from the same multiorgan donor.

BACKGROUND: Primary graft dysfunction (PGD) and acute cellular rejection (ACR) are important causes of early morbidity and mortality following lung and heart transplantation. While many studies have elucidated donor-related risk factors of PGD and ACR, these complications often occur even with "ideal" donors. Therefore, we investigated potential associations of PGD and ACR between bilateral lung and heart transplant recipients from the same multiorgan donor, respectively. METHODS: Between 2011 and 2017, 100 donors contributed 100 bilateral lung transplants and 100 heart transplants performed. Logistic regression analysis for PGD and Cox proportional hazards regression analysis for ACR were used to estimate the relationship of heart and lung transplants. RESULTS: The incidence of PGD was 33% among lung and 17% among heart transplant recipients. Similarly, the incidence of ACR grade ≥ A2 for lung recipients was 38% (30/80), and the incidence of ACR grade ≥ 2R for heart recipients was 19% (15/80). There was no association between the development of PGD and ACR in lung and heart transplant recipients from the same donor, respectively. CONCLUSIONS: These findings suggest that inherent donor factors are not critical to the development of PGD and ACR after lung and heart transplantation.

Routine Collection of Patient-Reported Outcomes in Thoracic Surgery: A Quality Improvement Study.

BACKGROUND: Patient-reported outcomes are critical for delivering high-quality surgical care, yet they are seldom collected in routine clinical practice. The objective of this quality improvement study was to improve routine patient-reported outcomes collection in a thoracic surgery clinic. METHODS: Thoracic surgery patients at a single academic institution were prospectively monitored from April 2019 to March 2020. The National Institutes of Health-validated Patient-Reported Outcomes Measurement Information System (PROMIS) was used. Using a Model for Improvement design and through multidisciplinary participant observation, we performed multiple plan-do-study-act cycles, an iterative, 4-stage model for rapidly testing interventions, to improve routine collection reliability. RESULTS: During the study period, 2315 patient visits occurred. The baseline PROMIS assessment collection rate was 53%. After convening a multidisciplinary stakeholder team, the key drivers for PROMIS collection were having engaged staff, engaged patients, adequate technological capacity, and adequate time for survey completion, including when to complete the survey during the patient visits. Regular meetings between stakeholders were initiated to promote these key drivers. Several plan-do-study-act cycles were then used to test different interventions, resulting in several positive system shifts, as demonstrated on a statistical process control chart. Adherence to survey collection reached 91% of office visits by approximately 7 months, a 72% relative improvement, which was sustained. CONCLUSIONS: Routine collection of patient-reported outcomes, such as PROMIS, are critical for improving thoracic surgical care. Our study shows that reliably collecting these data is possible in a clinical setting with minimal additional hospital resources.

The impact of pre-transplant allosensitization on outcomes after lung transplantation.

BACKGROUND: Allosensitization can be a significant barrier to transplantation for some patients, and previous studies suggested that pre-transplant allosensitization was associated with worse outcomes after lung transplantation. However, human leukocyte antigen (HLA) antibody testing has evolved significantly over the past 10 years, and current assays are highly sensitive and specific. METHODS: We examined the impact of pre-transplant allosensitization on post-transplant outcomes in the era of solid-phase multiplex HLA antibody detection assays in this retrospective, single-center study of 304 adult transplant recipients between January 1, 2006, and December 31, 2012. We accepted donor organs for allosensitized patients if a virtual crossmatch was compatible with all previously identified antibodies. RESULTS: In univariate and multivariate Cox proportional hazards models, pre-transplant allosensitization, the calculated panel reactive antibody, and the number of pre-transplant HLA antibodies were not associated with the development of acute cellular rejection, lymphocytic bronchiolitis, donor-specific HLA antibodies, chronic lung allograft dysfunction, or graft failure. CONCLUSIONS: Pre-transplant allosensitization does not adversely affect outcomes after lung transplantation when the potentially reactive HLAs are avoided in the donor by a virtual crossmatch with the recipient.

Attaining proficiency with endobronchial ultrasound-guided transbronchial needle aspiration.

OBJECTIVES: Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) is becoming the preferred method of mediastinal staging for lung cancer. We investigated the learning curve for EBUS-TBNA using risk-adjusted cumulative sum (Cusum). METHODS: A retrospective study of EBUS-TBNA was performed at a single academic institution for patients with mediastinal or hilar lymphadenopathy in the setting of proven or suspected lung cancer. A sampling pass was defined as a full retraction and repositioning of the aspiration needle. Rapid on-site evaluation was not available. To track proficiency, risk-adjusted Cusum analysis was performed using acceptable and unacceptable failure rates of 10% and 20%, respectively. Failure was defined as false negative or nondiagnostic results. RESULTS: During the study period, 231 patients underwent EBUS-TBNA. Prevalence of mediastinal or hilar malignancy was 66.7% (154 out of 231). Sensitivity was 92.2% (142 out of 154), and negative predictive value was 87.9% (58 out of 66). Node size was identified as a significant predictor of EBUS-TBNA success by multiple regression. Risk-adjusted Cusum analysis demonstrated that the first and only unacceptable decision interval was crossed at 22 cases. Individual practitioner learning curves were highly variable, and the operator with the highest volume was the most consistently proficient. CONCLUSIONS: In our experience, attainment of an acceptable failure rate for EBUS-TBNA required 22 cases. Node size is a predictor of EBUS-TBNA success. Risk-adjusted Cusum proved a powerful evaluative tool to monitor the training process of this new procedure.

Pre-transplant antibodies to Kα1 tubulin and collagen-V in lung transplantation: clinical correlations.

BACKGROUND: Immune responses to lung-associated self-antigens (SAgs) have been implicated in chronic lung allograft rejection. The goals of this study were to determine the prevalence of pre-existing antibodies (Abs) to the SAgs in pulmonary diseases and the association between pre-existing Abs to SAgs and the development of primary graft dysfunction (PGD), donor-specific antibodies (DSA), and chronic rejection. METHODS: Pre- and post-transplant sera were analyzed from 317 lung transplant (LTx) recipients between 2000 and 2011 with diagnosis of chronic obstructive disease (n = 161), idiopathic pulmonary fibrosis (IPF; n = 50), cystic fibrosis (CF; n = 55), and others (n = 51). Samples were analyzed for Abs to SAgs by enzyme-linked immunosorbent assay, and DSA and cytokines by Luminex. The clinical diagnosis of PGD and bronchiolitis obliterans syndrome (BOS) was based on International Society for Heart and Lung Transplantation guidelines. RESULTS: The overall prevalence of Abs to SAgs was 22.71%, including 18% in chronic obstructive pulmonary disease (p = 0.033), 34% in IPF (p = 0.0006), 29% in CF (p = 0.0023), and 19.6% in other diagnoses (p = 0.044). The incidence of PGD (88% vs 54%, p < 0.05), DSA (70% vs 45%, p < 0.01), and BOS (90% vs 38% (p < 0.001) after LTx was significantly higher in patients with pre-LTx Abs to SAgs than without. Pro-inflammatory cytokines (interleukin-1ß, interleukin-17, and interferon-γ) were elevated in patients who had pre-LTx Abs to SAgs, along with a reduction in anti-inflammatory interleukin-10. CONCLUSIONS: Patients with IPF and CF have the highest prevalence of Abs to SAgs. Patients with pre-existing Abs to SAgs are at increased risk for development of PGD, DSA, and BOS. Strategies to remove pre-existing Abs to SAgs should be considered to improve lung allograft outcome.

Antibodies to MHC class II molecules induce autoimmunity: critical role for macrophages in the immunopathogenesis of obliterative airway disease.

Previous studies have shown that intrabronchial administration of antibodies (Abs) to MHC class I resulted in development of obliterative airway disease (OAD), a correlate of chronic human lung allograft rejection. Since development of Abs specific to mismatched donor HLA class II have also been associated with chronic human lung allograft rejection, we analyzed the role of Abs to MHC class II in inducing OAD. Administration of MHC class II Abs (M5/114) to C57BL/6 mice induced the classical features of OAD even though MHC class II expression is absent de novo on murine lung epithelial and endothelial cells. The induction of OAD was accompanied by enhanced cellular and humoral immune responses to self-antigens (Collagen V and K- α1Tubulin). Further, lung-infiltrating macrophages demonstrated a switch in their phenotype predominance from MΦ1 (F4/80(+)CD11c(+)) to MΦ2 (F4/80(+)CD206(+)) following administration of Abs and prior to development of OAD. Passive administration of macrophages harvested from animals with OAD but not from naïve animals induced OAD lesions. We conclude that MHC class II Abs induces a phenotype switch of lung infiltrating macrophages from MΦ1 (F4/80(+)CD11c(+)) to MΦ2 (F4/80(+)CD206(+)) resulting in the breakdown of self-tolerance along with an increase in autoimmune Th17 response leading to OAD.

Risk of recurrence of resected stage I non-small cell lung cancer in elderly patients as compared with younger patients.

PURPOSE: Half of all patients with non-small cell lung cancer (NSCLC) are 70 years or older at the time of diagnosis. Surgery is an option for fit elderly patients with early stage disease, but rates of disease recurrence after surgical resection are not well described. We report the outcomes in elderly patients (70 years or older) with stage I NSCLC after surgical resection. PATIENTS AND METHODS: We conducted a retrospective study of patients diagnosed with stage I NSCLC after surgical resection at Washington University School of Medicine-Alvin J. Siteman Cancer Center from 1990 to 2000. Demographic, pathologic, treatment, and follow-up data were collected. Recurrence rates and overall survival were calculated by the Kaplan-Meier method. Multivariate Cox proportional hazards models were used to detect associations between potential prognostic factors and survival and recurrence. RESULTS: Of the 715 patients with stage I NSCLC, 286 were 70 years or older at diagnosis. In this elderly cohort, the median age was 74 years (range, 70-89 years) and 140 of them were women (49%). Lobectomy was performed in 237 patients (83%) whereas 43 patients (15%) had a wedge or segmental resection, and six patients (2%) underwent pneumonectomy. Clinical and pathologic characteristics were not statistically different between the elderly and younger cohorts, with the exception that older patients were more likely to be white (90% versus 80%, p = 0.0003) and less likely to be smokers (88% versus 95%, p = 0.019) compared with the younger cohort. With a median follow-up of 4.6 years, the overall 5-year survival rate was 52% with a 5-year recurrence rate of 24%. In comparison, the patients younger than 70 years had a 5-year survival rate of 67% (p < 0.001) and a 5-year recurrence rate of 24%. CONCLUSIONS: Although overall survival was worse in elderly patients, estimated disease recurrence rates after resection were identical.