Lung transplantation following death by drowning: a review of the current literature.

While multiple donor characteristics have been cited as ideal for lung transplantation, there are minimal widely accepted exclusion criteria. One criterion that many centers view with hesitation is death by drowning. However, recent literature suggests such donors may result in acceptable outcomes following transplantation. This review highlights a case of a patient who underwent a successful bilateral lung transplant from a donor following a drowning event. A review of the current literature is presented, concluding with a new proposed set of favorable donor criteria following death by drowning.

Increased resource use in lung transplant admissions in the lung allocation score era.

RATIONALE: In 2005, the lung allocation score (LAS) was implemented to prioritize organ allocation to minimize waiting-list mortality and maximize 1-year survival. It resulted in transplantation of older and sicker patients without changing 1-year survival. Its effect on resource use is unknown. OBJECTIVES: To determine changes in resource use over time in lung transplant admissions. METHODS: Solid organ transplant recipients were identified within the Nationwide Inpatient Sample (NIS) data from 2000 to 2011. Joinpoint regression methodology was performed to identify a time point of change in mean total hospital charges among lung transplant and other solid-organ transplant recipients. Two temporal lung transplant recipient cohorts identified by joinpoint regression were compared for baseline characteristics and resource use, including total charges for index hospitalization, charges per day, length of stay, discharge disposition, tracheostomy, and need for extracorporeal membrane oxygenation. MEASUREMENTS AND MAIN RESULTS: A significant point of increased total hospital charges occurred for lung transplant recipients in 2005, corresponding to LAS implementation, which was not seen in other solid-organ transplant recipients. Total transplant hospital charges increased by 40% in the post-LAS cohort ($569,942 [$53,229] vs. $407,489 [$28,360]) along with an increased median length of stay, daily charges, and discharge disposition other than to home. Post-LAS recipients also had higher post-transplant use of extracorporeal membrane oxygenation (odds ratio, 2.35; 95% confidence interval, 1.56-3.55) and higher incidence of tracheostomy (odds ratio, 1.52; 95% confidence interval, 1.22-1.89). CONCLUSIONS: LAS implementation is associated with a significant increase in resource use during index hospitalization for lung transplant.

Phase I and pharmacokinetic study of bexarotene in combination with gefitinib in the third-line treatment of non-small-cell lung cancer: brief report.

Gefitinib (an epidermal growth factor receptor tyrosine kinase inhibitor) and bexarotene (a rexinoid) affect similar oncogenic pathways and are both metabolized through cytochrome P450 CYP3A4. We studied the combination of bexarotene and gefitinib in the third-line treatment of advanced non-small-cell lung cancer to examine pharmacokinetic interactions and establish the maximum tolerated dose. This was a single-institution, nonrandomized, open-label, phase I clinical trial with a standard 3+3 dose escalation. Three patients were enrolled at each dose level on the basis of pharmacokinetic analysis with dose level 1 including gefitinib (Iressa) 250 mg oral daily and bexarotene (Targretin) 400 mg/m oral daily and dose level +1 including gefitinib 500 mg oral daily and bexarotene 400 mg/m oral daily. Patients received gefitinib alone for 2 weeks to allow for steady state and thereafter, bexarotene was added. In dose level 1, two of three patients had undetectable gefitinib levels at day 15 for unknown reasons. However, the peak levels on day 29 for all three patients receiving 250 mg of gefitinib with bexarotene are lower than published peak levels. Among the three patients in dose level +1, ∼40% lower gefitinib plasma concentrations were noted on day 29 compared with day 15 along with a mean 44% reduction in area under the plasma concentration-time curve from 0 to 24 h (AUC0-24). Bexarotene appears to lower the C max and AUC0-24 of gefitinib through cytochrome P450 CYP3A4. Our results have pharmacokinetic implications for ongoing trials that combine bexarotene with other small molecules in the era of personalized cancer therapy.

Cystic fibrosis telemedicine in the era of COVID-19.

The coronavirus disease 2019 pandemic has resulted in large-scale changes to incorporate telemedicine for the delivery of care. People with cystic fibrosis (CF) have care considerations that pose challenges to telemedicine; they include frequent visits for pulmonary disease progression, medication management, and evaluation by a multidisciplinary team of providers. We share our center's experience with video visits replacing in-person clinic evaluation, using quality improvement strategies to create a replicable workflow. Key considerations include incorporation of the multidisciplinary team into the visit, limitations of remote delivery of care, as well as patient and staff perceptions of this care model. Results revealed that video visits were convenient, efficacious, and comparable to in-person visits, with interest for its continued incorporation into the traditional CF care model.

Machine Learning Algorithms to Differentiate Among Pulmonary Complications After Hematopoietic Cell Transplant.

BACKGROUND: Pulmonary complications, including infections, are highly prevalent in patients after hematopoietic cell transplantation with chronic graft-vs-host disease. These comorbid diseases can make the diagnosis of early lung graft-vs-host disease (bronchiolitis obliterans syndrome) challenging. A quantitative method to differentiate among these pulmonary diseases can address diagnostic challenges and facilitate earlier and more targeted therapy. STUDY DESIGN AND METHODS: We conducted a single-center study of 66 patients with CT chest scans analyzed with a quantitative imaging tool known as parametric response mapping. Parametric response mapping results were correlated with pulmonary function tests and clinical characteristics. Five parametric response mapping metrics were applied to K-means clustering and support vector machine models to distinguish among posttransplantation lung complications solely from quantitative output. RESULTS: Compared with parametric response mapping, spirometry showed a moderate correlation with radiographic air trapping, and total lung capacity and residual volume showed a strong correlation with radiographic lung volumes. K-means clustering analysis distinguished four unique clusters. Clusters 2 and 3 represented obstructive physiology (encompassing 81% of patients with bronchiolitis obliterans syndrome) in increasing severity (percentage air trapping 15.6% and 43.0%, respectively). Cluster 1 was dominated by normal lung, and cluster 4 was characterized by patients with parenchymal opacities. A support vector machine algorithm differentiated bronchiolitis obliterans syndrome with a specificity of 88%, sensitivity of 83%, accuracy of 86%, and an area under the receiver operating characteristic curve of 0.85. INTERPRETATION: Our machine learning models offer a quantitative approach for the identification of bronchiolitis obliterans syndrome vs other lung diseases, including late pulmonary complications after hematopoietic cell transplantation.

Adjuvant chemotherapy for resected non-small cell lung cancer.

Surgery remains the mainstay of therapy for early stage non-small cell lung cancer (NSCLC), but even for stage IA, disease relapse rates remain as high as 30%. Patients with completely resected (R0) N1 disease have about a 50% chance of relapse. In the past 5 years, the benefit of adjuvant chemotherapy has finally been demonstrated for patients with lung cancer. Improvements of 5% to 10% 5-year survival have been reported with cisplatin-based chemotherapy. Still, cure rates have significant room for improvement and ongoing trials with "targeted" agents such as those active against the vascular endothelial growth factor (VEGF), epidermal growth factor receptor (EGFR), and vaccine therapy will hopefully further increase the odds for patients with resected disease. Other studies looking at tumor gene and protein expression will lead us toward better identification of patients most likely to benefit from therapy.

A phase I dose-escalation and pharmacokinetic study of enzastaurin and erlotinib in patients with advanced solid tumors.

PURPOSE: Enzastaurin, an oral serine/threonine kinase inhibitor, targets the protein kinase C and AKT pathways with anti-tumor and anti-angiogenic effects. Erlotinib, an oral epidermal growth factor receptor (EGFR) inhibitor, has activity in solid tumors. Based on the promising combination of EGFR inhibitors and anti-angiogenic agents, this phase I trial was initiated. METHODS: This single-institution, open-label, non-randomized trial used a standard 3 + 3 dose-escalation model in patients with advanced solid malignancies including non-small-cell lung cancer (NSCLC). Two dose levels of enzastaurin (with loading doses) were explored: 250 mg daily and 500 mg daily. Erlotinib was given at 150 mg daily. RESULTS: Sixteen patients were enrolled in this study (median age, 64 years). Most patients were heavily pre-treated, female, and Caucasian and had NSCLC. The highest dose of enzastaurin, 500 mg daily, was tolerated with no unexpected adverse events and no alteration in the pharmacokinetics of either drug at this dose level. The mean clearance was 5.75 L/h for erlotinib and 53.8 L/h for enzastaurin. The most common possibly drug-related grade 3-4 adverse events included diarrhea (25.0%), neurologic symptoms (18.8%), and vomiting (18.8%). Activity was noted, with a partial response in one patient and prolonged disease stability for >12 cycles in three patients. CONCLUSION: The combination of enzastaurin 500 mg daily and erlotinib 150 mg daily is well tolerated and does not alter the pharmacokinetics of the individual drugs, with clinical activity seen. A phase II trial of this combination has been initiated in patients with advanced-stage NSCLC.

Clinical features of bronchioloalveolar carcinoma with new histologic and staging definitions.

INTRODUCTION: To assess clinical features of bronchioloalveolar carcinoma (BAC) based on the 1999 World Health Organization Classification ("pure BAC"), compare patients with pure BAC with patients previously diagnosed as BAC not meeting the 1999 definition, and compare survival changes of pure BAC based on the old and new (2009) staging systems. METHODS: A pulmonary pathologist reviewed each BAC tumor diagnosed between January 1, 1997, and December 31, 2007, identifying cases meeting the new criteria. Cases were restaged according to the seventh edition of the tumor, node, metastasis classification introduced in 2009. Patients with pure BAC were analyzed under both staging systems for changes in overall survival estimation. RESULTS: Of 338 total patients who were diagnosed with BAC, 117 were classified as pure and 221 were non-pure BAC. Seventy-eight of the 117 and 178 of the 221 had no other primary lung cancer. One-year and 5-year survival for the 78 patients with pure BAC were 94.8 and 83.5%, and for the 178 patients were 92.6 and 46.4%, respectively. Restaging for pure BAC cases resulted in nine of the 78 cases (12%) changing stage. Compared with the old staging, patients with advanced stage under the new stage had a worse 5-year survival (53% versus 45%), but no change was observed for stage IA. CONCLUSIONS: For patients with pure BAC, the new pathologic system favorably affects survival and the new staging system may more accurately reflect prognosis in advanced stage cancer. Our results have important implications for researchers, clinicians, and patients.

Adjuvant treatment of resected lung cancer.

Lung cancer is the leading cause of cancer mortality worldwide, and efforts to improve outcomes of patients with this disease require a multidisciplinary approach. While surgical resection is the optimal treatment for early stage lung cancer, the high rates of recurrence after resection pose a distinct challenge. In recent years, substantial evidence has accumulated to support adjuvant chemotherapy in Stage II and III non-small cell lung cancer (NSCLC). A recent meta-analysis of large clinical trials of cisplatin-based adjuvant chemotherapy for resected NSCLC showed that the 5-year survival benefit in favor of chemotherapy was 5.3% (hazard ratio for death, 0.89; 95% confidence interval, 0.82-0.96; P = 0.005). The use of adjuvant chemotherapy in Stage I NSCLC remains controversial. Current and future efforts are being directed toward identification of prognostic and predictive markers to select patients at highest risk for recurrence, and of chemotherapeutic agents to which their tumors are most likely to respond. The role of targeted therapies, including those directed at the epidermal growth factor receptor and vascular endothelial growth factor in adjuvant treatment, is currently under investigation. At this time, there are no data to support the routine use of adjuvant radiation treatment, except in cases in which surgical margins are positive.

Patients' attitudes and preferences about participation and recruitment strategies in clinical trials.

OBJECTIVE: To assess attitudes of patients about participation in clinical trials. PATIENTS AND METHODS: This is a self-report survey of 400 patients who underwent general medical evaluations between September and November 2006 at a tertiary care academic medical center in Rochester, MN. We measured knowledge of access to clinical trials, attitudes toward participation, recruitment preferences, and beliefs about research integrity. RESULTS: Of 485 consecutive patients, 400 (82%) completed the survey. Previous participation in clinical trials was reported by 112 patients (28%). Most were unaware of online information about clinical trials (330 [82%]), were satisfied with their current knowledge (233 [58%]), expected their treating physician to inform them about current trials (304 [76%]), and showed equal interest in participating in conventional or complementary intervention trials (174 [44%]). Of the 400 respondents, 321 (80%) found it appropriate to be contacted by mail and 253 (63%) by telephone regarding study participation. Most patients (364 [91%]) wanted to be informed about research findings or else would not participate in future clinical trials (272 [68%]). The most frequently expected compensation was free parking (234 [58%]). Most thought that their safety (373 [93%]) and privacy (376 [94%]) would be guarded. CONCLUSION: Patients are interested in participating in clinical trials but commonly lack adequate information. If patients received more information (through their treating physicians), enrollment might improve. This single-site study has limited generalizability. Future studies involving a diverse group of patients from a broader geographic distribution will help provide more definitive results.