With Comparable Outcomes, Should Early-Stage Lung Cancer Be a Contraindication to Lung Transplant?

BACKGROUND: Active primary lung malignancy remains a strong contraindication to lung transplantation (LTx). However, outcomes are unclear for patients with early-stage non-small cell lung cancer (NSCLC) who undergo LTx. We hypothesize that patients with early-stage NSCLC incidentally discovered in the explanted lungs have survival comparable to LTx recipients without incidental cancer identified. METHODS: We performed a single-center retrospective analysis of all LTx recipients from May 2007 to September 2021 with incidental cancer identified in the explanted lungs by pathologist report. Survival statistics were estimated using Kaplan-Meier analysis. RESULTS: Of the 1586 LTx performed, 23 patients (1.5%) were found to have incidental lung cancer in the explanted lungs. The most common indications for LTx were interstitial lung disease (n = 13) and chronic obstructive pulmonary disease (n = 7), and the most common histologic diagnosis was adenocarcinoma (n = 14). In the cohort with stage I disease (n = 9), the 1- and 5-year unadjusted Kaplan-Meier survival rates were 88.9% and 51.9%, respectively. The 1- and 5-year survival rates for transplant recipients without incidental cancer findings at LTx during this period were 86.7% and 59.4%, respectively, and did not differ significantly between the 2 strata (P = .96). CONCLUSIONS: Survival rates at 1 and 5 years were comparable between LTx recipients with incidentally noted pathologic stage I NSCLC and contemporary recipients without cancer. All cancer-related deaths occurred in recipients with incidentally noted advanced NSCLC. These results suggest that patients with pathologic stage I lung cancer at the time of transplant have outcomes comparable to those without cancer findings at the time of transplant.

Association Between Prenatal Exposure to Alcohol and Tobacco and Neonatal Brain Activity: Results From the Safe Passage Study.

Importance: Research to date has not determined a safe level of alcohol or tobacco use during pregnancy. Electroencephalography (EEG) is a noninvasive measure of cortical function that has previously been used to examine effects of in utero exposures and associations with neurodevelopment. Objective: To examine the association of prenatal exposure to alcohol (PAE) and tobacco smoking (PTE) with brain activity in newborns. Design, Setting, and Participants: This prospective cohort study enrolled mother-newborn dyads from December 2011 through August 2015, with data analyzed from June 2018 through June 2019. Pregnant women were recruited from clinical sites in Cape Town, South Africa, and the Northern Plains region of the US. Participants were a subset of newborns enrolled in the Safe Passage Study. Exclusions included birth at less than 37 or more than 41 weeks' gestation, multiple birth, or maternal use of psychiatric medication during pregnancy. Exposures: PAE and PTE groups were determined by cluster analysis. Main Outcomes and Measures: Analyses of covariance were run on EEG spectral power at 12 scalp locations across the frequency spectrum from 1 to 45 Hz in 3-Hz bins by sleep state. Results: The final sample consisted of 1739 newborns (median [interquartile range] gestational age at birth, 39.29 [1.57] weeks; 886 [50.9%] were female; median [interquartile range] newborn age at assessment, 48.53 [44.96] hours). Newborns whose mothers were in the low continuous (95% CI, -0.379 to -0.031; P < .05; 95% CI, -0.379 to -0.045; P < .05), quit (95% CI, -0.419 to -0.127; P < .001; 95% CI, -0.398 to -0.106; P < .005), and moderate or high continuous (95% CI, -0.430 to -0.124; P < .001; 95% CI, -0.420 to -0.119; P < .005) PAE clusters had increased 4- to 6-Hz and 7- to 9-Hz left-temporal EEG power. Newborns with moderate or high continuous PTE had decreased 19- to 21-Hz (95% CI, 0.034 to 0.327; P < .05) and 22- to 24-Hz (95% CI, 0.022 to 0.316; P < .05) right-central EEG compared with newborns with no PTE. Newborns with moderate or high continuous PTE had significantly decreased 22- to 36-Hz right-central EEG power compared with the quit smoking group (22-24 Hz, 95% CI, 0.001 to 0.579; P < .05; 25-27 Hz, 95% CI, 0.008 to 0.586; P < .05; 28-30 Hz, 95% CI, 0.028 to 0.607; P < .05; 31-33 Hz, 95% CI, 0.038 to 0.617; P < .05; 34-36 Hz, 95% CI, 0.057 to 0.636; P < .05). Conclusions and Relevance: These findings suggest that even low levels of PAE or PTE are associated with changes in offspring brain development.

Cluster Analysis of Alcohol Consumption during Pregnancy in the Safe Passage Study.

Characterization of patterns of alcohol consumption during pregnancy encompasses multiple factors such as magnitude, frequency, and timing of exposure throughout gestation. Traditional statistical models are limited in dealing with multivariate and diverse patterns of exposure as in the context of this analysis. We propose a finite mixture model-based approach to derive clusters of alcohol exposure of participants in the Safe Passage Study (PASS). Daily alcohol consumption data for 11,083 pregnant women have been clustered in 10 different exposed groups. The resulting cluster analysis was able to characterize alcohol consumption in a comprehensive framework capable of taking into account both quantity and timing of exposure as well as the occurrence of binge drinking.