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Bronchopulmonary dysplasia (BPD) is a chronic lung disease of prematurity. Exposure to noxious stimuli such as hyperoxia, volutrauma, and infection in infancy can have long-reaching impacts on lung health and predispose towards the development of conditions such as chronic obstructive pulmonary disease (COPD) in adulthood. BPD and COPD are both marked by lung tissue degradation, neutrophil influx, and decreased lung function. Both diseases also express a change in microbial signature characterized by firmicute depletion. However, the relationship between pulmonary bacteria and the mechanisms of downstream disease development has yet to be elucidated. We hypothesized that murine models of BPD would show heightened acetylated proline-glycine-proline (Ac-PGP) pathway and neutrophil activity, and through gain- and loss-of-function studies we show that Ac-PGP plays a critical role in driving BPD development. We further test a inhaled live biotherapeutic (LBP) using active Lactobacillus strains in in vitro and in vivo models of BPD and COPD. The Lactobacillus-based LBP is effective in improving lung structure and function, mitigating neutrophil influx, and reducing a broad swath of pro-inflammatory markers in these models of chronic pulmonary disease via the MMP-9/PGP (matrix metalloproteinase/proline-glycine-proline) pathway. Inhaled LBPs show promise in addressing common pathways of disease progression that in the future can be targeted in a variety of chronic lung diseases. Bronchopulmonary dysplasia and chronic obstructive pulmonary disease are marked by neutrophilic inflammation and microbial changes. Here, the authors show the efficacy of an inhaled live biotherapeutic in reducing inflammation and improving tissue structure across models of respiratory disease. [ABSTRACT FROM AUTHOR]

Background and Objectives: Several neurosurgical pathologies, ranging from glioblastoma to hemorrhagic stroke, use volume thresholds to guide treatment decisions. For chronic subdural hematoma (cSDH), with a risk of retreatment of 10%-30%, the relationship between preoperative and postoperative cSDH volume and retreatment is not well understood. We investigated the potential link between preoperative and postoperative cSDH volumes and retreatment., Methods: We performed a retrospective chart review of patients operated for unilateral cSDH from 4 level 1 trauma centers, February 2009-August 2021. We used a 3-dimensional deep learning, automated segmentation pipeline to calculate preoperative and postoperative cSDH volumes. To identify volume thresholds, we constructed a receiver operating curve with preoperative and postoperative volumes to predict cSDH retreatment rates and selected the threshold with the highest Youden index. Then, we developed a light gradient boosting machine to predict the risk of cSDH recurrence., Results: We identified 538 patients with unilateral cSDH, of whom 62 (12%) underwent surgical retreatment within 6 months of the index surgery. cSDH retreatment was associated with higher preoperative (122 vs 103 mL; P < .001) and postoperative (62 vs 35 mL; P < .001) volumes. Patients with >140 mL preoperative volume had nearly triple the risk of cSDH recurrence compared with those below 140 mL, while a postoperative volume >46 mL led to an increased risk for retreatment (22% vs 6%; P < .001). On multivariate modeling, our model had an area under the receiver operating curve of 0.76 (95% CI: 0.60-0.93) for predicting retreatment. The most important features were preoperative and postoperative volume, platelet count, and age., Conclusion: Larger preoperative and postoperative cSDH volumes increase the risk of retreatment. Volume thresholds may allow identification of patients at high risk of cSDH retreatment who would benefit from adjunct treatments. Machine learning algorithm can quickly provide accurate estimates of preoperative and postoperative volumes., (Copyright © Congress of Neurological Surgeons 2023. All rights reserved.)