Multimodal Analysis of the Interaction Between CD70-Directed Chimeric Antigen Receptor Natural Killer Cells and Target Tumors

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Oxygenation Fluctuations Associated with Severe Retinopathy of Prematurity

Purpose: Retinopathy of prematurity (ROP) is one of the leading causes of blindness in children. Although the role of oxygen in the pathophysiology of ROP is well established, a precise understanding of the dynamic relationship between oxygen exposure ROP incidence and severity is lacking. The purpose of this study was to evaluate the correlation between time-dependent oxygen variables and the onset of ROP. Design: Retrospective cohort study. Participants: Two hundred thirty infants who were born at a single academic center and met the inclusion criteria were included. Infants are mainly born between January 2011 and October 2022. Methods: Patient data were extracted from electronic health records (EHRs), with sufficient time-dependent oxygen data. Clinical outcomes for ROP were recorded as none/mild or moderate/severe (defined as type II or worse). Mixed-effects linear models were used to compare the 2 groups in terms of dynamic oxygen variables, such as daily average and the coefficient of variation (COV) fraction of inspired oxygen (FiO2). Support vector machine (SVM) and long-short-term memory (LSTM)-based multimodal models were trained with fivefold cross-validation to predict which infants would develop moderate/severe ROP. Gestational age (GA), birth weight, and time-dependent oxygen variables were used to develop predictive models. Main Outcome Measures: Model cross-validation performance was evaluated by computing the mean area under the receiver operating characteristic (AUROC) curve, precision, recall, and F1 score. Results: We found that both daily average and COV of FiO2 were associated with more severe ROP (adjusted P < 0.001). With fivefold cross-validation, the multimodal LSTM models had higher performance than the best static models (SVM using GA and 3 average FiO2 features) and SVM models trained on GA alone (mean AUROC = 0.89 ± 0.04 vs. 0.86 ± 0.05 vs. 0.83 ± 0.04). Conclusions: The development of severe ROP might not only be influenced by oxygen exposure but also by its fluctuation, which provides direction for future study of pathophysiological factors associated with severe ROP development. Additionally, we demonstrated that multimodal neural networks can be a method to extract useful information from time-series data, which may be a valuable methodology for the investigation of other diseases using EHR data. Financial Disclosure(s): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article

Potentially Preventable Hospitalization Among Adults with Hearing, Vision, and Dual Sensory Loss: A Case and Control Study

Objective: To evaluate the risk of potentially preventable hospitalizations (PPHs) among adults with sensory loss. We hypothesized a greater PPH risk among people with a sensory loss (hearing, vision, and dual) compared with controls. Patients and Methods: Using 2007-2016 Medicare fee-for-service claims, this retrospective, case-control study examined the risk of PPH among adults aged 65 years and older with hearing, vision, and dual sensory loss compared with their corresponding counterparts without sensory loss (between June 1, 2022, and February 1, 2023). We ran 3 step-in regression models for the 3 case and control cohorts examining PPH risk. Our generalized linear regression models controlled for age, sex, race, Elixhauser comorbidity count, rurality, neighborhood characteristics, and the number of primary care physicians and hospitals at the county level. Results: People with vision (adjusted odds ratio [aOR], 1.21; 95% CI, 0.84-0.87) and dual sensory loss (aOR, 1.26; 95% CI, 1.14-1.40) showed a higher PPH risks than their corresponding controls. For people with hearing loss, our unadjusted models showed a higher PPH risk (OR, 1.40; 95% CI, 1.38-1.43) but after adjustment, hearing loss showed a protective association against PPH risk (OR, 0.85; 95% CI, 0.84-0.87). Moreover, in all models, annual wellness visits reduced the PPH risk by about half (eg, aOR, 0.54; 95% CI, 0.52-0.55), whereas living in disadvantaged neighborhood increased the PPH risk (eg, aOR, 1.13; 95% CI, 1.10-1.15) for cases and controls. Conclusion: People with vision and dual sensory loss were at greater PPH risk. This study has important health policy implications in reducing PPH and is indicative of a need for more incentivized and systematic approaches to facilitating the use of preventive care, particularly among older adults living in a disadvantaged neighborhood

A Prospective Observational Study of Physical Activity Levels and Physical Fitness of People at High Risk for Lung Cancer

Introduction: Physical activity (PA) is a potentially modifiable risk factor for lung cancer, with previous research revealing that people who engage in more PA have lower risk of developing lung cancer. PA levels of lung cancer screening participants have not previously been explored. Methods: Participants at a single Australian International Lung Screen Trial site were eligible for assessment of self-reported PA levels (International Physical Activity Questionnaire and Physical Activity Scale for the Elderly) and physical assessments (6-min walk distance, hand grip muscle strength, daily step count, and body composition) at a single time point during lung cancer screening. Statistics were predominantly descriptive, with parametric data presented as mean and SD and nonparametric data presented as median and interquartile range (IQR). Results: A total of 178 participants were enrolled in this study, with a median age of 61 years. Of the participants, 61% were men and 51% were people who currently smoke. The median total International Physical Activity Questionnaire score was 1756 MET/min/wk (IQR 689, 4049). Mean total Physical Activity Scale for the Elderly score was 160 (SD 72), higher than described in healthy sedentary adults. The median daily step count was 7237 steps (IQR 5353, 10,038) and mean 6-minute walk distance was 545 m (SD 92). Median grip strengths were within predicted normal range, with an elevated median percentage body fat and low skeletal muscle mass found on body composition. Conclusion: Almost a quarter of International Lung Screen Trial participants assessed reported low levels of PA and have a potentially modifiable risk factor to improve health outcomes. Larger studies are needed to characterize the burden of inactivity among high-risk lung cancer screening populations

CNS Langerhans cell histiocytosis: Common hematopoietic origin for LCH-associated neurodegeneration and mass lesions.

BACKGROUND: Central nervous system Langerhans cell histiocytosis (CNS-LCH) brain involvement may include mass lesions and/or a neurodegenerative disease (LCH-ND) of unknown etiology. The goal of this study was to define the mechanisms of pathogenesis that drive CNS-LCH. METHODS: Cerebrospinal fluid (CSF) biomarkers including CSF proteins and extracellular BRAFV600E DNA were analyzed in CSF from patients with CNS-LCH lesions compared with patients with brain tumors and other neurodegenerative conditions. Additionally, the presence of BRAFV600E was tested in peripheral mononuclear blood cells (PBMCs) as well as brain biopsies from LCH-ND patients, and the response to BRAF-V600E inhibitor was evaluated in 4 patients with progressive disease. RESULTS: Osteopontin was the only consistently elevated CSF protein in patients with CNS-LCH compared with patients with other brain pathologies. BRAFV600E DNA was detected in CSF of only 2/20 (10%) cases, both with LCH-ND and active lesions outside the CNS. However, BRAFV600E CONCLUSION: In LCH-ND patients, BRAFV600

Assessment of Functional Rhinoplasty with Spreader Grafting Using Acoustic Rhinomanometry and Validated Outcome Measurements

Background:. Rhinoplasty is 1 of the most common aesthetic and reconstructive plastic surgical procedures performed within the United States. Yet, data on functional reconstructive open and closed rhinoplasty procedures with or without spreader graft placement are not definitive as only a few studies have examined both validated measurable objective and subjective outcomes of spreader grafting during rhinoplasty. The aim of this study was to utilize previously validated measures to assess objective, functional outcomes in patients who underwent open and closed rhinoplasty with spreader grafting. Methods:. We performed a retrospective review of consecutive rhinoplasty patients. Patients with internal nasal valve insufficiency who underwent an open and closed approach rhinoplasty between 2007 and 2016 were studied. The Cottle test and Nasal Obstruction Symptom Evaluation survey was used to assess nasal obstruction. Patient-reported symptoms were recorded. Acoustic rhinometry was performed pre- and postoperatively. Average minimal cross-sectional area of the nose was measured. Results:. One hundred seventy-eight patients were reviewed over a period of 8 years. Thirty-eight patients were included in this study. Of those, 30 patients underwent closed rhinoplasty and 8 open rhinoplasty. Mean age was 36.9 ± 18.4 years. The average cross-sectional area in closed and open rhinoplasty patients increased significantly (P = 0.019). There was a functional improvement in all presented cases using the Nasal Obstruction Symptom Evaluation scale evaluation. Conclusions:. Closed rhinoplasty with spreader grafting may play a significant role in the treatment of nasal valve collapse. A closed approach rhinoplasty including spreader grafting is a viable option in select cases with objective and validated functional improvement