Clinical effectiveness of nirmatrelvir plus ritonavir for patients with COVID-19 and preexisting psychiatric disorders.

OBJECTIVES: This study assessed the clinical effectiveness of the combination of nirmatrelvir and ritonavir (NMV-r) in treating nonhospitalized patients with COVID-19 who have preexisting psychiatric disorders. METHODS: Patients diagnosed with COVID-19 and psychiatric disorders between 1 March 2020, and 1 December 2022, were included using the TriNetX network. The primary outcome was the composite outcome of all-cause emergency department (ED) visits, hospitalization, or death within 30 days. RESULTS: Propensity score matching yielded two cohorts of 20,633 patients each. The composite outcome of all-cause ED visits, hospitalization, or death within 30 days was 3.57% (737 patients) in the NMV-r cohort and 5.69% (1176) in the control cohort, resulting in a reduced risk in the NMV-r cohort (HR: 0.657; 95% confidence interval (CI): 0.599-0.720). The NMV-r cohort exhibited a lower risk of all-cause hospitalization (HR: 0.385; 95% CI: 0.328-0.451) and all-cause death (HR: 0.110; 95% CI: 0.053-0.228) compared with the control group. CONCLUSION: NMV-r could mitigate the risk of adverse outcomes in nonhospitalized patients with COVID-19 and preexisting psychiatric disorders. However, only a limited number of patients in this population received adequate treatment, thus emphasizing the importance of promoting its appropriate use.

Pediatric dermatologists versus AI bots: Evaluating the medical knowledge and diagnostic capabilities of ChatGPT.

This study evaluates the clinical accuracy of OpenAI's ChatGPT in pediatric dermatology by comparing its responses on multiple-choice and case-based questions to those of pediatric dermatologists. ChatGPT's versions 3.5 and 4.0 were tested against questions from the American Board of Dermatology and the "Photoquiz" section of Pediatric Dermatology. Results show that human pediatric dermatology clinicians generally outperformed both ChatGPT iterations, though ChatGPT-4.0 demonstrated comparable performance in some areas. The study highlights the potential of AI tools in aiding clinicians with medical knowledge and decision-making, while also emphasizing the need for continual advancements and clinician oversight in using such technologies.

Stress and depression among male police officers in Taiwan: Severity, determinants, and coping strategies.

BACKGROUND: Police work, known for its high stress, exhibits elevated depression rates. OBJECTIVE: This study explores stress and depression in male officers, examining personality traits, coping strategies, family, and social support. Aligned with the diathesis-stress hypothesis and job demands-resources model, it aims to illuminate these factors in policing. METHODS: Two hundred and sixty-four male police officers from Yunlin, Taiwan were enrolled in this study. Structured measurements of stress level, depression symptoms, personality traits, family functioning, and social support were made. We used multiple regression analysis to assess predictors of stress level and depression and identified coping strategies used by the police officers. RESULTS: Of the 264 male police officers, 36.4% had clinically significant depression. Occupational stress was mostly related to organizational factors. Multivariate regression analyses showed that age, personality traits, officer's rank, and period of education obtained could predict police officers' occupational stress. Personality traits, social support, occupational stress, and period of education obtained could predict depression. The most frequently used coping strategies were drinking and smoking. CONCLUSIONS: The results of our study support the diathesis-stress hypothesis and the job demands-resources model. Enhancing male police officers' mental well-being requires addressing key factors like social support and occupational stress. Strategic measures, such as mental health education, destigmatization, counseling, and community-building, are vital. Policymakers should collaborate with mental health professionals for tailored interventions, fostering a healthier work environment.

Regimen for accelerated propranolol initial dosing (RAPID).

BACKGROUND: Infantile hemangiomas are common vascular tumors in children. Propranolol has proven effective in treating infantile hemangiomas and while generally safe, has potential risk for more serious side effects of hypoglycemia, hypotension, bradycardia, bronchospasm, and cardiovascular or respiratory compromise. Current prescribing guidelines recommend initiating propranolol doses at 1 mg/kg/day, with up-titration to 2 mg/kg/day. This study aims to compare the incidence of adverse events in infants and children treated with propranolol initiated at 1 mg/kg/day versus being initiated directly at 2 mg/kg/day. METHODS: A retrospective cohort study was conducted using medical records of patients receiving propranolol therapy for infantile hemangiomas between October 2018-March 2021 at the Children's Hospital of Philadelphia. Patients were categorized by initial propranolol dosage: 1 or 2 mg/kg/day. The primary outcome measures included parent-reported adverse events, hypotension (defined by the Pediatric Advanced Life Support criteria), and bradycardia (defined as <1st percentile for age) following propranolol initiation. RESULTS: Out of the 244 patients identified, 123 were initiated at the 1 mg/kg/day dose, and 121 at the 2 mg/kg/day dose. There was no significant difference in the incidence of adverse events between the two groups (p = .057). Additionally, among patients initiated at 2 mg/kg/day, there were no significant differences in the incidence of age-related or weight-related adverse events for those younger than 2 months or those in the 1st or 2nd quartile for weight (p = .53). CONCLUSION: Infants and children initiated at 2 mg/kg/day did not demonstrate an increased incidence of adverse events associated with propranolol compared to those initiated at 1 mg/kg/day. These findings provide clinical evidence for the practice of accelerated propranolol initiation dosing.

An Analysis of Solicitations From Predatory Journals in Ophthalmology.

PURPOSE: To evaluate trends associated with email communication from potentially predatory publishers to faculty in ophthalmology. DESIGN: Cross-sectional study METHODS: Ophthalmologists (n = 14) from various subspecialties and institutions were recruited to participate. Participants identified unsolicited emails that they had received originating from publishers in May 2021. Information collected included details on email contents and publisher organizations. Trends in communications from predatory publishers were evaluated. RESULTS: Over a 30-day study period, a total of 1813 emails were received from 383 unique publishers and 696 unique journals, with a mean (SD) of 4.73 (2.46) emails received per day per participant. Of the 1813 emails identified, 242 (13%) emails were invitations to conferences, whereas 1440 (80%) were solicitations for article submissions to open-access, pay-to-publish journals. A total of 522 (29.0%) emails were related to ophthalmology, and reference to a prior publication of the participant occurred in 262 emails (14%). Of the 696 unique journals identified, 174 (25%) journals were indexed on PubMed and 426 (61%) were listed on Beall's list. When comparing journals that were listed on PubMed vs those that were not, PubMed indexed journals had a higher impact factor (2.1 vs 1.5, P = .002), were less likely to use "greetings" (76% vs 91%, P < .001), had fewer spelling/grammar errors (40% vs 51%, P = .01), and were less likely to offer rapid publication (16% vs 25%, P = .02). CONCLUSIONS: Unsolicited requests to publish occur frequently and may diminish the quality of the scientific literature. We encourage individuals in ophthalmology to be aware of these trends in predatory publishing.

Multicenter Study of Long-Term Outcomes and Quality of Life in PHACE Syndrome after Age 10.

OBJECTIVE: To characterize long-term outcomes of PHACE syndrome. STUDY DESIGN: Multicenter study with cross-sectional interviews and chart review of individuals with definite PHACE syndrome ≥10 years of age. Data from charts were collected across multiple PHACE-related topics. Data not available in charts were collected from patients directly. Likert scales were used to assess the impact of specific findings. Patient-Reported Outcomes Measurement Information System (PROMIS) scales were used to assess quality of life domains. RESULTS: A total of 104/153 (68%) individuals contacted participated in the study at a median of 14 years of age (range 10-77 years). There were infantile hemangioma (IH) residua in 94.1%. Approximately one-half had received laser treatment for residual IH, and the majority (89.5%) of participants were satisfied or very satisfied with the appearance. Neurocognitive manifestations were common including headaches/migraines (72.1%), participant-reported learning differences (45.1%), and need for individualized education plans (39.4%). Cerebrovascular arteriopathy was present in 91.3%, with progression identified in 20/68 (29.4%) of those with available follow-up imaging reports. Among these, 6/68 (8.8%) developed moyamoya vasculopathy or progressive stenoocclusion, leading to isolated circulation at or above the level of the circle of Willis. Despite the prevalence of cerebrovascular arteriopathy, the proportion of those with ischemic stroke was low (2/104; 1.9%). PROMIS global health scores were lower than population norms by at least 1 SD. CONCLUSIONS: PHACE syndrome is associated with long-term, mild to severe morbidities including IH residua, headaches, learning differences, and progressive arteriopathy. Primary and specialty follow-up care is critical for PHACE patients into adulthood.

Hidradenitis suppurativa disease control associated with type of hormonal contraceptive use.

Hidradenitis suppurativa (HS) is a painful chronic skin condition of apocrine gland regions. This retrospective cohort study aimed to assess the impact of hormonal contraception type on HS disease control in adult women. In total, 160 patients were included, with the majority identifying as Black or African American (73.1%). Multivariate logistic regression showed that oestrogen-progesterone users were 3.14 times more likely to experience stable or improved HS than progesterone-only users (adjusted odds ratio 3.14, 95% CI 1.18-8.35; P = 0.02). Further investigation is needed to elucidate the antiandrogenic mechanisms affecting HS symptom response to hormonal contraceptives.

EMG-projected MEG High-Resolution Source Imaging of Human Motor Execution: Brain-Muscle Coupling above Movement Frequencies.

Magnetoencephalography (MEG) is a non-invasive functional imaging technique for pre-surgical mapping. However, movement-related MEG functional mapping of primary motor cortex (M1) has been challenging in presurgical patients with brain lesions and sensorimotor dysfunction due to the large numbers of trails needed to obtain adequate signal to noise. Moreover, it is not fully understood how effective the brain communication is with the muscles at frequencies above the movement frequency and its harmonics. We developed a novel Electromyography (EMG)-projected MEG source imaging technique for localizing M1 during ~1 minute recordings of left and right self-paced finger movements (~1 Hz). High-resolution MEG source images were obtained by projecting M1 activity towards the skin EMG signal without trial averaging. We studied delta (1-4 Hz), theta (4-7 Hz), alpha (8-12 Hz), beta (15-30 Hz), and gamma (30-90 Hz) bands in 13 healthy participants (26 datasets) and two presurgical patients with sensorimotor dysfunction. In healthy participants, EMG-projected MEG accurately localized M1 with high accuracy in delta (100.0%), theta (100.0%), and beta (76.9%) bands, but not alpha (34.6%) and gamma (0.0%) bands. Except for delta, all other frequency bands were above the movement frequency and its harmonics. In both presurgical patients, M1 activity in the affected hemisphere was also accurately localized, despite highly irregular EMG movement patterns in one patient. Altogether, our EMG-projected MEG imaging approach is highly accurate and feasible for M1 mapping in presurgical patients. The results also provide insight into movement related brain-muscle coupling above the movement frequency and its harmonics.

Underrecognition and un-dertreatment of stress-related psychiatric disorders in physicians: Determinants, challenges, and the impact of the COVID-19 pandemic.

Medical practitioners' duties are highly stressful and performed in a particularly challenging and competitive work environment. Stress and burnout among physicians have emerged as a worldwide public health problem in recent years. A high level of distress and burnout can lead to clinically significant behavioral health problems, such as stress-related psychiatric disorders. Mounting evidence shows that physicians have higher risks of insomnia, anxiety, and depression than the general population, especially during the coronavirus disease 2019 pandemic. However, the behavioral health problems of these vulnerable healthcare professionals are noteworthy for being underrecognized and undertreated. In this mini-review, we summarize the current progress of studies on the prevalence and determinants of distress and stress-related psychiatric disorders among phy-sicians and their healthcare-seeking behaviors. We discuss future research directions and the clinical approach that may maximize self-awareness and promote prompt and adequate treatment for clinically significant behavioral health problems of physicians.

Learning image representations for content-based image retrieval of radiotherapy treatment plans.

Objective.In this work, we propose a content-based image retrieval (CBIR) method for retrieving dose distributions of previously planned patients based on anatomical similarity. Retrieved dose distributions from this method can be incorporated into automated treatment planning workflows in order to streamline the iterative planning process. As CBIR has not yet been applied to treatment planning, our work seeks to understand which current machine learning models are most viable in this context.Approach.Our proposed CBIR method trains a representation model that produces latent space embeddings of a patient's anatomical information. The latent space embeddings of new patients are then compared against those of previous patients in a database for image retrieval of dose distributions. All source code for this project is available on github.Main results.The retrieval performance of various CBIR methods is evaluated on a dataset consisting of both publicly available image sets and clinical image sets from our institution. This study compares various encoding methods, ranging from simple autoencoders to more recent Siamese networks like SimSiam, and the best performance was observed for the multitask Siamese network.Significance.Our current results demonstrate that excellent image retrieval performance can be obtained through slight changes to previously developed Siamese networks. We hope to integrate CBIR into automated planning workflow in future works.

Harmonization and standardization of nucleus pulposus cell extraction and culture methods.

Background: In vitro studies using nucleus pulposus (NP) cells are commonly used to investigate disc cell biology and pathogenesis, or to aid in the development of new therapies. However, lab-to-lab variability jeopardizes the much-needed progress in the field. Here, an international group of spine scientists collaborated to standardize extraction and expansion techniques for NP cells to reduce variability, improve comparability between labs and improve utilization of funding and resources. Methods: The most commonly applied methods for NP cell extraction, expansion, and re-differentiation were identified using a questionnaire to research groups worldwide. NP cell extraction methods from rat, rabbit, pig, dog, cow, and human NP tissue were experimentally assessed. Expansion and re-differentiation media and techniques were also investigated. Results: Recommended protocols are provided for extraction, expansion, and re-differentiation of NP cells from common species utilized for NP cell culture. Conclusions: This international, multilab and multispecies study identified cell extraction methods for greater cell yield and fewer gene expression changes by applying species-specific pronase usage, 60-100 U/ml collagenase for shorter durations. Recommendations for NP cell expansion, passage number, and many factors driving successful cell culture in different species are also addressed to support harmonization, rigor, and cross-lab comparisons on NP cells worldwide.

Assessing Pediatric Mild Traumatic Brain Injury and Its Recovery Using Resting-State Magnetoencephalography Source Magnitude Imaging and Machine Learning.

The objectives of this machine-learning (ML) resting-state magnetoencephalography (rs-MEG) study involving children with mild traumatic brain injury (mTBI) and orthopedic injury (OI) controls were to define a neural injury signature of mTBI and to delineate the pattern(s) of neural injury that determine behavioral recovery. Children ages 8-15 years with mTBI (n = 59) and OI (n = 39) from consecutive admissions to an emergency department were studied prospectively for parent-rated post-concussion symptoms (PCS) at: 1) baseline (average of 3 weeks post-injury) to measure pre-injury symptoms and also concurrent symptoms; and 2) at 3-months post-injury. rs-MEG was conducted at the baseline assessment. The ML algorithm predicted cases of mTBI versus OI with sensitivity of 95.5 ± 1.6% and specificity of 90.2 ± 2.7% at 3-weeks post-injury for the combined delta-gamma frequencies. The sensitivity and specificity were significantly better (p < 0.0001) for the combined delta-gamma frequencies compared with the delta-only and gamma-only frequencies. There were also spatial differences in rs-MEG activity between mTBI and OI groups in both delta and gamma bands in frontal and temporal lobe, as well as more widespread differences in the brain. The ML algorithm accounted for 84.5% of the variance in predicting recovery measured by PCS changes between 3 weeks and 3 months post-injury in the mTBI group, and this was significantly lower (p < 10-4) in the OI group (65.6%). Frontal lobe pole (higher) gamma activity was significantly (p < 0.001) associated with (worse) PCS recovery exclusively in the mTBI group. These findings demonstrate a neural injury signature of pediatric mTBI and patterns of mTBI-induced neural injury related to behavioral recovery.

Fully automated segmentally boosted VMAT.

PURPOSE: Treatment planning for volumetric modulated arc therapy (VMAT) typically involves the use of multiple arcs to achieve sufficient intensity modulation. Alternatively, we can perform segment boosting to achieve similar intensity modulation while also reducing the number of control points used. Here, we propose the MetaPlanner Boosted VMAT (MPBV) approach, which generates boosted VMAT plans through a fully automated framework. METHODS: The proposed MPBV approach is an open-source framework that consists of three main stages: meta-optimization of treatment plan hyperparameters, fast beam angle optimization on a coarse dose grid to select desirable segments for boosting, and final plan generation (i.e., constructing the boosted VMAT arc and performing optimization). RESULTS: Performance for the MPBV approach is evaluated on 21 prostate cases and 6 head and neck cases using clinically relevant plan quality metrics (i.e., target coverage, dose conformity, dose homogeneity, and OAR sparing). As compared to two baseline methods with multiple arcs, MPBV maintains or improves dosimetric performance for the evaluated metrics while substantially reducing average estimated delivery times (from 2.6 to 2.1 min). CONCLUSION: Our proposed MPBV approach provides an automated framework for producing high-quality VMAT plans that uses fewer control points and reduces delivery time as compared to traditional approaches with multiple arcs. MPBV applies automated treatment planning to segmentally boosted VMAT to address the beam utilization inefficiencies of traditional VMAT approaches that use multiple full arcs.

Whole transcriptome-based skin virome profiling in typical epidermodysplasia verruciformis reveals α-, ß-, and γ-HPV infections.

HPVs are DNA viruses include approximately 450 types that are classified into 5 genera (α-, ß-, γ-, µ-, and ν-HPV). The γ- and ß-HPVs are present in low copy numbers in healthy individuals; however, in patients with an inborn error of immunity, certain species of ß-HPVs can cause epidermodysplasia verruciformis (EV), manifesting as recalcitrant cutaneous warts and skin cancer. EV presents as either typical or atypical. Manifestations of typical EV are limited to the skin and are caused by abnormal keratinocyte-intrinsic immunity to ß-HPVs due to pathogenic sequence variants in TMC6, TMC8, or CIB1. We applied a transcriptome-based computational pipeline, VirPy, to RNA extracted from normal-appearing skin and wart samples of patients with typical EV to explore the viral and human genetic determinants. In 26 patients, 9 distinct biallelic mutations were detected in TMC6, TMC8, and CIB1, 7 of which are previously unreported to our knowledge. Additionally, 20 different HPV species, including 3 α-HPVs, 16 ß-HPVs, and 1 γ-HPV, were detected, 8 of which are reported here for the first time to our knowledge in patients with EV (ß-HPV-37, -47, -80, -151, and -159; α-HPV-2 and -57; and γ-HPV-128). This study expands the TMC6, TMC8, and CIB1 sequence variant spectrum and implicates new HPV subtypes in the pathogenesis of typical EV.

Sub-second photon dose prediction via transformer neural networks.

BACKGROUND: Fast dose calculation is critical for online and real-time adaptive therapy workflows. While modern physics-based dose algorithms must compromise accuracy to achieve low computation times, deep learning models can potentially perform dose prediction tasks with both high fidelity and speed. PURPOSE: We present a deep learning algorithm that, exploiting synergies between transformer and convolutional layers, accurately predicts broad photon beam dose distributions in few milliseconds. METHODS: The proposed improved Dose Transformer Algorithm (iDoTA) maps arbitrary patient geometries and beam information (in the form of a 3D projected shape resulting from a simple ray tracing calculation) to their corresponding 3D dose distribution. Treating the 3D CT input and dose output volumes as a sequence of 2D slices along the direction of the photon beam, iDoTA solves the dose prediction task as sequence modeling. The proposed model combines a Transformer backbone routing long-range information between all elements in the sequence, with a series of 3D convolutions extracting local features of the data. We train iDoTA on a dataset of 1700 beam dose distributions, using 11 clinical volumetric modulated arc therapy (VMAT) plans (from prostate, lung, and head and neck cancer patients with 194-354 beams per plan) to assess its accuracy and speed. RESULTS: iDoTA predicts individual photon beams in ≈50 ms with a high gamma pass rate of 97.72 ± 1.93 % $97.72\pm 1.93\%$ (2 mm, 2%). Furthermore, estimating full VMAT dose distributions in 6-12 s, iDoTA achieves state-of-the-art performance with a 99.51 ± 0.66 % $99.51\pm 0.66\%$ (2 mm, 2%) pass rate and an average relative dose error of 0.75 ± 0.36%. CONCLUSIONS: Offering the millisecond speed prediction per beam angle needed in online and real-time adaptive treatments, iDoTA represents a new state of the art in data-driven photon dose calculation. The proposed model can massively speed-up current photon workflows, reducing calculation times from few minutes to just a few seconds.

Geographic and socioeconomic access disparities to Phase 3 clinical trials in ophthalmology in the United States.

BACKGROUND/OBJECTIVE: To identify geographic and socioeconomic variables associated with residential proximity to Phase 3 ophthalmology clinical trial sites. METHODS: The geographic location of clinical trial sites for Phase 3 clinical trials in ophthalmology was identified using ClinicalTrials.gov. Driving time from each United States (US) census tract centroid to nearest clinical trial site was calculated using real traffic patterns. Travel data were crosslinked to census-tract level public datasets from United States Census Bureau American Community Survey (ACS). Cross-sectional multivariable regression was used to identify associations between census-tract sociodemographic factors and driving time (>60 min) from each census tract centroid to the nearest clinical trial site. RESULTS: There were 2330 unique clinical trial sites and 71,897 census tracts. Shortest median time was to retina sites [33.7 min (18.7, 70.1 min)]. Longest median time was to neuro-ophthalmology sites [119.8 min (48.7, 240.4 min)]. Driving >60 min was associated with rural tracts [adjusted odds ratio (aOR) 7.60; 95% CI (5.66-10.20), p < 0.0001]; Midwest [aOR 1.84(1.15-2.96), p = 0.01], South [aOR 2.57 (1.38-4.79), p < 0.01], and West [aOR 2.52 (1.52-4.17), p < 0.001] v. Northeast; and tracts with higher visual impairment [aOR 1.07 (1.03-1.10), p < 0.001)]; higher poverty levels [4th v.1st Quartile of population below poverty, aOR 2.26 (1.72-2.98), p < 0.0001]; and lower education levels [high school v. Bachelor's degree or higher aOR 1.02 (1.00-1.03), p = 0.0072]. CONCLUSIONS: There are significant geographic and socioeconomic disparities in access to ophthalmology clinical trial sites for rural, non-Northeastern, poorer, and lower education level census tracts, and for census tracts with higher levels of self-reported visual impairment.

Characteristics of High-Volume Lung Segmentectomy Hospitals: A Propensity Score-Matched Analysis.

BACKGROUND: Segmental resection continues to gain favor in the treatment of early-stage non-small cell lung cancer, but there is limited data on outcomes as related to facility volume. The purpose of this study is to better define the relationship between segmentectomy outcomes, survival, and facility volume. METHODS: A retrospective cohort analysis was completed using the National Cancer Database. Patients with stage I disease undergoing segmentectomy 2004 to 2015 were included. Facility volume was determined per year; facilities performing higher than the median number of segmental resections were deemed high-volume and retained that classification for the remainder of the study. Propensity-score matching was used to compare 5-year survival and outcomes. RESULTS: Six hundred eighty-one centers performing 2481 segmentectomies were included. High-volume centers had higher utilization of minimally invasive approaches and lower conversion rates. There was no difference in readmission or 30-day mortality, but 90-day mortality differed between groups (1.2% vs. 2.6%, P = .03). High-volume centers were more likely to sample lymph nodes (88.5% vs. 80.7%, P < .01), and patients were less likely to have positives margins (1.3% vs. 2.7%, P = .03). Patients were no more likely to be upstaged based on facility volume (4.6% vs. 3.3%, P = .21). Overall, 5-year survival was better for patients treated at high-volume centers in the full cohort (69.5% vs. 66.4%, P = .014) but in propensity score-matched analysis this survival difference became non-significant (68.0% vs. 67.9% (P = .172). CONCLUSION: Segmentectomy performed at high-volume centers is associated with more frequent use of minimally invasive approach, more frequent negative margins, and improved 90-day survival.

Race is a Risk Factor for the Deferral of Resection and Radiation for Early-Stage Lung Cancer.

PURPOSE: There remain profound race-related disparities in the treatment of non-small cell lung cancer (NSCLC). Deferral of operative management for early-stage disease is recognized as driver of this disparity. Black race has been associated with higher rates of surgical deferral. It remains unclear how race impacts likelihood of receiving radiation therapy after declining surgical management of NSCLC. PATIENTS AND METHODS: A retrospective cohort analysis was completed using data from the National Cancer Database (NCBD) for patients 18 and over with stage I NSCLC offered surgical resection from 2004 to 2015 (N = 89,462). Multivariable logistic regression identified predictors of surgical deferral and predictors for deferral of radiation after deferral of surgery. Kaplan-Meier survival analysis with log-rank tests and multivariable Cox proportional hazards regressions were performed. RESULTS: 87,293 (97.6%) patients underwent surgery, 2169 (2.4%) deferred. Patients who deferred had 2.1 times higher hazard ratio for mortality, (HR = 2.08, [1.97, 2.29], P < .001). Of those that deferred, 1250 (57.6%) received postdeferral radiation. Compared to White patients, Black patients had OR of 1.82 for deferring both surgery and radiation (aOR: 1.82, [1.31, 2.53], P < .001) and Asian and Pacific Island (API) patients had an OR of 2.67 (aOR: 2.67, [1.27, 4.64], P = .008). Other predictors of deferral of therapy included: Medicare or lack of insurance, and treatment at nonacademic medical centers. CONCLUSION: Insurance status and Black race, and API race are associated with deferring surgical therapy and radiation therapy for NSCLC. These findings are consistent with the large body of work showing worse outcomes for treatment of NSCLC in minority patients.

National trends in pectus excavatum repair: patient age, facility volume, and outcomes.

Background: There is limited data on the adult repair of pectus excavatum (PE). Existing literature is largely limited to single institution experiences and suggests that adults undergoing modified Nuss repair may have worse outcomes than pediatric and adolescent patients. Using a representative national database, this analysis is the first to describe trends in demographics, outcomes, charges, and facility volume for adults undergoing modified Nuss procedure. Methods: Because of a coding change associated with ICD-10, a retrospective cohort analysis using the National Inpatient Sample (NIS) for patients 12 or older undergoing modified Nuss repair between 2016-2018 was possible. Pearson's χ2 and Student's t-tests were utilized to compare patient, clinical, and hospital characteristics. Complications were sub-classified into major and minor categories. Facilities performing greater than the mean number of operations were categorized as high-volume. Results: Of 360 patients, 79.2% were male. There was near gender parity for patients over 30 undergoing repair (55.2% male, 44.8% female). In all age cohorts, patients were predominantly Caucasian. Rates of any postoperative complication differed by age (12-17 years: 30.6%; 18-29 years: 45.2%; 30+ years: 62.1%; P<0.01); older patients had higher rates of all but two subclasses of complication. Age over 30 was associated with higher charges (12-17 years: $57,312; 18-29 years: $57,001; 30+ years: $67,014; P<0.01). High-volume centers operate on older patients, had shorter lengths of stay, and comparable charges to low-volume centers. Conclusions: Women comprise nearly half of patients undergoing modified Nuss repair after 30 years of age. There are significant differences in complication rates and charges when comparing patients by age. Patients undergoing repair at high-volume facilities benefitted from shorter lengths of stay.

A complete pedigree-based graph workflow for rare candidate variant analysis.

Methods that use a linear genome reference for genome sequencing data analysis are reference-biased. In the field of clinical genetics for rare diseases, a resulting reduction in genotyping accuracy in some regions has likely prevented the resolution of some cases. Pangenome graphs embed population variation into a reference structure. Although pangenome graphs have helped to reduce reference mapping bias, further performance improvements are possible. We introduce VG-Pedigree, a pedigree-aware workflow based on the pangenome-mapping tool of Giraffe and the variant calling tool DeepTrio using a specially trained model for Giraffe-based alignments. We demonstrate mapping and variant calling improvements in both single-nucleotide variants (SNVs) and insertion and deletion (indel) variants over those produced by alignments created using BWA-MEM to a linear-reference and Giraffe mapping to a pangenome graph containing data from the 1000 Genomes Project. We have also adapted and upgraded deleterious-variant (DV) detecting methods and programs into a streamlined workflow. We used these workflows in combination to detect small lists of candidate DVs among 15 family quartets and quintets of the Undiagnosed Diseases Program (UDP). All candidate DVs that were previously diagnosed using the Mendelian models covered by the previously published methods were recapitulated by these workflows. The results of these experiments indicate that a slightly greater absolute count of DVs are detected in the proband population than in their matched unaffected siblings.