Hypothalamic MRI-derived microstructure is associated with neurocognitive aging in humans.

The hypothalamus regulates homeostasis across the lifespan and is emerging as a regulator of aging. In murine models, aging-related changes in the hypothalamus, including microinflammation and gliosis, promote accelerated neurocognitive decline. We investigated relationships between hypothalamic microstructure and features of neurocognitive aging, including cortical thickness and cognition, in a cohort of community-dwelling older adults (age range 65-97 years, n=124). Hypothalamic microstructure was evaluated with two magnetic resonance imaging diffusion metrics: mean diffusivity (MD) and fractional anisotropy (FA), using a novel image processing pipeline. Hypothalamic MD was cross-sectionally positively associated with age and it was negatively associated with cortical thickness. Hypothalamic FA, independent of cortical thickness, was cross-sectionally positively associated with neurocognitive scores. An exploratory analysis of longitudinal neurocognitive performance suggested that lower hypothalamic FA may predict cognitive decline. No associations between hypothalamic MD, age, and cortical thickness were identified in a younger control cohort (age range 18-63 years, n=99). To our knowledge, this is the first study to demonstrate that hypothalamic microstructure is associated with features of neurocognitive aging in humans.

Neck strength alone does not mitigate adverse associations of soccer heading with cognitive performance in adult amateur players.

OBJECTIVES: Soccer heading is adversely associated with neurocognitive performance, but whether greater neck strength or anthropometrics mitigates these outcomes is controversial. Here, we examine the effect of neck strength or anthropometrics on associations of soccer heading with neurocognitive outcomes in a large cohort of adult amateur players. METHODS: 380 adult amateur league soccer players underwent standardized measurement of neck strength (forward flexion, extension, left lateral flexion, right lateral flexion) and head/neck anthropometric measures (head circumference, neck length, neck circumference and neck volume). Participants were assessed for heading (HeadCount) and cognitive performance (Cogstate) on up to 7 visits over a period of two years. Principal components analysis (PCA) was performed on 8 neck strength and anthropometric measures. We used generalized estimating equations to test the moderation effect of each of the three PCs on 8 previously identified adverse associations of 2-week and 12-month heading estimates with cognitive performance (psychomotor speed, immediate verbal recall, verbal episodic memory, attention, working memory) and of unintentional head impacts on moderate to severe central nervous system symptoms. RESULTS: 3 principal components (PC's) account for 80% of the variance in the PCA. In men, PC1 represents head/neck anthropometric measures, PC2 represents neck strength measures, and PC3 represents the flexor/extensor (F/E) ratio. In women, PC1 represents neck strength, PC2 represents anthropometrics, and PC3 represents the F/E ratio. Of the 48 moderation effects tested, only one showed statistical significance after Bonferroni correction, which was not robust to extensive sensitivity analyses. CONCLUSION: Neither neck strength nor anthropometrics mitigate adverse associations of soccer heading with cognitive performance in adult amateur players.

Exhaled breath condensate contains extracellular vesicles (EVs) that carry miRNA cargos of lung tissue origin that can be selectively purified and analyzed.

Lung diseases, including lung cancer, are rising causes of global mortality. Despite novel imaging technologies and the development of biomarker assays, the detection of lung cancer remains a significant challenge. However, the lung communicates directly with the external environment and releases aerosolized droplets during normal tidal respiration, which can be collected, stored and analzsed as exhaled breath condensate (EBC). A few studies have suggested that EBC contains extracellular vesicles (EVs) whose microRNA (miRNA) cargos may be useful for evaluating different lung conditions, but the cellular origin of these EVs remains unknown. In this study, we used nanoparticle tracking, transmission electron microscopy, Western blot analyses and super resolution nanoimaging (ONi) to detect and validate the identity of exhaled EVs (exh-EVs). Using our customizable antibody-purification assay, EV-CATCHER, we initially determined that exh-EVs can be selectively enriched from EBC using antibodies against three tetraspanins (CD9, CD63 and CD81). Using ONi we also revealed that some exh-EVs harbour lung-specific proteins expressed in bronchiolar Clara cells (Clara Cell Secretory Protein [CCSP]) and Alveolar Type II cells (Surfactant protein C [SFTPC]). When conducting miRNA next generation sequencing (NGS) of airway samples collected at five different anatomic levels (i.e., mouth rinse, mouth wash, bronchial brush, bronchoalveolar lavage [BAL] and EBC) from 18 subjects, we determined that miRNA profiles of exh-EVs clustered closely to those of BAL EVs but not to those of other airway samples. When comparing the miRNA profiles of EVs purified from matched BAL and EBC samples with our three tetraspanins EV-CATCHER assay, we captured significant miRNA expression differences associated with smoking, asthma and lung tumor status of our subjects, which were also reproducibly detected in EVs selectively purified with our anti-CCSP/SFTPC EV-CATCHER assay from the same samples, but that confirmed their lung tissue origin. Our findings underscore that enriching exh-EV subpopulations from EBC allows non-invasive sampling of EVs produced by lung tissues.

Imaging Utilization and Cost of Substance Use in an Urban Academic Medical Center During the Contemporary Opioid Epidemic.

RATIONALE AND OBJECTIVES: To determine the recent impact of illicit substance use on imaging utilization and associated costs. METHODS: Retrospective study from an inner city urban multi-site academic medical center. Institutional Review Board (IRB) approval was obtained with a waiver of informed consent. A substance use cohort comprised patients 12 years old presenting to the Emergency Department (ED) January 2017 to June 2019 with a positive urine toxicology and an ICD code associated with substance use. The comparison cohort was randomly selected from a group of ED patients who presented with no or negative urine toxicology and no documented substance use ICD code. Data extracted from the EMR included demographics, number and type of imaging studies, Charlson comorbidity index, and in-hospital mortality during the study period. RESULTS: The substance use and comparison cohorts comprised 3191 and 3200 patients, respectively. The substance use cohort was older on average (mean age 45.67 ± 14.88 vs 43.91 ± 20.57 years), more often male (63% [2026/3191] vs. 39% [1255/3200]) and had a mean Charlson score 88% higher than the comparison cohort (3.33 vs 1.78). The majority of both cohorts were ethnic minorities (<10% white). The substance use cohort had significantly more imaging vs the comparison cohort, total 36,413 (mean 11.41 exams/patient) vs total 12,399 (mean 3.87 exams/patient), p < 0.0001, and was higher for all modalities except mammography. Average imaging costs per patient were nearly 300% higher for the substance use vs comparison cohort, ($1287.18 vs. $434.70). CONCLUSION: Imaging utilization and associated costs were substantially higher for patients with a positive urine toxicology and substance use related ICD codes compared to the broader ED population in an underserved urban population.

Reduced healthcare access contributes to delay of care in endometrial cancer.

OBJECTIVE: We aimed to characterize delays to care in patients with endometrioid endometrial cancer and the role healthcare access plays in these delays. METHODS: A chart review was performed of patients with endometrioid endometrial cancer who presented with postmenopausal bleeding at a diverse, urban medical center between 2006 and 2018. The time from symptom onset to treatment was abstracted from the medical record. This interval was subdivided to assess for delay to presentation, delay to diagnosis, and delay to treatment. RESULTS: We identified 484 patients who met the inclusion criteria. The median time from symptom onset to treatment was 4 months with an interquartile range of 2 to 8 months. Most patients had stage I disease at diagnosis (88.6%). There was no significant difference in race/ethnicity or disease stage at time of diagnosis between different groups. Patients who had not seen a primary care physician or general obstetrician-gynecologist in the year before symptom onset were more likely to have significantly delayed care (27.7% vs 14.3%, p = 0.02) and extrauterine disease (20.2% vs 4.9%, p < 0.01) compared to those with established care. Black and Hispanic patients were more likely to experience significant delays from initial biopsy to diagnosis. CONCLUSIONS: Delays exist in the evaluation of endometrial cancer. This delay is most pronounced in patients without an established outpatient primary care provider or obstetrician-gynecologist.

Evolving brain and behaviour changes in rats following repetitive subconcussive head impacts.

There is growing concern that repetitive subconcussive head impacts, independent of concussion, alter brain structure and function, and may disproportionately affect the developing brain. Animal studies of repetitive subconcussive head impacts are needed to begin to characterize the pathological basis and mechanisms underlying imaging and functional effects of repetitive subconcussive head impacts seen in humans. Since repetitive subconcussive head impacts have been largely unexplored in animals, we aimed to characterize the evolution of imaging, behavioural and pathological effects of repetitive subconcussive head impacts in awake adolescent rodents. Awake male and female Sprague Dawley rats (postnatal Day 35) received 140 closed-head impacts over the course of a week. Impacted and sham-impacted animals were restrained in a plastic cone, and unrestrained control animals were included to account for effects of restraint and normal development. Animals (n = 43) underwent repeated diffusion tensor imaging prior to and over 1 month following the final impact. A separate cohort (n = 53) was assessed behaviourally for fine motor control, emotional-affective behaviour and memory at acute and chronic time points. Histological and immunohistochemical analyses, which were exploratory in nature due to smaller sample sizes, were completed at 1 month following the final impact. All animals tolerated the protocol with no overt changes in behaviour or stigmata of traumatic brain injury, such as alteration of consciousness, intracranial haemorrhage or skull fracture. We detected longitudinal, sex-dependent diffusion tensor imaging changes (fractional anisotropy and axial diffusivity decline) in corpus callosum and external capsule of repetitive subconcussive head impact animals, which diverged from both sham and control. Compared to sham animals, repetitive subconcussive head impact animals exhibited acute but transient mild motor deficits. Repetitive subconcussive head impact animals also exhibited chronic anxiety and spatial memory impairment that differed from the control animals, but these effects were not different from those seen in the sham condition. We observed trends in the data for thinning of the corpus callosum as well as regions with elevated Iba-1 in the corpus callosum and cerebral white matter among repetitive subconcussive head impact animals. While replication with larger study samples is needed, our findings suggest that subconcussive head impacts cause microstructural tissue changes in the developing rat brain, which are detectable with diffusion tensor imaging, with suggestion of correlates in tissue pathology and behaviour. The results point to potential mechanisms underpinning consequences of subconcussive head impacts that have been described in humans. The congruence of our imaging findings with human subconcussive head impacts suggests that neuroimaging could serve as a translational bridge to advance study of injury mechanisms and development of interventions.

Predictive Value of CT Biomarkers in Lung Transplantation Survival: Preliminary Investigation in a Diverse, Underserved, Urban Population.

INTRODUCTION: Survival following lung transplant is low. With limited donor lung availability, predicting post-transplant survival is key. We investigated the predictive value of pre-transplant CT biomarkers on survival. METHODS: In this single-center retrospective cohort study of adults in a diverse, underserved, urban lung transplant program (11/8/2017-5/20/2022), chest CTs were analyzed using TeraRecon to assess musculature, fat, and bone. Erector spinae and pectoralis muscle area and attenuation were analyzed. Sarcopenia thresholds were 34.3 (women) and 38.5 (men) Hounsfield Units (HU). Visceral and subcutaneous fat area and HU, and vertebral body HU were measured. Demographics and pre-transplant metrics were recorded. Survival analyses included Kaplan-Meier and Cox proportional hazard. RESULTS: The study cohort comprised 131 patients, 50 women, mean age 60.82 (SD 10.15) years, and mean follow-up 1.78 (SD 1.23) years. Twenty-nine percent were White. Mortality was 32.1%. Kaplan-Meier curves did not follow the proportional hazard assumption for sex, so analysis was stratified. Pre-transplant EMR metrics did not predict survival. Women without sarcopenia at erector spinae or pectoralis had 100% survival (p = 0.007). Sarcopenia did not predict survival in men and muscle area did not predict survival in either sex. Men with higher visceral fat area and HU had decreased survival (p = 0.02). Higher vertebral body density predicted improved survival in men (p = 0.026) and women (p = 0.045). CONCLUSION: Pre-transplantation CT biomarkers had predictive value in lung transplant survival and varied by sex. The absence of sarcopenia in women, lower visceral fat attenuation and area in men, and higher vertebral body density in both sexes predicted survival in our diverse, urban population.

Elaborate biologic approval process delays care of patients with moderate-to-severe asthma.

Background: mAbs (biologics) are indicated in patients with poorly controlled moderate-to-severe asthma. The process of prior authorization and administration of a biologic requires exceptional commitment from clinical teams. Objective: Our aim was to evaluate the process of approval and administration of biologics for asthma and determine the most common reasons associated with denials of biologics and delays in administration. Methods: We examined the records of patients with asthma who were prescribed biologics from January 2018 to January 2020 at 2 centers, Montefiore Medical Center (Bronx, NY) and Scripps Clinics (San Diego, Calif). Demographics, insurance information, and details on the approval process were collected. Results: After querying of electronic health records, the records of 352 and 70 patients with moderate-to-severe asthma were included from Montefiore and Scripps, respectively. Most patients at Montefiore (58.2%) were insured under Managed Care Medicaid (MC Medicaid), whereas most patients at Scripps (61.4%) had commercial insurance. The median times from prescription to administration of a biologic were similar: 34 days (interquartile range [IQR] = 18-63 days) and 34 days (IQR = 22.5-56.0 days) (P = .97) for Montefiore and Scripps, respectively. However, the median approval time for Montefiore was 6 days (IQR = 1-20 days) and that for Scripps was 22 days (IQR = 10-36 days) (P < .001). Approval times for prescriptions requiring appeals were significantly longer than for prescriptions approved after the initial submission: 23 days versus 2.5 days and 40.5 days versus 15.5 days (for Montefiore and Scripps, respectively [P < .001 for both]). Conclusions: Lengthy appeals contribute to delays between prescribing and administering a biologic. Site-specific practices and insurance coverage influence approval timing of the biologics for asthma.

Abdominopelvic CT in COVID-19 patients with abdominal complaints including both waves and controls: reader agreement and overcalls after consensus review.

BACKGROUND: Since many COVID-19 publications lack consensus reviews or controls, interpretive accuracy is unclear; abdominal processes unique or infrequent during the pandemic remain unknown. The incidence and nature of CT findings accounting for abdominal complaints in COVID patients, reader agreement and overcalling will be determined. METHODS: A retrospective study was performed on COVID patients with abdominal complaints from 3/15/2020-5/31/2020 and 11/1/2020-4/15/2021 including matched controls. Reviewers blinded to initial reads interpreted abdominopelvic CT exams, with discordant cases resolved in consensus. Reader agreement was measured by Cohen's Kappa, differences between cohorts by permutation tests and factors affecting false positive/negative rates by Fisher's Exact Test and logistic regression. RESULTS: 116 first wave (average age 65 years [±15.3], 63 [54%] women) and 194 second wave COVID cases (average age 64 years [±16.3], 103 [53%] women) including 116 wave 1 and 194 wave 2 prepandemic controls were included. Concordance was lower among COVID cases than controls (Cohen's Kappa of 0.58 vs. 0.82 [p ≤ 0.001]) and among wave 1 than wave 2 cases (Cohen's Kappa of 0.45 vs. 0.66 [p = 0.052]). With true positives defined as consensus between the initial reader and study reader, false positive rates were higher among COVID cases than controls (OR = 0.42, p = 0.003) and for initial than study reader (OR = 0.36, p ≤ 0.001), but lower in wave 2 than 1 (OR = 0.5, p = 0.028). CONCLUSION: Greater reader disagreement occurred during COVID than prepandemic with no reader bias as both initial and study readers called more false positives among COVID cases than controls. More overcalling occurred during COVID with colitis and cystitis most common.

Coronary Calcium Predicts All-Cause Mortality in Suspected Acute Aortic Syndrome.

Purpose: To determine long-term clinical outcomes in patients with suspected acute aortic syndrome (AAS) and evaluate the prognostic value of coronary calcium burden as assessed with CT aortography in this symptomatic population. Materials and Methods: A retrospective cohort of all patients who underwent emergency CT aortography from January 2007 through January 2012 for suspected AAS was assembled. A medical record survey tool was used to evaluate subsequent clinical events over 10 years of follow-up. Events included death, aortic dissection, myocardial infarction, cerebrovascular accident, and pulmonary embolism. Coronary calcium scores were computed from original images using a validated simple 12-point ordinal method and categorized into none, low (1-3), moderate (4-6), or high (7-12) groupings. Survival analysis with Kaplan-Meier curves and Cox proportional hazard modeling was performed. Results: The study cohort comprised 1658 patients (mean age, 60 years ± 16 [SD]; 944 women), with 595 (35.9%) developing a clinical event over a median follow-up of 6.9 years. Patients with high coronary calcium demonstrated the highest mortality rate (adjusted hazard ratio = 2.36; 95% CI: 1.65, 3.37). Patients with low coronary calcium demonstrated lower mortality, but rates were still almost twice as high compared with patients with no detectable calcium (adjusted hazard ratio = 1.89; 95% CI: 1.41, 2.53). Coronary calcium was a strong predictor of major adverse cardiovascular events (P < .001), which persisted after adjustment for common significant comorbidities. Conclusion: Patients with suspected AAS had a high rate of subsequent clinical events, including death. CT aortography-based coronary calcium scores strongly and independently predicted all-cause mortality.Keywords: Acute Aortic Syndrome, Coronary Artery Calcium, CT Aortography, Major Adverse Cardiovascular Events, Mortality Supplemental material is available for this article. © RSNA, 2023See also commentary by Weir-McCall and Shambrook in this issue.

Sharing parental genomes by siblings concordant or discordant for autism.

Studying thousands of families, we find siblings concordant for autism share more of their parental genomes than expected by chance, and discordant siblings share less, consistent with a role of transmission in autism incidence. The excess sharing of the father is highly significant (p value of 0.0014), with less significance for the mother (p value of 0.31). To compare parental sharing, we adjust for differences in meiotic recombination to obtain a p value of 0.15 that they are shared equally. These observations are contrary to certain models in which the mother carries a greater load than the father. Nevertheless, we present models in which greater sharing of the father is observed even though the mother carries a greater load. More generally, our observations of sharing establish quantitative constraints that any complete genetic model of autism must satisfy, and our methods may be applicable to other complex disorders.

Utility of the coned-down lateral view of the lumbosacral spine.

OBJECTIVE: At certain institutions and radiology practices, a routine lumbar radiographic exam may include 3 views: AP, lateral, and coned-down lateral of the lumbosacral junction. The purpose of this study is to determine whether the third coned-down-lateral view adds significant diagnostic information regarding pathology at the L4-L5 and L5-S1 levels. MATERIALS AND METHODS: This retrospective study includes patients (n = 74) who had a 3-view radiographic exam of the lumbar spine, as well as a CT or MRI within six months. The AP and lateral views were reviewed by three radiologists, both with and without the use of the third, coned-lateral view. Subsequently, the CT and MRI performed within 6 months was reviewed, and the results compared. The primary outcome was detection of abnormal alignment and disc disease at the L4-L5 and L5-S1 levels. RESULTS: For the combined findings of alignment and disc disease at each L4-L5 and L5-S1, there was disagreement between the 2-view and 3-view exams on 18 (of 296) evaluations. Of these 18, the 2-view and the 3-view exam each made positive findings on 9. By the binomial test, there is no evidence that either the 2-view or the 3-view exam tends to make more findings than the other (p = 1). Compared to CT/MRI, the 2-view exam agrees on 74.7 % of evaluations and the 3-view exam agrees on 75.3 %. There is therefore no evidence that the 3-view exam is more accurate than the 2-view exam. CONCLUSION: Elimination of the coned-down lateral view could reduce radiation exposure and imaging-related costs while maintaining diagnostic quality.

Frailty Resilience Score: A Novel Measure of Frailty Resilience Associated With Protection From Frailty and Survival.

Frailty is characterized by increased vulnerability to disability and high risk for mortality in older adults. Identification of factors that contribute to frailty resilience is an important step in the development of effective therapies that protect against frailty. First, a reliable quantification of frailty resilience is needed. We developed a novel measure of frailty resilience, the Frailty Resilience Score (FRS), that integrates frailty genetic risk, age, and sex. Application of FRS to the LonGenity cohort (n = 467, mean age 74.4) demonstrated its validity compared to phenotypic frailty and its utility as a reliable predictor of overall survival. In a multivariable-adjusted analysis, 1-standard deviation increase in FRS predicted a 38% reduction in the hazard of mortality, independent of baseline frailty (p < .001). Additionally, FRS was used to identify a proteomic profile of frailty resilience. FRS was shown to be a reliable measure of frailty resilience that can be applied to biological studies of resilience.

Initial development and testing of an exhaled microRNA detection strategy for lung cancer case-control discrimination.

For detecting field carcinogenesis non-invasively, early technical development and case-control testing of exhaled breath condensate microRNAs was performed. In design, human lung tissue microRNA-seq discovery was reconciled with TCGA and published tumor-discriminant microRNAs, yielding a panel of 24 upregulated microRNAs. The airway origin of exhaled microRNAs was topographically "fingerprinted", using paired EBC, upper and lower airway donor sample sets. A clinic-based case-control study (166 NSCLC cases, 185 controls) was interrogated with the microRNA panel by qualitative RT-PCR. Data were analyzed by logistic regression (LR), and by random-forest (RF) models. Feasibility testing of exhaled microRNA detection, including optimized whole EBC extraction, and RT and qualitative PCR method evaluation, was performed. For sensitivity in this low template setting, intercalating dye-based URT-PCR was superior to fluorescent probe-based PCR (TaqMan). In application, adjusted logistic regression models identified exhaled miR-21, 33b, 212 as overall case-control discriminant. RF analysis of combined clinical + microRNA models showed modest added discrimination capacity (1.1-2.5%) beyond clinical models alone: all subjects 1.1% (p = 8.7e-04)); former smokers 2.5% (p = 3.6e-05); early stage 1.2% (p = 9.0e-03), yielding combined ROC AUC ranging from 0.74 to 0.83. We conclude that exhaled microRNAs are qualitatively measureable, reflect in part lower airway signatures; and when further refined/quantitated, can potentially help to improve lung cancer risk assessment.

Dynamic Intestinal Stem Cell Plasticity and Lineage Remodeling by a Nutritional Environment Relevant to Human Risk for Tumorigenesis.

New Western-style diet 1 (NWD1), a purified diet establishing mouse exposure to key nutrients recapitulating levels that increase human risk for intestinal cancer, reproducibly causes mouse sporadic intestinal and colonic tumors reflecting human etiology, incidence, frequency, and lag with developmental age. Complex NWD1 stem cell and lineage reprogramming was deconvolved by bulk and single-cell RNA sequencing, single-cell Assay for Transposase-Accessible Chromatin using sequencing, functional genomics, and imaging. NWD1 extensively, rapidly, and reversibly, reprogrammed Lgr5hi stem cells, epigenetically downregulating Ppargc1a expression, altering mitochondrial structure and function. This suppressed Lgr5hi stem cell functions and developmental maturation of Lgr5hi cell progeny as cells progressed through progenitor cell compartments, recapitulated by Ppargc1a genetic inactivation in Lgr5hi cells in vivo. Mobilized Bmi1+, Ascl2hi cells adapted lineages to the nutritional environment and elevated antigen processing and presentation pathways, especially in mature enterocytes, causing chronic, protumorigenic low-level inflammation. There were multiple parallels between NWD1 remodeling of stem cells and lineages with pathogenic mechanisms in human inflammatory bowel disease, also protumorigenic. Moreover, the shift to alternate stem cells reflects that the balance between Lgr5-positive and -negative stem cells in supporting human colon tumors is determined by environmental influences. Stem cell and lineage plasticity in response to nutrients supports historic concepts of homeostasis as a continual adaptation to environment, with the human mucosa likely in constant flux in response to changing nutrient exposures. IMPLICATIONS: Although oncogenic mutations provide a competitive advantage to intestinal epithelial cells in clonal expansion, the competition is on a playing field dynamically sculpted by the nutritional environment, influencing which cells dominate in mucosal maintenance and tumorigenesis.

Intestinal stem cell aging at single-cell resolution: Transcriptional perturbations alter cell developmental trajectory reversed by gerotherapeutics.

The intestinal epithelium consists of cells derived from continuously cycling Lgr5hi intestinal stem cells (Lgr5hi ISCs) that mature developmentally in an ordered fashion as the cells progress along the crypt-luminal axis. Perturbed function of Lgr5hi ISCs with aging is documented, but the consequent impact on overall mucosal homeostasis has not been defined. Using single-cell RNA sequencing, the progressive maturation of progeny was dissected in the mouse intestine, which revealed that transcriptional reprogramming with aging in Lgr5hi ISCs retarded the maturation of cells in their progression along the crypt-luminal axis. Importantly, treatment with metformin or rapamycin at a late stage of mouse lifespan reversed the effects of aging on the function of Lgr5hi ISCs and subsequent maturation of progenitors. The effects of metformin and rapamycin overlapped in reversing changes of transcriptional profiles but were also complementary, with metformin more efficient than rapamycin in correcting the developmental trajectory. Therefore, our data identify novel effects of aging on stem cells and the maturation of their daughter cells contributing to the decline of epithelial regeneration and the correction by geroprotectors.

Lung Cancer Screening Penetration in an Urban Underserved County.

PURPOSE: To compare residential geography, sex, socioeconomic status (SES), and race/ethnicity of patients screened at Montefiore's Lung Cancer Screening Program with those of patients diagnosed with lung cancer, assessing whether screening efforts are appropriately focused. METHODS: This retrospective cohort study involved patients within a multisite urban medical center undergoing lung cancer screening or diagnosed with lung cancer from January 1, 2015 to December 31, 2019. Inclusion criteria were residence within the Bronx, NY and age between 55 and 80 years. Institutional review board approval was obtained. Data were analyzed using the Wilcoxon two-sample t test and χ2. RESULTS: The cohorts comprised 1568 (50.3%) women and 1551 (49.7%) men (mean age 65.6 ± 6.16). The Southeast Bronx had the most diagnosed lung cancers (29.96%) and screenings (31.22%). Sex did not significantly differ (p = 0.053). Cancer and screening cohorts were from impoverished neighborhoods with mean SES of - 3.11 ± 2.78 and - 3.44 ± 2.80 (p < 0.01). The lower tier SES neighborhoods demonstrated more patients in the screening cohort than cancer cohort (p = 0.01). Both cohorts included a majority of Hispanic patients, although race/ethnicity differed significantly (p = 0.01). Lower SES neighborhoods showed no significant difference in race/ethnicity between cancer and screening cohorts (p = 0.262). CONCLUSION: Though statistically significant differences were found between cohorts, likely due to sample size, few clinically meaningful differences were found, implying our lung cancer screening program was effective in reaching the desired population. Demographics-based programs should be considered in global efforts to screen vulnerable populations.

Age of first exposure to soccer heading: Associations with cognitive, clinical, and imaging outcomes in the Einstein Soccer Study.

Introduction: The objective of this study is to assess the role of age at first exposure (AFE) to soccer heading as a predictor of known adverse associations of recent and longer-term heading with brain microstructure, cognitive, and behavioral features among adult amateur soccer players. Methods: The sample included 276 active amateur soccer players (196 male and 81 female) aged 18-53 years old. AFE to soccer heading was treated as a binary variable, dichotomized at ≤ 10 years vs. >10 years old, based on a recently promulgated US Soccer policy, which bans heading for athletes ages 10 and under. Results: We found that soccer players who began heading at age 10 or younger performed better on tests of working memory (p = 0.03) and verbal learning (p = 0.02), while accounting for duration of heading exposure, education, sex, and verbal intelligence. No difference in brain microstructure or behavioral measures was observed between the two exposure groups. Discussion: The findings indicate that, among adult amateur soccer players, AFE to heading before age 10 compared to later start of heading, is not associated with adverse outcomes, and may be associated with better cognitive performance in young adulthood. Cumulative heading exposure across the lifespan, rather than early life exposure, may drive risk for adverse effects and should be the focus of future longitudinal studies to inform approaches to enhance player safety.

Clearing the Congestion: Chest Radiography and BNP to Rule-out Congestive Heart Failure.

PURPOSE: Ruling out congestive heart failure (CHF) is clinically important in Emergency Department (ED) patients. Normal serum brain natriuretic peptide (BNP) represents an important reference standard for excluding CHF. Results of chest radiographs (CXR) are also considered and, when discordant with BNP levels, may result in a clinical dilemma. The present study was designed to elucidate factors associated with CHF on CXR in an ED cohort with normal BNP. MATERIALS AND METHODS: All adults at our urban health system's EDs who underwent CXR within 24 hours and had a normal BNP (<300 pg/mL) within 24 hours of CXR were retrospectively identified. Of these, 0.9% (8/862) had equivocal CXRs and was excluded. Demographics, comorbidities, CXR report results for CHF, and portable technique were noted. Logistic regression was used to assess factors that are associated with the presence of CHF on CXR. RESULTS: The study cohort comprised 854 patients (433 men, mean age 60.99±15.30) with normal BNP; 91.5% (781/854) had no CHF on CXR and 8.5% (73/854) had CHF. Patients with CHF on CXR had a higher body mass index (32.9 vs. 29.8 kg/m 2 , P =0.0205) were more likely to have a history of CHF or diabetes with complications (OR: 2.72 and 2.53, respectively), had higher serum BNP levels (median 164 vs. 98 pg/mL, P =4.91×10 -5 ), and underwent portable examination more frequently (86.3% vs. 57.5%, OR: 4.65). CONCLUSIONS: Normal serum BNP was concordant with CXR results, adding diagnostic confidence in ruling out CHF in a large majority of ED patients. A higher body mass index, history of CHF, and diabetes with complications and portable CXR technique were associated with CHF on CXR among the minority with normal BNP.

Using Routine Chest Computed Tomography to Diagnose Pulmonary Embolism.

OBJECTIVE: This study investigated the use of routine contrast-enhanced chest computed tomography (CT) to diagnose unsuspected pulmonary embolism (PE). METHODS: All adult routine contrast-enhanced chest CTs performed at Montefiore in 2018 were included. Pulmonary artery enhancement was measured by placing regions of interest in the pulmonary vasculature. Adequate enhancement was defined as 200 Hounsfield units (HU) or greater. Presence or absence of PE was noted. Descriptive statistics and logistic regression analysis were performed. RESULTS: A total of 3164 CTs were evaluated (55.8% women; mean age, 63.2 years). Main pulmonary enhancement was highly correlated with peripheral enhancement. Of all cases, 28.7% (907 of 3164) reached the 200 HU threshold. Greater enhancement was associated with female sex, older age, outpatients, and contrast amount administered. Pulmonary embolism-positive cases comprised 1.8% (58 of 3164) of total cases. Furthermore, 39.7% (23 of 58) of PE-positive cases reached the 200 HU threshold. CONCLUSIONS: Over one quarter of routine contrast-enhanced chest CT scans met the 200 HU threshold indicative of adequate pulmonary artery enhancement, including nearly half of the 2% of examinations positive for PE.