Faculty Bibliography

Gliomas are the most common primary brain tumors and a major source of mortality and morbidity in adults and children. Recent genomic studies have identified multiple molecular subtypes; however metabolic characterization of these tumors has thus far been limited. We performed metabolic profiling of 114 adult and pediatric primary gliomas and integrated metabolomic data with transcriptomics and DNA methylation classes. We identified that pediatric tumors have higher levels of glucose and reduced lactate compared to adult tumors regardless of underlying genetics or grade, suggesting differences in availability of glucose and/or utilization of glucose for downstream pathways. Differences in glucose utilization in pediatric gliomas may be facilitated through overexpression of SLC2A4, which encodes the insulin-stimulated glucose transporter GLUT4. Transcriptomic comparison of adult and pediatric tumors suggests that adult tumors may have limited access to glucose and experience more hypoxia, which is supported by enrichment of lactate, 2-hydroxyglutarate (2-HG), even in isocitrate dehydrogenase (IDH) wild-type tumors, and 3-hydroxybutyrate, a ketone body that is produced by oxidation of fatty acids and ketogenic amino acids during periods of glucose scarcity. Our data support adult tumors relying more on fatty acid oxidation, as they have an abundance of acyl carnitines compared to pediatric tumors and have significant enrichment of transcripts needed for oxidative phosphorylation. Our findings suggest striking differences exist in the metabolism of pediatric and adult gliomas, which can provide new insight into metabolic vulnerabilities for therapy.

BACKGROUND:The goal of this study was to utilize preoperative computed-tomography(CT) scans to identify differences in the Hounsfield units(HU) of the acromion in patients who did and did not develop a postoperative acromial and scapular-spine fracture(ASF) after primary reverse total shoulder arthroplasty (rTSA). METHODS:A retrospective analysis was performed at a single institution. All patients undergoing a rTSA with either a 135° neck/shaft angle(NSA) humeral inlay design combined with a lateralized center-of-rotation(COR) glenosphere or a 145° NSA onlay combined with a medialized COR glenosphere design between 2011-2021 with a minimum follow-up of 24-months were included. Demographic characteristics and clinical outcome metric scores were recorded. Preoperative CT scans were analyzed to obtain acromion trabecular bone density measurements in HU in each zone of the scapula based on the Levy classification. Radiographic parameters were evaluated to determine their association with ASF. RESULTS:In total 263-patients were included, 140-patients with a 135° NSA humeral-inlay design;123-patients with a 145° NSA humeral-onlay design. There were no significant differences in baseline demographics between cohorts. The rate of ASF was 6.4%(9/140) for the 135° NSA-inlay-design versus 2.4%(3/123) in the 145° NSA-onlay design. In the non-fracture cohort there was a linear increase in bone density from zone-1(173.9HU)→zone-3(396.5HU)(lateral→medial). In the fracture cohort there was a decrease in bone density from zone-1(282.6HU)→zone-3(154.5HU). Measuring preoperative bone density in all Levy specific fracture-zones resulted in an AUC of 0.96 correlating to excellent predictive value. A threshold cutoff of 99.9 resulted in a sensitivity of 91.6% and specificity of 75.3%. A HU of 99.9 in any of the three-zones resulted in OR 5.1(p<0.0001) for sustaining an ASF postoperatively. A threshold of<50HU was associated with an 8-times higher-likelihood of developing a fracture in that specific zone. Greater than 5° of superior tilt in combination with ≥24mm of distalization was associated with an OR 6.4(p=0.0004) of sustaining an ASF. CONCLUSION/CONCLUSIONS:The current study demonstrates an accurate method of measuring HU at each of the described Levy fracture zones with excellent predictability of patients who are at risk of an ASF following rTSA. Additionally, we found that a HU threshold of <50 HU at any of the three Levy zones was associated with a nearly 8 times higher likelihood of developing a fracture in that specific zone. Lastly, we found that >5° of superior tilt in combination with ≥24mm of distalization was associated with 6.4 times higher likelihood of sustaining an ASF agnostic to prosthesis design.

BACKGROUND:In clinical settings, counseling patients on physical activity starts by assessing patients' current physical activity levels. Self-report measures of PA are generally easy to administer; however, they may be too long to be convenient and are known to correlate poorly with objective measures of physical activity. OBJECTIVE:To assess the concurrent validity of a self-report three-question physical activity vital sign with objective Fitbit step counts and the distance walked during a 6-min walk test. METHODS:This pilot study tested a best practice advisory embedded in the Epic electronic health record, which was designed to prompt providers in a preventive cardiology clinic to counsel patients reporting low levels of physical activity . Patients were invited to participate in the remote patient monitoring phase to assess the change in their physical activity by wearing a Fitbit for 12 weeks and completing a 6-min walk test at baseline and 12 weeks. This analysis used the cross-sectional data collected in this phase. Pearson correlations were conducted between self-reported physical activity, Fitbit step counts, and the distance walked during the 6-min walk-a measure associated with current physical activity levels. Kappa coefficients were calculated to assess agreement between the self-reported physical activity and step counts. RESULTS:Participants who enrolled in the Fitbit monitoring were approximately 50% female, with the majority identified as White non-Hispanic adults. Their most common cardiovascular risk factor was hypertension. The self-reported physical activity vital signs were significantly associated with step counts at baseline and 12 weeks but were not associated with the distance during the 6-min walk test. However, the distance walked was significantly associated with step counts at baseline and 12 weeks. The Kappa results demonstrate a poor level of agreement between two categories (meeting or not meeting current physical activity guidelines) of self-report physical activity vitals and the objective Fitbit step counts. DISCUSSION/CONCLUSIONS:There were moderate correlations between the self-reported physical activity vital signs and the Fitbit step counts, but there was lack of agreement when they were categorized. Further validation of this physical activity vital sign is warranted.

BackgroundAdvances in STN-DBS technology, among which directional stimulation, improved Parkinson's disease (PD) treatment efficacy, while increasing the clinical programming complexity. Lead localization software may aid the stimulation contact selection process.ObjectiveWe aimed to assess the concordance between imaging-suggested (IGP) and conventional-programming (CP) selected stimulation contacts one year after surgery and its impact on motor outcomes.MethodsSixty-four PD patients with bilateral STN-DBS were enrolled. Lead localization was reconstructed with Brainlab^TM software. For each electrode, the vertical contact level and, when applicable, the directionality predicted by the lead reconstruction software to be the most effective were established and compared to the stimulation parameters clinically activated one-year post-surgery. IGP/CP concordance ratio was calculated for both stimulation level and directional contacts. Post-operative modifications of PD motor symptoms severity were compared among groups of concordant and discordant IGP/CP programming.ResultsOne-year post-surgery, IGP/CP concordance was 80% for active stimulation vertical contact level and 51% for directionality. No significant difference in motor outcomes was found between IGP/CP concordant and discordant patients for contact level activation, whereas patients with concordant IGP/CP active directional stimulation (c-Direction) showed superior motor outcomes at one-year follow-up than those discordant (d-Direction) (UPDRS-III stimulation-induced improvement: c-Direction = -25.66 ± 13.74 vs. d-Direction = -12.54 ± 11.86; p = 0.011).ConclusionsVisual reconstruction software correctly predicted the most clinically effective stimulation contact levels in most patients. Imaging therefore facilitates classic STN-DBS clinical programming while assuring similar outcomes. Moreover, better motor outcomes were reached by patients with concordant IGP/CP directional parameters, suggesting that visualization can represent an added value in particular for directional stimulation programming.

BACKGROUND/UNASSIGNED:We investigated racial and ethnic disparities in telehealth counseling among Medicaid-insured patients in outpatient substance use disorder (SUD) treatment clinics and assessed whether the clinic-level proportion of Medicaid-insured patients moderated these disparities. METHODS/UNASSIGNED:Using New York State (NYS) Medicaid and statewide treatment registry data, we analyzed 24,814 admission episodes across 399 outpatient SUD clinics during the first 6 months of COVID-19 (April-September 2020). Our outcome measure was the number of tele-counseling sessions within the first 90 days of treatment. Key independent variables included beneficiary race/ethnicity and the clinic-level proportion of Medicaid-insured patients, divided into four quartiles: lowest, second, third, and highest. Mixed effects negative binomial models assessed the associations between race/ethnicity, Medicaid proportions, and telehealth use, with interaction terms evaluating the moderating role of Medicaid proportions. RESULTS/UNASSIGNED:Black and Latinx patients received fewer telehealth sessions than non-Latinx White patients, with adjusted incidence rate ratios (aIRRs) of 0.86 (95% CI: 0.82, 0.91) for Black patients and 0.93 (95% CI: 0.88, 0.98) for Latinx patients. Black patients at clinics with the highest Medicaid proportions had higher telehealth usage rates compared to those at clinics with the lowest Medicaid proportions (aIRR, 1.20; 95% CI, 1.03-1.41). Patients in clinics with the highest Medicaid proportions were more likely to use individual telehealth counseling (aIRR, 1.02-1.88; 95% CI, 1.01-3.04). CONCLUSIONS/UNASSIGNED:Significant racial disparities in telehealth use exist, with variations persisting across clinics with different Medicaid proportions. Targeted interventions are needed to address these access gaps.

PURPOSE/OBJECTIVE:The purpose of this study is to compare the quality and clinical outcomes of patients who underwent open reduction internal fixation for a proximal humerus fracture in a "timely manner" which was defined to be within 5 days of injury compared to those with "delayed intervention" (>5 Days) to determine the effect this had. METHODS:This IRB-approved study evaluated patients who sustained a proximal humerus fracture treated with plate and screw fixation (ORIF) between January 2004 and October 2022 and had time from injury to surgery documented. Patients were grouped based on the time to surgery (TTS) - Less than 5 Days (L5) vs. More than 5 Days (M5). TTS was also evaluated as a continuous variable. Univariable and multivariable analysis compared patient demographics, injury/surgical characteristics, postoperative complications, and clinical outcomes to determine effect of TTS. Clinical outcomes included shoulder range of motion (ROM) and Disabilities of the Arm, Shoulder, and Hand (DASH) score at least 1 year following the date of injury. Standard statistical tests were used (p<0.05 considered significant). RESULTS:, p=0.03, β= -0.27, 95% CI = -41.71- -2.89) surgery was associated with less passive forward elevation. CONCLUSION/CONCLUSIONS:Timing of surgery did not impact outcomes of patients who underwent open reduction internal fixation for proximal humerus fractures. Surgical intervention after 14 days was associated with diminished passive forward elevation only.

OBJECTIVES/OBJECTIVE:To evaluate the yield of CT-guided biopsy of 18F-piflufolastat PET avid osseous lesions in suspected prostate metastases. METHODS:Retrospective review of computed tomography guided biopsies targeting 18F-piflufolastat avid lesions on PET/CT or PET/MR performed between 2022 and 2024. Demographics, image modality, biopsy system, number of cores, lesion location, lean body mass corrected SUV (SUL) and pathology were recorded. Biopsied lesions were compared to the PROMISE (prostate cancer molecular imaging standardized evaluation) scoring system, version 2. RESULTS:Eighteen patients were included, average age 68.7 years. Lesions were defined as: ≥ 50 % sclerotic (n = 10), <50 % sclerotic (n = 7), occult (n = 0), and lytic (n = 1). A technically successful pathologic diagnosis was made in 94 % of biopsies (n = 17). Histopathological diagnosis included: metastatic prostate adenocarcinoma (n = 12), benign with fibrotic/densely sclerotic bone or normocellular bone marrow (n = 5), and metastatic non-small cell lung carcinoma (n = 1). The median SUL on PET for all patients was 7.9 (IQR 13.3), 2.6 (0.3) for benign biopsies, and 8.8 (12.5) for malignant biopsies. Major identifiable differences between biopsies yielding a metastatic versus benign diagnosis included: higher SUL (p-value = 0.03), target lesion volume (p-value = 0.01), and higher incidence of sclerotic lesions (p value = 0.003); however, multivariate analysis did not find these to be statistically significant predictors (p-value >0.05). The prostate cancer lesion biopsy positive group had significantly higher PROMISE scores than the negative group (p = 0.03). CONCLUSION/CONCLUSIONS:CT-guided biopsy of bone lesions demonstrating avidity for 18F-piflufolastat can be performed with a high diagnostic yield.

BACKGROUND:Parents of pediatric heart transplant (HTx) recipients have a unique perspective on the challenges associated with the transition into adult care networks. We sought to assess parental perceptions of the challenges pediatric HTx recipients face daily and parental concerns around the transition from pediatric care networks. METHODS:A 15-item online survey was developed in partnership with parent-stakeholders and administered to parents of pediatric HTx recipients in September 2023. Closed and open-ended questions assessed (1) the patients' diagnosis, age at diagnosis, and age at transplant, (2) parents' daily concerns about their child's well-being, (3) parents' overall concerns about their child's well-being as they transition into adulthood, (4) parents' perceptions of their child's quality-of-life (QoL) and health, and (5) parents' demographic characteristics. RESULTS:Eighty-six parents completed the survey. On a scale of 1 (worst) to 10 (best), 75% of parents rated their child's overall QoL at 8 or higher and 76% rated their child's health-related QoL at 8 or higher. Parents' daily concerns about their child's well-being included infectious diseases, health behaviors and care management, transplant-related concerns, socialization and education, mental health, and care coordination. Concerns related to the transition into adulthood included health behaviors and self-management, life satisfaction, finances, family, transplant-related concerns, and care coordination. CONCLUSIONS:Although parents of pediatric HTx recipients reported mostly positive QoL outcomes, they have concerns related to care management, life satisfaction, and healthcare access as their children transition into adulthood. Comprehensive transition-specific interventions and guidelines are needed to support families during this high-risk period.

BACKGROUND AND OBJECTIVES/OBJECTIVE:This study aimed to evaluate whether a 6-month (limited) course of early IVIG is an effective strategy for relapse prevention in children with myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) versus only acute therapies or other early immunotherapies. METHODS:This was a retrospective multicenter observational study of pediatric MOGAD patients from the US Network of Pediatric Multiple Sclerosis Centers with disease onset between October 1996 and December 2022. Controls were matched to limited early IVIG subjects using a 3:1 ratio. Hazard ratios of time to relapse and rate ratios of annualized relapse rate were calculated. The cumulative probability of remaining relapse-free was evaluated with the Kaplan-Meier method. RESULTS:We identified 130 unique control subjects treated before second attack with acute treatments only used in matching, 18 subjects treated with limited early IVIG, and 23 subjects treated with other early immunotherapy. The time to relapse was not different between either the limited early IVIG group and control group (HR 0.60 [0.22, 1.66], p = 0.32) or other early immunotherapy group (HR 0.98 [0.27, 3.6], p = 0.98). The limited early IVIG group showed a lower annualized relapse rate, although not statistically significant (RR 0.44 [0.17, 1.14], p = 0.09) compared with controls and a similar annualized relapse rate compared with the other early immunotherapy group (RR 0.56 [0.19, 1.69], p = 0.30). DISCUSSION/CONCLUSIONS:Although underpowered, our results suggest that the use of a limited, 6-month course of early IVIG may reduce the risk of multiphasic disease in pediatric MOGAD.