Citations

Background Extended sedentary behavior is a risk factor for chronic disease and mortality, even among those who exercise regularly. Given the time constraints of incorporating physical activity into daily schedules, and the high likelihood of sitting during office work, this environment may serve as a potentially feasible setting for interventions to reduce sedentary behavior. Methods and Results A randomized cross‐over clinical trial was conducted at an employee wellness center. Four office settings were evaluated on 4 consecutive days: stationary or sitting station on day 1 (referent), and 3 subsequent active workstations (standing, walking, or stepper) in randomized order. Neurocognitive function (Selective Attention, Grammatical Reasoning, Odd One Out, Object Reasoning, Visuospatial Intelligence, Limited‐Hold Memory, Paired Associates Learning, and Digit Span) and fine motor skills (typing speed and accuracy) were tested using validated tools. Average scores were compared among stations using linear regression with generalized estimating equations to adjust standard errors. Bonferroni method adjusted for multiple comparisons. Healthy subjects were enrolled (n=44), 28 (64%) women, mean±SD age 35±11 years, weight 75.5±17.1 kg, height 168.5±10.0 cm, and body mass index 26.5±5.2 kg/m 2 . When comparing active stations to sitting, neurocognitive test either improved or remained unchanged, while typing speed decreased without affecting typing errors. Overall results improved after day 1, suggesting habituation. We observed no major differences across active stations, except decrease in average typing speed 42.5 versus 39.7 words per minute with standing versus stepping ( P =0.003). Conclusions Active workstations improved cognitive performance, suggesting that these workstations can help decrease sedentary time without work performance impairment. Registration URL: https://www.clinicaltrials.gov ; Unique identifier: NCT06240286.

Abstract Introduction: Despite the enactment of the 1993 NIH Revitalization Act to improve accrual of women and minorities in clinical trials, these groups remain underrepresented. This study aims to uncover drivers of therapeutic clinical trial enrollment that are unique to women and minority patients with low- and high-grade glioma. Methods: Adult glioma patients who received care from the UCSF Brain Tumor Center between 1997-2017 were identified in a prospective registry. Dividing the cohort into subgroups by gender and NIH-designated minority status, factors associated with therapeutic clinical trial enrollment on univariate logistic regression (p<0.2) were selected for multivariate logistic regression. Results: There were 351 trial participants (41% women, 12% minority) and 627 non-trial participants (44% women, 17% minority). Among women only, seizure at presentation (OR 2.10, p=0.008) was associated with increased odds of trial enrollment. In contrast, among men only, higher median household income (OR 1.09 per $10,000 increase, p=0.006), higher WHO tumor grade (OR 1.89, p=0.045), and occupational status according to the International Standard Classification of Occupations [professionals (e.g., physicians) vs managers (e.g., supervisory positions), OR 2.87, p=0.043] were associated with increased odds of trial enrollment. Among both women and men, lack of insurance (women: OR 0.49, p=0.02; men: OR 0.55, p=0.031) and no treatment with chemotherapy (women: OR 0.18, p=0.001; men: OR 0.34, p=0.002) were associated with decreased odds of clinical trial enrollment, whereas higher KPS (women: 90 vs <80, OR 3.16, p=0.003; men: 90 vs <80, OR 3.15, p=0.002) was associated with increased odds of trial enrollment. Among NIH-designated minority patients, older age (OR 0.66 per 10-year increase, p=0.033) and non-English preferred language (OR: 0.30, p=0.035) were associated with decreased odds of trial enrollment on univariate analysis, but not on multivariate analysis. Among non-minority patients, lack of insurance (OR 0.58, p=0.008) and no chemotherapy treatment (OR 0.25, p<0.001) were associated with decreased odds of trial enrollment, whereas seizure at presentation (OR 1.80, p=0.001), higher neighborhood household income (OR 1.07 per $10,000 increase, p=0.004), higher WHO grade (4 vs 2-3, OR 1.86, p=0.015), higher KPS (90 vs <80, OR 3.21, p<0.0001), and lower extent of tumor resection (80-89% vs 100%, OR 2.16, p=0.047) were associated with increased odds of trial enrollment. Conclusion: Drivers of trial enrollment differed for women and minority patients with glioma. Non-English-speaking minority patients may face additional barriers to trial enrollment requiring targeted interventions. Our findings can revitalize and tailor efforts to recruit women and minority patients to therapeutic clinical trials in neuro-oncology. Citation Format: Mulki Mehari, Gayathri Warrier, Sheantel Reihl, Abraham Dada, Aymen Kabir, Mikias Negussie, Cesar Nava Gonzales, Ugonma Chukwueke, Alyx Porter, Shawn Hervey-Jumper. Revitalizing the accrual of women and minorities: Unique drivers of therapeutic clinical trial enrollment for underrepresented patients with diffuse glioma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 1006.

Introduction Burnout in medicine is an occupational hazard and has emerged as a pressing concern in recent years. Organizational changes can be impactful in countering burnout (1). The factors leading to burnout in medicine are multifaceted, encompassing organizational factors such as workload, inadequate support, and inefficient administrative systems. The purpose of this study is to investigate current organizational measures to support physician well‐being. This study was an initiative led by the SVIN wellness committee. Methods A 39‐question online survey investigating current organizational well‐being practices was distributed to physicians both nationally and internationally practicing stroke, neurocritical care, and interventional neurology. Data analysis was performed using Python, utilizing the libraries “pandas” and “sklearn”. Results This study analyzed burnout among 109 healthcare professionals, predominantly from the U.S. (93.6%) and Canada (6.4%). The majority were neurointerventional specialists (53.2%), aged 35‐44 years (52.3%), and male (62.4%). Burnout frequency was measured on a 0 (Never) to 4 (Every day) scale. Using a Random Forest model, the study identified key burnout predictors from questions, which covered organizational leadership, wellness resources, compensation, and workload. The most influential predictors were: adequacy of compensation relative to specialty, workload, and stress (17.7% importance); leadership accountability for workforce wellbeing (9.1%); and establishment of wellness or burnout as a critical metric (7.5%). Other factors included provision of wellness screenings (7.1%), and dedication of resources toward professional well‐being (4.9%). Conclusion The study identifies compensation, leadership accountability, and wellness resources as key predictors of burnout among healthcare professionals. These findings highlight the need for targeted organizational strategies to enhance physician well‐being and mitigate burnout. Further research is warranted to validate and expand upon these findings.

Abstract Objectives The objective of this study was to explore the prevalence, characteristics and risk factors of COVID-19 breakthrough infections (BIs) in idiopathic inflammatory myopathies (IIMs) using data from the COVID-19 Vaccination in Autoimmune Diseases (COVAD) study. Methods A validated patient self-reporting e-survey was circulated by the COVAD study group to collect data on COVID-19 infection and vaccination in 2022. BIs were defined as COVID-19 occurring ≥14 days after two vaccine doses. We compared BI characteristics and severity among patients with IIMs, patients with other autoimmune rheumatic and non-rheumatic diseases (AIRD, nrAID), and healthy controls (HCs). Multivariable Cox regression models were used to assess the risk factors for BI, severe BI ,and hospitalizations among patients with IIMs. Results Among the 9449 included responses, BIs occurred in 1447 respondents (15.3%). The median age was 44 years [interquartile range (IQR) 21], 77.4% were female, and 182 BIs (12.9%) occurred among the 1406 patients with IIMs. Multivariable Cox regression among the data for patients with IIMs showed increasing age to be a protective factor for BIs [hazard ratio (HR) = 0.98, 95% CI = 0.97–0.99], and HCQ and SSZ use were risk factors (HR = 1.81, 95% CI = 1.24–2.64, and HR = 3.79, 95% CI = 1.69–8.42, respectively). Glucocorticoid use was a risk factor for a severe BI (HR = 3.61, 95% CI = 1.09–11.8). Non-white ethnicity (HR = 2.61, 95% CI = 1.03–6.59) was a risk factor for hospitalization. Compared with other groups, patients with IIMs required more supplemental oxygen therapy (IIMs = 6.0% vs AIRDs = 1.8%, nrAIDs = 2.2% and HCs = 0.9%), intensive care unit admission (IIMs = 2.2% vs AIRDs = 0.6%, nrAIDs and HCs = 0%), advanced treatment with antiviral or monoclonal antibodies (IIMs = 34.1% vs AIRDs = 25.8%, nrAIDs = 14.6% and HCs = 12.8%) and had more hospitalization (IIMs = 7.7% vs AIRDs = 4.6%, nrAIDs = 1.1% and HCs = 1.5%). Conclusion Patients with IIMs are susceptible to severe COVID-19 BIs. Age and immunosuppressive treatments were related to the risk of BIs.

Abstract Objectives To investigate health-related quality of life in patients with idiopathic inflammatory myopathies (IIMs) compared with those with non-IIM autoimmune rheumatic diseases (AIRDs), non-rheumatic autoimmune diseases (nrAIDs) and without autoimmune diseases (controls) using Patient-Reported Outcome Measurement Information System (PROMIS) instrument data obtained from the second COVID-19 vaccination in autoimmune disease (COVAD-2) e-survey database. Methods Demographics, diagnosis, comorbidities, disease activity, treatments and PROMIS instrument data were analysed. Primary outcomes were PROMIS Global Physical Health (GPH) and Global Mental Health (GMH) scores. Factors affecting GPH and GMH scores in IIMs were identified using multivariable regression analysis. Results We analysed responses from 1582 IIM, 4700 non-IIM AIRD and 545 nrAID patients and 3675 controls gathered through 23 May 2022. The median GPH scores were the lowest in IIM and non-IIM AIRD patients {13 [interquartile range (IQR) 10–15] IIMs vs 13 [11–15] non-IIM AIRDs vs 15 [13–17] nrAIDs vs 17 [15–18] controls, P < 0.001}. The median GMH scores in IIM patients were also significantly lower compared with those without autoimmune diseases [13 (IQR 10–15) IIMs vs 15 (13–17) controls, P < 0.001]. Inclusion body myositis, comorbidities, active disease and glucocorticoid use were the determinants of lower GPH scores, whereas overlap myositis, interstitial lung disease, depression, active disease, lower PROMIS Physical Function 10a and higher PROMIS Fatigue 4a scores were associated with lower GMH scores in IIM patients. Conclusion Both physical and mental health are significantly impaired in IIM patients, particularly in those with comorbidities and increased fatigue, emphasizing the importance of patient-reported experiences and optimized multidisciplinary care to enhance well-being in people with IIMs.

Background and importance Neurointervention is a very competitive specialty in the United States due to the limited number of training spots and the larger pool of applicants. The training standards are continuously updated to ensure solid training experiences. Factors affecting candidate(s) selection have not been fully established yet. Our study aims to investigate the factors influencing the selection process. Methods A 52-question survey was distributed to 93 program directors (PDs). The survey consisted of six categories: (a) Program characteristics, (b) Candidate demographics, (c) Educational credentials, (d) Personal traits, (e) Research and extracurricular activities, and (f) Overall final set of characteristics. The response rate was 59.1%. As per the programs’ characteristics, neurosurgery was the most involved specialty in running the training programs (69%). Regarding demographics, the need for visa sponsorship held the greatest prominence with a mean score of 5.9 [standard deviation (SD) 2.9]. For the educational credentials, being a graduate from a neurosurgical residency and the institution where the candidate's residency training is/was scored the highest [5.4 (SD = 2.9), 5.4 (SD = 2.5), respectively]. Regarding the personal traits, assessment by faculty members achieved the highest score [8.9 (SD = 1)]. In terms of research/extracurricular activities, fluency in English had the highest score [7.2 (SD = 1.9)] followed by peer-reviewed/PubMed-indexed publications [6.4 (SD = 2.2)]. Conclusion Our survey investigated the factors influencing the final decision when choosing the future neurointerventional trainee, including demographic, educational, research, and extracurricular activities, which might serve as valuable guidance for both applicants and programs to refine the selection process.

212 Background: Patients with prostate cancer with liver metastases are known to have a worse prognosis. In this study, we evaluated ctDNA in mCRPC (metastatic castration-resistant prostate cancer) patients with and without liver metastases. Methods: A retrospective chart review identified mCRPC patients with liver metastases at Tulane Cancer Center and Huntsman Cancer Institute. Liver metastases were confirmed via molecular or conventional imaging. All patients had ctDNA assessed with a multi-gene cancer panel via the Guardant 360 assay. Alterations with <0.1% allelic fraction, synonymous alterations, and variants of unknown significance were excluded from analyses. Statistical analyses were performed using Fisher’s Exact and Wilcoxon Rank Sum Tests. Correction for multiple testing was not performed, hence these alterations may be subject to a type 1 error. Results: 53 mCRPC patients with liver metastases and 144 mCRPC patients without liver metastases were included in the study. We found seven genes that are more likely to be pathologically altered in ctDNA in mCRPC patients with liver metastases (See Tables 1-3): AR (OR=2.38, 95% CI: [1.25, 4.52], p=0.01), BRAF (OR=2.74, 95% CI:[1.05, 7.18], p=0.05), BRCA2 (OR=5.33, 95% CI:[1.49, 19.02], p=0.01), CDK6 (OR=4.09, 95% CI:[1.35, 12.42], p=0.01), EGFR (OR=3.12, 95% CI:[1.22, 7.99], p=0.02), FGFR1 (OR=5.69, 95% CI:[1.81, 17.86], p-value=0.003), MYC (OR=4.55, 95% CI:[1.63, 12.68], p=0.004), and PIK3CA (OR=4.34, 95% CI:[1.87, 10.06], p=0.01). Additionally, mCRPC patients with liver metastases are more likely to have copy number alterations (CNA) (p= 0.01) compared to mCRPC patients without liver involvement. There were no other significant differences in the remaining 70 genes interrogated. Germline pathogenic alterations did not vary between the two groups. Conclusions: In mCRPC patients with liver metastases, these exploratory analyses suggest ctDNA testing is more likely to detect pathologic alterations in AR, BRAF, BRCA2, CDK6, EGFR, FGFR1, MYC, and PIK3CA. Additionally, mCRPC patients were more likely to have copy number alterations (CNA). Limitations of the Guardant 360 assays are notable in this setting given the incomplete ascertainment of gene deletions and the incomplete number of prostate-relevant genes assessed. [Table: see text]

Background The C-C motif chemokine receptor 5 (CCR5)/C-C motif chemokine ligand 5 (CCL5) axis plays a major role in colorectal cancer (CRC). We aimed to characterize the molecular features associated with CCR5 / CCL5 expression in CRC and to determine whether CCR5 / CCL5 levels could impact treatment outcomes. Methods 7604 CRCs tested with NextGen Sequencing on DNA and RNA were analyzed. Molecular features were evaluated according to CCR5 and CCL5 tumor gene expression quartiles. The impact on treatment outcomes was assessed in two cohorts, including 6341 real-world patients and 429 patients from the Cancer and Leukemia Group B (CALGB)/SWOG 80405 trial. Results CCR5 / CCL5 expression was higher in right-sided versus left-sided tumors, and positively associated with consensus molecular subtypes 1 and 4. Higher CCR5 / CCL5 expression was associated with higher tumor mutational burden, deficiency in mismatch repair and programmed cell death ligand 1 (PD-L1) levels. Additionally, high CCR5 / CCL5 were associated with higher immune cell infiltration in the tumor microenvironment (TME) of MMR proficient tumors. Ingenuity pathway analysis revealed upregulation of the programmed cell death protein 1 (PD-1)/PD-L1 cancer immunotherapy pathway, phosphatase and tensin homolog (PTEN) and peroxisome proliferator-activated receptors (PPAR) signaling, and cytotoxic T-lymphocyte antigen 4 (CTLA-4) signaling in cytotoxic T lymphocytes, whereas several inflammation-related pathways were downregulated. Low CCR5 / CCL5 expression was associated with increased benefit from cetuximab-FOLFOX treatment in the CALGB/SWOG 80405 trial, where significant treatment interaction was observed with biologic agents and chemotherapy backbone. Conclusions Our data show a strong association between CCR5/CCL5 gene expression and distinct molecular features, gene expression profiles, TME cell infiltration, and treatment benefit in CRC. Targeting the CCR5/CCL5 axis may have clinical applications in selected CRC subgroups and may play a key role in developing and deploying strategies to modulate the immune TME for CRC treatment.

Background: Life's Simple 7 (LS7) have been identified as key health factors aimed at achieving ideal cardiovascular health (CVH) and improving healthy life expectancy; however, it is unclear if different patient populations respond similarly to optimization of health behaviors. We sought to quantify the contribution of sex and age differences to changes in LS7 components in patients participating in cardiac rehabilitation. Methods: We included 937 adult patients who participated in CR from January 2018 to September 2020. LS7 metrics at baseline (pre-CR) and completion of CR (post-CR) were collected and changes in LS7 components (body mass index (BMI), diet, smoking, physical activity (PA), blood pressure (PB), cholesterol, glucose) were assessed by sex and age groups (<65 vs ≥65 years old). Each LS7 component was assigned 0 (poor), 1 (intermediate), or 2 (ideal) points and a final score was computed to estimate an individual’s level of CVH (0-14 pts): 0-6 = poor, 7-8= intermediate, 9 -14= ideal. Results: The mean age was 64±13 years, and 34% were female. Patients attended a mean of 11.1±12.5 CR sessions. LS7 components with the highest proportion within the poor category were HbA1c (41%) and BMI (50%) at the time of CR enrollment; neither women nor men showed improvement on either component. The trend towards improvement from poor to intermediate range on cholesterol and BP metrics was seen only in older patients (Table 1). Mean LS7 score improvement was greater in the older group, P=.01 (Fig 1). Both women and men equally improved LS7 scores (Table 2, Fig 2). Conclusions: Patients participating in CR demonstrated improvement in overall LS7 scores regardless of sex and age. However, age disparities exist in LS7 metrics, with exacerbated differences noted by a lack of improvement in LS7 components such as BP and cholesterol in younger patients. Our insights provide opportunities to explore equitable CVH.