Sex-specific Differences in IDH1-Wildtype Glioblastoma patients in the ReSPOND Consortium.

BACKGROUND: Understanding sex-based differences in glioblastoma patients is necessary for accurate personalized treatment planning to improve patient outcomes. PURPOSE: To investigate sex-specific differences in molecular, clinical and radiological tumor parameters, as well as survival outcomes in glioblastoma, isocitrate dehydrogenase-1 wildtype (IDH1-WT), grade 4 patients. METHODS: Retrospective data of 1832 glioblastoma, IDH1-WT patients with comprehensive information on tumor parameters was acquired from the Radiomics Signatures for Precision Oncology in Glioblastoma (ReSPOND) consortium. Data imputation was performed for missing values. Sex-based differences in tumor parameters, such as, age, molecular parameters, pre-operative KPS score, tumor volumes, epicenter and laterality were assessed through non-parametric tests. Spatial atlases were generated using pre-operative MRI maps to visualize tumor characteristics. Survival time analysis was performed through log-rank tests and Cox proportional hazard analyses. RESULTS: GBM was diagnosed at a median age of 64 years in females compared to 61.9 years in males (FDR = 0.003). Males had a higher Karnofsky Performance Score (above 80) as compared to females (60.4% females Vs 69.7% males, FDR = 0.044). Females had lower tumor volumes in enhancing (16.7 cm3 Vs. 20.6 cm3 in males, FDR = 0.001), necrotic core (6.18 cm3 Vs. 7.76 cm3 in males, FDR = 0.001) and edema regions (46.9 cm3 Vs. 59.2 cm3 in males, FDR = 0.0001). Right temporal region was the most common tumor epicenter in the overall population. Right as well as left temporal lobes were more frequently involved in males. There were no significant differences in survival outcomes and mortality ratios. Higher age, unmethylated O6-methylguanine-DNAmethyltransferase (MGMT) promoter and undergoing subtotal resection increased the mortality risk in both males and females. CONCLUSIONS: Our study demonstrates significant sex-based differences in clinical and radiological tumor parameters of glioblastoma, IDH1-WT, grade 4 patients. Sex is not an independent prognostic factor for survival outcomes and the tumor parameters influencing patient outcomes are identical for males and females. ABBREVIATIONS: IDH1-WT = isocitrate dehydrogenase-1 wildtype; MGMTp = O6-methylguanine-DNA-methyltransferase promoter; KPS = Karnofsky performance score; EOR = extent of resection; WHO = world health organization; FDR = false discovery rate.

Associations between post-acute sequelae of SARS-CoV-2, COVID-19 vaccination and HIV infection: a United States cohort study.

Background: People with HIV (PWH) are at higher risk of complications from acute COVID-19, but their risk of subsequent post-acute sequelae of SARS-CoV2 (PASC) remains unclear. Although vaccination is protective of PASC among survivors in the general population, its effectiveness in PWH has not been explored. Methods: We used the TriNetX health research database to identify patients with and without HIV aged ≥18 years with confirmed SARS-CoV-2 between January 1, 2020 and July 20, 2023. We employed 1:1 propensity score matching to balance HIV and non-HIV cohorts based on demographics and key comorbidities. The primary outcomes accessed odds of PASC and mortality and secondary outcomes assessed odds of PASC and mortality by vaccination status. PASC was defined as new-onset conditions ≥ 28 days after COVID-19 diagnosis. We reported odd ratios (OR) of outcomes with 95% confidence intervals (CI), with statistical significance set at p < 0.05. Results: Of 3,029,340 people with confirmed SARS-CoV-2 infection, 0.5% (n=13,214) were PWH, with 7.5% of PWH (n=989) vaccinated. After 28 days post-COVID-19, PWH had higher odds of mortality compared with their non-HIV counterparts (OR 1.22, 95% CI 1.06-1.40) and developing new-onset HTN (OR 1.18, 95% CI 1.03-1.36), heart disease (OR 1.35 95% CI 1.18-1.54), malignancy (OR 1.49, 95% CI 1.22-1.81), and mental disorders (OR 1.62, 95% CI 1.42-1.85). Furthermore, vaccinated PWH had significantly lower odds of death (OR 0.63, 95% CI 0.42-0.93) and new-onset PASC outcomes: DM (OR 0.65, 95% CI 0.43-0.99), heart disease (OR 0.58, 95% CI 0.4-0.85), mental disorders (OR 0.66, 95% CI 0.43-1.00), fatigue (OR 0.82, 95% CI 0.67-0.98), respiratory (OR 0.82, 95% CI 0.70-0.95) and gastrointestinal symptoms (OR 0.78, 95% CI 0.67-0.90). Conclusion: HIV-positive status increased PASC odds, while COVID-19 vaccination reduced PASC and all-cause mortality risks in PWH.

New-onset autoimmune disease after COVID-19.

Introduction: Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) may trigger autoimmune disease (AD) through initial innate immune activation with subsequent aberrations in adaptive immune cells leading to AD. While there are multiple reports of incident AD diagnosed after COVID-19, the risk in the context of key circulating strains is unknown. Methods: TriNetX, a global, federated, health research network providing access to electronic medical records across 74 healthcare organizations, was utilized to define an adult cohort between January 1, 2020, and March 3, 2023. Exposure was defined as COVID-19 diagnosis (ICD-10 code or positive laboratory test). Age- and sex-propensity score-matched controls never had COVID-19 diagnosed. Outcomes were assessed 1 month to 1 year after the index date. Patients with AD prior to or within 1 month after the index date were excluded from the primary analysis. Incidence and risk ratios of each AD were assessed. Results: A total of 3,908,592 patients were included. Of 24 AD patients assessed, adjusted risk ratios for eight AD patients who had COVID-19 were higher compared to those who had no COVID-19. Cutaneous vasculitis (adjusted hazard ratio (aHR): 1.82; 95% CI 1.55-2.13), polyarteritis nodosa (aHR: 1.76; 95% CI 1.15-2.70), and hypersensitivity angiitis (aHR: 1.64; 95% CI 1.12-2.38) had the highest risk ratios. Overall, psoriasis (0.15%), rheumatoid arthritis (0.14%), and type 1 diabetes (0.13%) had the highest incidence during the study period, and of these, psoriasis and diabetes were more likely after COVID-19. The risk of any AD was lower if COVID-19 was diagnosed when Omicron variants were the predominant circulating strains. A positive antinuclear antibody was more likely and predictive of AD after COVID-19. Discussion: SARS-CoV-2 may be a potential trigger for some AD, but the risk for AD may decrease with time given the apparent lower risk after infection with Omicron variants.

Evaluation of an emergency department opt-out provider-driven HIV and syphilis screening and linkage-to-care program.

OBJECTIVE: While the effectiveness of emergency departments (ED) in screening for HIV and syphilis is understood, less is known about dual screening programs. We aim to evaluate the impact of an opt-out provider-initiated HIV and syphilis program on screening, diagnosis, and linkage to care outcomes. METHODS: We performed a retrospective review of patients screened pre (2014-2017) and post (2017-2021) program implementation. Primary outcomes include HIV and syphilis screening, incidence of positive tests, and proportion of patients linked to care. Secondary outcomes included pre-exposure prophylaxis (PrEP) referral and successful linkage rates for HIV-negative syphilis-positive patients. RESULTS: Pre-implementation, 882 HIV tests were performed, of which 22 (2.49%) were new cases and 18 (81.82%) were linked to care; 754 syphilis tests were performed, of which 33 (4.38%) were active infections and 30 (90.91%) were treated. No eligible patients received PrEP referral. Post-implementation, 12,999 HIV tests were performed, of which 73 (0.56%) were new cases and 55 (75.34%) were linked to care; 10,885 syphilis tests were performed, of which 216 (1.98%) were active infections and 188 (87.04%) were treated. 25 (9.09%) eligible patients were referred for PrEP, and four (16.0%) attended their appointment. CONCLUSIONS: Post-implementation, there was a 1373.81% and 1343.63% increase in screening, and a 231.82% and 554.55% increase in positive cases of HIV and syphilis, respectively. Dual screening programs can be successfully implemented within the existing ED framework to increase screening and early detection for HIV and syphilis.

Isolated Diastolic Hypertension and Kidney and Cardiovascular Outcomes in CKD: The Chronic Renal Insufficiency Cohort (CRIC) Study.

Rationale & Objective: The clinical significance of isolated diastolic hypertension in patients with chronic kidney disease (CKD) is unclear. We assessed the prevalence of isolated diastolic hypertension and its association with adverse kidney and cardiovascular outcomes in participants in the Chronic Renal Insufficiency Cohort (CRIC) study. Study Design: Prospective cohort study. Setting & Population: CRIC study participants with complete baseline data on systolic blood pressure (SBP) and diastolic BP (DBP) (N=5,621). Exposure: Isolated diastolic hypertension defined as SBP ≤ 130 mm Hg and DBP >80 mm Hg. Reference Group: Normotension, defined as SBP ≤ 130 mm Hg and DBP ≤ 80 mm Hg. Outcomes: Composite kidney events (50% decline in estimated glomerular filtration rate or onset of kidney failure), composite cardiovascular events (myocardial infarction, heart failure, stroke, or peripheral arterial disease), and all-cause mortality. Analytical Approach: Cox proportional hazards models adjusted for demographic, health behavior, and clinical covariates. Results: Of the 5,621 participants, 347 (6.2%) had isolated diastolic hypertension. Among the 347 participants with isolated diastolic hypertension, there was no association between isolated diastolic hypertension and the composite kidney outcome (HR, 1.17; 95% CI, 0.93-1.47; P = 0.18), composite cardiovascular events (HR, 0.91; 95% CI, 0.65-1.27; P = 0.58), or all-cause mortality (HR, 0.82; 95% CI, 0.57-1.19; P = 0.30). Limitations: Older age of cohort and low number of participants of Asian ethnicity limit generalizability of findings. A relatively small sample size is inadequate to detect modest associations with outcomes. Conclusions: Isolated diastolic hypertension was not associated with the risk of adverse kidney and cardiovascular events in participants with CKD. Plain Language Summary: Clinicians frequently encounter patients with kidney disease who have controlled systolic blood pressure (BP) but high diastolic BP and do not know whether they should intensify BP treatment in an attempt to control the diastolic BP. We examined whether having controlled systolic BP but uncontrolled diastolic BP leads to worse heart and kidney outcomes in patients with chronic kidney disease. We did not find any such association. However, our study was relatively small and had a number of limitations. Till larger studies confirm or refute this finding, we recommend not increasing blood pressure medications to improve the diastolic BP control if the systolic BP is already well controlled in patients with chronic kidney disease.

Prevalence and geographic features of patients eligible for extracorporeal cardiopulmonary resuscitation.

OBJECTIVE: This study sought to identify Out of Hospital Cardiac Arrests (OHCA) eligible for Extracorporeal Cardiopulmonary Resuscitation (ECPR), use Geographic Information Systems (GIS) to investigate geographic patterns, and investigate if correlation between ECPR candidacy and Social Determinants of Health (SDoH) exist. METHODS: This study is of emergency medical service (EMS) runs for OHCA to an urban medical center from January 1, 2016 to December 31, 2020. All runs were filtered to inclusion criteria for ECPR: age 18-65, initial shockable rhythm, and no return of spontaneous circulation within initial defibrillations. Address level data were mapped in a GIS. Cluster detection assessed for granular areas of high concentration. The Center for Disease Control and Prevention (CDC) Social Vulnerability Index (SVI) was overlaid. The SVI ranges from 0-1 with higher values indicating increasing social vulnerability. RESULTS: There were 670 EMS transports for OHCA during the study period. 12.7% (85/670) met inclusion criteria for ECPR. 90% (77/85) had appropriate addresses for geocoding. Three geographic clusters of events were detected. Two were residential areas and one was concentrated over a public use area of downtown Cleveland. The SVI for these locations was 0.79, indicative of high social vulnerability. Nearly half (32/77, 41.5%) occurred in neighborhoods with the highest level of social vulnerability (SVI ≥ 0.9). CONCLUSION: A significant proportion of OHCAs were eligible for ECPR based on prehospital criteria. Utilizing GIS to map and analyze ECPR patients provided insights into the locations of these events and the SDoH that may be driving risk in these places.

Platelets and hemostatic proteins are co-localized with chronic neuroinflammation surrounding implanted intracortical microelectrodes.

Intracortical microelectrodes induce vascular injury upon insertion into the cortex. As blood vessels rupture, blood proteins and blood-derived cells (including platelets) are introduced into the 'immune privileged' brain tissues at higher-than-normal levels, passing through the damaged blood-brain barrier. Blood proteins adhere to implant surfaces, increasing the likelihood of cellular recognition leading to activation of immune and inflammatory cells. Persistent neuroinflammation is a major contributing factor to declining microelectrode recording performance. We investigated the spatial and temporal relationship of blood proteins fibrinogen and von Willebrand Factor (vWF), platelets, and type IV collagen, in relation to glial scarring markers for microglia and astrocytes following implantation of non-functional multi-shank silicon microelectrode probes into rats. Together with type IV collagen, fibrinogen and vWF augment platelet recruitment, activation, and aggregation. Our main results indicate blood proteins participating in hemostasis (fibrinogen and vWF) persisted at the microelectrode interface for up to 8-weeks after implantation. Further, type IV collagen and platelets surrounded the probe interface with similar spatial and temporal trends as vWF and fibrinogen. In addition to prolonged blood-brain barrier instability, specific blood and extracellular matrix proteins may play a role in promoting the inflammatory activation of platelets and recruitment to the microelectrode interface. STATEMENT OF SIGNIFICANCE: Implanted microelectrodes have substantial potential for restoring function to people with paralysis and amputation by providing signals that feed into natural control algorithms that drive prosthetic devices. Unfortunately, these microelectrodes do not display robust performance over time. Persistent neuroinflammation is widely thought to be a primary contributor to the devices' progressive decline in performance. Our manuscript reports on the highly local and persistent accumulation of platelets and hemostatic blood proteins around the microelectrode interface of brain implants. To our knowledge neuroinflammation driven by cellular and non-cellular responses associated with hemostasis and coagulation has not been rigorously quantified elsewhere. Our findings identify potential targets for therapeutic intervention and a better understanding of the driving mechanisms to neuroinflammation in the brain.

The MIF promoter SNP rs755622 is associated with immune activation in glioblastoma.

Intratumoral heterogeneity is a defining hallmark of glioblastoma, driving drug resistance and ultimately recurrence. Many somatic drivers of microenvironmental change have been shown to affect this heterogeneity and, ultimately, the treatment response. However, little is known about how germline mutations affect the tumoral microenvironment. Here, we find that the single-nucleotide polymorphism (SNP) rs755622 in the promoter of the cytokine macrophage migration inhibitory factor (MIF) is associated with increased leukocyte infiltration in glioblastoma. Furthermore, we identified an association between rs755622 and lactotransferrin expression, which could also be used as a biomarker for immune-infiltrated tumors. These findings demonstrate that a germline SNP in the promoter region of MIF may affect the immune microenvironment and further reveal a link between lactotransferrin and immune activation.

Neonatal Intensive Care Unit Mixed Lipid Emulsion Use Associated With Reduced Cholestasis at Discharge in Surgical Patients.

INTRODUCTION: Parenteral nutrition associated cholestasis (PNAC) is a common morbidity in neonates requiring total parenteral nutrition (TPN). Previous studies in infants with intestinal failure have shown a benefit of mixed lipid emulsion (MLE) in reducing PNAC. It is not known whether this benefit extends to a general neonatal intensive care unit (NICU) population, where MLE is used on a selective basis. The objective of this study is to examine associations between MLE use and PNAC rate in the general NICU setting. METHODS: This is a retrospective review of NICU patients who received TPN for 7 or more days. We compared patients born between 1/1/2014 and 12/31/2015 (pre-MLE) to patients born between 7/1/2017 and 12/31/2018 (post-MLE). Fisher's exact test and two-sample t-test were used to compare the two groups. RESULTS: There were 353 patients in 2014-2015 and 271 patients in 2017-2018. Demographics were similar between the two groups, but there were more patients with congenital heart disease in the MLE era (P < 0.001). Mortality was similar (6.2% pre-MLE versus 6.3% post-MLE). There was no significant difference in PNAC rate between the pre-MLE (11.5%) and post-MLE (14.1%) patient cohorts (P = 0.342). Among patients receiving MLE (n = 38), 58% developed PNAC, while only 6.4% of the post-MLE cohort not receiving MLE developed PNAC. Of the patients coded with a surgical diagnosis, there was no significant difference in PNAC rates between pre-MLE and post-MLE groups. Discharge rates of PNAC did differ between pre-MLE surgical patients (13.0%) and post-MLE surgical patients (8.2%). In the subgroup of post-MLE surgical patients, PNAC rate differed significantly between those receiving MLE (43.5%) and not receiving MLE (15.4%). However, this difference was resolved by discharge (8.7% versus 7.7%). CONCLUSIONS: There were no significant differences in PNAC rates between the pre-MLE and post-MLE cohorts. However, in surgical patients, MLE was associated with reduced PNAC at discharge, with levels equivalent to those seen in neonates receiving TPN for 7 or more days, despite having a higher starting rate of PNAC. Further studies are needed to determine whether the general NICU population may benefit from MLE or certain selective subpopulations like surgical patients.

Novel 3D magnetic resonance fingerprinting radiomics in adult brain tumors: a feasibility study.

OBJECTIVES: To test the feasibility of using 3D MRF maps with radiomics analysis and machine learning in the characterization of adult brain intra-axial neoplasms. METHODS: 3D MRF acquisition was performed on 78 patients with newly diagnosed brain tumors including 33 glioblastomas (grade IV), 6 grade III gliomas, 12 grade II gliomas, and 27 patients with brain metastases. Regions of enhancing tumor, non-enhancing tumor, and peritumoral edema were segmented and radiomics analysis with gray-level co-occurrence matrices and gray-level run-length matrices was performed. Statistical analysis was performed to identify features capable of differentiating tumors based on type, grade, and isocitrate dehydrogenase (IDH1) status. Receiver operating curve analysis was performed and the area under the curve (AUC) was calculated for tumor classification and grading. For gliomas, Kaplan-Meier analysis for overall survival was performed using MRF T1 features from enhancing tumor region. RESULTS: Multiple MRF T1 and T2 features from enhancing tumor region were capable of differentiating glioblastomas from brain metastases. Although no differences were identified between grade 2 and grade 3 gliomas, differentiation between grade 2 and grade 4 gliomas as well as between grade 3 and grade 4 gliomas was achieved. MRF radiomics features were also able to differentiate IDH1 mutant from the wild-type gliomas. Radiomics T1 features for enhancing tumor region in gliomas correlated to overall survival (p < 0.05). CONCLUSION: Radiomics analysis of 3D MRF maps allows differentiating glioblastomas from metastases and is capable of differentiating glioblastomas from metastases and characterizing gliomas based on grade, IDH1 status, and survival. KEY POINTS: • 3D MRF data analysis using radiomics offers novel tissue characterization of brain tumors. • 3D MRF with radiomics offers glioma characterization based on grade, IDH1 status, and overall patient survival.

Anterior and Lateral Skull Base Spontaneous CSF Leaks: Evaluation of Comorbidities and Treatment Outcomes.

OBJECTIVES: To evaluate clinical characteristics and outcomes of patients diagnosed with anterior (ASB) or lateral skull base (LSB) spontaneous cerebrospinal fluid (sCSF) leak. METHODS: Single center retrospective review of patients diagnosed with sCSF leaks of ASB or LSB between 1/1/2009 and 11/1/2019 (n = 69). Body mass index (BMI), gender, age at diagnosis, origin of CSF leak (ASB vs LSB), surgical approach, lumbar drain use, recurrence, pre-operative diagnosis of diabetes mellitus (DM), and obstructive sleep apnea (OSA) were collected. RESULTS: 69 patients included in this study met criteria for sCSF leak without a traumatic or iatrogenic cause (Female: 51 (74%); average BMI: 37.0 ± 7.9). Forty-eight (70.0%) presented with sCSF leaks of the lateral skull base. All ASB leaks were treated with an endoscopic transnasal approach. Eleven (22.9%) LSB leak patients were treated using transmastoid approaches and 35 (72.9%) patients with a middle cranial fossa approach. Eleven patients (15.9%) reported sCSF leak recurrence. Two patients (9.5%) with anterior skull base and 9 patients (18.8%) with lateral skull base leaks had recurrence. LSB sCSF leaks had a relative risk of 2.192 of recurrence compared to ASB leaks (95% CI: 0.431-11.157, P = .483). A 5.017 times increased risk (95% CI: 1.285-19.583, P = .020) was reported for patients with OSA, while the risks for DM and BMI were 1.351 (95% CI: 0.67-9.105, P = .177) and 1.026 (95% CI: 0.963-1.094, P = .426) respectively. Patients with sCSF leak recurrence had significantly lower lumbar drain use (33.3%) than those without recurrence (72.7%) (P = .049). CONCLUSION: Spontaneous CSF leak recurrence is complex and multifactorial, and while patients with both DM and OSA had the higher risk of recurrence, OSA is likely an independent clinical risk factor for sCSF leak recurrence in this patient population.

Efficacy of X-ray in the diagnosis of pediatric nasal fracture.

OBJECTIVE: Nasal fracture is one of the most common pediatric fractures, and diagnosis can be made with clinical findings or with radiographic imaging. The objective of this study is to determine the extent of x-ray utilization in decision-making regarding closed reduction of pediatric nasal fracture. METHODS: This a case-control study of 117 patients ages 0-18 with a diagnosis of nasal fracture seen at University Hospitals Cleveland Medical Center between January 2015 and January 2020. The exposure group had x-ray imaging of the nasal bones, and the control group had no x-ray imaging. RESULTS: A total of 59 (50.4%) patients had surgical intervention. The odds ratio to compare x-ray utilization to the control group for patients who underwent closed reduction surgery was .3951 (95% CI: 0.1848-0.8448, p-value = .0166). CONCLUSION: The statistical analysis suggests that x-ray use is associated with decreased rates of closed reduction surgery. It is likely that while not necessary for the diagnosis of nasal fracture, x-ray serves as an additional data point for diagnosis confirmation, and may reduce the rate of unnecessary surgery for false positive cases of nasal fracture.

Aligning the Central Brain Tumor Registry of the United States (CBTRUS) histology groupings with current definitions.

Background: The Central Brain Tumor Registry of the United States (CBTRUS) uses a histology grouping model based on the World Health Organization (WHO) classifications to group records for clinically relevant statistical reporting. Newly identified genetic markers more accurately stratify patients than histology alone and were incorporated into the 2016 update to the WHO Classification. Methods: CBTRUS and consulting neuropathologists reviewed and aligned histology groupings with the 2016 WHO update. "Obsolete" (terms not currently in use) histology nomenclature along with their International Classification of Disease, Oncology 3rd edition (ICD-O-3) codes were identified, some histologies were reclassified to 2016 WHO, and new codes found in 2016 WHO were incorporated. An evaluation of the frequency of histology codes affected in the realignment process, and incidence and survival pre- and post-realignment was conducted. Results: After review, 67 codes were noted as obsolete, 51 codes were reclassified, and 12 new codes were incorporated. Histology groups most affected were mesenchymal tumors and neuronal/mixed neuronal-glial tumors. Reorganization resulted in 2588 (0.65%) cases with grouping reassignment or reporting change, indicating that the 2016 WHO Classification revision has impacted the collection and reporting of primary brain and other CNS tumors. Conclusion: This work demonstrates the need to be responsive to changes in classification and coding in order to ensure the most up-to-date and accurate statistics for brain and CNS tumors. This will require collaboration from all stakeholders within the brain tumor community, so to have the ability to reconcile clinical practices and surveillance requirements.

Associations of Racial and Ethnic Category, Age, Comorbidities, and Socioeconomic Factors on Concordance to NCCN Guidelines for Patients With High-Risk Biliary Tract Cancers After Surgery.

Background: Biliary tract cancers (BTC) have a limited prognosis even for localized cancers, emphasizing the importance of multidisciplinary management. NCCN guidelines recommend adjuvant chemotherapy (CT) +/- radiotherapy (RT) for high-risk disease. We analyzed the association between racial and ethnic category along with other demographic factors and concordance to NCCN guidelines among patients following surgery for high-risk BTC. Methods: Subjects were identified from the National Cancer Database (NCDB) for BTC patients who underwent surgery and found to have metastatic lymph nodes (LN+) or positive surgical margins (M+) from 2004 to 2015. We defined concordance to NCCN guidelines as receiving surgery + CT +/- RT and non-concordance to the guidelines as surgery +/- RT. Descriptive studies and multivariate logistic regression analysis was performed. Results: A total of 3,792 patients were identified with approximately half being female (55.4%) and between the ages of 50-69 (52.8%). Most were White (76.3%) followed by Black (10.6%), Hispanic (8.5%), and Asian (5.3%). The BTC included extrahepatic cholangiocarcinoma (CCA) (48.6%), gallbladder cancer (43.5%), and intrahepatic CCA (7.9%). Most patients had an M- resection (71.9%) but also had LN+ disease (88.0%). There were no significant differences between racial groups in disease presentation (histological grade, tumor stage) and surgical outcomes (LN+, M+, hospital readmission, and 90 day post-surgery mortality). Hispanic patients as compared to White patients were less likely to be insured (85.7% vs 96.3%, p<0.001) and less likely to be treated at an academic facility (42.1% vs 52.1%, p=0.008). Overall, almost one-third (29.7%) of patients received non-concordant NCCN guideline care with Hispanic patients having the highest proportion of non-concordance as compared to Whites patients (36.1% vs 28.7%, p=0.029). On multivariate analysis, Hispanic ethnicity (HR=1.51, 95% CI: 1.15-1.99) remained significantly associated with non-concordance to NCCN guidelines. Conclusion: This study indicates that Hispanic patients with high-risk BTC are significantly less likely to receive NCCN-concordant treatment in comparison to White patients. More research is needed to confirm and understand the observed disparities and guide targeted interventions at the system-level.

Epidemiology of primary malignant non-osseous spinal tumors in the United States.

BACKGROUND CONTEXT: Primary malignant non-osseous spinal tumors are relatively rare and this has led to a paucity of studies specifically examining the epidemiology of malignant spinal tumors. PURPOSE: To provide an updated and more comprehensive study examining the epidemiology and relative survival of these rare tumors. STUDY DESIGN/SETTING: Data was retrospectively acquired from the Central Brain Tumor Registry of the United States (CBTRUS). PATIENT SAMPLE: Primary malignant non-osseous spinal tumor cases diagnosed between 2000 and 2017 in the United States. OUTCOME MEASURES: Incidence rates (IRs), relative survival rates, and hazard ratios (HR) were measured. METHODS: IRs were calculated only for histologically-confirmed cases between 2000 and 2017. Relative survival estimates were calculated from survival information on malignant spinal tumors between 2001 and 2016 for death from any cause. Multivariable Cox proportional hazards regression models were constructed to control for age, sex, race, and ethnicity. RESULTS: From 2000 to 2017, approximately 587 new cases of malignant non-osseous spinal tumors were diagnosed every year in the United States. The overall IR was 0.178 per 100,000 persons. Ependymomas were the most commonly diagnosed tumor in all age groups. The 10-year relative survival rates were 94.1%, 62.1%, 62.0%, and 13.3% for ependymomas, lymphomas, diffuse astrocytomas, and high-grade astrocytomas, respectively. Females have a significantly lower risk of death as compared with males for ependymomas (HR: 0.74, p<.001) and diffuse astrocytomas (HR: 0.70, p=.005). African-Americans have a significantly higher risk of death compared with Caucasians when diagnosed with ependymomas (HR: 1.52, p=.009) or lymphomas (HR: 1.55, p=.009). CONCLUSION: Primary malignant non-osseous spinal tumors are primarily diagnosed in adulthood or late adulthood. Ependymal tumors are the most commonly diagnosed primary malignant non-osseous spinal tumors and have the highest 10-year relative survival rates. High-grade astrocytomas are rare and portend the worst prognosis.

A population study of clinical trial accrual for women and minorities in neuro-oncology following the NIH Revitalization Act.

BACKGROUND: The NIH Revitalization Act, implemented 29 years ago, set to improve the representation of women and minorities in clinical trials. In this study, we investigate progress made in all phase therapeutic clinical trials for neuroepithelial CNS tumors stratified by demographic-specific age-adjusted disease incidence and mortality. Additionally, we identify workforce characteristics associated with clinical trials meeting established accrual benchmarks. METHODS: Registry study of published clinical trials for World Health Organization defined neuroepithelial CNS tumors between January 2000 and December 2019. Study participants were obtained from PubMed and ClinicalTrials.gov. Population-based data originated from the CBTRUS for incidence analyses. SEER-18 Incidence-Based Mortality data was used for mortality analysis. Descriptive statistics, Fisher exact, and χ 2 tests were used for data analysis. RESULTS: Among 662 published clinical trials representing 49 907 participants, 62.5% of participants were men and 37.5% women (P < .0001) representing a mortality specific over-accrual for men (P = .001). Whites, Asians, Blacks, and Hispanics represented 91.7%, 1.5%, 2.6%, and 1.7% of trial participants. Compared with mortality, Blacks (47% of expected mortality, P = .008), Hispanics (17% of expected mortality, P < .001) and Asians (33% of expected mortality, P < .001) were underrepresented compared with Whites (114% of expected mortality, P < .001). Clinical trials meeting accrual benchmarks for race included minority authorship. CONCLUSIONS: Following the Revitalization Act, minorities and women remain underrepresented in therapeutic clinical trials for neuroepithelial tumors, relative to disease incidence and mortality. Study accrual has improved with time. This study provides a framework for clinical trial accrual efforts and offers guidance regarding workforce considerations associated with enrollment of underserved patients.