miRNA-mediated loss of m6A increases nascent translation in glioblastoma.

Within the glioblastoma cellular niche, glioma stem cells (GSCs) can give rise to differentiated glioma cells (DGCs) and, when necessary, DGCs can reciprocally give rise to GSCs to maintain the cellular equilibrium necessary for optimal tumor growth. Here, using ribosome profiling, transcriptome and m6A RNA sequencing, we show that GSCs from patients with different subtypes of glioblastoma share a set of transcripts, which exhibit a pattern of m6A loss and increased protein translation during differentiation. The target sequences of a group of miRNAs overlap the canonical RRACH m6A motifs of these transcripts, many of which confer a survival advantage in glioblastoma. Ectopic expression of the RRACH-binding miR-145 induces loss of m6A, formation of FTO/AGO1/ILF3/miR-145 complexes on a clinically relevant tumor suppressor gene (CLIP3) and significant increase in its nascent translation. Inhibition of miR-145 maintains RRACH m6A levels of CLIP3 and inhibits its nascent translation. This study highlights a critical role of miRNAs in assembling complexes for m6A demethylation and induction of protein translation during GSC state transition.

The epidemiology of crib-related head injuries: A ten-year nationwide analysis.

INTRODUCTION: Falls from cribs resulting in head injury are understudied and poorly characterized. The purpose of this study was to advance current understanding of the prevalence, descriptive characteristics of injury victims, and the types of crib fall-related head injuries (CFHI) using queried patient cases from the National Electronic Injury Surveillance System (NEISS) database. METHODS: Using the US Consumer Product Safety Commission's System NEISS database, we queried all CFHIs among children from over 100 emergency departments (EDs). Patient information regarding age, race, sex, location of the incident, diagnoses, ED disposition, and sequelae were analyzed. The number of CFHI from all US EDs during each year was also collected from the database. RESULTS: There were an estimated 54,799 (95% CI: 30,228-79,369) total visits to EDs for CFHIs between 2012 and 2021, with a decrease in incidence of approximately 20% during the onset of the COVID-19 pandemic (2019: 5616 cases, 2020: 4459 cases). The annual incidence of injuries showed no significant trend over the 10-year study period. An available subset of 1782 cases of head injuries from approximately 100 EDs was analyzed, and 1442 cases were included in final analysis. Injuries were sorted into three primary categories: unspecified closed head injury (e.g., closed head injury, blunt head trauma, or traumatic brain injury), concussion, or open head injury and skull fracture. Unspecified closed head injuries were the most common of all head injuries (95.4%, 1376/1442). Open head injuries (14/1442, 0.97%) and concussions 3.6% (52/1442, 3.6%) were rare. Most injuries involved children under the age of 1 (42.6%) compared to children who were 1, 2, 3, or 4-years old. About a fourth of patients had other diagnoses in addition to their primary injury including scalp/forehead hematomas, emesis, and contusions. Female patients were more likely to present with other diagnoses in addition to their primary head injury (Difference: 12.3%, 95% CI: 9.87%-15.4%, p < .0001). CONCLUSION: Despite minimum rail height requirements set by the Consumer Safety Product Commission (CPSC), head injuries associated with crib falls are prevalent in the United States. However, most injuries were minor with a vast majority of patients being released following examination and treatment.

Diagnostic Accuracy of the World Health Organization Pediatric Emergency Triage, Assessment and Treatment Tool Plus Among Patients Seeking Care in Nairobi, Kenya: A Cross-sectional Study.

INTRODUCTION: The World Health Organization developed Emergency Triage Assessment and Treatment Plus (ETAT+) guidelines to facilitate pediatric care in resource-limited settings. ETAT+ triages patients as nonurgent, priority, or emergency cases, but there is limited research on the performance of ETAT+ regarding patient-oriented outcomes. This study assessed the diagnostic accuracy of ETAT+ in predicting the need for hospital admission in a pediatric emergency unit at Kenyatta National Hospital in Nairobi, Kenya. METHODS: This was a secondary analysis of a cross-sectional study of pediatric emergency unit patients enrolled over a 4-week period using fixed random sampling. Diagnostic accuracy of ETAT+ was evaluated using receiver operating curves (ROCs) and respective 95% confidence intervals (CIs) with associated sensitivity and specificity (reference category: nonurgent). The ROC analysis was performed for the overall population and stratified by age group. RESULTS: A total of 323 patients were studied. The most common reasons for presentation were upper respiratory tract disease (32.8%), gastrointestinal disease (15.5%), and lower respiratory tract disease (12.4%). Two hundred twelve participants were triaged as nonurgent (65.6%), 60 as priority (18.6%), and 51 as emergency (15.8%). In the overall study population, the area under the ROC curve was 0.97 (95% CI, 0.95-0.99). The ETAT+ sensitivity was 93.8% (95% CI, 87.0%-99.0%), and the specificity was 82.0% (95% CI, 77.0%-87.0%) for admission of priority group patients. The sensitivity and specificity for the emergency patients were 66.0% (95% CI, 55.0%-77.0%) and 98.0% (95% CI, 97.0%-100.0%), respectively. CONCLUSIONS: ETAT+ demonstrated diagnostic accuracy for predicting patient need for hospital admission. This finding supports the utility of ETAT+ to inform emergency care practice. Further research on ETAT+ performance in larger populations and additional patient-oriented outcomes would enhance its generalizability and application in resource-limited settings.

Brain tumor craniotomy outcomes for dual-eligible medicare and medicaid patients: a 10-year nationwide analysis.

INTRODUCTION: Dual-eligible (DE) patients, simultaneous Medicare and Medicaid beneficiaries, have been shown to have poorer clinical outcomes while incurring higher resource utilization. However, neurosurgical oncology outcomes for DE patients are poorly characterized. Accordingly, we examined the impact of DE status on perioperative outcomes following glioma, meningioma, or metastasis resection. METHODS: We identified all admissions undergoing a craniotomy for glioma, meningioma, or metastasis resection in the National Inpatient Sample from 2002 to 2011. Assessed outcomes included inpatient mortality, complications, discharge disposition, length of stay (LOS), and hospital costs. Multivariable regression adjusting for 13 patient, severity, and hospital characteristics assessed the association between DE status and outcomes, relative to four reference insurance groups (Medicare-only, Medicaid-only, private insurance, self-pay). RESULTS: Of 195,725 total admissions analyzed, 3.0% were dual-eligible beneficiaries (n = 5933). DEs were younger than Medicare admissions (P < 0.001) but older than Medicaid, private, and self-pay admissions (P < 0.001). Relative to other insurance groups, DEs also exhibited higher severity of illness, risk of mortality, and Charlson Comorbidity Index scores as well as treatment at low-volume hospitals (all P < 0.001). DEs had lower mortality than self-pay admissions (odds ratio [OR] 0.47, P = 0.017). Compared to Medicare, Medicaid, private, and self-pay admissions, DEs had lower rates of discharge disposition (OR 0.53, 0.50, 0.34, and 0.27, respectively, all P < 0.001). DEs also had higher complications (OR 1.23 and 1.20, respectively, both P < 0.05) and LOS (ß = 1.06 and 1.13, respectively, both P < 0.01) than Medicare and private insurance beneficiaries. Differences in discharge disposition remained significant for all three tumor subtypes, but only glioma DE admissions continued to exhibit higher complications and LOS. CONCLUSIONS: DEs undergoing definitive craniotomy for brain tumor had higher rates of unfavorable discharge disposition compared to all other insurance groups and, especially for glioma surgery, had higher inpatient complication rates and LOS. Practice and policy reforms to improve outcomes for this vulnerable clinical population are warranted.

Predicting access to postoperative treatment after glioblastoma resection: an analysis of neighborhood-level disadvantage using the Area Deprivation Index (ADI).

PURPOSE: Social determinants of health (SDoH)-socioeconomic and environmental factors-impact outcomes. The Area Deprivation Index (ADI), a composite of seventeen SDoH factors, has been correlated with poorer outcomes. We aimed to compare outcomes and treatment access for glioblastoma, a universally fatal malignant brain tumor, in patients more (ADI 34-100%) versus less disadvantaged (ADI 0-33%). METHODS: A 5-year retrospective study of Rhode Island Hospital and Mayo Clinic databases was conducted from 2012 to 2017 for patients ≥ 18 years with glioblastoma. Patient addresses were matched to ADI percentiles and grouped into more (top 66% ADI) and less disadvantaged. Adjusted multivariable regressions were used to compare outcomes between groups. RESULTS: A total of 434 patients met inclusion; 92.9% were insured, 56.2% were more disadvantaged (n = 244), and the more disadvantaged cohort was younger on average (62 years). After adjustment, the more disadvantaged group had decreased odds of receiving gross total resection (adjusted odds ratio (aOR) 0.43, 95% CI [0.27-0.68]; p < 0.001). This cohort also had decreased odds of undergoing chemotherapy (aOR 0.51[0.26-0.98]), radiation (aOR 0.39[0.20-0.77]), chemoradiation (aOR 0.42[0.23-0.77]), tumor-treating fields (aOR 0.39[0.16-0.93]), and clinical trial participation (aOR 0.47[0.25-0.91]). No differences in length of survival or postoperative Karnofsky Performance Status Scale were observed. CONCLUSION: More disadvantaged glioblastoma patients had decreased odds of receiving gross total resection. They also exhibited decreased odds of receiving standard of care like chemoradiation as well as participating in a clinical trial, compared to the less disadvantaged group. More research is needed to identify modifiable SDoH barriers to post-operative treatment in disadvantaged patients with glioblastoma.

Patient frailty association with cerebral arteriovenous malformation microsurgical outcomes and development of custom risk stratification score: an analysis of 16,721 nationwide admissions.

OBJECTIVE: Patient frailty is associated with poorer perioperative outcomes for several neurosurgical procedures. However, comparative accuracy between different frailty metrics for cerebral arteriovenous malformation (AVM) outcomes is poorly understood and existing frailty metrics studied in the literature are constrained by poor specificity to neurosurgery. This aim of this paper was to compare the predictive ability of 3 frailty scores for AVM microsurgical admissions and generate a custom risk stratification score. METHODS: All adult AVM microsurgical admissions in the National (Nationwide) Inpatient Sample (2002-2017) were identified. Three frailty measures were analyzed: 5-factor modified frailty index (mFI-5; range 0-5), 11-factor modified frailty index (mFI-11; range 0-11), and Charlson Comorbidity Index (CCI) (range 0-29). Receiver operating characteristic curves were used to compare accuracy between metrics. The analyzed endpoints included in-hospital mortality, routine discharge, complications, length of stay (LOS), and hospitalization costs. Survey-weighted multivariate regression assessed frailty-outcome associations, adjusting for 13 confounders, including patient demographics, hospital characteristics, rupture status, hydrocephalus, epilepsy, and treatment modality. Subsequently, k-fold cross-validation and Akaike information criterion-based model selection were used to generate a custom 5-variable risk stratification score called the AVM-5. This score was validated in the main study population and a pseudoprospective cohort (2018-2019). RESULTS: The authors analyzed 16,271 total AVM microsurgical admissions nationwide, with 21.0% being ruptured. The mFI-5, mFI-11, and CCI were all predictive of lower rates of routine discharge disposition, increased perioperative complications, and longer LOS (all p < 0.001). Their AVM-5 risk stratification score was calculated from 5 variables: age, hydrocephalus, paralysis, diabetes, and hypertension. The AVM-5 was predictive of decreased rates of routine hospital discharge (OR 0.26, p < 0.001) and increased perioperative complications (OR 2.42, p < 0.001), postoperative LOS (+49%, p < 0.001), total LOS (+47%, p < 0.001), and hospitalization costs (+22%, p < 0.001). This score outperformed age, mFI-5, mFI-11, and CCI for both ruptured and unruptured AVMs (area under the curve [AUC] 0.78, all p < 0.001). In a pseudoprospective cohort of 2005 admissions from 2018 to 2019, the AVM-5 remained significantly associated with all outcomes except for mortality and exhibited higher accuracy than all 3 earlier scores (AUC 0.79, all p < 0.001). CONCLUSIONS: Patient frailty is predictive of poorer disposition and elevated complications, LOS, and costs for AVM microsurgical admissions. The authors' custom AVM-5 risk score outperformed age, mFI-5, mFI-11, and CCI while using threefold less variables than the CCI. This score may complement existing AVM grading scales for optimization of surgical candidates and identification of patients at risk of postoperative medical and surgical morbidity.

Determinants of brain tumor malpractice litigation outcome and indemnity payments: a 29-year nationwide analysis.

OBJECTIVE: Medical malpractice litigation is a significant challenge in neurosurgery, with more than 25% of a neurosurgeon's career on average spent with an open malpractice claim. While earlier research has elucidated characteristics of litigation related to brain tumor treatment, factors impacting outcome and indemnity payment amount are incompletely understood. METHODS: The authors identified all medical malpractice cases related to brain tumors from 1988 to 2017 in VerdictSearch, a database of 200,000 cases from all 50 states. The outcome for each case was dichotomized from the perspective of the defendant physician as favorable (defendant victory) or unfavorable (plaintiff victory or settlement). Indemnity payments were recorded for cases that resulted in settlement or plaintiff victory. Univariate regression was used to assess the association between case characteristics and case outcome as well as indemnity payment amount. Subsequently, significant variables were used to generate multivariate models for each outcome. Statistical significance was maintained at p < 0.05. RESULTS: A total of 113 cases were analyzed, resulting most commonly in defendant (physician) victory (46.9%), followed by settlement and plaintiff victory (both 26.5%). The most common specialty of the primary defendant was neurosurgery (35.4%), and the most common allegation was improper diagnosis (59.3%). Indemnity payments totaled $191,621,392, with neurosurgical defendants accounting for $109,000,314 (56.9%). The average payments for cases with a plaintiff victory ($3,333,654) and for settlements ($3,051,832) did not significantly differ (p = 0.941). The highest rates of unfavorable outcomes were observed among radiologists (63.6%) and neurosurgeons (57.5%) (p = 0.042). On multivariate regression, severe disability was associated with a lower odds of favorable case outcome (OR 0.21, p = 0.023), while older plaintiff age (> 65 years) predicted higher odds of favorable outcome (OR 5.75, p = 0.047). For 60 cases resulting in indemnity payment, higher payments were associated on univariate analysis with neurosurgeon defendants (ß-coefficient = 2.33, p = 0.017), whether the plaintiff underwent surgery (ß-coefficient = 2.11, p = 0.012), and the plaintiff experiencing severe disability (ß-coefficient = 4.30, p = 0.005). Following multivariate regression, only medical outcome was predictive of increased indemnity payments, including moderate disability (ß-coefficient = 4.98, p = 0.007), severe disability (ß-coefficient = 6.96, p = 0.001), and death (ß-coefficient = 3.23, p = 0.027). CONCLUSIONS: Neurosurgeons were the most common defendants for brain tumor malpractice litigation, averaging more than $3 million per claim paid. Older plaintiff age was associated with case outcome in favor of the physician. Additionally, medical outcome was predictive of both case outcome and indemnity payment amount.

Volume-outcome relationship in pediatric neurotrauma care: analysis of two national databases.

OBJECTIVE: Previous research has demonstrated the association between increased hospital volume and improved outcomes for a wide range of neurosurgical conditions, including adult neurotrauma. The authors aimed to determine if such a relationship was also present in the care of pediatric neurotrauma patients. METHODS: The authors identified 106,146 pediatric admissions for traumatic intracranial hemorrhage (tICH) in the National Inpatient Sample (NIS) for the period 2002-2014 and 34,017 admissions in the National Trauma Data Bank (NTDB) for 2012-2015. Hospitals were stratified as high volume (top 20%) or low volume (bottom 80%) according to their pediatric tICH volume. Then the association between high-volume status and favorable discharge disposition, inpatient mortality, complications, and length of stay (LOS) was assessed. Multivariate regression modeling was used to control for patient demographics, severity metrics, hospital characteristics, and performance of neurosurgical procedures. RESULTS: In each database, high-volume hospitals treated over 60% of pediatric tICH admissions. In the NIS, patients at high-volume hospitals presented with worse severity metrics and more frequently underwent neurosurgical intervention over medical management (all p < 0.001). After multivariate adjustment, admission to a high-volume hospital was associated with increased odds of a favorable discharge (home or short-term facility) in both databases (both p < 0.001). However, there were no significant differences in inpatient mortality (p = 0.208). Moreover, high-volume hospital patients had lower total complications in the NIS and lower respiratory complications in both databases (all p < 0.001). Although patients at high-volume hospitals in the NTDB had longer hospital stays (ß-coefficient = 1.17, p < 0.001), they had shorter stays in the intensive care unit (ß-coefficient = 0.96, p = 0.024). To determine if these findings were attributable to the trauma center level rather than case volume, an analysis was conducted with only level I pediatric trauma centers (PTCs) in the NTDB. Similarly, treatment at a high-volume level I PTC was associated with increased odds of a favorable discharge (OR 1.28, p = 0.009), lower odds of pneumonia (OR 0.60, p = 0.007), and a shorter total LOS (ß-coefficient = 0.92, p = 0.024). CONCLUSIONS: Pediatric tICH patients admitted to high-volume hospitals exhibited better outcomes, particularly in terms of discharge disposition and complications, in two independent national databases. This trend persisted when examining level I PTCs exclusively, suggesting that volume alone may have an impact on pediatric neurotrauma outcomes. These findings highlight the potential merits of centralizing neurosurgery and pursuing regionalization policies, such as interfacility transport networks and destination protocols, to optimize the care of children affected by traumatic brain injury.

Comparison of Surgical Modalities for Giant Pituitary Adenoma: A Systematic Review and Meta-Analysis of 1413 Patients.

BACKGROUND AND OBJECTIVES: Giant pituitary adenomas (GPAs) are a challenging clinical entity, composing 5% to 15% of all pituitary adenomas. While the endoscopic endonasal transsphenoidal (EET) approach has surpassed the microsurgical transsphenoidal (MT) and transcranial (TC) approaches as the first-line surgical modality in most institutions, a systematic review comparing the 3 approaches has not been undertaken since 2012. Given growing adoption of EET and development of novel operative techniques over the past decade, an updated comparison of GPA surgical modalities is warranted. METHODS: We identified all studies related to the surgical management of GPAs in PubMed, Embase, and Web of Science from inception to December 31, 2021. End points assessed included gross total resection (GTR) rates, postoperative visual improvement, mortality, and perioperative complications. RESULTS: After screening of 1701 studies, we identified 45 studies on the surgical management of GPAs for meta-analysis. Thirty-one used the EET approach (n = 1413), 11 studies used the MT approach (n = 601), and 10 used the TC approach (n = 416). The cumulative number of patients treated by EET did not exceed that of patients treated by the TC or MT approaches until 2014 and 2015, respectively. Despite patients undergoing EET having the highest average tumor diameter, pooled rates for GTR were significantly higher for EET (42%) than MT (33%, P < .001) and TC (8%, P < .001) and EET similarly exhibited superior rates of visual improvement (85%) than MT (73%, P < .001) and TC (56%, P < .001). Mortality rates were comparable between EET (0.6%) and MT (1.6%), but EET had significantly lower mortality than TC (2.7%, P < .001). Compared with MT, EET had lower rates of hypopituitarism (8.5% vs 14.9%, P = .012) but higher rates of diabetes insipidus (3.1% vs 0.5%, P = .001). CONCLUSION: In an updated meta-analysis of 1413 patients with GPA, EET resection conferred significantly higher rates of visual improvement and GTR, when compared with the MT and TC approaches.

Factors influencing disparities in epilepsy surgery: analysis of the National Inpatient Sample and Kids' Inpatient Database.

OBJECTIVE: Despite the proven efficacy of surgical intervention for achieving seizure freedom and improved quality of life for many epilepsy patients, this treatment remains underutilized. In this study, the authors assessed sociodemographic trends in epilepsy surgery in the National Inpatient Sample (NIS) and the Kids' Inpatient Database (KID) and sought to determine whether disparities in surgical intervention for epilepsy may be attributed to insurance and comorbidity status. METHODS: This cross-sectional study utilized data from the NIS database and KID from the Healthcare Cost and Utilization Project between the years 2012 and 2018. Outcomes of interest were rates of neurosurgical intervention, including resection, neuromodulation, or laser ablation. The authors utilized logit regression models to test the association between rates of neurosurgical intervention and the variables of interest and calculated the adjusted mean proportion of patients who received surgery using marginal effects. RESULTS: Of 336,015 admissions with intractable epilepsy in the NIS, 6.1% were patients who underwent neurosurgical treatment. Of 39,655 admissions from KID, 5.0% received surgical treatment. Private insurance was associated with a greater odds of surgical intervention compared with Medicaid (NIS: OR 1.63, KID: OR 1.62; p < 0.001). Patients assigned White race had an increased odds ratio of undergoing surgery when compared with those assigned Black race, adjusted for comorbidity burden (NIS: OR 1.59, p < 0.001; KID: OR 1.44, p = 0.027). Patients with an Elixhauser Comorbidity Index score of 0 or 1 were associated with a lower likelihood of surgery when compared to their higher scoring counterparts who had 4 or more comorbidities (NIS: OR 0.74, KID: OR 0.62; both p < 0.001). CONCLUSIONS: This study demonstrates that marginalized patients and those with Medicaid had decreased odds of neurosurgical intervention for epilepsy. Results of this research support the need for increased attention toward epilepsy patients from marginalized groups. Further investigation into the root cause of socioeconomic inequities in epilepsy surgery is necessary.

Endoluminal Sigmoid Sinus Occlusion During Jugular Foramen Tumor Surgery: Novel Technique, Operative Nuances, and Clinical Experience With 33 Patients.

BACKGROUND AND IMPORTANCE: Surgery of jugular foramen tumors (JFTs) often requires vascular control by means of ligating the internal jugular vein and sigmoid sinus (SS) to allow intrabulbar access. Occlusion of the SS traditionally involves presigmoid and retrosigmoid durotomies allowing introduction of ligature devices, predisposing to cerebrospinal fluid (CSF) leakage and pseudomeningoceles. We describe a simple and novel endoluminal sigmoid sinus occlusion (ESSO) technique with Gelfoam that is entirely extradural. CLINICAL PRESENTATION: An extended anterolateral infralabyrinthine approach with ESSO was performed in 33 patients with JFTs. After ligating the internal jugular vein, the SS is opened and Gelfoam is placed endoluminally into the proximal SS. Care is taken to avoid occlusion of the venous outflow of the vein of Labbe to avoid temporal lobe venous infarction. Hemostatic gelatin matrix is injected distally to stop venous backflow from the inferior petrosal sinus. The jugular venous system is isolated, and the outer jugular wall can be opened to expose the JFT for resection. There were no complications of temporal lobe venous infarction or postoperative hematoma observed. Four patients with intradural tumor extension developed pseudomeningoceles. For patients with purely extradural JFTs, none developed postoperative incisional CSF leaks and one had pseudomeningocele. CONCLUSION: This ESSO technique is fast and effective, permitting occlusion of the SS during JFT surgery. It has the advantage of being entirely extradural, avoiding durotomy which can result in postoperative CSF leak. It is important to keep the Gelfoam distal to the transverse-sigmoid junction to avoid occlusion of the vein of Labbe inlet and temporal lobe venous infarction.

Evidence Against a Traumatic Brain Injury "July Effect": An Analysis of 3 160 452 Patients From the National Inpatient Sample.

BACKGROUND AND OBJECTIVES: The "July Effect" hypothesizes increased morbidity and mortality after the addition of inexperienced physicians at the beginning of an academic year. However, the impact of newer members on neurosurgical teams managing patients with traumatic brain injury (TBI) has yet to be examined. This study conducted a nationwide analysis to evaluate the existence of the "July Effect" in the setting of patients with TBI. METHODS: The Healthcare Cost and Utilization Project Central Distributor's National Inpatient Sample data set was queried for patients with TBI using International Classification of Diseases (ICD)-9 and ICD-10 codes. Discharges were included for diagnoses of traumatic epidural, subdural, or subarachnoid hemorrhages. Only patients treated at teaching hospitals were included to ensure resident involvement in care. Patients were grouped into July admission and non-July admission cohorts. A subgroup of patients with neurotrauma undergoing any form of cranial surgery was created. Perioperative variables were recorded. Rates of different complications were assayed. Groups were compared using χ2 tests (qualitative variables) and t-tests or Mann-Whitney U-tests (quantitative variables). Logistic regression was used for binary variables. Gamma log-linked regression was used for continuous variables. RESULTS: The National Inpatient Sample database yielded a weighted average of 3 160 452 patients, of which 312 863 (9.9%) underwent surgical management. Patients admitted to the hospital in July had a 5% decreased likelihood of death (P = .027), and a 5.83% decreased likelihood of developing a complication (P < .001) compared with other months of the year. July admittance to a hospital showed no significant impact on mean length of stay (P = .392) or routine discharge (P = .147). Among patients with TBI who received surgical intervention, July admittance did not significantly affect the likelihood of death (P = .053), developing a complication (P = .477), routine discharge (P = .986), or mean length of stay (P = .385). CONCLUSION: The findings suggested that there is no "July Effect" on patients with TBI treated at teaching hospitals in the United States.

Derivation and Internal Validation of a Mortality Prognostication Machine Learning Model in Ebola Virus Disease Based on Iterative Point-of-Care Biomarkers.

Background: Although multiple prognostic models exist for Ebola virus disease mortality, few incorporate biomarkers, and none has used longitudinal point-of-care serum testing throughout Ebola treatment center care. Methods: This retrospective study evaluated adult patients with Ebola virus disease during the 10th outbreak in the Democratic Republic of Congo. Ebola virus cycle threshold (Ct; based on reverse transcriptase polymerase chain reaction) and point-of-care serum biomarker values were collected throughout Ebola treatment center care. Four iterative machine learning models were created for prognosis of mortality. The base model used age and admission Ct as predictors. Ct and biomarkers from treatment days 1 and 2, days 3 and 4, and days 5 and 6 associated with mortality were iteratively added to the model to yield mortality risk estimates. Receiver operating characteristic curves for each iteration provided period-specific areas under curve with 95% CIs. Results: Of 310 cases positive for Ebola virus disease, mortality occurred in 46.5%. Biomarkers predictive of mortality were elevated creatinine kinase, aspartate aminotransferase, blood urea nitrogen (BUN), alanine aminotransferase, and potassium; low albumin during days 1 and 2; elevated C-reactive protein, BUN, and potassium during days 3 and 4; and elevated C-reactive protein and BUN during days 5 and 6. The area under curve substantially improved with each iteration: base model, 0.74 (95% CI, .69-.80); days 1 and 2, 0.84 (95% CI, .73-.94); days 3 and 4, 0.94 (95% CI, .88-1.0); and days 5 and 6, 0.96 (95% CI, .90-1.0). Conclusions: This is the first study to utilize iterative point-of-care biomarkers to derive dynamic prognostic mortality models. This novel approach demonstrates that utilizing biomarkers drastically improved prognostication up to 6 days into patient care.

Demographic Representation in 3 Leading Artificial Intelligence Text-to-Image Generators.

Importance: The progression of artificial intelligence (AI) text-to-image generators raises concerns of perpetuating societal biases, including profession-based stereotypes. Objective: To gauge the demographic accuracy of surgeon representation by 3 prominent AI text-to-image models compared to real-world attending surgeons and trainees. Design, Setting, and Participants: The study used a cross-sectional design, assessing the latest release of 3 leading publicly available AI text-to-image generators. Seven independent reviewers categorized AI-produced images. A total of 2400 images were analyzed, generated across 8 surgical specialties within each model. An additional 1200 images were evaluated based on geographic prompts for 3 countries. The study was conducted in May 2023. The 3 AI text-to-image generators were chosen due to their popularity at the time of this study. The measure of demographic characteristics was provided by the Association of American Medical Colleges subspecialty report, which references the American Medical Association master file for physician demographic characteristics across 50 states. Given changing demographic characteristics in trainees compared to attending surgeons, the decision was made to look into both groups separately. Race (non-White, defined as any race other than non-Hispanic White, and White) and gender (female and male) were assessed to evaluate known societal biases. Exposures: Images were generated using a prompt template, "a photo of the face of a [blank]", with the blank replaced by a surgical specialty. Geographic-based prompting was evaluated by specifying the most populous countries on 3 continents (the US, Nigeria, and China). Main Outcomes and Measures: The study compared representation of female and non-White surgeons in each model with real demographic data using χ2, Fisher exact, and proportion tests. Results: There was a significantly higher mean representation of female (35.8% vs 14.7%; P < .001) and non-White (37.4% vs 22.8%; P < .001) surgeons among trainees than attending surgeons. DALL-E 2 reflected attending surgeons' true demographic data for female surgeons (15.9% vs 14.7%; P = .39) and non-White surgeons (22.6% vs 22.8%; P = .92) but underestimated trainees' representation for both female (15.9% vs 35.8%; P < .001) and non-White (22.6% vs 37.4%; P < .001) surgeons. In contrast, Midjourney and Stable Diffusion had significantly lower representation of images of female (0% and 1.8%, respectively; P < .001) and non-White (0.5% and 0.6%, respectively; P < .001) surgeons than DALL-E 2 or true demographic data. Geographic-based prompting increased non-White surgeon representation but did not alter female representation for all models in prompts specifying Nigeria and China. Conclusion and Relevance: In this study, 2 leading publicly available text-to-image generators amplified societal biases, depicting over 98% surgeons as White and male. While 1 of the models depicted comparable demographic characteristics to real attending surgeons, all 3 models underestimated trainee representation. The study suggests the need for guardrails and robust feedback systems to minimize AI text-to-image generators magnifying stereotypes in professions such as surgery.

Social determinants of health and outcome disparities in spine tumor surgery. Part 2: Neighborhood disadvantage and long-term outcomes.

OBJECTIVE: Neighborhood-level resource disadvantage has been previously shown to predict extent of resection, oncological follow-up, adjuvant treatment, and clinical trial participation for malignancies, including glioblastoma. The authors aimed to characterize the association between neighborhood disadvantage and long-term outcomes after spine tumor surgery. METHODS: The authors analyzed all patients who underwent surgery for primary or secondary (all metastatic pathologies) spine tumors at a single spinal oncology specialty center in the United States from 2015 to 2022. The Area Deprivation Index (ADI), a validated metric compositing 17 social determinants of health variables that ranges continuously from 0% (higher advantage) to 100% (higher disadvantage), was used to quantify neighborhood disadvantage. Patient addresses were matched to ADI on the basis of the census block of residence. Subsequently, the study population was dichotomized into advantaged (ADI 0%-33%) and disadvantaged (ADI 34%-100%) cohorts. The primary endpoint was functional status, as defined by Eastern Cooperative Oncology Group (ECOG) Performance Status Scale grade, with secondary endpoints including inpatient outcomes, mortality, readmissions, reoperations, and clinical research participation. Multivariable logistic, gamma log-link, and Cox regression adjusted for 14 confounders, including patient and oncological characteristics, general and tumor-related presenting severity, and treatment. RESULTS: In total, 237 patients underwent spine tumor surgery from 2015 to 2022, with an average age of 53.9 years, and 57.0% had primary tumors whereas 43.0% had secondary tumors; 55.3% (n = 131) were classified by ADI into the disadvantaged cohort. This cohort had higher rates of ambulation deficits on presentation (39.1% vs 23.5%, p = 0.015) and nonelective surgery (35.1% vs 23.6%, p = 0.030). Postoperatively, disadvantaged patients exhibited higher odds of residual tumor (OR 2.55, p = 0.026), especially for secondary tumors (OR 4.92, p = 0.045). Patients from disadvantaged neighborhoods additionally exhibited significantly higher odds of poor functional status at follow-up (OR 3.94, p = 0.002). Postoperative survival was 74.7% (mean follow-up 17.6 months), with the disadvantaged cohort experiencing significantly shorter survival (HR 1.92, p = 0.049). Moreover, this population had higher odds of readmission (OR 1.92, p = 0.046) and, for primary tumors, reoperation (OR 9.26, p = 0.005). Elective participation in prospective clinical research was lower among the disadvantaged cohort (OR 0.45, p = 0.016). CONCLUSIONS: Neighborhood disadvantage predicts higher rates of residual tumor, readmission, and reoperation, as well as poorer functional status, shorter postoperative survival, and decreased elective research participation. The ADI may be used to risk stratify spine oncology patients and guide targeted interventions to ameliorate neurosurgical disparities and to reduce barriers to research participation.

Social determinants of health and outcome disparities in spine tumor surgery. Part 1: An analysis of 6.6 million nationwide admissions.

OBJECTIVE: Earlier research has demonstrated that social determinants of health (SDoH) impact neurosurgical access and outcomes, but these trends are less characterized for spine tumors relative to intracranial tumors. The authors aimed to elucidate the association between SDoH and outcomes for a nationwide cohort of spine tumor surgery admissions. METHODS: The authors identified all admissions with a spine tumor diagnosis in the National Inpatient Sample (NIS) from 2002 to 2019. Four SDoH were analyzed: race and ethnicity, insurance, household income, and safety-net hospital (SNH) treatment. Hospitals in the top quartile of safety-net burden (in terms of percentage of patients receiving Medicaid or uninsured) were categorized as SNHs. Multivariable regression queried the association between 22 variables and 5 perioperative outcomes: mortality, discharge disposition, complications, length of stay (LOS), and hospitalization costs. Interaction term analysis with hospitalization year was used to assess longitudinal changes in outcome disparities. Finally, the authors constructed random forest machine learning models to assess the impact of SDoH variables on prognostic accuracy and to quantify the relative importance of predictors for disposition. RESULTS: Of 6,593,392 total admissions with spine tumors, 219,380 (3.3%) underwent surgery. Non-White race (OR 0.80-0.91, p < 0.001) and nonprivate insurance (OR 0.76-0.83, p < 0.001) were associated with lower odds of receiving surgery. Among surgical admissions, presenting severity, including of myelopathy and plegia, was elevated among non-White, nonprivate insurance, and low-income admissions (all p < 0.001). Black race (OR 0.70, p < 0.001), Medicare (OR 0.70, p < 0.001), Medicaid (OR 0.90, p < 0.001), and lower income (OR 0.88-0.93, all p < 0.001) were associated with decreased odds of favorable discharge disposition. Increased LOS and costs were observed among non-White (+6%-10% in LOS and +5%-9% in costs, both p < 0.001) and Medicaid (+16% in LOS and +6% in costs, both p < 0.001) admissions. SNH treatment was also associated with higher mortality (OR 1.49, p < 0.001) and complication (OR 1.20, p < 0.001) rates. From 2002 to 2019, disposition improved annually for Medicaid patients (OR 1.03 per year, p = 0.022) but worsened for Black patients (OR 0.98 per year, p = 0.046). Random forest models identified household income as the most important predictor of discharge disposition. CONCLUSIONS: For spine tumor admissions, SDoH predicted surgical intervention, presenting severity, and perioperative outcomes. Over 2 decades, disparities improved for Medicaid patients but worsened for Black patients. Finally, SDoH significantly improve prognostic accuracy for outcomes after spine tumor surgery. Further study toward ameliorating patient disparities for this population is warranted.

Bridging the literacy gap for surgical consents: an AI-human expert collaborative approach.

Despite the importance of informed consent in healthcare, the readability and specificity of consent forms often impede patients' comprehension. This study investigates the use of GPT-4 to simplify surgical consent forms and introduces an AI-human expert collaborative approach to validate content appropriateness. Consent forms from multiple institutions were assessed for readability and simplified using GPT-4, with pre- and post-simplification readability metrics compared using nonparametric tests. Independent reviews by medical authors and a malpractice defense attorney were conducted. Finally, GPT-4's potential for generating de novo procedure-specific consent forms was assessed, with forms evaluated using a validated 8-item rubric and expert subspecialty surgeon review. Analysis of 15 academic medical centers' consent forms revealed significant reductions in average reading time, word rarity, and passive sentence frequency (all P < 0.05) following GPT-4-faciliated simplification. Readability improved from an average college freshman to an 8th-grade level (P = 0.004), matching the average American's reading level. Medical and legal sufficiency consistency was confirmed. GPT-4 generated procedure-specific consent forms for five varied surgical procedures at an average 6th-grade reading level. These forms received perfect scores on a standardized consent form rubric and withstood scrutiny upon expert subspeciality surgeon review. This study demonstrates the first AI-human expert collaboration to enhance surgical consent forms, significantly improving readability without sacrificing clinical detail. Our framework could be extended to other patient communication materials, emphasizing clear communication and mitigating disparities related to health literacy barriers.

Repeated peripheral infusions of anti-EGFRvIII CAR T cells in combination with pembrolizumab show no efficacy in glioblastoma: a phase 1 trial.

We previously showed that chimeric antigen receptor (CAR) T-cell therapy targeting epidermal growth factor receptor variant III (EGFRvIII) produces upregulation of programmed death-ligand 1 (PD-L1) in the tumor microenvironment (TME). Here we conducted a phase 1 trial (NCT03726515) of CAR T-EGFRvIII cells administered concomitantly with the anti-PD1 (aPD1) monoclonal antibody pembrolizumab in patients with newly diagnosed, EGFRvIII+ glioblastoma (GBM) (n = 7). The primary outcome was safety, and no dose-limiting toxicity was observed. Secondary outcomes included median progression-free survival (5.2 months; 90% confidence interval (CI), 2.9-6.0 months) and median overall survival (11.8 months; 90% CI, 9.2-14.2 months). In exploratory analyses, comparison of the TME in tumors harvested before versus after CAR + aPD1 administration demonstrated substantial evolution of the infiltrating myeloid and T cells, with more exhausted, regulatory, and interferon (IFN)-stimulated T cells at relapse. Our study suggests that the combination of CAR T cells and PD-1 inhibition in GBM is safe and biologically active but, given the lack of efficacy, also indicates a need to consider alternative strategies.

Optimizing CAR-T Therapy for Glioblastoma.

Chimeric antigen receptor T-cell therapies have transformed the management of hematologic malignancies but have not yet demonstrated consistent efficacy in solid tumors. Glioblastoma is the most common primary malignant brain tumor in adults and remains a major unmet medical need. Attempts at harnessing the potential of chimeric antigen receptor T-cell therapy for glioblastoma have resulted in glimpses of promise but have been met with substantial challenges. In this focused review, we discuss current and future strategies being developed to optimize chimeric antigen receptor T cells for efficacy in patients with glioblastoma, including the identification and characterization of new target antigens, reversal of T-cell dysfunction with novel chimeric antigen receptor constructs, regulatable platforms, and gene knockout strategies, and the use of combination therapies to overcome the immune-hostile microenvironment.

The Surgical Histopathology of the Filum Terminale: Findings from a Large Series of Patients with Tethered Cord Syndrome.

This study investigated the prevalence of embryonic and connective tissue elements in the filum terminale (FT) of patients with tethered cord syndrome (TCS), examining both typical and pathological histology. The FT specimens from 288 patients who underwent spinal cord detethering from 2013 to 2021 were analyzed. The histopathological examination involved routine hematoxylin and eosin staining and specific immunohistochemistry when needed. The patient details were extracted from electronic medical records. The study found that 97.6% of the FT specimens had peripheral nerves, and 70.8% had regular ependymal cell linings. Other findings included ependymal cysts and canals, ganglion cells, neuropil, and prominent vascular features. Notably, 41% showed fatty infiltration, and 7.6% had dystrophic calcification. Inflammatory infiltrates, an underreported finding, were observed in 3.8% of the specimens. The research highlights peripheral nerves and ganglion cells as natural components of the FT, with ependymal cell overgrowth and other tissues potentially linked to TCS. Enlarged vessels may suggest venous congestion due to altered FT mechanics. The presence of lymphocytic infiltrations and calcifications provides new insights into structural changes and mechanical stress in the FT, contributing to our understanding of TCS pathology.