Faculty Bibliography

INTRODUCTION/BACKGROUND:Survival outcomes among patients with World Health Organization grade III gliomas and IDH-mutant (IDHmt) gliomas treated with immunotherapy (IT) remain understudied, with most research focusing on grade IV (G4) glioblastomas or IDH wild-type (IDHwt) tumors. METHODS:A systematic literature search was conducted in PubMed/MEDLINE, SCOPUS, Embase, Google Scholar, and Science Direct databases following PRISMA guidelines. A random-effects meta-analysis was conducted to assess overall survival and 5-year mortality. Outcomes were compared across IT treatments and between historically designated grade III versus grade IV/GBM cohorts and explicitly reported IDHmt versus IDHwt glioma cohorts within each included study. RESULTS:A total of 21 studies involving 207 patients with grade III gliomas and 11 studies involving 115 patients with IDHmt gliomas were included. IT agents studied included dendritic cell and peptide vaccines (32 grade III, 45 IDHmt), immune checkpoint inhibitors (1 grade III, 39 IDHmt), oncolytic viruses (10 grade III, 20 IDHmt), modified lymphocyte therapies (1 grade III, 11 IDHmt), cytokine immunotherapy (47 IDHmt) and radioimmunotherapy (110 grade III). Most treated grade III (65.6%) and IDHmt (72.7%) gliomas were recurrent tumors. Across all immunotherapy agents, recurrent and newly diagnosed grade III glioma did not exhibit significant differences in overall survival (21.90 versus 29.71 months, p = 0.237), 5-year mortality (77.10% versus 60.89%, p = 0.481), or overall mortality at last follow-up (78.91% versus 70.37%, p = 0.553). Newly diagnosed IDHmt glioma had significantly greater overall survival than recurrent IDHmt glioma (43.13 versus 19.57 months, p = 0.005) and significantly lower 5-year mortality (10.26% versus 59.78%, p < 0.001). Between immunotherapy modalities, grade III glioma did not exhibit differences in overall survival compared to GBM in equivalent treated cohorts (p = 0.123). However, dendritic cell and peptide vaccines had a higher overall survival compared to all other immunotherapy agents in IDHmt glioma (p = 0.002), including when compared to IDHwt glioma in equivalent treatment arms (p = 0.044). CONCLUSION/CONCLUSIONS:Our study summarizes reported survival outcomes among patients with historically designated grade III and IDHmt gliomas treated with immunotherapy. Observed differences by histological grade, IDH status, and recurrence status are consistent with the established prognostic importance of these tumor features, and should not be interpreted as evidence that immunotherapy caused improved survival. Survival outcomes appeared more favorable in newly diagnosed IDHmt glioma and in IDHmt cohorts treated with dendritic cell or peptide vaccines; however, these findings are descriptive and hypothesis-generating given the predominance of single-arm studies, limited sample size, and potential confounding by baseline prognosis. Future prospective controlled trials are needed to determine whether specific immunotherapy approaches provide benefit in these glioma subgroups.

IMPORTANCE/UNASSIGNED:Public concern and speculation have emerged around a possible link between neonatal male circumcision (NMC) and autism spectrum disorder (ASD). Evidence is limited and inconsistent. OBJECTIVE/UNASSIGNED:To examine associations between NMC and child ASD and autism-related traits and behaviors. DESIGN, SETTING, AND PARTICIPANTS/UNASSIGNED:This prospective cohort study was conducted among cohort sites participating in the Environmental Influences on Child Health Outcomes (ECHO) Cohort between February 2003 and September 2025. Statistical analyses were conducted from November 2025 to February 2026. The analysis included male, singleton children with data on NMC status and child ASD. EXPOSURE/UNASSIGNED:NMC status within 28 days of birth at a medical facility. MAIN OUTCOMES AND MEASURES/UNASSIGNED:ASD diagnosis was based on parent report of diagnosis by a medical professional or documentation of criterion standard clinical assessments. Social Responsiveness Scale (SRS-2) T-scores assessed the presence and distribution of autism traits, and Diagnostic and Statistical Manual of Mental Disorders (Fifth Edition) Autism Spectrum Problems subscale T-scores from the Child Behavior Checklist (CBCL) 1.5/5 assessed the occurrence of child autism-related behaviors. RESULTS/UNASSIGNED:The sample included 2771 male children from 14 ECHO sites, of whom 1840 (66%) were circumcised before hospital discharge, and 192 (7%) had an autism diagnosis. Among 1840 circumcised males, 108 (6%) had autism, compared with 84 of 931 uncircumcised males (9%). Mean (SD) age at autism diagnosis was 3.8 (2.2) years. Among circumcised males, 31 (4%) were administered acetaminophen during the procedure, and 128 (7%) within the 30 days after birth. After adjusting for confounders, there was no association between NMC and ASD diagnosis (odds ratio [OR], 0.83; 95% CI, 0.59-1.17). After stratification by region, preterm birth, and neonatal intensive care unit admission, an inverse or no association was observed between NMC and ASD diagnosis. Adjusted analyses showed no associations between NMC and SRS-2 continuous (β = -0.62; 95% CI, -1.46 to 0.22) or binary (OR, 0.75; 95% CI, 0.48-1.15) T-scores. Similarly, no associations were observed between NMC and CBCL 1.5/5 continuous (β = 0.01; 95% CI, -0.54 to 0.56) or binary (OR, 1.30; 95% CI, 0.75-2.26) T-scores. Overall, inverse or no associations were observed across all strata for SRS-2 and CBCL 1.5/5 outcomes. CONCLUSIONS AND RELEVANCE/UNASSIGNED:This cohort study yielded no evidence that NMC was associated with ASD risk, whether assessed by parent report of medical professional diagnosis or validated instruments measuring autism-related traits and behavior. These findings may provide reassurance for families who are considering or have elected NMC for their child.

Consciousness science is fragmented, and empirical investigations are largely confined within the framework of each theory of consciousness (ToC). Proliferating ToCs accumulate anomalies without progress, operating orthogonally. The principle of recurrency, functional and architectural, specifies a unifying, mechanistic scaffold for consciousness to arise. We show that all theories tacitly invoke feedback loops and can be re-expressed along a single axis of recursion. Four nested levels, viz., cellular, local inter-areal, global, and lateral, map onto state consciousness, phenomenal (P) content, conscious access (A), and phenomenal character, respectively, thus tying evolved anatomy to phenomenality. The classical P-A distinction dissolves into a graded cascade wherein deeper recursion expands the set of reportable, behaviour-driving variables. Recurrency, defined as structural, causal, and/or functional feedforward and feedback connections between elements within a system, is favoured in biological architectures, and supports the closed-loop interactions between brain, body, and environment that underlie adaptive behaviour and self-related processing. Disparities in the explanatory mechanisms across theories of consciousness can thus be resolved by converging onto this shared principle on the implementation axis, rather than deal with phenomenal-first or functional-first ontologies. The field urgently requires this implementation-first distillation that is biologically plausible, mechanistic, and empirically testable.

Tractography is a key component of efforts to map brain connectivity. As a rapidly evolving field of neuroscience, current tractography methods are diverse, often varying across research laboratories and different software pipelines. Therefore, it suffers from a lack of standardization, leading to inconsistencies in results, which can limit reproducibility and affect the robustness needed for research and clinical applications of these methods. Variability in data acquisition procedures, inconsistencies in spatial referencing schemes and implementations, and anatomical heterogeneity-at the individual level, across the lifespan, and across species-hinder comparative analyses. Additionally, the lack of consensus on best practices complicates the development of robust automated quality control pipelines and limits the clinical translation of tractography-based procedures. Establishing standardized protocols for acquisition, preprocessing, and tractography reconstruction is critical toward enabling reliable tract-specific analyses, facilitating cross-study harmonization, and supporting replicable large-scale population studies. The present article provides an overview of the current challenges in tractography standardization and identifies the key aspects that require standardization for reliable, reproducible, and robust tractography.

BACKGROUND:There are limited data to guide antiseizure medication (ASM) prophylaxis in patients with aneurysmal subarachnoid hemorrhage (SAH). This results in practice variation in the use and duration of ASM prophylaxis. METHODS:We conducted a systematic review and meta-analysis of articles assessing ASM prophylaxis in adults with aneurysmal SAH. The population, intervention, comparator, and outcome (PICO) questions were as follows: (1) Should ASM or no ASM be used in patients hospitalized for aneurysmal subarachnoid hemorrhage who have no history of clinical or electrographic seizures? (2) If an ASM is used, should levetiracetam or phenytoin/fosphenytoin be preferentially used? (3) If an ASM is used, should a long (> 3 days) or short (≤ 3 days) duration of prophylaxis be used? The main outcomes were early seizure (≤ 14 days), late seizures (> 14 days), adverse events, mortality, and functional outcomes. We used Grading of Recommendations Assessment, Development, and Evaluation (GRADE) methodology to generate recommendations. RESULTS:The initial literature search yielded 1988 articles, of which 10 formed the basis of the recommendations: Regarding PICO 1, we did not find a significant difference in outcomes of early seizure, adverse events, mortality, or functional outcomes when comparing ASM to no ASM. In regard to PICO 2, we found fewer early seizures with phenytoin/fosphenytoin and lower risk for neurologic decline with levetiracetam; however, there was low certainty of evidence. There was no significant difference in mortality between the different treatment types. Regarding PICO 3, we found extended use of ASM may be associated with lower seizure risk, but at the same time be associated with higher risk for adverse effects. CONCLUSIONS:Overall, the quality of evidence is low, precluding strong recommendations. We suggest that ASM or no ASM may be used in patients hospitalized with aneurysmal subarachnoid hemorrhage (conditional recommendation, low quality of evidence). If used, we suggest either levetiracetam or phenytoin/fosphenytoin (conditional recommendation, very low quality of evidence) for a short or long duration (conditional recommendation, moderate quality of evidence).

Nasoalveolar molding (NAM) is an established form of presurgical infant orthopedics (PSIO), whereas presurgical lip, alveolus, and nose approximation (PLANA) is a novel approach. This study compared presurgical outcomes between infants with a unilateral cleft lip treated with PLANA and NAM using an objective method for assessment of cleft severity and PSIO outcomes. A single-institution retrospective review was conducted of all patients treated with NAM (2017-2019) and PLANA (2023-2025). Anthropometric measurements including columellar angle, nostril width ratio, and lateral subnasale displacement were collected at the initiation and completion of therapy, and predefined thresholds were used to classify patients by cleft severity (mild, moderate, severe, and very severe) and outcome (poor, good, and excellent). A total of 64 patients were identified, including 36 patients treated with NAM and 28 treated with PLANA. At baseline, the 2 cohorts exhibited similar distributions in cleft severity categories. At the completion of therapy, statistically significant differences were observed between NAM (27.8% mild, 52.8% moderate, 16.7% severe, and 2.8% very severe) and PLANA (67.9% mild, 28.6% moderate, 3.6% severe, 0.0% very severe). This translated to significant differences in PSIO outcomes between NAM (11.1% excellent, 55.6% good, and 33.3% poor) and PLANA (60.7% excellent, 35.7% good, and 3.6% poor). Numerically, the 2 cohorts were statistically similar at baseline, but after PSIO the PLANA cohort displayed more favorable anthropometrics and larger improvements in all 3 parameters. Using an objective method for evaluating cleft severity, patients treated with PLANA exhibited superior morphologic outcomes in comparison to NAM.

OBJECTIVES/OBJECTIVE:The use of #pathology and #pathologist is increasing on TikTok, a short-form video platform with over 1 billion users. As of July 2024, #pathology had over 21 000 posts and 468 million views, while #pathologist had over 3000 posts. It could be a useful tool for education and recruitment if the content is accurate and engaging. METHODS:To assess the accuracy, engagement, and educational value of this growing content, we conducted a cross-sectional study analyzing 105 English-language TikTok videos identified using these keywords over a 72-hour period. Videos were evaluated using the Patient Education Assessment Tool for audiovisual material (PEMAT-AV) for audiovisual quality, the Global Quality Scale (GQS) for overall content quality, and a modified JAMA benchmark score for information accountability. Additionally, a harm-benefit score categorized educational impact. RESULTS:Statistical analysis revealed that educational content demonstrated significantly higher quality scores on GQS (P = .0001) and PEMAT-AV (P = .0007) than other content types. In contrast, medical profile type was associated with higher PEMAT-AV (P = .0147), JAMA (P = .0332), and harm-benefit (P = .0004) scores. CONCLUSIONS:While the volume of pathology-specific content is currently limited, the high average engagement metrics-298 100 followers, 1.5 million views, and 67 884 likes per video-indicate substantial user interest. The higher-quality scores for educational and medical content suggest that pathology content creators are generally knowledgeable and accurately represent the field on TikTok, highlighting TikTok's potential as a valuable platform for disseminating reliable pathology-related information.

BACKGROUND/UNASSIGNED:Patient-centered prognostic assessment in chronic coronary disease is vital for treatment optimization. Although the Seattle Angina Questionnaire Summary Score (SAQ-SS) correlates with clinical outcomes, clinicians lack guidance on how to weigh prior, current, or changes in scores, and whether prognostic significance varies by revascularization strategy. METHODS/UNASSIGNED:The ISCHEMIA trial (International Study of Comparative Health Effectiveness with Medical and Invasive Approaches; 2012-2019) was a global, multicenter, randomized controlled trial. This secondary analysis evaluated the prognostic value of serial SAQ-SS assessments. The SAQ-SS ranges from 0 to 100, with higher scores indicating better health status. To simulate routine clinical care, the follow-up in ISCHEMIA was equated to outpatient clinic visits-we defined the 3-month SAQ-SS as the prior score and the 6-month assessment as the current score in the clinic. Analyses were stratified by treatment strategy: conservative management and invasive management with revascularization. Cox proportional hazards models assessed the association of the prior score, the current score, and the change in scores with ISCHEMIA's primary composite end point (cardiovascular death, myocardial infarction, hospitalization for unstable angina, heart failure, and resuscitated cardiac arrest), adjusting for 17 clinical covariates. RESULTS/UNASSIGNED:This analysis included 3405 participants (1965 in conservative management: 77.4% male, mean age 64.3 years±9.5; 1440 in invasive management: 77.6% male, mean age 64.0 years±9.4). Over a median follow-up of 3.2 years, 215 (11.0%) and 96 (6.7%) participants in the conservative and invasive cohorts, respectively, experienced the primary composite end point. Higher prior, current, and change SAQ-SS were each independently associated with a lower risk of cardiovascular events. In the conservative cohort, each 5-point increase in the current SAQ-SS was associated with a 7% lower risk of the primary end point (hazard ratio, 0.93 [95% CI, 0.90-0.96]); in the invasive cohort, the association was 9% (hazard ratio, 0.91 [95% CI, 0.86-0.96]). CONCLUSIONS/UNASSIGNED:In patients with chronic coronary disease, the most recent SAQ-SS is the strongest health status predictor of future cardiovascular events. Serial SAQ-SS assessments provide a practical, dynamic, and patient-centered approach for updating prognosis in chronic coronary disease management. REGISTRATION/UNASSIGNED:URL: https://www.clinicaltrials.gov; Unique identifier: NCT01471522.

OBJECTIVE:The quality of discharge processes impacts adverse outcomes post hospitalization for children with medical complexity (CMC). Perspectives of caregivers at risk for communication challenges (eg, non-English speakers, those with limited health literacy, immigrants) on understandability and feasibility of discharge instructions for CMC are understudied. Our objective was to explore their perspectives on barriers and facilitators to comprehension and implementation of discharge instructions for CMC. PATIENTS AND METHODS/METHODS:In this qualitative, descriptive study, we used maximum variation sampling to enroll caregivers of CMC (N = 40) discharged from acute or intensive care units of 2 urban hospitals. English- and Spanish-speaking caregivers of CMC (Pediatric Medical Complexity Algorithm) aged 18 years or older and discharged on 1 or more daily medications were eligible. We conducted semistructured interviews, audio-recorded and transcribed interviews, and performed content analysis. Two team members applied codes from a codebook (developed based on prior literature and preliminary analyses) and identified emerging themes. RESULTS:Equal numbers of participants spoke English and Spanish (n = 20 per language) and were recruited from each hospital (n = 20 per hospital). Half (47.5%) had low health literacy; 85% were of non-US birth. Themes emerged across 4 categories: (1) clinician and medication access; (2) patient- and family-centered approaches to discharge planning and education; (3) caregiver prior experience; and (4) resources and support systems. CONCLUSIONS:Caregivers identified barriers and facilitators affecting discharge plan comprehension and implementation. Optimizing postdischarge care for CMC is complex and requires family-centered, language-concordant, and health literacy-informed processes. Future interventions should focus on systems-level changes that enhance access and account for caregiver perspectives.

OBJECTIVE:Fentanyl is a major driver of the overdose crisis in the United States, yet little is known about the intentionality of fentanyl use and its correlates among people who use drugs (PWUD). We examined the intentionality of fentanyl use and associated factors among PWUD. METHODS:We recruited 246 PWUD in New York City in 2023. Participants completed structured interviews and provided urine samples for toxicology screening. Fentanyl use was classified as no use (negative in both self-report and urine toxicology), unintentional use (self-report negative but toxicology positive), and intentional use (positive in self-report with or without positive toxicology). We used multinomial logistic regression to identify factors associated with fentanyl use intentionality. RESULTS:Fentanyl was detected in 40.7%, while 26.0% self-reported intentional fentanyl use. Intentional fentanyl use was significantly associated with chronic pain (RRR: 2.21; 95% CI: 1.02-4.80) and higher Risk Assessment Battery (RAB) scores (RRR: 1.09; 95% CI: 1.01-1.18), and inversely associated with high cannabis use severity (RRR: 0.16; 95% CI: 0.05-0.61). Unintentional fentanyl use was positively associated with older age (RRR: 1.08; 95% CI: 1.02-1.13) and negatively with moderate alcohol use severity (RRR: 0.25; 95% CI: 0.09-0.69). CONCLUSIONS:Unintentional fentanyl use was more common among older PWUD, highlighting the need for targeted outreach and fentanyl education. Intentional fentanyl use, while reflecting awareness of the drug supply, was associated with chronic pain and elevated HIV risk behaviors, indicating a subgroup with greater health and prevention needs. Tailored interventions integrating harm reduction, pain management, and HIV prevention are needed.