Faculty Bibliography

UNLABELLED:Inflammation, particularly mediated through interleukin-6 (IL-6) signaling, plays a critical role in stroke pathophysiology. High levels of IL-6 are associated with poor outcomes in stroke patients. Therapeutic inhibition of IL-6 signaling may offer a novel strategy to mitigate post-stroke damage and improve recovery. This study evaluated the efficacy of tocilizumab (TCZ), a clinically approved monoclonal antibody that blocks IL-6 receptor signaling, using data from the Stroke Preclinical Assessment Network (SPAN), a multi-center, randomized, blinded, placebo-controlled trial in preclinical stroke models. METHODS:We analyzed behavioral and MRI morphometry data from 701 rodents (both males and females; 1:1), including healthy young mice, diet-induced obese mice, aging mice, and spontaneously hypertensive rats (SHR) treated with saline (N = 348) or TCZ (N = 353) at a dose of 100 mg/kg for mice, 10 mg/kg for rats after middle cerebral artery occlusion (MCAO). RESULTS:In the overall mouse cohort, TCZ did not significantly improve long-term sensorimotor recovery or reduce brain tissue loss measured by MRI. However, aging mice exhibited modest motor function improvements. In SHRs, TCZ treatment resulted in improved sensory-motor function, particularly in male rats, as demonstrated by enhanced corner test scores on days 7 and 28 post-MCAO. While TCZ in SHRs provided early (day 2) cerebroprotection with reduced lesion volume, it did not alter subsequent tissue loss, as measured by tissue atrophy at day 30. CONCLUSIONS:These results suggest that IL-6R blockade with TCZ was associated with functional improvement in aging mice (modest) and hypertensive rats (notably males), without durable effect of brain tissue loss. No benefit was observed in the overall mouse cohort. These findings support IL-6 signaling as a viable therapeutic target and warrant further investigation into IL-6 receptor inhibition as a potential treatment strategy for stroke recovery.

BACKGROUND:While immune checkpoint inhibitors (ICI) induce potent responses against several systemic malignancies, clinical efficacy against high-grade glioma has been limited by immunosuppression, low mutational burden and limited lymphocyte infiltration into tumors. Laser interstitial thermal therapy (LITT) induces coagulative necrosis and disrupts the peritumoral blood-brain barrier (BBB), creating a potentially antigenic milieu. We hypothesized that neoadjuvant and adjuvant ICI would synergize with LITT to potentiate antitumor immune responses and enhance survival. METHODS:This retrospective study is an exploratory case series that includes 9 adult patients with recurrent IDH wild-type glioblastoma (GBM, n = 6), IDH mutant high-grade astrocytoma (n = 2) and H3K27M mutant diffuse midline glioma (n = 1). All patients received neoadjuvant anti-PD1 ICI prior to LITT and most received adjuvant ICI (8/9). Disease burden was followed through radiographic volume segmentation of gadolinium-enhancing disease. Patients were followed for progression-free (PFS) and overall survival (OS). RESULTS:). There were no perioperative complications. All patients showed an initial increase in gadolinium-enhancing volume after LITT. Seven of 9 (78 %) patients demonstrated subsequent regression in total gadolinium-enhancing volume. Three non-contiguous satellite lesions naïve to laser ablation exhibited complete or near-complete regression in 2 patients. Median PFS was 5.90 months (range 1.00-41.23), and median OS was 9.97 months (range 1.20-41.23). CONCLUSIONS:Combination therapy with neoadjuvant and adjuvant pembrolizumab and LITT is feasible and safe in recurrent high-grade glioma. Responses may be more robust in certain molecular subtypes of glioma. Further studies are needed to investigate this potential synergy.

Fibromuscular dysplasia (FMD) is a rare idiopathic, noninflammatory, nonatherosclerotic arteriopathy that leads to wall abnormalities in medium- and small-caliber arteries, typically resulting in alternating areas of stenosis and dilatation, or "beading" at angiography. Stenosis, dissection, and aneurysm can also be seen, and clinical manifestations depend on the vascular territory affected by FMD, with the renal and carotid arteries being most frequently involved. The diagnosis of FMD is made based on imaging features of FMD classified according to the angiographic appearance as focal FMD or multifocal FMD. Early diagnosis is often challenging, as mimics of FMD must first be excluded. The presence of aneurysm, dissection, or tortuosity alone is inadequate to establish the diagnosis, as these are variant manifestations; however, if a patient has focal or multifocal manifestations such as stenosis or stenosis and dilatation in one vascular bed, establishing the diagnosis of FMD, the presence of aneurysm, dissection, or tortuosity in additional vascular beds is considered multivessel involvement of all affected vascular beds. The cerebrovascular system, coronary arteries, renal and mesenteric arteries, and extremities should be evaluated for FMD involvement. The most serious potential complications of FMD are hypoperfusion secondary to aneurysm, dissection, or arterial occlusion, which can lead to hypertension, stroke, or myocardial infarction, as well as subarachnoid hemorrhage. Prompt intervention, blood pressure management, and revascularization are necessary to avoid devastating complications. Radiologists play an important role in timely identification of diverse FMD-associated morbidities and thus may contribute to early diagnosis and treatment of FMD. ^©RSNA, 2026 Supplemental material is available for this article.

Insurance type is a key indicator of structural vulnerability in pediatric mental health care and may be associated with differences in psychiatric presentation, treatment course, and diagnosis among hospitalized youth, particularly Black and Hispanic/Latino children insured by Medicaid. Despite these inequities, their impact remains understudied among psychiatrically hospitalized pediatric populations. This retrospective study analyzed 1,101 child and adolescent psychiatric patients admitted to an urban psychiatric hospital between June 2018 and November 2021. Clinical presentation, psychiatric history, treatment course, and discharge diagnoses were compared between patients' insurance by Medicaid (72%) and those with commercial insurance (28%). Compared with commercially insured patients, children and adolescents with Medicaid were more likely to be Black or Hispanic/Latino and had higher rates of trauma exposure, prior psychiatric emergency visits, and higher rates of attention-deficit/hyperactivity disorder (ADHD), impulsive/behavioral disorders, and developmental/intellectual disorders. They were more frequently admitted for aggression-related crises, more likely to receive emergency injectable medications for agitation, and had longer hospital stays. Commercially insured patients had higher rates of anxiety disorders and suicide attempt related admissions. These findings suggest children and adolescents with Medicaid who required psychiatric hospitalization had greater severity of psychosocial histories and higher-acuity inpatient courses, highlighting how structural inequities reflected by insurance type, may shape differing psychiatric treatment pathways, underscoring the need for equity-oriented interventions, particularly during periods of healthcare system strains.

OBJECTIVES/OBJECTIVE:Most pediatric residency programs introduce PICU rotations in postgraduate year (PGY) 2, although it is unclear whether this timing best supports trainees' skill development. Introduction during PGY1 may pose challenges due to clinical intensity, but could also have benefits in uniquely preparing residents for PGY2 responsibilities and autonomy. To address this question, this study explored the experiences and self-perceived impacts of a PGY1 PICU rotation among senior pediatric residents. DESIGN/METHODS:A multi-institutional qualitative study was conducted using semi-structured interviews of senior (PGY2 and PGY3) residents who completed a PGY1 PICU rotation. Stratified purposive sampling was used at both institutional and resident levels. Data were coded using constant comparison and analyzed thematically. SETTING/METHODS:Seven institutions requiring a 4-week PGY1 PICU rotation. PARTICIPANTS/METHODS:Senior pediatric residents at participating institutions. INTERVENTIONS/METHODS:None. MEASUREMENTS AND MAIN RESULTS/RESULTS:Twenty-one interviews across seven institutions identified three key themes: 1) PGY1s can succeed in the PICU setting when supervisors actively cultivate a learning environment of inclusion, support, and appropriate autonomy; 2) PGY1 PICU rotations can foster self-perceived competence in skills that translate to the PGY2 year; and 3) Participants generally believed the benefits of early PICU exposure outweighed the challenges. CONCLUSIONS:PGY1 PICU rotations can fall within the Zone of Proximal Development when the experience includes strong supervisory support. Findings highlighted the importance of psychologic safety for optimal learning, suggesting that strengthening psychologic safety may enhance the educational experience and outcomes. Further research exploring the impact of PGY1s on team dynamics and patient care, and comparing the effects of PGY1 vs. PGY2 introduction, could guide evidence-based recommendations on the optimal sequencing of PICU rotations for pediatric residents.

INTRODUCTION/BACKGROUND:Multiple sclerosis (MS) is a chronic, immune-mediated neurological disease, leading to significant morbidity. Over 25 disease-modifying therapies (DMTs) are approved for MS; however, older patients may benefit less from high-efficacy DMTs. We compared the risk of severe infections (SIs) and annualized relapse rate (ARR) by age (< 45 and ≥ 45 years) between diroximel fumarate (DRF) and anti-CD20 monoclonal antibodies (mAbs) in patients with MS. METHODS:This retrospective study utilized the Komodo Health Claims database to identify patients treated with DRF or anti-CD20 agents. Patients were propensity score matched 1:1 on baseline characteristics and stratified by age (younger: < 45 years; older: ≥ 45 years). Infection-related encounters were identified by diagnosis codes; SIs required hospitalization or intravenous antibiotics. MS relapses were based on inpatient or outpatient claims and associated treatments. RESULTS:Between 2016 and 2025, 2894 propensity score-matched patients with MS who initiated DRF (n = 1447) or anti-CD20s (n = 1447) were included. DRF-treated patients had a lower proportion of SIs at 12 and 24 months compared with anti-CD20-treated patients (p ≤ 0.002 at 24 months). Younger DRF-treated patients had significantly fewer SIs (p = 0.005), while older DRF-treated patients had lower non-SI rates. COVID-19-related SIs were also significantly lower in DRF-treated patients (p < 0.001). ARRs were similar between the two groups. CONCLUSION/CONCLUSIONS:DRF-treated patients with MS had a significantly lower risk of SI compared with anti-CD20-treated patients, with no difference in ARR. More real-world studies are needed to understand the efficacy and safety of DMTs in the setting of de-escalation in aging patients with MS.

PURPOSE/OBJECTIVE:Intensity-modulated radiation therapy (IMRT) is increasingly used for total body irradiation (TBI) due to its ability to deliver myeloablative doses while sparing radiosensitive organs. To enable consistent evaluation in future National Clinical Trials Network (NCTN) studies, the xxx Hematologic Malignancies Working Group (HMWG) convened IMRT-TBI experts and NCTN leaders to develop consensus recommendations for standardized multi-institutional implementation. METHODS:A 47-question survey was distributed to NRG institutions utilizing IMRT-TBI to characterize current planning and delivery practices. Responses were analyzed for commonalities and variations. A multidisciplinary working group reviewed survey findings, developed consensus-based technical and clinical recommendations, and created a standardized template for IMRT-TBI integration into NCTN protocols. Topics included simulation, contouring, planning, organ-at-risk (OAR) constraints, quality assurance (QA), image-guided radiotherapy (IGRT), commissioning, credentialing, and safeguards for clinical trial conduct. RESULTS:Eight institutions with collective experience treating more than 750 patients with IMRT-TBI responded. Most centers used VMAT to the upper body with anteroposterior/posteroanterior (AP/PA) fields to the lower body, 3-9 isocenters, lower dose rates for lung fields (100-200 MU/min), and no physical bolus. Common OAR constraints included lungs mean dose <8 Gy, kidneys mean dose <6-8 Gy, and lenses maximum dose <90% of prescription. All respondents used auto-segmentation; 50% used auto-planning. QA practices varied, but patient-specific QA passing rates were high (>95% with 3%/2 mm gamma). Consensus recommendations for clinical trial use were established, including standardized PTV definitions, OAR sparing goals, dosimetric constraints, QA requirements, and credentialing processes. CONCLUSIONS:IMRT-TBI offers the potential for reduced toxicity and improved dose precision compared with 2D-TBI, but its complexity requires careful standardization in multi-institutional trials. The xxx HMWG and collaborating NCTN experts developed the consensus-based technical and clinical framework for incorporating IMRT-TBI into cooperative group protocols. Adoption of these recommendations will facilitate consistent implementation and enable rigorous evaluation of outcomes.

ObjectiveWe designed a survey to determine the prevalence of sexual dysfunction among cancer patients and to understand the gaps in provider-patient communication.MethodsAn IRB-approved 36-item survey was distributed through the Jefferson Recruitment Enhancement Service team and social media. Questions assessed the impact of cancer treatment on sexual health, provider communication, how sexual health was assessed, and possible interventions. Chi-square test or Fisher's exact test were used to compare the group differences with a P-value threshold (α) of 0.05 for statistical significance.Results916 patients responded to the survey, with most being diagnosed with breast (n = 271, 29.6%) and prostate cancer (n = 358, 39.1%). 71.8% of patients experienced an impact on sexual function by cancer treatment. Most experienced issues with their sexual desire, body image, arousal, comfort during intercourse, and ability to achieve orgasm (α < 0.001). Only 35.5% reported being asked about their sexual health by an oncologist and only 22.2% were given a questionnaire to assess their sexual health (α < 0.001). 49.8% of breast patients and 15.4% of prostate patients were never told their sexual health could be affected by their cancer treatment (α < 0.001). 60.3% of prostate patients were formally asked about their sexual health by an oncologist compared to 21.4% of breast patients (α < 0.001). 74% of respondents stated it is essential for oncologists to speak to patients about sexual health.ConclusionCancer survivors believe it is important for providers to discuss sexual health. However, providers are more inclined to address sexual health concerns with male patients than with female counterparts.

BACKGROUND:Physical activity and sedentary behavior are associated with adolescent mental health. However, prior studies have not assessed whether these associations differ across varying levels of mental health severity. This study uses objectively measured physical activity and sedentary behavior to examine their associations with adolescent mental health and to determine how these associations vary across the distribution of mental health symptoms. METHODS:This longitudinal prospective study examined data from the Adolescent Brain Cognitive Development (ABCD) Study, a large cohort of children and adolescents recruited from 21 study sites in the United States. This analysis included 5640 participants whose physical activity and sedentary behavior data were recorded using Fitbit wearable devices when aged 11-12 years. Outcomes were internalizing and externalizing symptoms assessed a year later by the caregiver using the Child Behavior Checklist. RESULTS:More daily steps (b = -0.43, 95% CI [-0.58, -0.29]), longer moderate-to-vigorous physical activity (MVPA) (b = -0.34, 95% CI [-0.47, -0.22]) and less sedentary time (b = 0.32, 95% CI [0.15, 0.48]) were each associated with fewer internalizing symptoms a year later. The associations were stronger for youth at higher internalizing symptom quantiles. Limited or no effects were found for externalizing symptoms. Sex differences were also observed. CONCLUSION/CONCLUSIONS:Objectively measured daily steps, MVPA, and sedentary behavior are prospectively associated with adolescent internalizing symptoms. The associations differ substantially among adolescents with varying levels of symptom severity and between sexes. Findings may inform targeted physical activity interventions to enhance adolescent mental health.

BACKGROUND:The American College of Gastroenterology (ACG) assembled a multidisciplinary task force to evaluate the current state and future direction of artificial intelligence (AI) in gastroenterology, hepatology, and endoscopy leading to the development of consensus-based recommendations for responsible AI integration in clinical practice. METHODS:A total of 32 subject-matter experts and 12 industry partners, representing diverse practice settings and expertise, conducted subgroup literature reviews across five key areas (endoscopy, practice management clinical applications, training and education, IBD and liver disease, ethics and equity). Draft statements were developed and rated on a 5-point Likert scale using a modified Delphi process. A consensus was set at ≥70% combined agreement. Non-consensus items were revised and re-voted electronically. RESULTS:A total of 43 statements, 40 (93%) reached consensus in round 1 and the remaining 3 achieved consensus after round 2. Evidence supports computer-aided detection (CADe) improving adenoma detection rate and miss rate in controlled studies, with mixed "real-world" impact and insufficient long-term outcomes (e.g., interval colon cancer rate). Recommendations emphasize thorough validation and reduction of bias via heterogeneous datasets. Outside endoscopy, ambient AI scribes, NLP-enabled coding, workflow optimization, and prior authorization support show potential. Training recommendations endorse a structured AI curriculum while preserving independent procedural competence to avoid "deskilling". In IBD and hepatology, AI could help improve diagnostic accuracy, help predict risk for disease progression, and help guide therapy. Equity, governance, and reimbursement statements call for chain-of-custody data protections, specialty-society oversight, and payment models that reward quality and cost reduction. CONCLUSIONS:This consensus outlines how AI can augment rather than replace clinical expertise while promoting safety, transparency, interoperability, and equity. Priorities include pragmatic and prospective trials, multi-institutional data-sharing consortia, bias mitigation, and workforce training to enable trustworthy and clinically impactful AI adoption in GI, liver, and endoscopy care.