Faculty Bibliography
Searched for:
school:LISOM
Total Results:
14022
Evaluating tocilizumab in ischemic stroke: Findings from the SPAN multicenter trial
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.
PMID: 41354124
ISSN: 1873-7064
CID: 5997802
Journal of clinical neuroscience : official journal of the Neurosurgical Society of Australasia. 2026:145.DOI: 10.1016/j.jocn.2025.111823
Neoadjuvant PD1 blockade with laser interstitial thermal therapy for recurrent high-grade glioma
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.
PMID: 41456377
ISSN: 1532-2653
CID: 6000922
Radiographics : a review publication of the Radiological Society of North America, Inc. 2026:46(3).DOI: 10.1148/rg.240239
Multisystem Imaging Manifestations of Fibromuscular Dysplasia
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.
PMID: 41642726
ISSN: 1527-1323
CID: 6000382
Intimacy After Diagnosis: Navigating Sexual Health Conversations and Disparities Among Cancer Survivors
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.
PMID: 41689813
ISSN: 1938-2715
CID: 6002672
Associations of Fitbit measured physical activity and sedentary behavior with mental health in U.S. youth: a quantile regression analysis
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.
PMID: 41670396
ISSN: 1475-357x
CID: 6002162
Medical Mistrust and the Patient Experience: A National Survey on What Shapes Engagement in OB/GYN Care
OBJECTIVES/OBJECTIVE:To examine how media, geography, race, and social factors shaped patient experiences to inform strategies for improving trust and care. DESIGN/METHODS:We conducted a cross-sectional online survey of experiences and perceptions of OB/GYN care and medical mistrust using a stratified, randomised sampling approach. SETTING/METHODS:The survey was distributed through Prolific. POPULATION/METHODS:Inclusion criteria included assigned female at birth, age between 18 and 40 years, and residing in the United States. MAIN OUTCOME MEASURES/METHODS:Gender preference of OB/GYN clinician, demographic association with negative OB/GYN experiences, and degree of medical mistrust. RESULTS:Of 579 respondents, 93% identified as women, 33.9% as LGBTQIA+, and 45.2% had a history of pregnancy. Anxiety was the most common (46.4%) emotion experienced when receiving OB/GYN care, and 25.8% reported negative experiences, primarily from minimization of concerns (68.5%). A majority (65.3%) preferred receiving care from a female OB/GYN. Identifying as Republican was associated with higher odds of having had a negative experience with an OB/GYN, whereas Asian race and lower education were linked to lower odds. Black, Asian, and multiracial participants were more likely to have a racial preference for clinicians. Medical mistrust was higher among Black respondents and those with lower education. Feeling heard by a clinician was the strongest predictor of care satisfaction. CONCLUSION/CONCLUSIONS:Anxiety and negative experiences were prevalent among participants. Feeling heard was the strongest predictor of patient satisfaction, highlighting the importance of patient-centred OB/GYN care to reduce mistrust and improve patient experiences, particularly for marginalised groups.
PMID: 41667132
ISSN: 1471-0528
CID: 6002042
Artificial Intelligence for Gastroenterology Practice: A Modified Delphi Consensus
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.
PMID: 41665234
ISSN: 1572-0241
CID: 6001912
Histology of amiodarone-induced liver injury revisited: A retrospective morphologic analysis
Amiodarone-induced liver injury (AILI) is a known risk of amiodarone therapy, with presentations ranging from asymptomatic aminotransferase elevations to severe or fatal hepatitis and cirrhosis. Due to limited understanding of its histopathologic features, we conducted a retrospective cross-sectional re-analysis of liver biopsy samples from patients on amiodarone from two centers. Of the 48 liver biopsy samples, 42 (87%) exhibited histologic evidence of AILI. All patients showed minimal or mild macrovesicular steatosis. Ballooned hepatocytes were observed in 36 cases (86%), with 25 (69%) displaying a periportal distribution, 8 (22%) centrilobular, and 3 (8%) panacinar in distribution. Mallory-Denk bodies were found in 36 samples (76%)-18 (50%) were numerous and 18 (50%) multiple. Cholestasis was present in 10 patients, 7 (70%) of whom died. In contrast, 10 (31%) of the 32 patients without cholestasis died. This represents a significantly increased mortality risk for patients with AILI and cholestasis (p = 0.03). While AILI shares features with the more generally known metabolic dysfunction-associated steatotic liver disease, our findings indicate that a prominence of periportal distribution of ballooned hepatocytes and Mallory-Denk bodies despite a minimum of macrovesicular steatosis are characteristic of AILI. Furthermore, cholestasis in biopsy samples may suggest a poorer prognosis in patients on amiodarone.
PMID: 41671912
ISSN: 1532-8198
CID: 6002282
The International Guideline for the Definition, Classification, Diagnosis and Management of Urticaria
This update and revision of the international guideline for urticaria was developed in accordance with the methods recommended by Cochrane and the Grading of Recommendations Assessment, Development and Evaluation (GRADE) working group. It is an initiative of the Global Allergy and Asthma Excellence Network (GA2LEN) and its Urticaria and Angioedema Centers of Reference and Excellence (UCAREs and ACAREs), with the participation of 210 delegates from 107 national and international societies, from 59 countries. The consensus conference was held on December 6th, 2024. This guideline was acknowledged and accepted by the European Union of Medical Specialists (UEMS). Urticaria is a frequent, mast cell-driven disease, defined by a rapid appearance of wheals, angioedema, or both. The lifetime prevalence of acute urticaria is estimated to be approximately 20%. Chronic urticaria, categorized as either chronic spontaneous urticaria or chronic inducible urticaria, is disabling, impairs quality of life, and affects performance at work and school, however, novel therapies are available. This updated version of the international guideline for urticaria covers the definition and classification of urticaria and outlines expert-guided and evidence-based diagnostic and therapeutic approaches for the different subtypes of urticaria.
PMID: 41649409
ISSN: 1398-9995
CID: 6000592
Exploring Sex Differences in Stroke Outcomes: A Comprehensive Analysis From the SPAN 1 Trial
BACKGROUND:Stroke is a sexually dimorphic disease, with different risk factors, incidence, outcomes, and treatment responses in men and women. While sex differences have been documented in preclinical studies, these findings often come from single-site studies with small sample sizes and require validation across diverse research settings. METHODS:We used data from the SPAN (Stroke Preclinical Assessment Network), a randomized, placebo-controlled, blinded, multilaboratory trial, to determine if sex differences in neurological outcomes are present in preclinical stroke models. We analyzed data from 665 stroke animals treated with saline, including young mice, diet-induced obese mice, aging mice, young rats, and spontaneously hypertensive rats. We compared the corner test index and brain morphology between the sexes using linear random effect models and assessed the mortality rate using Cox proportional hazard regression models. RESULTS:No significant sex differences were found in neurological outcome measured with the corner test on either day 7 or day 30 after stroke, regardless of the mouse or rat stroke model used. Additionally, female and male mice exhibited similar infarct sizes on day 2 magnetic resonance imaging and on brain atrophy measures on day 30 after stroke, indicating a lack of sex differences in brain injury. Similarly, no sex differences were observed in acute or chronic sensorimotor or tissue outcomes in young rats. In 1 subanalysis, sex differences were seen in the spontaneously hypertensive rats cohort. Female rats exhibited a higher corner test index on day 30 than males, indicating more severe sensorimotor injury. CONCLUSIONS:In this multicenter preclinical study, we did not detect sex differences in stroke outcomes in mice, although sex differences in behavioral outcomes were observed in spontaneously hypertensive rats. These findings highlight that sex differences may be model-specific and subtle, emphasizing the need for methodological consistency and thoughtful inclusion of diverse animal models in translational stroke research to better understand if sex-specific responses contribute to stroke outcomes.
PMID: 41631765
ISSN: 2047-9980
CID: 5997812
