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On-site exposure to clinical epilepsy practice for experimental scientists engaged in epilepsy research: A pilot study by the ILAE commission on neurobiology
Educational initiatives that address the gap between basic/preclinical and clinical practices are important to effectively translate basic science discoveries to benefit patients. The ILAE Neurobiology Commission conducted a pilot project aimed at exposing basic and preclinical scientists engaged in epilepsy research to general clinical issues pertaining to the diagnosis and care of people with epilepsy. This aim was addressed through a two-week-long, on-site clinical training program for 50 basic scientists in 21 epilepsy centers across 18 countries in the six ILAE regions (with a maximum of 3 basic scientists per center). The learning objectives and the training module were discussed and defined by the project organizing committee, which consisted of Neurobiology Commission members and a team of epileptologists representing different geographical regions. The training activities were conducted at each epilepsy center under the local supervision of clinical tutors. Each basic scientist was exposed to 50.3 ± 23.3 (range 16-89) hours of intensive and dedicated clinical training, coordinated by 2-3 tutors per center, assisted by 6.8 ± 3.6 colleagues. A structured test consisting of 17 general clinical epilepsy questions was completed by the trainees before and after the training activity. The learning assessment was based on the comparison between responses to the exit and entry tests. After the on-site clinical exposure, the proportion of correct answers increased to 87% compared to 61% in the entry test. Structured post-training questionnaires demonstrated very high satisfaction of trainees and all involved tutors across the different aspects of the training module. This global pilot study demonstrated that on-site attendance by basic scientists in specialized clinical settings up-scaled their knowledge of clinical epileptology and facilitated networking with clinicians. Expansion of this pilot to further centers should be considered to understand how exposure to clinical practice affects research direction and quality of translational epilepsy research. PLAIN LANGUAGE SUMMARY: Epilepsy research has long benefitted from collaboration between scientists and clinicians. Early exposure of researchers to people with epilepsy and their care teams may strengthen future impact. This pilot study tested a two-week immersive experience where small teams of basic scientists shadowed clinicians during their work at hospitals around the world. Questionnaires showed high satisfaction among both groups. Results support expanding such training, with the backing of the International League Against epilepsy and aligned centers, to build understanding, interest, and long-term commitment, ensuring bench research is informed by and translates to clinical practice and improved quality of life for patients.
PMID: 42220231
ISSN: 2470-9239
CID: 6043402
Imaging Features of Herpetic Interstitial Keratitis by Anterior Segment Optical Coherence Tomography
PURPOSE/OBJECTIVE:Herpes simplex virus (HSV) and varicella zoster virus (VZV) are known causes of chronic and recurrent interstitial keratitis. Determination of active corneal inflammation is important for appropriate management. This study aimed to investigate features of clinically active herpetic interstitial keratitis (HIK) by anterior segment optical coherence tomography (AS-OCT). METHODS:Twenty-seven patients with active HIK (17 with HSV, 10 with VZV) and AS-OCT imaging were retrospectively identified. Five patients also had stromal scarring (SS), presumably from prior HIK episodes. An additional 4 patients with SS, but without a history of HIK, were also identified. The AS-OCT images were analyzed qualitatively, followed by an automated segmentation analysis. Deidentified images were shown to 3 masked graders after a training module, and their diagnoses were compared with slit-lamp diagnoses. RESULTS:Qualitative analysis of AS-OCT images of active HIK revealed anterior stromal hyperreflectivity, often with a hazy border and convex posterior contour comparable with "posterior bowing" historically seen on slit lamp. Borders were sharper and typically more linear for SS. Automated segmentation analyses identified that epithelium overlying the stromal area of interest was thicker in SS than HIK. Survey results revealed a high degree of correlation with slit-lamp diagnoses. CONCLUSIONS:AS-OCT may be a useful adjunct to slit-lamp examination in the evaluation of active inflammation in patients with a history of HIK. Hyperreflectivity, hazy borders, convex contour, and epithelial thickness may be informative. Future studies could elucidate a role for deep learning algorithms in diagnosing active HIK.
PMID: 42228428
ISSN: 1536-4798
CID: 6043732
International journal of gynecological cancer : official journal of the International Gynecological Cancer Society. 2026:36(8).DOI: 10.1016/j.ijgc.2026.104727
Associations between molecular classification and response to intra-uterine levonorgestrel device therapy in patients with medically managed endometrial cancer and endometrial intra-epithelial neoplasia: a multi-center Endometrial Cancer Molecularly Targeted Therapy (ECMT2) Consortium study
OBJECTIVE:To determine the association between molecular classification and response in patients with endometrial intra-epithelial neoplasia or endometrial cancer treated with a levonorgestrel intra-uterine device. METHODS:Eligible patients were treated with a levonorgestrel intra-uterine device for endometrial intra-epithelial neoplasia or endometrial cancer for at least 6 months. Immunohistochemistry for MLH1, MSH2, MSH6, PMS2, and p53 was performed. Specimens were categorized using a modified Proactive Molecular Risk Classifier for Endometrial Cancer algorithm as deficient mismatch repair, p53 abnormal, or p53 wild-type. A subset underwent single-gene POLE sequencing. Best response was recorded as pathologic complete response, partial response, stable disease, or progressive disease. Kruskal-Wallis tests and Fisher exact tests were used for statistical analysis. RESULTS:There were 143 patients, including 83 with endometrial intra-epithelial neoplasia and 60 with endometrial cancer. Fertility preservation was desired in 35.7%, 53.8% had significant medical co-morbidities precluding hysterectomy, and 10.5% had levonorgestrel intra-uterine device placement for other indications, including patient preference, placement during the coronavirus disease 2019 pandemic, and logistical considerations for other cancer diagnoses. Molecular characterization showed 90.9% p53 wild-type, 7.0% deficient mismatch repair, and 2.1% p53 abnormal. Only 4.4% of specimens with sequencing had a POLE mutation (2 of 45). The overall response rate was 86.7% (endometrial cancer: complete response 38.3%, partial response 36.7%; endometrial intra-epithelial neoplasia: complete response 67.5%, partial response 27.7%). In patients with endometrial cancer, the response rate was 75% (45 of 60), varying by molecular sub-group: 50% in the p53 abnormal group (1 of 2) and 50% in the deficient mismatch repair group (5 of 10). Only 1 patient with endometrial intra-epithelial neoplasia had p53 abnormal expression; the remaining patients had intact MMR expression and p53 wild-type. CONCLUSIONS:The complete response to levonorgestrel intra-uterine device therapy was lower than expected for endometrial intra-epithelial neoplasia. Response rates varied by molecular classification, with worse outcomes observed in deficient mismatch repair and p53 abnormal sub-types. Although limited by sample size, these findings suggest that levonorgestrel intra-uterine device therapy may not be sufficient for all molecular sub-groups.
PMID: 42235254
ISSN: 1525-1438
CID: 6044122
Ultrasound criteria for transmural healing and response in Crohn's disease: a systematic review of definitions and thresholds
BACKGROUND:Transmural healing (TMH) indicates resolution of inflammation in all bowel wall layers and is an emerging therapeutic target in Crohn's disease (CD). Standardized sonographic criteria for TMH and early improvement, termed Transmural Response (TMR), have not been established. This systematic review synthesizes published definitions to provide an up-to-date overview of the current evidence base for intestinal ultrasound (IUS)-based assessment in CD. METHODS:This systematic review was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Comprehensive searches of databases identified full-text articles that pre-specified TMH, TMR or normal/abnormal bowel on trans-abdominal IUS in pediatric or adult participants with CD. Definitions were summarized descriptively. RESULTS:Eighty-three full-text studies (8033 patients) met eligibility criteria; 39 (47%) defined TMH and 22 (27%) defined TMR. TMH definitions most often included bowel-wall thickness (BWT) ≤ 3mm (31/39, 79%), absent or minimal Doppler flow (25/39, 64%), and preserved bowel wall stratification (10/39, 26%). All TMR definitions required BWT reduction, but thresholds varied (absolute ≥ 1 mm or relative ≥ 25% in 16/22, 73%). Nine studies (9/22, 41%) also required Doppler flow improvement and 4/22 (18%) included additional criteria. Pediatric-specific criteria were reported in 2 TMH and one TMR studies, extrapolating from adult BWT values. Heterogeneity precluded quantitative pooling. CONCLUSIONS:Standardized IUS definitions of TMH and TMR in CD are lacking. Consistent, validated criteria are essential to enable reproducible ultrasound endpoints, support treat-to-target strategies, and facilitate incorporation of IUS into CD clinical trials and routine care.
PMID: 42222916
ISSN: 1536-4844
CID: 6043472
Focal Cryo-ablation for Treatment of Intermediate Favorable Risk (Grade Group 2) Prostate Cancer
OBJECTIVE:To report 7-year oncological outcomes of focal cryo-ablation (FCA) for focal intermediate favorable risk prostate cancer (IFRPCa). PATIENTS AND METHODS/METHODS:Beginning March 2017, all men with focal IFRPCa undergoing FCA meeting the following eligibility criteria were enrolled in our longitudinal prospective study: a single MRI PIRADS 2-5 target concordant with unilateral IFRPCa, no gross extra-prostatic extension or very distal apical disease on MRI, and no Grade Group (GG) ≥2 contralateral to the MRI target. The oncological surveillance protocol included PSA testing every 6 months, and MRI testing at 6-12 months, 2, 3.5, 5.0, and 7.5 years. Prostate biopsy was performed for rising PSA, suspicious MRI's or at the discretion of the surgeons. The main outcome measure was clinically significant prostate cancer (csPCa) recurrence. RESULTS:276 men were enrolled in the study. Overall, 39 (14.1%) developed a csPCa recurrence. Baseline mean PSA was significantly greater in subjects developing csPCa recurrence. There were no prostate cancer mortalities and 3 (0.01%) developed metastasis. The csPCa recurrence free survival at 3, 5 and 7 years was 90.20%, 78.36%, and 70.31%, respectively. African American race was the only significant independent predictor for developing a csPCa recurrence. Compliance with protocol MRI at 7.5 years was 90.9%. CONCLUSIONS:The present study supports FCA as a treatment option for focal IFRPCa associated with an MRI target with no evidence of extra-capsular extension or distal apical disease on MRI, and no contralateral GG> 1 disease.
PMID: 42229815
ISSN: 1527-9995
CID: 6043832
Journal of clinical oncology : official journal of the American Society of Clinical Oncology. 2026.DOI: 10.1200/JCO-26-00835
Intismeran Autogene Plus Pembrolizumab Versus Pembrolizumab Alone in High-Risk Resected Melanoma: 5-Year Update of the Randomized Phase 2b KEYNOTE-942 Study
Intismeran autogene (intismeran; formerly V940 or mRNA-4157) is an mRNA-based individualized neoantigen therapy. We report 5-year outcomes of intismeran plus pembrolizumab from the phase 2b KEYNOTE-942 study (NCT03897881). Eligible patients with resected stage IIIB‒IV cutaneous melanoma were randomized 2:1 to receive 9 doses of intramuscular intismeran 1 mg Q3W plus 18 doses of intravenous pembrolizumab 200 mg Q3W or 18 doses of intravenous pembrolizumab 200 mg Q3W. Primary endpoint was recurrence-free survival (RFS); secondary endpoints included distant metastasis-free survival (DMFS) and safety. Five-year analyses were descriptive. Among 157 randomized patients (intismeran plus pembrolizumab, n=107; pembrolizumab, n=50), median planned follow-up at data cutoff (December 15, 2025) was 60.3 (range, 50.5‒76.4) months. Intismeran plus pembrolizumab continued to prolong RFS (HR, 0.510; 95% CI, 0.294‒0.887) and DMFS (0.411; 0.200‒0.843), with a favorable trend in overall survival (0.471; 0.165‒1.345) versus pembrolizumab. Safety profile continued to be manageable, with no new safety signals. Intismeran plus pembrolizumab was associated with increased T-cell receptor clonality and novel clonotypes versus pembrolizumab; greater novel clone expansion was observed in patients without versus with recurrence in the combination arm. After 5 years' follow-up, intismeran plus pembrolizumab demonstrated sustained, durable treatment benefits versus pembrolizumab alone in resected high-risk melanoma.
PMID: 42223134
ISSN: 1527-7755
CID: 6043492
In Vivo Effect of a Synthetic Amniotic Fluid on Fetal Lung and Gastrointestinal Tract: A Pre-Clinical Rodent Model
OBJECTIVE:Amnioinfusions in anhydramnios aim to promote fetal lung development, but currently used fluids (Normal Saline [NS], Lactated Ringer's [LR]) fail to mimic the intrauterine environment and increase reactive oxygen species (ROS). We developed a synthetic amniotic fluid (Amnio-well, AW) designed to reduce intrauterine ROS. This study evaluated the pulmonary and gastrointestinal effects of 2 formulations of AW compared with those of NS and LR in a pre-clinical model. METHOD:At gestational age E17.5, pregnant rats underwent amniotic fluid replacement with NS, LR, AW, AW plus epidermal growth factor and transforming growth factor-β (AW++), or sham control. Fetal lungs were harvested at E20.5 for histology, fractional airspace, and blinded pathological evaluation. Surfactant protein (SP-A, SP-B, SP-C) expression and inflammatory gene panels were assessed in lungs and gastrointestinal (GI) tissue. RESULTS:NS and LR lungs demonstrated edema, macrophage infiltration, and reduced airspace (p < 0.001). AW improved SP-B and SP-C relative to control, whereas AW++ suppressed SP-B and SP-C (p < 0.05). Lung gene profiling showed NS/LR induced alterations in histamines, annexins, and immune recruitment, while AW closely resembled control. GI histology was similar across groups, though NS/LR altered TNF, prostaglandin, and adhesion pathways (p < 0.05). CONCLUSION:AW reduced lung inflammation and enhanced surfactant expression compared with NS or LR, with minimal GI effects.
PMCID:13070220
PMID: 41882498
ISSN: 1097-0223
CID: 6042882
Convalescent Spontaneous Coronary Artery Dissection With Elevated Pericoronary Fat Attenuation Index [Case Report]
BACKGROUND:Myocardial infarction with nonobstructive coronary arteries (MINOCA) is defined by the presence of the universal acute myocardial infarction criteria in the absence of obstructive disease on angiography. Multimodal imaging can be invaluable in determining the underlying etiology of MINOCA. Spontaneous coronary artery dissection (SCAD) is among the most common etiologies. CASE SUMMARY/METHODS:This report describes a case of unrecognized/asymptomatic myocardial infarction due to SCAD in an active 62-year-old woman whose care was facilitated by comprehensive evaluation of MINOCA. DISCUSSION/CONCLUSIONS:Pericoronary fat attenuation indexing (FAI) has yet to be extensively studied in the setting of MINOCA. Initial studies suggest elevated pericoronary FAI in MINOCA and SCAD, providing introductory evidence that vascular insult increases coronary artery inflammation appreciably via pericoronary FAI. TAKE-HOME MESSAGE/CONCLUSIONS:This case report further substantiates that claim and demonstrates that coronary computed tomography angiography with pericoronary FAI may prove useful in working up MINOCA.
PMID: 42240253
ISSN: 2666-0849
CID: 6044382
Adverse Outcomes After Mandibular Distraction Osteogenesis in Robin Sequence
Mandibular distraction osteogenesis (MDO) is a common procedure used to correct upper airway obstruction in patients with Robin sequence. However, analysis of predictors of adverse outcomes after MDO has relied on small single-institution cohorts. This retrospective cohort study leveraged the Epic Cosmos multicenter database to evaluate predictors of morbidity and mortality in patients with Robin sequence undergoing MDO from January 2015 to December 2024. A multivariable logistic regression was used to evaluate associations between perinatal factors, airway anomalies, genetic syndromes, and congenital anomalies affecting the cardiopulmonary, gastrointestinal and central nervous system (CNS), and postoperative outcomes including 1-year mortality, tracheostomy, intensive care unit (ICU) admission within 30 days, 30-day hospital readmission, 30-day emergency department visit, ICU length of stay (LOS), and overall hospital LOS. Across a total of 685 patients, CNS anomalies were statistically significantly associated with 1-year mortality; cardiopulmonary anomalies and bronchomalacia were predictive of tracheostomy; tracheal stenosis was associated with ICU admission; CNS anomalies were associated with 30-day emergency department visit; and no variables were significantly associated with 30-day readmission. Age at surgery was inversely associated with longer ICU LOS and overall LOS, whereas prematurity, prenatal drug exposure, gastroesophageal reflux, and CNS anomalies were associated with longer overall LOS. These results highlight the burden of comorbidities of the airway, cardiopulmonary system, and central nervous system for patients with Robin sequence undergoing MDO and can inform surgeons on the likelihood of adverse events based on the diagnostic characteristics of the patient.
PMID: 42228516
ISSN: 1536-3732
CID: 6043742
Investigating the analytical robustness of the social and behavioural sciences
The same dataset can be analysed in different justifiable ways to answer the same research question, potentially challenging the robustness of empirical science1-3. In this crowd initiative, we investigated the degree to which research findings in the social and behavioural sciences are contingent on analysts' choices. We examined a stratified random sample of 100 studies published between 2009 and 2018, in which, for one claim per study, at least five reanalysts independently reanalysed the original data. The statistical appropriateness of the reanalyses was assessed in peer evaluations, and the robustness indicators were inspected along a range of research characteristics and study designs. We found that 34% of the independent reanalyses yielded the same result (within a tolerance region of ±0.05 Cohen's d) as the original report; with a four times broader tolerance region, this indicator increased to 57%. Of the reanalyses conducted, 74% reached the same conclusion as the original investigation, 24% yielded no effects or inconclusive results and 2% reported the opposite effect. This exploratory study indicates that the common single-path analyses in social and behavioural research should not be simply assumed to be robust to alternative analyses4. Therefore, we recommend the development and use of practices to explore and communicate this neglected source of uncertainty.
PMID: 41922703
ISSN: 1476-4687
CID: 6041172
