Digital Commons Network^™

Targeting Aldh16a1 Mediated Thioredoxin Lysosomal Degradation To Enhance Ferroptosis Susceptibility In Smarca4-Deficient Nsclc, Guoshu Bi, Jiaqi Liang, Yunyi Bian, Guangyao Shan, Shencheng Ren, Haochun Shi, Xiaolong Huang, Junkan Zhu, Qun Wang, Wei Jiang, Boyi Gan, Cheng Zhan

Faculty, Staff and Student Publications

Ferroptosis, an iron-dependent form of cell death, holds promise for cancer therapy. However, the intricate link between ferroptosis and oncogenic mutations remains unclear. Here we show that SMARCA4, a well-established tumour suppressor whose deficiency is associated with poor prognosis and resistance to treatments, sensitizes non-small cell lung cancer (NSCLC) cells to ferroptosis. Mechanistically, SMARCA4 promotes chromatin accessibility and expression of ALDH16A1. Surprisingly, ALDH16A1 lacks ALDH enzymatic activity, but binds to the anti-ferroptotic oxidoreductase thioredoxin (TXN), facilitating its translocation to the lysosome and subsequent degradation. Meanwhile, ALDH16A1 directly inhibits TXN's oxidoreductase function by occluding its active site. We also show that …

Efficacy Of Atr Kinase Inhibitor Elimusertib Monotherapy Or Combination In Tumors With Dna Damage Response Pathway And Other Genomic Alterations, Kaushik Varadarajan, Christian X Cruz Pico, Kurt W Evans, Maria Gabriela Raso, Yasmeen Qamar Rizvi, Xiaofeng Zheng, Dhruv Chachad, Timothy P Diperi, Bailiang Wang, Stephen M Scott, Ming Zhao, Argun Akcakanat, Antje M Wengner, Timothy A Yap, Funda Meric-Bernstam

Faculty, Staff and Student Publications

The ataxia telangiectasia and RAD3-related (ATR) kinase functions with ataxia telangiectasia-mutated (ATM) kinase as a modulator of DNA damage response (DDR). We assessed the antitumor effects of the ATR inhibitor elimusertib (BAY-1895344) in patient-derived xenograft (PDX) models with DDR alterations. Antitumor activity was assessed by change in tumor volume (TV) from baseline. Responses were categorized as follows: partial response (PR), ≥30% decrease in TV; ≥20% increase in TV, progressive disease; and non-PR/progressive disease, stable disease (SD). Event-free survival was defined as time for tumor doubling (EFS-2). Of 21 PDX models tested, 11 had significant prolongation of EFS-2 with elimusertib monotherapy. …

Delayed Venous Thromboembolism Diagnosis And Mortality Risk, Min-Jeoung Kang, Richard Schreiber, Veysel Karani Baris, Frank Chang, Shadi Hijjawi, Alice Kim, John Novoa-Laurentiev, Tim Nye, Stuart Lipsitz, Khalid Nawab, Michael Sainlaire, Wenyu Song, Ania Syrowatka, Gregory Piazza, Tien Thai, Li Zhou, Lipika Samal, David W Bates, Patricia C Dykes

Faculty, Staff and Students Publications

Importance: Nonspecific symptoms of venous thromboembolism (VTE) hinder timely recognition, and no automated tools exist to monitor diagnostic delay.

Objective: To evaluate rates of diagnostic delay of VTE (DOVE) at 2 health care systems using different electronic health record (EHR) systems, to categorize missed diagnoses, and to assess the association of diagnostic delays with 30-day all-cause mortality.

Design, setting, and participants: This diagnostic study used retrospective EHR data from Mass General Brigham (MGB) and Penn State Health (PSH). For MGB, data from 2016 to 2021 were extracted, whereas for PSH, data from 2019 to 2022 data were used. An electronic …

Patient-Centered Measures Of Goal Concordance In Geriatrics And Palliative Care: A Scoping Review, Isaac S Chua, Annelise Berler, Kacy Ninteau, Paul A Bain, Erik K Fromme, Maria Edelen, Andrea L Pusic, Christine S Ritchie, David W Bates

Faculty, Staff and Students Publications

Importance: Goal concordance underpins high-quality care for patients with serious illness and older adults with multimorbidity and geriatric syndromes; however, a criterion standard for measurement is lacking.

Objective: To identify and describe patient- and caregiver-reported measures of goal concordance for patients with serious illness, geriatric syndromes, and multimorbidity to create a conceptual model of goal-concordance measurement.

Evidence review: This scoping review included an electronic search across MEDLINE, Embase, Web of Science Core Collection, the CINAHL, and PsycINFO through September 2024. Search terms included goals, priorities, preferences, value, expectations, concordance, discordance, match, attain, achieve, align, congruence, dissonance, respect, and terms related …

Trends In Radiation Use From 2004 To 2020 Among Adolescents And Young Adults With Hodgkin Lymphoma, Kelsey L Corrigan, Amy M Berkman, Jillian Gunther, Clark R Andersen, Susan Wu, Amber Gibson, Branko Cuglievan, Miriam B Garcia, Gohar Manzar, Penny Fang, Brian De, Sairah Ahmed, Cesar Nunez, Michelle A T Hildebrandt, David C Mccall, Susan K Parsons, Michael E Roth

Faculty, Staff and Student Publications

Background: Hodgkin lymphoma has excellent survival rates in adolescents and young adults (AYA, diagnosed between ages 15 and 39 years). However, survivors are at risk of treatment-related late effects. Whereas radiotherapy (RT) de-escalation/omission has emerged as an approach to minimize late effects, no prior studies have evaluated RT use over time in AYAs with Hodgkin lymphoma.

Methods: Using the National Cancer Database, we identified 40,717 AYAs diagnosed with Hodgkin lymphoma between 2004 and 2020. Differences in sociodemographic and clinical variables were assessed using a two-sample two-sided t test or χ2 test. RT use was summarized per year by frequency with …

What Next? A Challenging Case Of Refractory Hypertension With End-Organ Dysfunction In A 33-Year-Old Male, Rezane Miftari Md, Shaun Abid, Anton Stolear, Irma Fotjhadi

Posters

We present a challenging case of a 33-year-old male with history of longstanding hypertension since high school, which progressed to RH complicated by severe left ventricular hypertrophy and hypertensive nephrosclerosis.

Premenopausal Transition In Neurodivergent Women With Musculoskeletal Syndromes: Mechanisms, Risks, And Neuroinclusive Therapeutics, Piper Hutson, James Hutson

Faculty Scholarship

Neurodivergent women with chronic musculoskeletal syndromes experience disproportionate premenopausal symptom burdens that are poorly characterized in extant clinical paradigms and practice. The compounded interplay of estrogen fluctuations in premenopause with sensory–executive differences and baseline nociception from joint or connective-tissue pathology yields intensified pain, mood dysregulation, and functional decline. Evidence indicates estrogen modulates nociception, neuroinflammation, bone remodeling, and monoaminergic signaling; premenopausal variability magnifies pain, affective lability, and cognitive drift—effects accentuated in autism and ADHD. Coexisting hypermobility, fibromyalgia, or connective-tissue disorders compromise joint integrity and proprioception, increasing susceptibility to estrogen-dependent changes in bone microarchitecture and tendon homeostasis. This article advances an integrative …

Airway Management In Patients With Vocal Cord Paralysis: A Review Of Intubation Techniques, Intraoperative Challenges, And Outcomes., Rayyan Bhutta, Ali Osman, Tala Maya, Justin Ma, Ali Al Saeed, Sumit Sidhu, Mariya Wood, Bilal Akhtar, Sirimas Lau, Matthias Franzen

Surgery Articles

Vocal cord paralysis (VCP) presents with unique challenges when managing airways, particularly during endotracheal intubation. This literature review explores the effects of unilateral and bilateral VCP on intubation technique, first-pass success, extubation safety, and perioperative airway planning. While video laryngoscopy (VL) is becoming increasingly favored for its superior airway visualization, it does not always confirm successful placement in patients with VCP. Complications such as airway edema, aspiration risk, and cuff misplacements are increased in this patient population, and they may be more vulnerable to post-extubation complications, especially without the use of steroid prophylaxis or intensive post-operative planning. A comparison of …

High-Frequency And Conventional Ventilation In Very Low Birth Weight Neonates During Interfacility Transport, Trevor Cabrera, Janelle R. Noel-Macdonnell, Emily Mcnellis

Posters

Background: Very low birth weight (VLBW) neonates (≤1500 grams) transported across neonatal facilities often require advanced respiratory support, including high-frequency ventilation (HFV). While HFV use in this setting has increased, data evaluating its safety and efficacy in the VLBW population remain limited. We hypothesized that HFV will provide a safe modality to transport sick VLBW infants. Objectives: To present a comparative experience of safety and efficacy of HFV and CV in VLBW neonates during interfacility transport. Methods: We retrospectively reviewed neonates ≤1500g who received invasive ventilation during interfacility transport by our transport team between January 2019 and December 2022. HFV …

Discontinuous Or Attenuated Background, Absent Sleep Architecture, Absent Reactivity, And Presence Of Subclinical Seizures On Continuous Electroencephalography Are Associated With Unfavorable Short-Term Outcome Following Pediatric Severe Traumatic Brain Injury​, Xuexin Lu, Ara Hall, Yong Y. Han, Madeline Burdick, Avner Moeded, Isabella Boedefeld, Christian Kaufman, Jessica S. Wallisch

Presentations

BACKGROUND/PURPOSE: Accurate prognostication following pediatric severe traumatic brain injury (sTBI) remains challenging. Adult neuroprognostication guidelines recommend the use of prediction models that have not yet been validated in pediatric patients. We hypothesized certain continuous electroencephalography (cEEG) characteristics would be associated with unfavorable short-term outcome. METHODS: This was an IRB-approved, 7-year retrospective cohort study of children aged 1.5-18 years admitted to our PICU from 01/2018-12/2024 with sTBI and receiving cEEG monitoring per institutional standard management protocol. cEEG patterns (background, sleep architecture, reactivity, and electrographic seizure) during the first 12-hours of monitoring were analyzed for association with unfavorable short-term outcome at PICU …

Severe Thiopurine-Induced Myelosuppression In A Pediatric All Patient With The Nudt15 *1/*6 Genotype, Jillian Fry, Keith August, Terrie Flatt Do, Laura B. Ramsey

Posters

Introduction: Genetic variants in TPMT and NUDT15 that affect the metabolism of mercaptopurine (6MP) are routinely tested for to guide 6MP dosing. Nudix hydroxylase 15 (NUDT15) deficiency can cause myelosuppression when affected patients are treated with 6MP. The NUDT15 *6 allele is classified as having uncertain function by the Clinical Pharmacogenetics Implementation Consortium Guidelines given insufficient data to determine its phenotype. Here, we present the case of a pediatric patient with the NUDT15 *1/*6 genotype experiencing significant mercaptopurine-induced myelosuppression. Case Description: We present a 4-year-old female with standard risk-average precursor B-cell acute lymphoblastic leukemia treated per AALL1731. Exome sequencing reported …

Knowledge, Attitude, And Practice Towards Cervical Cancer Screening Among Women Aged 20 Years And Above In Mysuru, India, Sneha Manosh Kumar, Rashmi S, Amogha Shree

Digital Journal of Clinical Medicine

Background: Cervical cancer remains the fourth most common cancer among women globally and a leading cause of cancer-related mortality in India. Despite being largely preventable through screening, uptake remains suboptimal due to socio-cultural and systemic barriers.

Methods: A community-based cross-sectional study was conducted among 300 women aged ≥20 years residing in urban and rural areas of Mysuru. Data were collected using a pre-tested, semi-structured questionnaire and analyzed with SPSS version 30.

Results: Awareness of cervical cancer was reported by 90% of participants and of screening methods by 80%. However, only 21% had ever undergone screening and 17% within the preceding …

Reliability And Spatial Consistency Of Mr Diffusion Tensor Imaging Measures Along The Cerebral Perivascular Space, Enchao Qiu, Joga Chaganti, Phillip Phan, M. Alizadeh, Devon Middleton, Kiran Talekar, Prabath Mondel, Scott H. Faro, Feroze Mohamed, Hsiangkuo Yuan

Department of Radiology Faculty Papers

BACKGROUND AND PURPOSE: Diffusion tensor imaging analysis along the perivascular space (DTI-ALPS) has emerged as a promising noninvasive method for evaluating water motion that may reflect glymphatic system function. However, the reliability of DTI-ALPS measurements across different region-of-interest (ROI) selection methods remains underinvestigated. This study aimed to assess the interrater reliability among three neuroradiologists in native space and compare DTI-ALPS indices derived from ROIs placed in subjects' native space versus standardized Montreal Neurological Institute (MNI) space.

METHODS: DTI-ALPS indices from 16 healthy subjects were calculated from both left and right hemispheres using two ROI placement approaches: (1) native space ROIs …

Diagnostic Journey In The Recognition Of Oncogenic Osteomalacia, Steven B. Nagelberg, Mihaela Biscoveanu, Barbara Bix, Carrie Andrews, Srinivas Prasad

Jefferson Health - Northeast Papers (formerly Aria Health Papers)

A 73-year-old woman with a remote history of successfully treated primary hyperparathyroidism was referred to our office because of multiple skeletal fractures and proximal muscle weakness. Prior laboratory evaluation demonstrated hypocalcemia, vitamin D deficiency, elevated PTH, and elevated alkaline phosphatase. Updated evaluation in our clinic additionally showed hypophosphatemia prompting measurement of serum fibroblast growth factor 23 (FGF23). FGF23 proved to be markedly elevated prompting consideration of tumor-induced osteomalacia. Positron emission tomography with Cu-64 oxodotreotide revealed an enhancing focus in the left thoracic spine that was confirmed on magnetic resonance imaging to be a 1.5-cm extradural mass. The patient underwent surgical …

Deepmvp: Deep Learning Models Trained On High-Quality Data Accurately Predict Ptm Sites And Variant-Induced Alterations, Bo Wen, Chenwei Wang, Kai Li, Ping Han, Matthew V Holt, Sara R Savage, Jonathan T Lei, Yongchao Dou, Zhiao Shi, Yi Li, Bing Zhang

Center on Aging Staff Publications

Post-translational modifications (PTMs) are critical regulators of protein function, and their disruption is a key mechanism by which missense variants contribute to disease. Accurate PTM site prediction using deep learning can help identify PTM-altering variants, but progress has been limited by the lack of large, high-quality training datasets. Here, we introduce PTMAtlas, a curated compendium of 397,524 PTM sites generated through systematic reprocessing of 241 public mass-spectrometry datasets, and DeepMVP, a deep learning framework trained on PTMAtlas to predict PTM sites for phosphorylation, acetylation, methylation, sumoylation, ubiquitination and N-glycosylation. DeepMVP substantially outperforms existing tools across all six PTM types. Its …

From Imaging To Impact: A Multi-Disciplinary T32 Program Framework And Initial Insights For Training In Image-Guided Cancer Therapy, Kari J Brewer Savannah, Stephen Y Lai, Clifton D Fuller, Kristy K Brock

Faculty, Staff and Student Publications

As multi-disciplinary image-guided assessment and therapies become increasingly important for precision oncology, the need for comprehensive training opportunities that effectively prepare the next generation of clinician-scientists and scientists is evident. We present an innovative, evidence-based research training framework that integrates the following critical features: 1) intentional and personalized mentoring and career development, 2) immersive research in image-guided cancer therapy, 3) strategic mentored clinical exposure, 4) structured didactic learning and professional development opportunities, and 5) mentored grant writing. Designed to foster scientific rigor, translational thinking, and multi-disciplinary collaboration, the Image-Guided Cancer Therapy T32 Training Program (IGCT-T32) aims to prepare postdoctoral fellows …

Plasma Lipidome Dysregulation In Frontotemporal Dementia Reveals Shared, Genotype-Specific, And Severity-Linked Alterations., Yohannes A Ambaw, Peter A Ljubenkov, Shubham Singh, Abdi Hamed, Sebastian Boland, Adam L Boxer, Tobias C Walther, Robert V Farese

Duncan NRI Faculty and Staff Publications

Introduction: Biomarkers are essential for monitoring the progression of frontotemporal dementia (FTD). Although dysregulated brain lipid metabolism, particularly sphingolipids enriched in the nervous system, is a key feature of neurodegeneration, plasma lipids remain underexplored as biomarkers compared to imaging and serum proteins.

Methods: We examined plasma lipidomes using liquid chromatography-tandem mass spectrometry (LC-MS/MS) from individuals carrying pathogenic variants linked to autosomal dominant FTD (GRN, C9orf72, MAPT) and non-carriers.

Results: FTD subjects exhibited increased plasma levels of gangliosides (GM3(d18:1_16:0), GM3(d18:1_24:1)), ceramide Cer(d18:1_23:0), and select polyunsaturated triacylglycerols. In contrast, phosphatidylethanolamine (PE(18:0_24:0) and sphingomyelin (SM(38:0) were reduced. Subtype-specific changes included elevated glucosylsphingosine (GlcSph(d18:1) …

International Accreditation For Acute Stroke Care: Lessons Learnt From A Kenyan Stroke Centre, Dilraj Sokhi

Internal Medicine, East Africa

Background: The prevalence of stroke is increasing in Africa, yet resources remain limited in managing the disease. Whilst there are international guidelines on how to set up and manage stroke services, even in resource-limited settings, the uptake remains low. We describe here the opportunities and challenges we faced whilst setting up a stroke care pathway of international standards in a regional referral hospital in East Africa.

Methods: We describe how we adapted international stroke care guidelines for acute primary stroke (including both ischemic and hemorrhagic stroke), and used these to inform our stroke care pathway. We highlight opportunities of leveraging …

Fetal Myocardial Performance Index In The Late Third Trimester For The Prediction Of Intrapartum Cardiotocographic Abnormalities, Sikolia Wanyonyi, Ingrid Gichere

Obstetrics and Gynaecology, East Africa

Objective

We sought to determine whether fetal myocardial performance index (MPI) performed in the late third trimester could predict abnormal intrapartum cardiotocographic (CTG) patterns.

Methods

A prospective observational study including women presenting for fetal growth ultrasound from 32 weeks. Three consecutive measurements of the left ventricular MPI were obtained and averaged. The patients’ intrapartum CTG events were later observed.

Results

A total of 299 women were analyzed. The fetal MPI across the population were 0.41, 0.50 and 0.63, representing 10th, 50th and 90th centiles, respectively. A one-way analysis of variance (ANOVA) did not show a significant difference in MPI values …

Bridging Gaps In Breast Cancer Care: A Breast Cancer Care Quality Index To Improve Outcomes Worldwide, Eduardo Cazap, Benjamin Anderson, Giuseppe Curigliano, Sandeep Sehdev, Fatima Cardoso, Ana Gonzalez, Emad Shash, Cheng-Har Yip, André Mattar, Miriam Mutebi

General Surgery, East Africa

Background: Breast cancer (BC) care faces challenges in early detection, timely diagnosis and comprehensive management. Disparities persist, with underserved populations facing the greatest barriers. Addressing these requires policies that support consistent, evidence-based practices and enhance healthcare capacity and technology advancements. This document presents the development of the Breast Cancer Care Quality Index (BCCQI), supported by evidence to promote equitable care and improve BC outcomes globally, and discusses its adoption as a strategic tool within National Cancer Control Plans.

Methods: A two-part methodology identified challenges in BC care and defined dimensions, targets and indicators for the BCCQI, aligned with …

Fractures In Parkinson's Disease: Pathophysiology, Prevention, And Orthopedic Outcomes., Ali Osman, Tala Maya, Rayyan Bhutta, Natasha Doshi, Maryam Khan, Sara Shah, Paslene Periceles, Janae Rasmussen

Surgery Articles

Fractures are an important comorbidity in Parkinson's disease (PD), which can result in disability, mortality, and high healthcare costs. Impaired mobility, postural instability, bradykinesia, muscle rigidity, and decreased bone mineral density (BMD) contribute to the increased risk of falls, which often result in hip and upper extremity fractures. Hip fractures in patients with PD are associated with an increased hospital length of stay and a decline in functional independence. Multimodal fall prevention in PD is well established, but prevention of fractures is often underutilized, despite evidence-based interventions. Information on fall-related fracture outcomes after exercise interventions is an area warranting further …

Advancements In Diversity In Dermatology: A 5-Year Retrospective Analysis Of Racial And Ethnic Trends In U.S. Dermatology Residency Programs (2020-2024), Devin Barzallo, Afua Ofori-Darko, Larissa De Souza, Precious Nwanwa, Timmie Sharma

Student Scholarship

Diversity in residency programs is important for achieving health equity. Although targeted initiatives have led to some progress, dermatology residency trainees do not proportionally reflect the growing diversity of the U.S. population. We analyzed data from the Association of American Medical Colleges on residents from 2020 to 2024 to evaluate evolving diversity trends.

Malignancy-Associated Renal Infarction: A Case Of Prostate Cancer Presenting With Flank Pain And Hematuria., Connor J Stinson, Alec Pupo, Patrick Laird

Internal Medicine Resident Research

Renal infarction is an uncommon but critical diagnosis that is frequently overlooked due to its nonspecific presentation and overlap with more common causes of abdominal or flank pain. Patients with malignancy, including metastatic prostate cancer, are at increased risk of thromboembolic events due to the intrinsic hypercoagulable state promoted by cancer, yet arterial events, such as renal infarction, remain underrecognized. We present the case of a 74-year-old male with metastatic castrate-sensitive prostate cancer who developed acute abdominal pain, nausea, and vomiting. Evaluation revealed elevated blood pressure, microscopic hematuria, and increased lactate dehydrogenase (LDH). CT scan of the abdomen and pelvis …

Determining Risk Factors And Rate Of Surgery After Collagenase Injections For Dupuytren Contracture, Ryan C. Cha, Juliet S. Chung, Sina Ramtin, Asif M. Ilyas

Department of Orthopaedic Surgery Faculty Papers

Purpose: Collagenase injections are a nonsurgical treatment for Dupuytren contracture, but their long-term effectiveness in preventing surgery remains unclear. This study aimed to evaluate the rate of surgical intervention following collagenase treatment and identify whether specific risk factors increase the likelihood of future surgical correction. Methods: This retrospective cohort study utilized the TriNetX US Collaborative network to identify patients diagnosed with Dupuytren contracture between January 2007 and September 2024. Patients initially treated with collagenase injections were identified using relevant current procedural terminology codes. Procedure-specific current procedural terminology codes were then used to determine which patients underwent a subsequent fasciectomy or …

Prenatal Genetic Consultation And Testing, Sarah Araji, Lauren Westerfield, Roni Zemet, Ignatia B Van Den Veyver

Duncan NRI Faculty and Staff Publications

The evolution of prenatal genetic testing has transformed prenatal diagnosis into a more precise and individualized approach. Advanced tools such as chromosomal microarray analysis and exome sequencing have enabled the prenatal diagnosis of more genetic conditions, including anomalies and disorders eligible for fetal therapy. When in utero therapy is considered, accurate genetic diagnosis is essential for guiding providers' and patients' decisions regarding management and outcomes. This chapter reviews available prenatal genetic screens and tests, their indications, and counseling strategies. It also explores genetic abnormalities associated with fetal structural anomalies and their implications for decision-making in fetal interventions.

The Effect Of Tert Promoter Mutation On Predicting Meningioma Outcomes: A Multi-Institutional Cohort Analysis, Karenna J Groff, Ruchit V Patel, Yang Feng, Hia S Ghosh, Miguel A Millares Chavez, Joseph O'Brien, William C Chen, Vijay Nitturi, Akshay V Save, Mark W Youngblood, Craig M Horbinski, James P Chandler, Felix Ehret, Chloe Gui, Justin Z Wang, Kristen Park, Sonia Ajmera, Marc Rosenblum, Abigail K Suwala, Catena Kresbach, Christopher W Mount, Ulrich Schüller, Sandro Santagata, Felix Sahm, Tejus A Bale, Christina Jackson, Timothy E Richardson, Chunyu Cai, Farshad Nassiri, Gelareh Zadeh, David Kaul, David Capper, Stephen T Magill, John G Golfinos, Chandra Sen, Akash J Patel, David R Raleigh, Jennifer Moliterno, Donato Pacione, Matija Snuderl, Wenya Linda Bi

Duncan NRI Faculty and Staff Publications

Background: Molecular aberrations have been incorporated into tumour classification guidelines of meningioma. TERT-promoter (TERTp) mutation is associated with worse prognosis and is designated a WHO grade 3 biomarker. However, it remains unclear whether TERTp mutation is context-dependent, with other co-occurring genetic alterations potentially driving its association with prognosis. We sought to characterise the role of TERTp mutation in meningioma and guide TERTp sequencing.

Methods: We identified 1492 patients of all ages who had previously received surgery for meningioma across 14 medical centres in the USA, Canada, and Germany. Patients were eligible if they had post-surgical clinical or radiographical assessment of …

Eular/Acr Classification Criteria For Paediatric Chronic Nonbacterial Osteomyelitis (Cno)., Yongdong Zhao, Melissa S. Oliver, Anja Schnabel, Eveline Y. Wu, Zhaoyi Wang, Achille Marino, Cassyanne L. Aguiar, Jonathan D. Akikusa, Ummusen Kaya Akca, Beverley Almeida, Simone Appenzeller, Erin Balay-Dustrude, Ozge Basaran, Matthew L. Basiaga, Yelda Bilginer, David A. Cabral, Martina Capponi, Nathan Donaldson, Bugra Han Egeli, Emily Fox, Antonella Insalaco, Ramesh S. Iyer, Annette F. Jansson, Inna Kostik, Mikhail Kostik, Leonard K. Kovalick, Katia Tomie Kozu, Sivia K. Lapidus, Tzielan C. Lee, Aleksander Lenert, Kamran Mahmood, Edoardo Marrani, Doaa Mosad Mosa, Ian Muse, Alexander Mushkin, Katherine D. Nowicki, Farzana Nuruzzaman, Karen Onel, Manuela Pardeo, Trang Sophia Pham, Lauren Potts, Athimalaipet V. Ramanan, Angelo Ravelli, Nathan D. Rogers, Andrew W. Grim, Micol Romano, Natalie Rosenwasser, Takashi Shawn Sato, Gabriele Simonini, Jennifer B. Soep, Sara M. Stern, Timmy Strauss, Angela Taneja Kohli, Alexander C. Theos, Lori B. Tucker, Leslie F. Vogel, Shima Yasin, Stephen C. Wong, Katerina Bouchalova, Alison M. Hendry, Kevin C. Cain, Hermann J. Girschick, Fatma Dedeoglu, Christian M. Hedrich, Ronald M. Laxer, Polly J. Ferguson, Raymond Naden, Seza Ozen

Manuscripts, Articles, Book Chapters and Other Papers

OBJECTIVES: To develop and validate classification criteria for paediatric chronic nonbacterial osteomyelitis (CNO) jointly supported by the European Alliance of Associations for Rheumatology (EULAR) and the American College of Rheumatology (ACR).

METHODS: This international initiative had 4 phases: (1) candidate items were proposed in a survey of paediatric rheumatologists, (2) criteria definition and reduction by Delphi and nominal group technique exercises, (3) criteria weighting using multicriteria decision analysis, and (4) refinement of weights and threshold score in a development cohort of 441 patients and validation in another cohort of 514 patients.

RESULTS: The new EULAR/ACR classification criteria for CNO require …

Contemporary Characteristics And Outcomes Of Pediatric Oncology Patients Participating In Early Phase Clinical Trials., Avina Rami, Kira Bona, Suzanne Shusterman, Karen Wright, Andrew E. Place, Puja J. Umaretiya, Ketki Bhushan, Steven G. Dubois, Kevin Campbell

Manuscripts, Articles, Book Chapters and Other Papers

BACKGROUND: Phase 1 or phase 1/2 trials are a first step in pediatric cancer drug development. Currently, there is a paucity of information regarding contemporary outcomes for pediatric patients enrolled in these trials. We describe characteristics and outcomes of patients enrolled in pediatric phase 1 clinical trials over a 9-year period at a single institution.

METHODS: We queried our clinical trials management system to generate a list of patients enrolled and treated on pediatric phase 1 or phase 1/2 trials from 2011 to 2019. We collected baseline demographics, clinical data, efficacy, and safety endpoints post-enrollment including: time to death, objective …

Association Between Chd And Cerebral Abscess: Insights From A National Database., Keats Ewing, Rohit Seath Loomba, Saul Flores, Enrique G. Villarreal, Juan S. Farias, Matthew Taylor Coghill

Manuscripts, Articles, Book Chapters and Other Papers

CHD has been historically associated with the development of cerebral abscess. This retrospective cohort study examines the association of CHD with the occurrence of cerebral abscess in an inpatient paediatric population. We analysed data from the Pediatric Health Information System database, an administrative database that captures data from participating children's hospitals in the United States. We included all patients admitted to participating paediatric ICUs between 2016 and 2021 for a total of 426,029 admissions. Including all admissions, 1,387 (0.3%) patients experienced a cerebral abscess, and of 80,927 (19%) patients with CHD, only 88 (0.1%) experienced a cerebral abscess (odds ratio …

Evaluating The Consistency Of Smarcb1 Variant Classification And Assertions Of Genotype-Phenotype Relationships In Clinvar, Samarth Satish, Matan Bone, Deborah Ritter, Sharon E Plon

Faculty, Staff and Students Publications

Pathogenic SMARCB1 variants are associated with multiple Mendelian syndromes: Schwannomatosis (SM), Rhabdoid Tumour Predisposition Syndrome (RTPS1), and/or Coffin-Siris Syndrome (CSS). Although some data suggests genotype/phenotype relationships based on mutation type and location, this is not used consistently potentially due to inconsistent or absent phenotypic data. We used ClinVar, the largest public platform of variant classifications, to evaluate variant-specific data from clinical laboratories and cited publications to assess reporting consistency and genotype-phenotype relationships. When available, we extracted the mutation type, HGVS nomenclature, submitters, publications, and disease conditions. We compared the disease assertions made by laboratory submissions with those made in cited …