Medicine and Health Sciences Commons^™

Neuroimaging-Based Variability In Subtyping Biomarkers For Psychiatric Heterogeneity, Zhenfu Wen, Mira Z Hammoud, Carole E Siegel, Eugene M Laska, Duna Abu-Amara, Amit Etkin, Mohammed R Milad, Charles R Marmar

Faculty, Staff and Student Publications

Neuroimaging-based subtyping is increasingly used to explain heterogeneity in psychiatric disorders. However, the clinical utility of these subtyping efforts remains unclear, and replication has been challenging. Here we examined how the choice of neuroimaging measures influences the derivation of neuro-subtypes and the consequences for clinical delineation. On a clinically heterogeneous dataset (total n = 566) that included controls (n = 268) and cases (n = 298) of psychiatric conditions, including individuals diagnosed with post-traumatic stress disorder (PTSD), traumatic brain injury (TBI), and comorbidity of both (PTSD&TBI), we identified neuro-subtypes among the cases using either structural, resting-state, or task-based measures. The …

Malperfusion In Patients With Acute Type A Aortic Dissection: A Nationwide Analysis, Nicholas J Goel, John J Kelly, William L Patrick, Yu Zhao, Joseph E Bavaria, Maral Ouzounian, Anthony L Estrera, Hiroo Takayama, Edward P Chen, T Brett Reece, G Chad Hughes, Eric E Roselli, Karen M Kim, Himanshu J Patel, Michael E Bowdish, Jason S Sperling, Bradley G Leshnower, Ourania Preventza, William T Brinkman, Nimesh D Desai

Faculty, Staff and Student Publications

Background: This study describes in detail the clinical burden of malperfusion associated with acute type A aortic dissection (ATAAD) in a large, national cohort and the effect of treatment strategy on outcomes.

Methods: All patients undergoing repair of ATAAD between 2017 and 2020 in The Society of Thoracic Surgeons (STS) Adult Cardiac Surgery Database were studied. Malperfusion was defined using STS definitions on the basis of imaging or the surgeon's evaluation. Multivariable logistic regression was used to analyze the effect of patient and treatment factors on outcomes in patients with and without malperfusion.

Results: A total of 9958 patients undergoing …

Bmal1-Hif2a Heterodimer Modulates Circadian Variations Of Myocardial Injury, Wei Ruan, Tao Li, In Hyuk Bang, Jaewoong Lee, Wankun Deng, Xinxin Ma, Cong Luo, Fang Du, Seung-Hee Yoo, Boyun Kim, Jiwen Li, Xiaoyi Yuan, Katherine Figarella, Yu A An, Yin-Ying Wang, Yafen Liang, Matthew Deberge, Dongze Zhang, Zhen Zhou, Yanyu Wang, Joshua M Gorham, Jonathan G Seidman, Christine E Seidman, Sary F Aranki, Ragini Nair, Lei Li, Jagat Narula, Zhongming Zhao, Alemayehu A Gorfe, Jochen D Muehlschlegel, Kuang-Lei Tsai, Holger K Eltzschig

Faculty, Staff and Student Publications

Acute myocardial infarction is a leading cause of morbidity and mortality worldwide1. Clinical studies have shown that the severity of cardiac injury after myocardial infarction exhibits a circadian pattern, with larger infarcts and poorer outcomes in patients experiencing morning-onset events2–7. However, the molecular mechanisms underlying these diurnal variations remain unclear. Here we show that the core circadian transcription factor BMAL17–11 regulates circadian-dependent myocardial injury by forming a transcriptionally active heterodimer with a non-canonical partner—hypoxia-inducible factor 2 alpha (HIF2A)12–16—in a diurnal manner. To substantiate this finding, we determined …

Longevity Humans Have Youthful Erythrocyte Function And Metabolic Signatures, Fang Yu, Changhan Chen, Wuping Liu, Zhixiang Zhao, Yuhua Fan, Zhenjiang Li, Weilun Huang, Tingting Xie, Cheng Luo, Zhouzhou Yao, Qi Guo, Zhiyu Yang, Juan Liu, Yujin Zhang, Rodney E Kellems, Jian Xia, Ji Li, Yang Xia

Faculty, Staff and Student Publications

Longevity individuals have lower susceptibility to chronic hypoxia, inflammation, oxidative stress, and aging-related diseases. It has long been speculated that "rejuvenation molecules" exist in their blood to promote extended lifespan. We unexpectedly discovered that longevity individuals exhibit erythrocyte oxygen release function similar to young individuals, whereas most elderly show reduced oxygen release capacity. Untargeted erythrocyte metabolomics profiling revealed that longevity individuals are characterized by youth-like metabolic reprogramming and these metabolites effectively differentiate the longevity from the elderly. Quantification analyses led us to identify multiple novel longevity-related metabolites within erythrocytes including adenosine, sphingosine-1-phosphate (S1P), and glutathione (GSH) related amino acids. Mechanistically, …

Targeting Discrepancies In Linear Growth Measurements In The Neonatal Intensive Care Unit Through Nursing Interventions: A Quality Improvement Initiative, Gail Snyder, Rebekah Wilkinson, Raina Evans, Meagan Owen, Akram Yazdani, Covi Tibe, Catherine Perez, Lindsay F Holzapfel

Faculty, Staff and Student Publications

Objective: Accurate length measurements are essential for infants to identify growth deficiencies and adjust nutrition accordingly. The gold standard for length measurement in infants is using a length board with two people to obtain an accurate clinical assessment. We aimed to improve the number of measurements with the desired minimal difference, defined as a discrepancy ≤1 cm between nurse and audit measurements, in our center. Our secondary aim was to increase and maintain the number of length boards available.

Methods: This quality improvement (QI) study used a before-and-after intervention comparison design in a single-level IV neonatal intensive care unit between …

Randomized Controlled Trial Of "Bounce Back Now," A Mobile App To Reduce Post-Disaster Symptoms Of Posttraumatic Stress, Depressed Mood, And Sleep Disturbance, Kenneth J Ruggiero, Arthur Andrews, Tatiana M Davidson, Yulia Gavrilova, Brian E Bunnell, Jennifer Dahne, Matthew Price, Zoe M F Brier, Gregory Cohen, Dean Kilpatrick, Ron Acierno, Sandro Galea

Faculty, Staff and Student Publications

Objective: There is tremendous public health interest in cost-efficient, scalable interventions to improve post-disaster mental health. The authors examined the efficacy of Bounce Back Now (BBN), a mobile application, versus an enhanced usual care app (EUC).

Methods: A population-based trial was conducted with a diverse sample of 1,357 adults affected by Hurricane Harvey, Irma, Maria, Florence, or Michael in 2017 and 2018. Participants were eligible if they were ≥18 years of age, had access to an Internet-accessible device, were English speaking, and lived in a hurricane-affected area. BBN is designed to address symptoms of posttraumatic stress, depression, and sleep disturbance …

Adherence To Life’S Essential 8 Is Associated With Delayed White Matter Aging, Li Feng, Zhenyao Ye, Yezhi Pan, Rozalina G Mccoy, Braxton D Mitchell, Peter Kochunov, Paul M Thompson, Jie Chen, Menglu Liang, Thu T Nguyen, Edmond Shenassa, Yan Li, Travis Canida, Hongjie Ke, Hwiyoung Lee, Song Liu, L Elliot Hong, Chixiang Chen, David K Y Lei, Shuo Chen, Tianzhou Ma

Faculty, Staff and Student Publications

Background: The American Heart Association introduced Life's Essential 8 (LE8) to promote cardiovascular health and longevity. However, its impact on brain ageing and interactions with genetic risk factors of dementia, such as APOE4, remains unclear. This study investigates the relationship between LE8 and white matter brain ageing and evaluates the moderating effects of the APOE4 allele.

Methods: This cross-sectional study utilized data from the UK Biobank, including genetic, neuroimaging, and health-related data from touchscreen questionnaires, physical examinations, and biological samples. Participants were non-pregnant whites with LE8 variables, diffusion tensor imaging (DTI) data, and APOE4 genetic information available, excluding those with …

Blood Pressure Misclassification Among Stroke Survivors Followed In A Comprehensive Stroke Prevention Clinic, M Carter Denny, Maha Almohamad, Emmanuel Ebirim, Adriana Morell, Munachi Okpala, Kevin O Hwang, Sean Savitz, Anjail Sharrief

Faculty, Staff and Student Publications

Background: Hypertension is the most important modifiable risk factor for secondary stroke prevention; however, blood pressure (BP) remains uncontrolled for at least 50 % of stroke survivors following an incident stroke. Accurate in-clinic assessment of BP is important for appropriate medication titration. We evaluated misclassification of clinic BP control in a racially diverse stroke clinic population using two BP measurement methods.

Observations: We followed ischemic stroke, intracerebral hemorrhage, and transient ischemic attack patients after hospital discharge in a comprehensive stroke clinic. Casual BP was obtained using a standard office automated machine, attended by a medical assistant. BP was also measured …

Air Embolism After Percutaneous Lung Biopsy Or Ablation: A Report Of Six Cases, Rebecca Choi, Haylie Kieu-Mi Phan, Varshana Gurusamy, Rahul A Sheth, Bruno C Odisio, Kelvin Hong, Alda L Tam

Faculty, Staff and Student Publications

Systemic air embolism is a rare but potentially life-threatening complication of percutaneous lung biopsy and ablation. This report describes six patients (four male, two female) with air embolism following CT-guided lung interventions at two institutions between January 2021 and March 2024. Air embolisms were identified in locations such as the pulmonary vein, left ventricle, and coronary arteries, with clinical presentations ranging from asymptomatic to life-threatening events. Prompt intervention, including oxygen therapy, patient repositioning, and intravenous administration of epinephrine in cases of cardiac arrest, resulted in favorable outcomes. This series highlights the importance of early detection of systemic air embolism and …

Safety, Efficacy, And Adjacent-Level Fracture Risk Following Vertebral Augmentation And Radiofrequency Ablation For The Treatment Of Spine Metastases In Patients With Cancer, Jeremiah Stringam, Koustav Pal, Andrew Niekamp, Rahim Jiwani, Iwan Paolucci, Joshua D Kuban, Zeyad Metwalli, Steven Huang, Peiman Habibollahi, Stephen Chen, Steven Yevich, Milan Patel, Sumit K Subudhi, Matthew Campbell, Amol Ghia, Claudio Tatsui, Rahul A Sheth

Faculty, Staff and Student Publications

Purpose: To evaluate the safety and efficacy of vertebral augmentation (VA) and radiofrequency ablation (RFA) for treating pathologic spinal fractures in patients with cancer and adjacent fracture risk following treatment.

Materials and Methods: This single-institution retrospective study, conducted from January 2017 to September 2020, included patients with cancer who underwent percutaneous VA with or without spine RFA for pathologic spine compression fractures. The primary outcome was pain reduction, assessed using the 10-point visual analog scale before the procedure, at first follow-up, and 2–4 weeks after the procedure. Logistic regression was performed to identify factors associated with epidural cement leak.

Results: …

Oral Microbiome Profile Of The Us Population, Anil K Chaturvedi, Emily Vogtmann, Jianxin Shi, Yukiko Yano, Martin J Blaser, Nicholas A Bokulich, J Gregory Caporaso, Maura L Gillison, Barry I Graubard, Xing Hua, Autumn G Hullings, Lisa Kahle, Rob Knight, Shilan Li, Jody Mclean, Vaishnavi Purandare, Yunhu Wan, Neal D Freedman, Christian C Abnet

Faculty, Staff and Student Publications

Importance: The oral microbiome likely plays key roles in human health. Yet, population-representative characterizations are lacking.

Objective: To characterize the composition, diversity, and correlates of the oral microbiome in US adults.

Design, setting, and participants: This cross-sectional study analyzed data from the population-representative National Health and Nutrition Examination Survey (NHANES) from 2009 to 2012. Microbiome data were made publicly available in 2024. NHANES participants were aged 18 to 69 years and provided oral rinse samples in 1 of 2 consecutive NHANES cycles (2009-2010 and 2011-2012).

Exposures: Demographic, socioeconomic, behavioral, anthropometric, metabolic, and clinical characteristics.

Main outcomes and measures: Oral microbiome …

Chd1 Loss Reprograms Srebp2-Driven Cholesterol Synthesis To Fuel Androgen-Responsive Growth And Castration Resistance In Spop-Mutated Prostate Tumors, Feiyu Chen, Haoyan Li, Yin Wang, Ximing Tang, Kevin Lin, Qidong Li, Chenling Meng, Wei Shi, Javier Leo, Xin Liang, Jie Zhang, Vivien Van, Iqbal Mahmud, Bo Wei, Philip L Lorenzi, Maria G Raso, Ana Aparicio, Yue Lu, Daniel E Frigo, Boyi Gan, Di Zhao

Faculty, Staff and Student Publications

Despite undergoing castration, most individuals with prostate cancer (PCa) experience progression to castration-resistant PCa (CRPC), in which the androgen receptor (AR) remains an important driver. Concurrent genetic alterations in SPOP and CHD1 define a unique subtype of PCa, but their interactions in tumor progression and therapy response remain unclear. Here, we provide genetic evidence supporting that CHD1 loss accelerates disease progression and confers resistance to castration in males with SPOP-mutated PCa. By leveraging genetic engineering and multiomics, we uncovered a noncanonical function of CHD1 in lipid metabolism reprogramming via repressing the SREBP2 transcriptome. Loss of CHD1 induces cholesterol production, supplies …

Defining The Optimal Radiation-Induced Lymphopenia Metric To Discern Its Survival Impact In Esophageal Cancer, Pim J J Damen, Max Peters, Brian Hobbs, Yiqing Chen, Uwe Titt, Remi Nout, Radhe Mohan, Steven H Lin, Peter S N Van Rossum

Faculty, Staff and Student Publications

Purpose: A detrimental association between radiation-induced lymphopenia (RIL) and oncologic outcomes in patients with esophageal cancer has been established. However, an optimal metric for RIL remains undefined but is important for the application of this knowledge in clinical decision-making and trial designs. The aim of this study was to find the optimal RIL metric discerning survival.

Methods and materials: Patients with esophageal cancer treated with concurrent chemoradiation therapy (CRT; 2004-2022) were selected. Studied metrics included absolute lymphocyte counts (ALCs) and neutrophil counts-and calculated derivatives-at baseline and during CRT. Multivariable Cox regression models for progression-free survival (PFS) and overall survival (OS) …

Deciphering The Longitudinal Trajectories Of Glioblastoma Ecosystems By Integrative Single-Cell Genomics, Avishay Spitzer, Kevin C Johnson, Masashi Nomura, Luciano Garofano, Djamel Nehar-Belaid, Noam Galili Darnell, Alissa C Greenwald, Lillian Bussema, Young Taek Oh, Frederick S Varn, Fulvio D'Angelo, Simon Gritsch, Kevin J Anderson, Simona Migliozzi, L Nicolas Gonzalez Castro, Tamrin Chowdhury, Nicolas Robine, Catherine Reeves, Jong Bae Park, Anuja Lipsa, Frank Hertel, Anna Golebiewska, Simone P Niclou, Labeeba Nusrat, Sorcha Kellet, Sunit Das, Hyo-Eun Moon, Sun Ha Paek, Franck Bielle, Alice Laurenge, Anna Luisa Di Stefano, Bertrand Mathon, Alberto Picca, Marc Sanson, Shota Tanaka, Nobuhito Saito, David M Ashley, Stephen T Keir, Keith L Ligon, Jason T Huse, W K Alfred Yung, Anna Lasorella, Antonio Iavarone, Roel G W Verhaak, Itay Tirosh, Mario L Suvà

Faculty, Staff and Student Publications

The evolution of isocitrate dehydrogenase (IDH)-wildtype glioblastoma (GBM) after standard-of-care therapy remains poorly understood. Here we analyzed matched primary and recurrent GBMs from 59 patients using single-nucleus RNA sequencing and bulk DNA sequencing, assessing the longitudinal evolution of the GBM ecosystem across layers of cellular and molecular heterogeneity. The most consistent change was a lower malignant cell fraction at recurrence and a reciprocal increase in glial and neuronal cell types in the tumor microenvironment (TME). The predominant malignant cell state differed between most matched pairs, but no states were exclusive or highly enriched in either time point, nor was there …

Further Delineation Of The Scaf4-Associated Neurodevelopmental Disorder, Cosima M Schmid, Anne Gregor, Anna Ruiz, Carmen Manso Bazús, Isabella Herman, Farah Ammouri, Urania Kotzaeridou, Vanda Mcniven, Lucie Dupuis, Katharina Steindl, Anaïs Begemann, Anita Rauch, Aude-Annick Suter, Bertrand Isidor, Sandra Mercier, Mathilde Nizon, Benjamin Cogné, Wallid Deb, Thomas Besnard, Tobias B Haack, Ruth J Falb, Amelie J Müller, Tobias Linden, Chad R Haldeman-Englert, Charlotte W Ockeloen, Francesca Mattioli, Alexandre Reymond, Nazia Ibrahim, Shagufta Naz, Elodie Lacaze, Jennifer A Bassetti, Julia Hoefele, Theresa Brunet, Korbinian M Riedhammer, Houda Z Elloumi, Richard Person, Fanggeng Zou, Juliette J Kahle, Kirsten Cremer, Axel Schmidt, Marie-Ange Delrue, Pedro M Almeida, Fabiana Ramos, Siddharth Srivastava, Aisling Quinlan, Stephen Robertson, Eva Manka, Alma Kuechler, Stephanie Spranger, Malgorzata J M Nowaczyk, Reem M Elshafie, Hind Alsharhan, Paul R Hillman, Leslie A Dunnington, Hilde M H Braakman, Shane Mckee, Angelica Moresco, Andrea-Diana Ignat, Ruth Newbury-Ecob, Guillaume Banneau, Olivier Patat, Jeffrey Kuerbitz, Susan Rzucidlo, Susan S Sell, Patricia Gordon, Sarah Schuhmann, André Reis, Yosra Halleb, Radka Stoeva, Boris Keren, Zainab Al Masseri, Zeynep Tümer, Sophia Hammer-Hansen, Sofus Krüger Sølyst, Connolly G Steigerwald, Nicolas J Abreu, Helene Faust, Amica Müller-Nedebock, Frédéric Tran Mau-Them, Heinrich Sticht, Christiane Zweier

Faculty, Staff and Student Publications

While mostly de novo truncating variants in SCAF4 were recently identified in 18 individuals with variable neurodevelopmental phenotypes, knowledge on the molecular and clinical spectrum is still limited. We assembled data on 50 novel individuals with SCAF4 variants ascertained via GeneMatcher and personal communication. With detailed evaluation of clinical data, in silico predictions and structural modeling, we further characterized the molecular and clinical spectrum of the autosomal dominant SCAF4-associated neurodevelopmental disorder. The molecular spectrum comprises 25 truncating, eight splice-site and five missense variants. While all other truncating variants were classified as pathogenic/likely pathogenic, significance of one C-terminal truncating variant, one …

Diroximel Fumarate Acts Through Nrf2 To Attenuate Methylglyoxal-Induced Nociception In Mice And Decrease Isr Activation In Drg Neurons, Muhammad Saad Yousuf, Marisol Mancilla Moreno, Brodie J Woodall, Vikram Thakur, Jiahe Li, Lucy He, Rohita Arjarapu, Danielle Royer, Jennifer Zhang, Munmun Chattopadhyay, Peter M Grace, Theodore J Price

Faculty, Staff and Student Publications

Diabetic neuropathic pain is associated with elevated plasma levels of methylglyoxal (MGO). MGO is a metabolite of glycolysis that causes pain hypersensitivity in mice by stimulating the phosphorylation of eukaryotic initiation factor 2α (p-eIF2α) and subsequently activating the integrated stress response (ISR). We first established that Zucker diabetic fatty rats have enhanced MGO signaling, engage ISR, and develop pain hypersensitivity. Since nuclear factor erythroid 2-related factor 2 (Nrf2) regulates the expression of antioxidant proteins that neutralize MGO, we hypothesized that fumarates, like diroximel fumarate (DRF), will stimulate Nrf2 signaling, and prevent MGO-induced ISR and pain hypersensitivity. DRF (100 mg/kg) treated …

Colour Changes In The Feet: A Sign Of Autonomic Symptoms In Systemic Sclerosis, Brittany L Adler, Kamini Kuchinad, Seeun Judy Jeong, Lauren E Stiles, Ami A Shah, Tae Chung, Zsuzsanna H Mcmahan

Faculty, Staff and Student Publications

Objectives: Patients with autonomic dysfunction, or dysautonomia, often report discolouration of their dependent extremities, which is thought to be from venous pooling or acrocyanosis. A subset of patients with SSc are affected by dysautonomia but may be challenging to identify. We sought to determine whether patients with SSc who report discolouration in their feet have a higher burden of autonomic symptoms, including orthostatic, gastrointestinal (GI), urinary, secretomotor and pupillomotor.

Methods: 167 patients with SSc completed the Composite Autonomic Symptom Score (COMPASS)-31 survey, which queries whether the patient experiences discolouration of the feet or hands. We compared the COMPASS-31 subdomain scores …

Sustained Improvement In Health-Related Quality Of Life In Transplant-Ineligible Newly Diagnosed Multiple Myeloma Treated With Daratumumab, Lenalidomide, And Dexamethasone: Maia Final Analysis Of Patient-Reported Outcomes, Aurore Perrot, Thierry Facon, Torben Plesner, Saad Z Usmani, Shaji Kumar, Nizar J Bahlis, Cyrille Hulin, Robert Z Orlowski, Hareth Nahi, Peter Mollee, Karthik Ramasamy, Murielle Roussel, Arnaud Jaccard, Michel Delforge, Lionel Karlin, Bertrand Arnulf, Ajai Chari, George Wang, Niodita Gupta-Werner, Shuchita Kaila, Huiling Pei, Kathryn Matt, Katharine S Gries, Robin Carson, Fredrik Borgsten, Katja Weisel

Faculty, Staff and Student Publications

Objectives: This final post hoc analysis evaluated patient-reported outcomes from the Phase 3 MAIA study of daratumumab, lenalidomide, and dexamethasone (D-Rd) versus lenalidomide and dexamethasone (Rd) after median 64.5-month follow-up in transplant-ineligible patients with newly diagnosed multiple myeloma (NDMM), including patient subgroups.

Methods: Key scales from the EORTC QLQ-C30 (global health status [GHS], physical functioning, pain, and fatigue) were assessed. Scores were evaluated every 3 months for 1 year, then every 6 months until disease progression.

Results: The intent-to-treat population (n = 737) included 46.3% frail, 35.4% 70 to < 75 years old, and 43.6% ≥ 75 years old. D-Rd-treated patients showed improvements from baseline that were sustained over 5 years in the intent-to-treat population and across subgroups by age, frailty, and bone lesions. Greater proportions of patients treated with D-Rd versus Rd achieved minimally important changes for improvement at cycle 36 (year ~3) in GHS (odds ratio, 1.84 [95% CI, 1.16-2.91]), physical functioning (1.93 [1.18-3.14]), pain (1.41 [0.90-2.22]), and fatigue (2.00 [1.24-3.23]). Greater proportions of patients with bone lesions improved with D-Rd versus Rd on GHS and physical functioning.

Conclusions: In transplant-ineligible patients with NDMM, D-Rd improved health-related quality of …

T2-Weighted Imaging Of Rectal Cancer Using A 3d Fast Spin Echo Sequence With And Without Deep Learning Reconstruction: A Reader Study, Dan Nguyen, Sarah Palmquist, Ken-Pin Hwang, Jingfei Ma, Usama Salem, Jia Sun, Xinzeng Wang, Jong Bum Son, Randy Ernst, Peng Wei, Harmeet Kaur, Nir Stanietzky

Faculty, Staff and Student Publications

Purpose: To compare image quality and clinical utility of a T2-weighted (T2W) 3-dimensional (3D) fast spin echo (FSE) sequence using deep learning reconstruction (DLR) versus conventional reconstruction for rectal magnetic resonance imaging (MRI).

Methods: The study included 50 patients with rectal cancer who underwent rectal MRI consecutively between July 7, 2020 and January 20, 2021 using a T2W 3D FSE sequence with DLR and conventional reconstruction. Three radiologists reviewed the two sets of images, scoring overall SNR, motion artifacts, and overall image quality on a 3-point scale and indicating clinical preference for DLR or conventional reconstruction based on those three …

Multiparametric Mri Scoring System Of The Pancreas For The Diagnosis Of Chronic Pancreatitis, Temel Tirkes, Dhiraj Yadav, Darwin L Conwell, Xuandong Zhao, Anil K Dasyam, Vivek Gowdra Halappa, Aashish Patel, Zarine K Shah, Jordan Swensson, Naoki Takahashi, Sudhakar Venkatesh, Ashley Wachsman, Liang Li, Kristofer Jennings, Yunlong Yang, Phil A Hart, Stephen J Pandol, Walter G Park, Santhi Swaroop Vege, Mark Topazian, Paul R Territo, Scott A Persohn, Dana K Andersen, Evan L Fogel, Consortium For The Study Of Chronic Pancreatitis, Diabetes, And Pancreatic Cancer (Cpdpc)

Faculty, Staff and Student Publications

Background: Ductal features alone may not offer high diagnostic sensitivity or most accurate disease severity of chronic pancreatitis (CP).

Purpose: Diagnose CP based on multiparametric MRI and MRCP features.

Study type: Prospective.

Population: Between February 2019 and May 2021, 46 control (23 males, 49.3 ± 14.1 years), 45 suspected (20 males, 48.7 ± 12.5 years), and 46 definite (20 males, 53.7 ± 14.6 years) CP patients were enrolled at seven hospitals enrolled in the MINIMAP study. CP classification was based on imaging findings and clinical presentation.

Field strength and sequences: 1.5 T. T1-weighted (T1W) spoiled gradient echo, T1 map with …

Temporal Trends Of Subsequent Central Nervous System Malignancies Among Survivors Of Childhood Cancer, Robert T Galvin, Yan Chen, Yan Yuan, Tabitha Cooney, Rebecca Howell, Susan Smith, Michael A Arnold, Miriam Conces, Wendy Leisenring, Gregory T Armstrong, Joseph P Neglia, Lucie M Turcotte

Faculty, Staff and Student Publications

Background: It is not known whether temporal changes in childhood cancer therapy have reduced risk of subsequent malignant neoplasms of the central nervous system (CNS), a frequently fatal late effect of cancer therapy.

Methods: Five-year survivors of primary childhood cancers diagnosed between 1970 and 1999 in the Childhood Cancer Survivor Study with CNS subsequent malignant neoplasms were identified. Cumulative incidence rates and standardized incidence ratios were compared among survivors diagnosed between 1970-1979 (n = 6223), 1980-1989 (n = 9680), and 1990-1999 (n = 8999). Multivariable models assessed risk factors for CNS subsequent malignant neoplasms.

Results: A total of 157 CNS …

Research Participant Interest In Learning Results Of Biomarker Tests For Alzheimer Disease, Spondita Goswami, Sarah M Hartz, Amy Oliver, Sacha Jackson, Tomi Ogungbenle, Alissa Evans, Erin Linnenbringer, Krista L Moulder, John C Morris, Jessica Mozersky

2020-Current year OA Pubs

IMPORTANCE: While available evidence suggests there are not major psychosocial harms of return of research results, there are limited data on uptake of Alzheimer disease (AD) research results or reasons for declining to learn results among participants in AD research studies.

OBJECTIVES: To quantitatively and qualitatively evaluate who declines to learn individual AD biomarker research results and what factors are associated with the decision.

DESIGN, SETTING, AND PARTICIPANTS: This observational cohort study was conducted between November 1, 2020, and April 15, 2024, among participants aged 65 years or older with unimpaired cognition and available biomarker data (apolipoprotein E genotype and …

Clinical Correlates Of A High Cardiorespiratory Risk Score For Very Low Birth Weight Infants, Sherry L Kausch, Claire C Slevin, Amanda Duncan, Karen D Fairchild, Douglas E Lake, Jessica Keim-Malpass, Zachary A Vesoulis, Brynne A Sullivan

2020-Current year OA Pubs

BACKGROUND: A pulse oximetry warning system (POWS) to analyze heart rate and oxygen saturation data and predict risk of sepsis was developed for very low birth weight (VLBW) infants.

METHODS: We determined the clinical correlates and positive predictive value (PPV) of a high POWS score in VLBW infants. In a two-NICU retrospective study, we identified times when POWS increased above 6 (POWS spike). We selected an equal number of control times, matched for gestational and chronologic age. We reviewed records for infection and non-infection events around POWS spikes and control times. We calculated the frequencies and PPV of a POWS …

Brain Morphometry In Infants Later Diagnosed With Autism Is Related To Later Language Skills, Luke E Moraglia, Kelly N Botteron, Natasha Marrus, Et Al.

2020-Current year OA Pubs

Autism spectrum disorder (ASD) presents early in life with distinct social and language differences. This study explores the association between infant brain morphometry and language abilities using an infant-sibling design. Participants included infants who had an older sibling with autism (high likelihood, HL) who were later diagnosed with autism (HL-ASD; n = 31) and two non-autistic control groups: HL-Neg (HL infants not diagnosed with autism; n = 126) and LL-Neg (typically developing infants who did not have an older sibling with autism; n = 77). Using a whole-brain approach, we measured cortical thickness and surface area at 6 and 12 …

Clinical, Immunologic, And Genetic Characteristics Of 148 Patients With Natural Killer Cell Deficiency, Manar Abdalgani, Evelyn R Hernandez, Luis A Pedroza, Ivan K Chinn, Lisa R Forbes Satter, Nicholas L Rider, Pinaki P Banerjee, M Cecilia Poli, Sanjana Mahapatra, Debra Canter, Tram Cao, Linda M Shawver, Sarada L Nandiwada, James R Lupski, Jennifer E Posey, Rajasekhar Ramakrishnan, Emily M Mace, Jordan S Orange

Faculty, Staff and Students Publications

Background: Natural killer (NK) cell deficiency (NKD) is an immunodeficiency phenotype in which abnormality of NK cells is the major clinically relevant immune defect.

Objective: We sought to define the clinical, immunologic, and genetic characteristics of patients with NKD to aid in the understanding of these individuals and this cell type and guide future research and clinical practice.

Methods: During 2006-2022, 168 individuals with a suspected diagnosis of NKD were enrolled, with comprehensive clinical, immunologic, and genetic data collected and analyzed. Research exome sequencing was performed to identify both known and novel genetic associations.

Results: NK cell abnormalities consistent with …

Goal Attainment In Pmm2-Cdg: A New Approach Measuring Meaningful Clinical Outcomes, Sanne Verberkmoes, Gina L Mazza, Andrew C Edmondson, Fernando Scaglia, Seishu Horikoshi, Bryce Kuschel, Mirian C H Janssen, Jehan Mousa, Austin Larson, Rameen Shah, Georgia Mcdonald, Kyriaki Sarafoglou, Gerard Berry, Tamas Kozicz, Christina Lam, Eva Morava

Faculty, Staff and Students Publications

Patient-centered outcomes, including patient-reported outcomes (PROs), are increasingly important in healthcare and research, though their use in rare diseases remains limited. In disorders with significant phenotypic variation, selecting appropriate outcome measures is crucial to ensuring the relevance of clinical trials for the patient population. Phosphomannomutase 2-CDG (PMM2-CDG) involves a complex genotype-phenotype relationship, making it challenging to predict clinical outcomes and select reliable measures for clinical trials. Caused by biallelic pathogenic variants in the PMM2, PMM2-CDG displays highly variable clinical severity, underscoring the need for personalized outcome measures. One such so far unexplored, individualized approach is Goal Attainment Scaling (GAS), which …

Efficacy And Safety Of Epicutaneous Immunotherapy In Peanut-Allergic Toddlers: Open-Label Extension To Epitope, Matthew Greenhawt, Deborah Albright, Sara Anvari, Nicolette Arends, Peter D Arkwright, Philippe Bégin, Katharina Blümchen, Terri Brown-Whitehorn, Heather Cassell, Edmond S Chan, Christina E Ciaccio, Antoine Deschildre, Amandine Divaret-Chauveau, Stacy Dorris, Morna Dorsey, George Du Toit, Thomas Eiwegger, Michel Erlewyn-Lajeunesse, David M Fleischer, Lara S Ford, Maria Garcia-Lloret, Jonathan O'B Hourihane, Nicola Jay, Stacie M Jones, Edwin H Kim, Kirsten Kloepfer, Stephanie Leonard, Guillaume Lezmi, Jay Lieberman, Jeanne Lomas, Melanie Makhija, Michael O'Sullivan, Christopher Parrish, Jane Peake, Kirsten P Perrett, Daniel Petroni, Jacqueline A Pongracic, Patrick Quinn, Rachel G Robison, Georgiana Sanders, Lynda Schneider, Hemant Sharma, Sayantani B Sindher, Juan Trujillo, Paul J Turner, Katherine Tuttle, Julia Upton, Pooja Varshney, Brian P Vickery, Christian Vogelberg, Brynn Wainstein, Julie Wang, Robert Wood, Katharine J Bee, Dianne E Campbell, Todd D Green, Rihab Rouissi, Henry T Bahnson, Timothée Bois, Hugh A Sampson, A Wesley Burks

Faculty, Staff and Students Publications

Background: The pivotal phase 3 EPITOPE trial, a 12-month, double-blind, placebo-controlled study of epicutaneous immunotherapy with the VIASKIN patch containing 250 μg of peanut protein (VP250), previously reported significant treatment response versus placebo in peanut-allergic toddlers aged 1 through 3 years.

Objective: To assess the interim efficacy and safety of VP250 from the first year of the EPITOPE open-label extension (OLE) study.

Methods: Eligible participants enrolled in the OLE study for up to 3 years of total treatment with annual double-blind, placebo-controlled food challenges (DBPCFCs) and safety assessments; here we report the first-year OLE (year 2) results.

Results: A total …

Long-Term Safety Of Epicutaneous Immunotherapy In Peanut-Allergic Children: An Open-Label Active Treatment (Realise Study), Jacqueline A Pongracic, Rémi Gagnon, Gordon Sussman, Dareen Siri, Roxanne C Oriel, Terri F Brown-Whitehorn, Sara Anvari, William E Berger, J Andrew Bird, Edmond S Chan, R Sharon Chinthrajah, Hey J Chong, Stanley M Fineman, David M Fleischer, Erika Gonzalez-Reyes, Edwin H Kim, Bruce J Lanser, Andrew Macginnitie, Hemalini Mehta, Daniel Petroni, Ned Rupp, Lynda C Schneider, Amy M Scurlock, Lawrence D Sher, Wayne G Shreffler, Sayantani B Sindher, Robert Wood, William H Yang, Hugh A Sampson, Timothée Bois, Todd D Green, Dianne E Campbell, Katharine J Bee, Philippe Bégin

Faculty, Staff and Students Publications

Background: Owing to limited treatment options for peanut allergy, patients remain at risk for allergic reactions due to accidental exposure. Epicutaneous immunotherapy (EPIT) is a novel treatment being investigated for peanut allergy.

Objective: This study assessed long-term safety of EPIT with VIASKIN peanut patch 250 μg (VP250) via an open-label extension of the REAL Life Use and Safety of EPIT (REALISE) trial.

Methods: REALISE was a phase 3 trial in peanut-allergic children aged 4 through 11 years that included a 6-month, randomized, double-blind, placebo-controlled treatment phase, followed by an open-label, single-arm, active treatment period for up to 36 months.

Results: …

Evaluating The Test-Negative Design For Covid-19 Vaccine Effectiveness Using Randomized Trial Data: A Secondary Cross-Protocol Analysis Of 5 Randomized Clinical Trials, Leah I B Andrews, M Elizabeth Halloran, Kathleen M Neuzil, Lars Van Der Laan, Yunda Huang, Jessica Andriesen, Mayur Patel, Leigh H Fisher, Holly Janes, Nadine Rouphael, Stephen R Walsh, Deborah A Theodore, Hong-Van Tieu, Magdalena Sobieszczyk, Hana M El Sahly, Lindsey R Baden, Ann R Falsey, Thomas B Campbell, Colleen F Kelley, Catherine Mary Healy, Lilly Immergluck, Benjamin Luft, Ian Hirsch, Guy De Bruyn, Carla Truyers, Frances Priddy, Kelsey M Sumner, Brendan Flannery, Dean Follmann, Peter B Gilbert, Covid-19 Prevention Network (Covpn)

Faculty, Staff and Students Publications

Importance: The test-negative design (TND) has been widely used to assess postmarketing COVID-19 vaccine effectiveness but requires further evaluation for this application.

Objective: To determine whether the TND reliably evaluates vaccine effectiveness against symptomatic COVID-19 using placebo-controlled vaccine efficacy randomized clinical trials (RCTs).

Design, setting, and participants: This secondary cross-protocol analysis constructed TND study datasets from study sites in 16 countries across 5 continents using the blinded phase cohorts of 5 harmonized phase 3 COVID-19 Prevention Network RCTs: COVE (Coronavirus Vaccine Efficacy and Safety), AZD1222, ENSEMBLE, PREVENT-19 (Prefusion Protein Subunit Vaccine Efficacy Novavax Trial COVID-19), and VAT00008. Participants included adults …

Testing For Bleeding Disorders In Child Abuse: Aap Recommendation Adherence And Testing Results, Lyndsey Hultman, Angela Doswell, Henry T Puls, Shannon L Carpenter, Angela Bachim, Caitlin R Mcnamara, Farah W Brink, Lori D Frasier, Nancy S Harper, Natalie Laub, Kristine A Campbell, Daniel M Lindberg, Joanne N Wood, James Anderst

Faculty, Staff and Students Publications

Objectives: Using a multicenter child abuse pediatrics research network (CAPNET), the study objectives were to characterize the adherence to American Academy of Pediatrics (AAP) recommendations for bleeding disorder testing and the frequency of bleeding disorder identification.

Methods: We performed a descriptive study of bleeding disorder evaluations among children younger than 10 years of age who presented with bruising and/or intracranial hemorrhage (ICH) concerning for abuse from February 2021-May 2022 utilizing CAPNET. Cases were classified as bruising without ICH or ICH with or without bruising. Based on AAP guidance, testing was not recommended in cases with concomitant suspicious injuries, inflicted injury …