Digital Commons Network^™

Machine Learning-Based Prediction Model For Icu Mortality After Continuous Renal Replacement Therapy Initiation In Children, Sameer Thadani, Tzu-Chun Wu, Danny T Y Wu, Aadil Kakajiwala, Danielle E Soranno, Gerard Cortina, Rachana Srivastava, Katja M Gist, Shina Menon, Worldwide Exploration Of Renal Replacement Outcomes Collaborative In Kidney Diseases (We-Rock) Collaborators

Faculty, Staff and Students Publications

BACKGROUND: Continuous renal replacement therapy (CRRT) is the favored renal replacement therapy in critically ill patients. Predicting clinical outcomes for CRRT patients is difficult due to population heterogeneity, varying clinical practices, and limited sample sizes.

OBJECTIVE: We aimed to predict survival to ICUs and hospital discharge in children and young adults receiving CRRT using machine learning (ML) techniques.

DERIVATION COHORT: Patients less than 25 years of age receiving CRRT for acute kidney injury and/or volume overload from 2015 to 2021 (80%).

VALIDATION COHORT: Internal validation occurred in a testing group of patients from the dataset (20%).

PREDICTION MODEL: Retrospective international …

Lenvatinib Plus Ifosfamide And Etoposide In Children And Young Adults With Relapsed Osteosarcoma: A Phase 2 Randomized Clinical Trial, Nathalie Gaspar, Giun-Yi Hung, Sandra J Strauss, Quentin Campbell-Hewson, Filemon S Dela Cruz, Julia L Glade Bender, Kyung-Nam Koh, Sarah B Whittle, Godfrey Chi-Fung Chan, Nicolas U Gerber, Sauli Palmu, Daniel A Morgenstern, Alessandra Longhi, Fredrik Baecklund, Jun Ah Lee, Franco Locatelli, Catalina Márquez Vega, Katherine A Janeway, Geoffrey Mccowage, Martin G Mccabe, Behzad Bidadi, Jie Huang, Jodi Mckenzie, Chinyere E Okpara, Francisco Bautista, Olie Study Investigators

Faculty, Staff and Students Publications

IMPORTANCE: The combination of ifosfamide and etoposide (IE) is commonly used to treat relapsed or refractory osteosarcoma; however, second-line treatment recommendations vary across guidelines.

OBJECTIVE: To evaluate whether the addition of lenvatinib to IE (LEN-IE) improves outcomes in children and young adults with relapsed or refractory osteosarcoma.

DESIGN, SETTING, AND PARTICIPANTS: The OLIE phase II, open-label, randomized clinical trial was conducted globally across Europe, Asia and the Pacific, and North America. From March 22, 2020, through November 11, 2021, the trial enrolled patients aged 2 to 25 years with high-grade osteosarcoma, measurable or evaluable disease per Response Evaluation Criteria in …

Veterans' Experiences Of And Preferences For Patient-Centered, Measurement-Based Ptsd Care, Marcela C Weber, Ashlyn M Jendro, Ellen P Fischer, Karen L Drummond, Trenton M Haltom, Natalie E Hundt, Michael A Cucciare, Jeffrey M Pyne

Faculty, Staff and Students Publications

Background: Up to 50% of veterans drop out of trauma-focused evidence-based psychotherapies (TF-EBP) without completing treatment or recovering; evidence suggests this is in part because their posttraumatic stress disorder (PTSD) care is insufficiently patient-centered. There is also evidence that measurement-based care (MBC) for mental health should be personalized to the patient, yet this is not common practice in VA PTSD care.

Objectives: To explore veterans' experiences and preferences for aligning measurement-based PTSD care with their own treatment goals.

Method: Qualitative interviews were conducted with veterans (n=15) with PTSD who had received at least 2 sessions of a TF-EBP.

Measures: Survey …

Random C-Peptide And Islet Antibodies At Onset Predict Β Cell Function Trajectory And Insulin Dependence In Pediatric Diabetes, Mustafa Tosur, Saima Deen, Xiaofan Huang, Serife Uysal, Marcela Astudillo, Richard A Oram, Maria J Redondo, Farook Jahoor, Ashok Balasubramanyam

Children’s Nutrition Research Center Staff Publications

Objective: Identification of prognostic biomarkers in pediatric diabetes is important for precision medicine. We assessed whether C-peptide and islet autoantibodies are useful to predict the natural history of children with new-onset diabetes.

Methods: We prospectively studied 72 children with new-onset diabetes (median follow-up: 8 months) by applying the Aβ classification system ("A+": islet autoantibody positive, "β+": random serum C-peptide ≥1.3 ng/mL at diagnosis). Beta-cell function was assessed longitudinally with 2 hours postprandial/stimulated urinary C-peptide-to-creatinine ratio (UCPCR) 3-12 weeks (V1) and 6 to 12 months after diagnosis (V2). We obtained a type 1 diabetes genetic risk score for each participant, and …

Langerhans Cell Histiocytosis In Children Born After Assisted Reproductive Technology, Carrie L Williams, Kathryn J Bunch, Charles Stiller, Michael F G Murphy, Beverley J Botting, Melanie C Davies, Barbara Luke, Philip J Lupo, Alastair G Sutcliffe

Center for Medical Ethics and Health Policy Staff Publications

Research question: Are children born after assisted reproductive technology (ART) at higher risk of developing Langerhans cell histiocytosis (LCH)?

Design: Records of children born after ART recorded by the UK Human Fertilisation & Embryology Authority were linked to National Registry of Childhood Tumours records to determine the number of children developing LCH. Calculated person-years at risk were used in conjunction with the incidence of LCH in the general population to determine the expected number of cases if the cohort had the same incidence as the general population with similar age and sex, over the same calendar years. The standardized incidence …

Persistent Growth-Promoting Effects Of Vosoritide In Children With Achondroplasia Are Accompanied By Improvements In Physical And Social Aspects Of Health-Related Quality Of Life, Ravi Savarirayan, Melita Irving, William R Wilcox, Carlos A Bacino, Julie E Hoover-Fong, Paul Harmatz, Lynda E Polgreen, Klaus Mohnike, Carlos E Prada, Takuo Kubota, Paul Arundel, Antonio Leiva-Gea, Richard Rowell, Andrea Low, Ian Sabir, Alice Huntsman-Labed, Jonathan Day

Faculty, Staff and Students Publications

Purpose: Evaluate the impact of vosoritide on health-related quality of life in children with achondroplasia.

Methods: Participants received vosoritide (15 μg/kg/day) in an extension trial (NCT03424018) after having participated in a placebo-controlled trial (NCT03197766).

Results: The population comprised 119 participants (mean [SD] age 9.7 [2.6] years). Mean treatment duration was 4 (0.78) years. At year 3, the largest mean (SD) changes were observed in the Quality of Life of Short Stature Youth physical score (5.99 [19.41], caregiver reported; 6.32 [20.15], self-reported) and social score (2.85 [8.29] and 6.76 [22.64], respectively). Changes were greatest in participants with …

Diabetter Together: Clinical Trial Protocol For A Strengths-Based Peer Mentor Intervention For Young Adults With Type 1 Diabetes Transitioning To Adult Care, Samantha A Carreon, Charles G Minard, Sarah K Lyons, Wendy Levy, Stephanie Camey, Kishan Desai, Brenda Duran, Randi Streisand, Barbara J Anderson, Siripoom V Mckay, Tricia S Tang, Sridevi Devaraj, Ryan Ramphul, Marisa E Hilliard

Faculty, Staff and Students Publications

Background: Type 1 diabetes (T1D) management is challenging for young adults, who are expected to transfer from the pediatric to adult T1D healthcare system while also managing typical developmental demands (e.g., social, financial, work/school, residential). Many young adults have extended gaps in care before following up in adult care, increasing risk for poor health outcomes. There are few evidence-based programs to support young adults with T1D to promote a timelier transition during this period. This paper reports on the design of DiaBetter Together, a randomized controlled trial to evaluate a 12-month Peer Mentor-delivered intervention compared to usual care among young …

Implementation Of Delirium Screening In The Emergency Department: A Qualitative Study With Early Adopters, Anita N Chary, Annika R Bhananker, Elise Brickhouse, Beatrice Torres, Ilianna Santangelo, Kyler M Godwin, Aanand D Naik, Christopher R Carpenter, Shan W Liu, Maura Kennedy

Faculty, Staff and Students Publications

Introduction: Delirium affects 15% of older adults presenting to emergency departments (EDs) but is detected in only one-third of cases. Evidence-based guidelines for ED delirium screening exist, but are underutilized. Frontline staff perceptions about delirium and time and resource constraints are known barriers to ED delirium screening uptake. Early adopters of ED delirium screening can offer valuable lessons about successful implementation.

Methods: We conducted semi-structured interviews with clinician-administrators leading ED delirium screening initiatives from 20 EDs in the United States and Canada. Interviews focused on experiences of planning and implementing ED delirium screening. Interviews lasted 15 to 50 minutes and …

Efficacy Of Letermovir For Cytomegalovirus Prophylaxis Following Alemtuzumab T-Cell Depleted Allogeneic Hematopoietic Stem Cell Transplant, Ibrahim N Muhsen, Kristen E Shaver, Tao Wang, Mengfen Wu, Premal Lulla, Carlos A Ramos, Rammurti T Kamble, Helen E Heslop, George Carrum, Laquisa C Hill

Faculty, Staff and Students Publications

In vivo T-cell depletion (TCD) using alemtuzumab decreases the risk of Graft vs Host Disease (GvHD) in recipients of allogeneic hematopoietic stem cell transplant (allo-HSCT). However, this approach increases the risk of infections post-allo-HSCT, including Cytomegalovirus (CMV). Letermovir is approved for the use in CMV prophylaxis post-allo-HSCT. Few studies have investigated the efficacy of letermovir in patients receiving alemtuzumab. This is a single-center retrospective study describing our institutional experience using letermovir in recipients of alemtuzumab TCD allo-HSCT from unrelated donors (URD). The primary outcome was the cumulative incidence of significant CMV infection (defined as viremia leading to preemptive antiviral therapy …

Parental Report Of Indoor Air Pollution Is Associated With Respiratory Morbidities In Bronchopulmonary Dysplasia, Jessica L Rice, Joseph M Collaco, Michael C Tracy, Catherine A Sheils, Lawrence M Rhein, Antonia P Popova, Paul E Moore, Audrey N Miller, Winston M Manimtim, Khanh Lai, Jacob A Kaslow, Lystra P Hayden, Julie L Fierro, Manvi Bansal, Eric D Austin, Brianna Aoyama, Stamatia Alexiou, Gangaram Akangire, Amit Agarwal, Natalie Villafranco, Roopa Siddaiah, Joanne M Lagatta, Mehtap Haktanir Abul, A Ioana Cristea, Christopher D Baker, Steven H Abman, Sharon A Mcgrath-Morrow

Faculty, Staff and Students Publications

Objective: To determine the association between indoor air pollution and respiratory morbidities in children with bronchopulmonary dysplasia (BPD) recruited from the multicenter BPD Collaborative.

Study design: A cross-sectional study was performed among participants < 3 years old in the BPD Collaborative Outpatient Registry. Indoor air pollution was defined as any reported exposure to tobacco or marijuana smoke, electronic cigarette emissions, gas stoves, and/or wood stoves. Clinical data included acute care use and chronic respiratory symptoms in the past 4 weeks.

Results: A total of 1011 participants born at a mean gestational age of 26.4 ± 2.2 weeks were included. Most (66.6%) had severe BPD. More than 40% of participants were exposed to ≥1 source of indoor air pollution. The odds of reporting an emergency department visit (OR, 1.7; 95% CI, 1.18-2.45), antibiotic use (OR, 1.9; 95% CI, 1.12-3.21), or a systemic steroid course (OR, 2.18; 95% CI, …

Understanding Health-Related Quality Of Life After Hypospadias Repair: A Qualitative Study With Pre-Adolescent Males And Parents, Vinaya Bhatia, Shannon Cannon, Anjali N Patel, Heidi W Brown, Walid A Farhat, Marisa E Hilliard

Faculty, Staff and Students Publications

Introduction: Hypospadias is a common disease that affects approximately 1 in every 200 live male births in the United States, and long-term studies of individuals who have undergone repair demonstrate complication rates of 15%-70%. The Hypospadias-Specific Health-related Quality of Life (HRQOL) Conceptual Framework for youth and adults suggests that additional morbidity may be incurred from poor psychological, social, and sexual health. The current study sought to clarify hypospadias-specific HRQOL and care priorities in a pre-pubertal population.

Material and methods: This IRB-approved, semi-structured interview study used rigorous qualitative research methods. Eligible patients were English-speaking 8-12-year-old males with hypospadias and their parents. …

Pediatric High Blood Pressure Recognition Associated With Electronic Decision Support: A Cohort Analysis, Justin P Zachariah, Tavleen Singh, Shannon Collinson, Justin Rahman, Alisa A Acosta, Jessica F Campbell, Mary Hoang, Katharine E Sigler, Elizabeth A Onugha, Shweta S Shah, S Kristen Sexson-Tejtel, Mark Farrior, Scott Watson

Faculty, Staff and Students Publications

Background: Pediatric high blood pressure (BP) predicts future cardiovascular disease events. High BP is improperly measured, underrecognized, and undermanaged especially in disadvantaged populations. In a large, diverse, academic pediatric practice, we detail the associations of a comprehensive initiative with high BP provider recognition.

Methods: A comprehensive BP initiative was promulgated including (1) retraining providers and staff on BP management; (2) deploying equipment at 55+ sites; and (3) electronic decision support tool alerting staff and clinicians and suggesting management. During the 14-month preintervention and 14-month postintervention periods, data on BP and patient characteristics were collected. The outcome was incident BP recognition …

Efficacy And Feasibility Of Intradialytic Plantar Electrical Stimulation In Patients With Diabetes: A Randomized Double-Blind Controlled Trial, Myeounggon Lee, Abdullah Hamad, Mehrnaz Azarian, Jaewon Beom, Abderrahman Ouattas, Mohammad Dehghan Rouzi, Naima Rodriguez, Nhi Quach, Rania Ibrahim, Mincy Mathew, Talal Talal, Fadwa Al-Ali, Bijan Najafi

Center on Aging Staff Publications

Objective: This study investigates the efficacy and feasibility of electrical stimulation (E-Stim) on sensory fibers of the plantar region during hemodialysis sessions, aiming to improve mobility in patients with diabetes by providing a connection between E-Stim and enhanced mobility with minimal patient effort required.

Research design and methods: Participants aged ≥18 years with diabetes undergoing hemodialysis and able to walk at least 10 m with or without aid were recruited and divided into an intervention group receiving 1-h intradialytic E-Stim three times a week and a control group using an identical nonfunctional device for 12 weeks. Gait, physical activity, patient-reported …

Individual Dynamic Prediction For Cure And Survival Based On Longitudinal Biomarkers, Can Xie, Xuelin Huang, Ruosha Li, Alexander Tsodikov, Kapil Bhalla

Faculty, Staff and Student Publications

To optimize personalized treatment strategies and extend patients' survival times, it is critical to accurately predict patients' prognoses at all stages, from disease diagnosis to follow-up visits. The longitudinal biomarker measurements during visits are essential for this prediction purpose. Patients' ultimate concerns are cure and survival. However, in many situations, there is no clear biomarker indicator for cure. We propose a comprehensive joint model of longitudinal and survival data and a landmark cure model, incorporating proportions of potentially cured patients. The survival distributions in the joint and landmark models are specified through flexible hazard functions with the proportional hazards as …

Association Of Common And Rare Variants With Alzheimer’S Disease In More Than 13,000 Diverse Individuals With Whole-Genome Sequencing From The Alzheimer’S Disease Sequencing Project, Wan-Ping Lee, Seung Hoan Choi, Margaret G Shea, Po-Liang Cheng, Beth A Dombroski, Achilleas N Pitsillides, Nancy L Heard-Costa, Hui Wang, Katia Bulekova, Amanda B Kuzma, Yuk Yee Leung, John J Farrell, Honghuang Lin, Brian W Kunkle, Adam Naj, Elizabeth E Blue, Frederick Nusetor, Dongyu Wang, Eric Boerwinkle, William S Bush, Xiaoling Zhang, Philip L De Jager, Josée Dupuis, Lindsay A Farrer, Myriam Fornage, Eden Martin, Margaret Pericak-Vance, Sudha Seshadri, Ellen M Wijsman, Li-San Wang, Alzheimer's Disease Sequencing Project, Gerard D Schellenberg, Anita L Destefano, Jonathan L Haines, Gina M Peloso

Center for Medical Ethics and Health Policy Staff Publications

Introduction: Alzheimer's disease (AD) is a common disorder of the elderly that is both highly heritable and genetically heterogeneous.

Methods: We investigated the association of AD with both common variants and aggregates of rare coding and non-coding variants in 13,371 individuals of diverse ancestry with whole genome sequencing (WGS) data.

Results: Pooled-population analyses of all individuals identified genetic variants at apolipoprotein E (APOE) and BIN1 associated with AD (p < 5 × 10-8). Subgroup-specific analyses identified a haplotype on chromosome 14 including PSEN1 associated with AD in Hispanics, further supported by aggregate testing of rare coding and non-coding variants in the region. Common variants in LINC00320 were observed associated with AD in Black individuals (p = 1.9 × 10-9). Finally, we observed rare non-coding variants in the promoter of TOMM40 distinct of APOE in pooled-population analyses (p = 7.2 × 10-8).

Discussion: We observed that complementary pooled-population and subgroup-specific analyses offered unique insights into the genetic architecture of AD.

Highlights: We determine the association of genetic variants with Alzheimer's disease (AD) using …

Analysis Of 1386 Epileptogenic Brain Lesions Reveals Association With Dyrk1a And Egfr, Christian M Boßelmann, Costin Leu, Tobias Brünger, Lucas Hoffmann, Sara Baldassari, Mathilde Chipaux, Roland Coras, Katja Kobow, Hajo Hamer, Daniel Delev, Karl Rössler, Christian G Bien, Thilo Kalbhenn, Tom Pieper, Till Hartlieb, Kerstin Becker, Lisa Ferguson, Robyn M Busch, Stéphanie Baulac, Peter Nürnberg, Imad Najm, Ingmar Blümcke, Dennis Lal

Faculty, Staff and Student Publications

Lesional focal epilepsy (LFE) is a common and severe seizure disorder caused by epileptogenic lesions, including malformations of cortical development (MCD) and low-grade epilepsy-associated tumors (LEAT). Understanding the genetic etiology of these lesions can inform medical and surgical treatment. We conducted a somatic variant enrichment mega-analysis in brain tissue from 1386 individuals who underwent epilepsy surgery, including 599 previously unpublished individuals with ultra-deep ( > 1600x) targeted panel sequencing. Here we confirm four known associations (BRAF, SLC35A2, MTOR, PTPN11), support eight associations without prior statistical support (FGFR1, PIK3CA, AKT3, NF1, PTEN, RHEB, KRAS, NRAS), and identify novel associations for two genes, …

Validation Studies Of The Flash-Tv System To Passively Measure Children’S Tv Viewing, Anil Kumar Vadathya, Tatyana Garza, Uzair Alam, Alex Ho, Salma M A Musaad, Alicia Beltran, Jennette P Moreno, Tom Baranowski, Nimah Haidar, Sheryl O Hughes, Jason A Mendoza, Ashok Veeraraghavan, Joseph Young, Akane Sano, Teresia M O'Connor

Children’s Nutrition Research Center Staff Publications

TV viewing is associated with health risks, but existing measures of TV viewing are imprecise due to relying on self-report. We developed the Family Level Assessment of Screen use in the Home (FLASH)-TV, a machine learning pipeline with state-of-the-art computer vision methods to measure children's TV viewing. In three studies, lab pilot (n = 10), lab validation (n = 30), and home validation (n = 20), we tested the validity of FLASH-TV 3.0 in task-based protocols which included video observations of children for 60 min. To establish a gold-standard to compare FLASH-TV output, the videos were labeled by trained staff …

Maternal Low-Protein Diet Leads To Mitochondrial Dysfunction And Impaired Energy Metabolism In The Skeletal Muscle Of Male Rats, Vipin A Vidyadharan, Ancizar Betancourt, Craig Smith, Chellakkan S Blesson, Chandra Yallampalli

Faculty, Staff and Students Publications

A prenatal low-protein (LP) diet disrupts glucose homeostasis in adult offspring. Skeletal muscles are one of the main sites of glucose clearance, and mitochondria residing in the muscle fibers are central to glucose homeostasis. Our previous studies indicated that impaired mitochondrial health is central to dysregulated glucose metabolism in the gastrocnemius muscle of the LP-programmed female rats. In addition, dysfunctional mitochondria are often an indicator of underlying irregularities in energy metabolism and metabolic inflexibility. Therefore, this study examined the mitochondrial function and metabolic flexibility in the skeletal muscles of prenatal LP-programmed adult male rats. Pregnant Wistar rats were randomly allotted …

Maternal Low-Protein Diet Leads To Mitochondrial Dysfunction And Impaired Energy Metabolism In The Skeletal Muscle Of Male Rats, Vipin A Vidyadharan, Ancizar Betancourt, Craig Smith, Chellakkan S Blesson, Chandra Yallampalli

Faculty, Staff and Students Publications

A prenatal low-protein (LP) diet disrupts glucose homeostasis in adult offspring. Skeletal muscles are one of the main sites of glucose clearance, and mitochondria residing in the muscle fibers are central to glucose homeostasis. Our previous studies indicated that impaired mitochondrial health is central to dysregulated glucose metabolism in the gastrocnemius muscle of the LP-programmed female rats. In addition, dysfunctional mitochondria are often an indicator of underlying irregularities in energy metabolism and metabolic inflexibility. Therefore, this study examined the mitochondrial function and metabolic flexibility in the skeletal muscles of prenatal LP-programmed adult male rats. Pregnant Wistar rats were randomly allotted …

A Comprehensive Analysis Of In-Hospital Adverse Events After Scopolamine Administration: Insights From A Retrospective Cohort Study Using A Large Nationwide Inpatient Database, George Sun, Marc Torjman, Kevin Min

Department of Anesthesiology Faculty Papers

BACKGROUND: Scopolamine is a widely used antiemetic in anesthetic practice, particularly for postoperative and post-discharge nausea and vomiting. Despite its frequent usage and recognized efficacy, concerns have emerged regarding the potential for increased side effects, particularly in elderly patients. Further research is needed to assess safety and determine age thresholds for adverse events. This study hypothesizes associations between perioperative scopolamine use, worse clinical outcomes, increased pneumonia, delirium, urinary retention, and readmissions.

METHODS: A large, retrospective cohort study was performed using the TriNetX Analytics Network database on patients undergoing major surgical procedures between Jan 1, 2009, and March 21, 2018, to …

Host Dna Depletion On Frozen Human Respiratory Samples Enables Successful Metagenomic Sequencing For Microbiome Studies, Minsik Kim, Raymond C Parrish, Michael J Tisza, Viral S Shah, Thi Tran, Matthew Ross, Juwan Cormier, Aribah Baig, Ching-Ying Huang, Laura Brenner, Isabel Neuringer, Katrine Whiteson, J Kirk Harris, Amy D Willis, Peggy S Lai

Faculty, Staff and Students Publications

Most respiratory microbiome studies use amplicon sequencing due to high host DNA. Metagenomics sequencing offers finer taxonomic resolution, phage assessment, and functional characterization. We evaluated five host DNA depletion methods on frozen nasal swabs from healthy adults, sputum from people with cystic fibrosis (pwCF), and bronchoalveolar lavage (BAL) from critically ill patients. Median sequencing depth was 76.4 million reads per sample. Untreated nasal, sputum, and BAL had 94.1%, 99.2%, and 99.7% host reads, respectively. Host depletion effects varied by sample type, generally increasing microbial reads, species and functional richness; this was mediated by higher effective sequencing depth. Rarefaction curves showed …

Mechanisms Of Memory-Supporting Neuronal Dynamics In Hippocampal Area Ca3, Yiding Li, John J Briguglio, Sandro Romani, Jeffrey C Magee

Faculty, Staff and Students Publications

Hippocampal CA3 is central to memory formation and retrieval. Although various network mechanisms have been proposed, direct evidence is lacking. Using intracellular Vm recordings and optogenetic manipulations in behaving mice, we found that CA3 place-field activity is produced by a symmetric form of behavioral timescale synaptic plasticity (BTSP) at recurrent synapses among CA3 pyramidal neurons but not at synapses from the dentate gyrus (DG). Additional manipulations revealed that excitatory input from the entorhinal cortex (EC) but not the DG was required to update place cell activity based on the animal’s movement. These data were captured by a computational model that …

Cognition In Patients With Mild Autonomous Cortisol Secretion At Baseline And Post-Adrenalectomy, Jasmine Saini, Rohit Nathani, Sumitabh Singh, Andreas Ebbehoj, Karthik Thangamuthu, Malavika Suresh, Catherine D Zhang, Sophia Nevin, Vanessa Fell, Elizabeth J Atkinson, Sara J Achenbach, Nikki H Stricker, Irina Bancos

Faculty, Staff and Students Publications

Objectives: The impact of mild autonomous cortisol secretion (MACS) on cognition is incompletely characterized. We aimed to assess cognition in patients with MACS, identify factors associated with lower cognition, and determine the impact of adrenalectomy on cognition.

Methods: We conducted a cross-sectional study (4/2019 to 10/2022) and a longitudinal cohort study (10/2021 to 9/2023) of adults with MACS and referent subjects. Cognition was assessed with National Institute of Health Toolbox Cognition Battery and reported as standardized T scores (adjusted for age, sex, race/ethnicity, and education) for fluid, crystallized, and total composite cognition. Participants were assessed with urine steroid profiling (liquid …

Modulation Of Energetic And Lipid Pathways By Curcumin As A Potential Chemopreventive Strategy In Human Prostate Cancer Cells, Michele Pellegrino, Maria Antonietta Occhiuzzi, Fedora Grande, Ilaria Stefania Pagani, Stefano Aquaro, Paola Tucci

Staff and Researcher Publications

In Western industrialized countries, prostate cancer (PCa) is the second most common malignant disease and prevalent cause of death for men. Epidemiological studies have shown that curcumin (CUR) either prevents PCa initiation or delays its progression to a more aggressive and treatment-refractory form, thus reducing related mortality. Our previous studies have proven the anticancer, antioxidant, and anti-inflammatory properties of CUR on PCa cells. However, there are few reports of the effect of CUR on energy and lipid pathways in PCa. Herein, we show that CUR can modulate the two metabolic energy pathways, increasing glycolytic reserve and reducing oxidative phosphorylation. Moreover, …

Clinical Effects Of Dexamethasone Among Patients With Sickle Cell Disease Hospitalized With Covid-19: Outcomes From A Single Academic Health System, William M. Garneau, Matthew J. Lankiewicz, Catherine R. Lesko, Ashley P. Lauriello, Kelly A. Gebo, Sophie M. Lanzkron

Department of Medicine Faculty Papers

BACKGROUND: Dexamethasone is a steroid used in the treatment of hospitalized patients with severe COVID-19. However, the effect of dexamethasone in patients with SCD remains unclear given that steroids may precipitate vaso-occlusive crisis (VOC) in patients with SCD.

METHODS AND FINDINGS: We performed a retrospective analysis of patients with SCD who were hospitalized at Johns Hopkins Health System between June 1, 2020 and June 26, 2022. We reviewed individual charts to assess severity of illness and eligibility for dexamethasone treatment. The exposure of interest was treatment with dexamethasone. Outcomes of interest included incident VTE, length of hospital stay, ICU admission, …

Real-World Impact Of Emicizumab And Immunosuppression On Acquired Hemophilia A: A Multicenter Us Cohort, Jacqueline N Poston, Cassandra Bryan, Annette Von Drygalski, Kadhim Al Banaa, Jenny Y Zhou, Aric Parnes, Evan C Chen, Osman Khan, Patrick Ellsworth, Lorraine Cafuir, Christopher Walsh, Miguel A Escobar, James F Wu, Lynn M Malec, Craig M Kessler, Maissaa Janbain, Rebecca Kruse-Jarres

Faculty, Staff and Student Publications

Acquired hemophilia A (AHA) is an autoimmune bleeding disorder that is caused by factor VIII (FVIII) autoantibodies with high morbidity and mortality due to bleeding and complications from immunosuppression (IST). To address the real-world implications of the FVIII mimetic antibody, emicizumab, and the role of IST, we retrospectively collected de-identified data on 62 patients with AHA who were treated off-label with emicizumab for a median of 10 weeks at 12 US-based hemophilia treatment centers. Most patients (95.2%) had acute bleeding at diagnosis, and 62.9% had partial or no control of bleeds despite the use of hemostatic agents at the time …

Surgical Treatment Of Brachiocephalic Artery Aneurysm With Impending Rupture And Tracheal Communication, Soon Jin Kim, Kyung Hwa Kim, Jong Hun Kim, Tae Yun Kim

The Texas Heart Institute Journal

Brachiocephalic artery aneurysm is uncommon but may require surgery because it tends to enlarge, rupture, or cause symptoms related to thrombosis or compression. This case report describes a brachiocephalic artery aneurysm in a 72-year-old man who presented at the hospital with dyspnea and hemoptysis resulting from impending rupture and tracheal communication.

Intervention Mapping For Refining A Sport-Based Public Health Intervention In Rural Schools, Mckenna G Major, Janette M Watkins, Janelle M Goss, Derek W Craig, Zack Waggoner, Vanessa M Martinez Kercher, Kyle A Kercher

Faculty, Staff and Student Publications

Sport-based youth development programs, delivered through campus-community partnerships, can create impactful experiences for college students, meet university objectives, and improve the health of children in under-resourced rural communities. This study aimed to pilot test intervention mapping (IM), a systematic approach to intervention development and implementation, to refine the Hoosier Sport intervention, which is a local public health initiative that utilizes the Obesity-Related Behavioral Intervention Trials (ORBITs) model to improve physical activity in middle school children. The IM process, which included a diverse IM planning and advisory group of university representatives and local schools, was guided by self-determination theory (SDT) and …

Association Of Type 2 Diabetes Mellitus With Sensorineural Hearing Loss - A Population-Based Analysis, Marwin Li, Natalie Perlov, Jena Patel, Dev Amin, Ayan Kumar, Zachary D. Urdang, Thomas O. Willcox, Rebecca C. Chiffer

Department of Otolaryngology - Head and Neck Surgery Faculty Papers

OBJECTIVE: To test the hypothesis that patients with poorly controlled type 2 diabetes mellitus are more likely to develop sensorineural hearing loss (SNHL) than non-diabetic patients.

STUDY DESIGN: Retrospective cohort study.

SETTING: TriNetX US Collaborative Network (2003-2022).

METHODS: Electronic medical record data from the TriNetX US Collaborative Network was queried for subjects without prior hearing loss, defined using medical billing codes (ICD-10, CPT, etc.), who were diagnosed with type 2 diabetes mellitus after January 2003. Patients were stratified by most recent HbA1c (8.0-13.9% or ≥14.0%) and by age at diagnosis (21-30, 31-40, 41-50, 51-60, 61-70, ≥71 years). Primary outcome was …

Mitochondrial Heteroplasmy Improves Risk Prediction For Myeloid Neoplasms, Yun Soo Hong, Sergiu Pasca, Wen Shi, Daniela Puiu, Nicole J Lake, Monkol Lek, Meng Ru, Megan L Grove, Anna Prizment, Corinne E Joshu, Elizabeth A Platz, Eliseo Guallar, Dan E Arking, Lukasz P Gondek

Faculty, Staff and Student Publications

Clonal hematopoiesis of indeterminate potential is the primary pathogenic risk factor for myeloid neoplasms, while heteroplasmy (mutations in a subset of cellular mitochondrial DNA) is another marker of clonal expansion associated with hematological malignancies. We explore how these two markers relate and influence myeloid neoplasms incidence, and their role in risk stratification. We find that heteroplasmy is more common in individuals with clonal hematopoiesis of indeterminate potential, particularly those with higher variant allele fractions, multiple mutations, or spliceosome machinery mutations. Individuals with both markers have a higher risk of myeloid neoplasms than those with either alone. Furthermore, heteroplasmic variants with …