Digital Commons Network^™

Does Stem Design Affect Primary Stability Of Splined Tapered Fluted Stems? A Biomechanical Cadaver Study, Shuyang Han, Daniel C Mascarenhas, Camryn A Pletka, Jonathan E Gold, Sabir K Ismaily, Matthew Cao, Matthew W Brewer, Robert Frangie, Philip C Noble, David Rodriguez-Quintana

Faculty, Staff and Student Publications

Background: Tapered fluted stems are an excellent solution for revision hip arthroplasty following periprosthetic fractures. However, existing implant designs differ in terms of the number of splines, taper angle, and cross-sectional design, and there is a lack of knowledge on the biomechanical effect of these design variations. Therefore, the objective of this study was to compare the primary stability of two representative stem designs and the extent and distribution of stem-bone contact in a periprosthetic fracture model. It was hypothesized that a greater number of splines would lead to greater stability.

Methods: There were six pairs of cadaver femora included …

Trop2 Expression In Salivary Gland Adenoidcystic Carcinoma (Acc) According To Histologic Subtype: Therapeutic Implications, Juliana Mota Siqueira, Yoshitsugu Mitani, Mario L Marques-Piubelli, Camilla Oliveira Hoff, Flavia Bonini, Luana Guimaraes De Sousa, Mutsumi Mitani, Giovanna Lopes Carvalho, Fabio Daumas Nunes, Leandro Luongo Matos, Shiaw-Yih Lin, Michael T Spiotto, Ehab Y Hanna, Daniel J Mcgrail, Adel K El-Naggar, Renata Ferrarotto

Faculty, Staff and Student Publications

Background: Adenoid cystic carcinoma (ACC) is a common salivary gland carcinoma with high recurrence and distant metastasis rates. Currently, there is no standard systemic treatment available. TROP2 is a transmembrane glycoprotein involved in the oncogenesis of several tumors that can be therapeutically targeted by a TROP2-antibody-drug conjugate (ADC). We aimed to characterize TROP2 expression in ACC and assess TROP2 as a potential therapeutic target.

Methods: TROP2 immunohistochemistry was performed in a tissue microarray including 165 ACC of salivary gland. The tumors were grouped according to the histological pattern as non-solid, solid + non-solid, or solid. TROP2 protein expression in ACC …

Wuse-Oil Compound 03 Mitigates Radiation-Induced Oral Mucositis By Modulating Oral Microbiota To Mediate Tlr4/Nf-Κb Pathway And Inhibit M1 Macrophage Polarization, Liqun Jia, Rong Huang, Chen Chen, Feng Teng, Tian Gu, Huafeng Liu, Li Ma, Ye Feng, Jingyi Long, Zihan Jin, Dong Li, Dongmei Chen, Yanni Lou

Faculty, Staff and Student Publications

Background: Radiation-induced oral mucositis (RIOM) is a prevalent condition among patients with head and neck cancer undergoing radiotherapy. It is characterized by a high incidence and severe symptoms that significantly compromise patients' quality of life. Currently, there exists no consensus regarding an effective treatment modality. Wuse-oil Compound 03 (WC03), a Traditional Chinese Herbal Medicine, demonstrates potential in managing RIOM.

Purpose: This study aims to investigate the efficacy of WC03 in treating RIOM through the modulation of oral microbiota and associated biological pathways.

Study design: Mechanism study experimental design.

Methods: A rat model of RIOM was established via radiation exposure. WC03 …

Which Score For What? Operationalizing Standardized Cognitive Test Performance For The Assessment Of Change, Cristan Farmer, Audrey Thurm, Tanvi Das, E Martina Bebin, Jonathan A Bernstein, Elizabeth Berry-Kravis, Joseph D Buxbaum, Charis Eng, Thomas Frazier, Antonio Y Hardan, Alexander Kolevzon, Darcy A Krueger, Julian A Martinez-Agosto, Hope Northrup, Craig M Powell, Latha Valluripalli Soorya, Joyce Y Wu, Mustafa Sahin, Developmental Synaptopathies Consortium

Faculty, Staff and Student Publications

Developmental domains, such as cognitive, language, and motor, are key concepts of interest in longitudinal studies of intellectual and developmental disabilities (IDD). Normative scores (e.g., IQ) are often used to operationalize performance on standardized tests of these concepts, but it is the interval-distributed person-ability scores that are intended for the assessment of within-individual change. Here we illustrate the use and interpretation of several Stanford Binet, 5th Edition score types (IQ, extended IQ, Z-normalized raw score, developmental quotient, raw sum score, age equivalent, and ability score) using data from two longitudinal studies of rare genetic conditions associated with IDD. We found …

Auricular Point Acupressure For Older Adults With Chronic Low Back Pain: A Randomized Controlled Trial, Jennifer Kawi, Chao Hsing Yeh, Nada Lukkahatai, Hulin Wu, Natalia E Morone, Ronald Glick, Elizabeth A Schlenk, Claudia Campbell, Johannes Thrul, Xinran Huang, Hongyu Wang, Hejingzi Monica Jia, Paul Christo, Constance Johnson

Faculty, Staff and Student Publications

Objective: Efficacious modalities are limited in chronic low back pain (cLBP). We determined the efficacy of auricular point acupressure (APA) in older adults with cLBP.

Design: 3-arm randomized controlled trial.

Setting: Baltimore, Maryland.

Participants: Participants, ≥60 years with cLBP, were randomized (1:1:1) to APA with ear points targeted to cLBP (T-APA, n = 92), points nontargeted to cLBP (NT-APA, n = 91), or waitlist education control (n = 89), and followed up to 6 months (6M). Participants in the APA groups received 4 weekly APA sessions; the education control group received 4 weekly educational sessions.

Intervention: APA.

Main outcomes and …

The Late Positive Potential Predicts Contingency Management Outcomes For Cocaine Use Disorder, Heather E Webber, Douglas J Calvillo, Francesco Versace, Constanza De Dios, Robert Suchting, Charles E Green, Scott D Lane, Joy M Schmitz

Faculty, Staff and Student Publications

Contingency management (CM) relies on motivation and reward processing and is among the most effective treatments available for cocaine use disorder (CUD), yet success rates do not meet desired clinical efficacy. To improve treatment-individual fit, we investigated the late positive potential (LPP), a measure of incentive salience to cues, as a predictor of treatment response. Treatment-seeking adults with CUD (N = 58) completed an EEG task where they viewed pleasant, unpleasant, cocaine, and neutral images. Participants received CM and counseling for four weeks. Urine was collected thrice weekly. We defined incentive salience to cues by A) cluster analyses on LPP …

Launching! To Adulthood, A Culturally Adapted Treatment Program For Military-Dependent Autistic Young Adults And Their Military Parents: A Pilot Study, Antonio F Pagán, Jordan Kenemore, Maj Mark Ahlenius, Linda Hernandez, Stephen Armstrong, Katherine A Loveland, Ron Acierno

Faculty, Staff and Student Publications

Introduction: Military-dependent young adults (17-25 years old) with autism spectrum disorder (ASD) face significant barriers to accessing services during their transition to adulthood. Frequent relocations, disrupted care, and limited ASD-tailored interventions exacerbate the challenges for these families, with many young adults experiencing a "service cliff" as they age out of pediatric care and school-based services. Addressing these gaps is critical, particularly given the rising mental health challenges and executive dysfunction in this population. This study evaluates the preliminary efficacy of an adapted telehealth intervention, the Military-Launching! program, designed to support young adults with ASD and their military families.

Materials and …

Testing Measurement Invariance Of Self-Report And Interview Measures Of Borderline Personality Disorder Across Ethnic/Racial Groups Of Inpatient Adolescents, Salome Vanwoerden, Eric D Sumlin, Veronica Mclaren, Carla Sharp

Faculty, Staff and Student Publications

Borderline personality disorder (BPD) is a severe mental disorder that onsets during adolescence. Research examining sociocontextual differences in BPD presentation is limited and provides mixed results, highlighting the importance of further investigation and the evaluation of potential measure effects. This study assessed measurement invariance of two widely used adolescent measures (self-report—the Borderline Personality Features Scale for Children and semistructured interview—Childhood Interview of Diagnostic and Statistical Manual Borderline Personality Disorder) of BPD. Comparisons across inpatient psychiatric settings (n = 521 at a private inpatient; n = 378 at a public inpatient) and across self-identified Hispanic/Latinx (n = 193), Black …

Beyond Frequency Of Use: Exploring Additional Metrics For Quantifying Cocaine Use And Their Relation To Life Functioning And Treatment Outcome, Samantha Ellis, Rachel Sun, Angela Heads, Jin Ho Yoon, Heather Webber, Joy Schmitz, Margaret Wardle

Faculty, Staff and Student Publications

Background: Frequency of use - the number of days of use - is the most common metric for quantifying cocaine use and the most common target of treatment. However, frequency may not capture all important aspects of cocaine use. This study examined how other aspects of cocaine use (typical amount spent, variability etc.) relate to life functioning and cocaine use disorder (CUD) treatment outcomes.

Method: This is a secondary analysis of 3 clinical trials for CUD, N = 207 for the life functioning analysis and N = 173 for the outcomes analysis. Eight metrics of use were calculated from baseline …

Variants In Cald1, Esrp1, And Rbfox1 Are Associated With Orofacial Cleft Risk, Jenna C Carlson, Xinyi Zhang, Zeynep Erdogan-Yildirim, Terri H Beaty, Azeez Butali, Carmen J Buxó, Lord J J Gowans, Jacqueline T Hecht, Ross E Long, Lina Moreno, Jeffrey C Murray, Ieda M Orioli, Carmencita Padilla, George L Wehby, Eleanor Feingold, Elizabeth J Leslie-Clarkson, Seth M Weinberg, Mary L Marazita, John R Shaffer

Faculty, Staff and Student Publications

Nonsyndromic orofacial clefts (OFCs) are common, heritable birth defects caused by both genetic and environmental risk factors. Despite the identification of many genetic loci harboring OFC-risk variants, there are many unknown genetic determinants of OFC. Furthermore, while the process of embryonic facial development is well characterized, the molecular mechanisms that underly it are not. This represents a major hurdle in understanding how disruptions in these biological processes result in OFC. Thus, we sought to identify novel OFC-risk loci through a genome-wide multi-ancestry study of five nested OFC phenotypes (isolated cleft lip [CLO], isolated cleft palate [CPO], cleft lip and palate …

Polydrug Abuse: Choice Between Drugs As A Function Of Concurrent Nonindependent Ratio Sizes, Richard A Meisch, Thomas H Gomez, Scott D Lane

Faculty, Staff and Student Publications

Polydrug abuse is the persistent self-administration of more than one reinforcing drug. The present study provided rhesus monkeys concurrent access to two drugs: 8% alcohol and solutions of either cocaine or methadone. The liquids were available under concurrent nonindependent fixed-ratio (FR) schedules across increasing and then decreasing ratio sizes. These schedules generate high rates of changeover responses and yield a dependent variable of responses per delivery that is not rigidly tied to the ratio-schedule value. The programmed schedule size was equal for both liquids and increased in the sequence 8, 16, 32, and so on until responding decreased, whereupon the …

Mature And Migratory Dendritic Cells Promote Immune Infiltration And Response To Anti-Pd-1 Checkpoint Blockade In Metastatic Melanoma, Jiekun Yang, Cassia Wang, Doris Fu, Li-Lun Ho, Kyriakitsa Galani, Lee Chen, Jose Gonzalez, Jolene Fu, Amy Y Huang, Dennie T Frederick, Liang He, Mukta Asnani, Rahul Tacke, Emily J Robitschek, Sandeep K Yadav, Wentao Deng, Kelly P Burke, Tatyana Sharova, Ryan J Sullivan, Sarah Weiss, Kunal Rai, David Liu, Genevieve M Boland, Manolis Kellis

Faculty, Staff and Student Publications

Immune checkpoint inhibitors (ICIs) have revolutionized cancer therapy, yet most patients fail to achieve durable responses. To better understand the tumor microenvironment (TME), we analyze single-cell RNA-seq (~189 K cells) from 36 metastatic melanoma samples, defining 14 cell types, 55 subtypes, and 15 transcriptional hallmarks of malignant cells. Correlations between cell subtype proportions reveal six distinct clusters, with a mature dendritic cell subtype enriched in immunoregulatory molecules (mregDC) linked to naive T and B cells. Importantly, mregDC abundance predicts progression-free survival (PFS) with ICIs and other therapies, especially when combined with the TCF7 + /- CD8 T cell ratio. Analysis …

Generation Of Human Induced Pluripotent Stem Cell Line From A Familial Alzheimer’S Disease Patient Carrying Missense Mutations In Psen1 And Mapt Genes, Ashaq H Najar, Sofia E Sepulveda, Camila Gherardelli, Fatemeh Elahian, Amber Fontenot-Roberts, Aleksandar Bajic, David H Hunter, Claudio Soto, Paul E Schulz, Abhisek Mukherjee

Faculty, Staff and Student Publications

Alzheimer's disease (AD), pathologically characterized by misfolding and accumulation of amyloid beta (Aβ) and hyperphosphorylated tau, is the leading cause of neurodegenerative dementia, accounting for 60-80 % of cases. The familial form of AD is caused by mutations in amyloid precursor protein (APP), presenilin-1 (PSEN1), and presenilin-2 (PSEN2) genes. Here, we report the generation of an iPSC line from a 39-year-old AD patient carrying a missense mutation in PSEN1 (F177S), leading to very early onset of AD. The patient also carries a rare variant Q49E in the microtubule-associated protein tau gene (MAPT) with an as yet unknown clinical significance.

Baseline Α-Synuclein Seeding Activity And Disease Progression In Sporadic And Genetic Parkinson’S Disease In The Ppmi Cohort, Jackson G Schumacher, Xinyuan Zhang, Eric A Macklin, Jian Wang, Armin Bayati, Johannes M Dijkstra, Hirohisa Watanabe, Michael A Schwarzschild, Marianna Cortese, Xuehong Zhang, Xiqun Chen

Faculty, Staff and Student Publications

Background: α-Synuclein (α-syn) seed amplification assays (SAAs) have shown remarkable potential in diagnosing Parkinson's disease (PD). Using data from the Parkinson's Progression Markers Initiative (PPMI) cohort, we aimed to test whether baseline α-syn seeding activity and α-syn SAA kinetic parameters are associated with disease progression in sporadic PD, LRRK2-associated PD (LRRK2 PD), and GBA-associated PD (GBA PD).

Methods: We analysed 7 years of motor, non-motor, and cognitive assessments and 5 years of dopamine transporter imaging along with baseline α-syn SAA results from 564 PPMI participants (n = 332 sporadic PD, 162 LRRK2 PD, and 70 GBA PD) using linear mixed-effects …

Isatuximab Plus Bortezomib, Lenalidomide, And Dexamethasone For Transplant-Ineligible Newly Diagnosed Multiple Myeloma Patients: A Frailty Subgroup Analysis Of The Imroz Trial, Salomon Manier, Meletios-Athanasios Dimopoulos, Xavier P Leleu, Philippe Moreau, Michele Cavo, Hartmut Goldschmidt, Robert Z Orlowski, Muriel Tron, Christina Tekle, Marie-France Brégeault, Andrea T Shafer, Meral Beksac, Thierry Facon

Faculty, Staff and Student Publications

Patients with multiple myeloma (MM) meeting frailty criteria have worse outcomes than those identified as non-frail. Here, we present a post hoc subgroup analysis of IMROZ, a global, phase III, open-label study investigating isatuximab (Isa) with bortezomib, lenalidomide, and dexamethasone (VRd) followed by Isa-Rd (N=265) versus VRd followed by Rd (N=181) in newly diagnosed transplant-ineligible MM (Ti NDMM) patients using the simplified International Myeloma Working Group (sIMWG) frailty score. Although patients aged >80 years were excluded, there was no exclusion for patients meeting frailty criteria. All patients received standard VRd/Rd dosing; Isa-VRd patients received intravenous Isa (cycle 1, 10 mg/kg …

Exploring Boundaries With Food, Substances, And People In Substance Use Recovery: A Qualitative Analysis, Tiffany Champagne-Langabeer, Audrey Sarah Cohen, Kriti Shrestha, Jie Zhu, Audrey Lopez, Alisha Campbell, Christine Bakos-Block

Faculty, Staff and Student Publications

Background: In the United States, over 47 million youth and adults live with a substance use disorder (SUD). These individuals are frequently malnourished and have metabolic dysregulation as a result. Nutrition interventions incorporating a mindfulness-based approach help recovery efforts that are physical and mental.

Objective: The objective of this study was to explore and analyze the perspectives and experiences of individuals with SUD regarding emotional regulation and nutrition. The study used a mixed methods approach to generate insights for improving recovery support and developing future interventions.

Design: In 2024, an exploratory mixed methods study was conducted based on a large …

Predicting Clinical Success Of Ct-Based Functional Drained Liver Volume Assessment In Malignant Biliary Obstruction, Ethan Y Lin, Bruno C Odisio, Koustav Pal, Iwan Paolucci, Ryan P Kempen, Nicolas Cardenas, Paige Reed, Ketan Y Shah, Ahmed Awad, Rahul A Sheth, David Fuentes, Alda Tam

Faculty, Staff and Student Publications

Purpose

To compare the predictive accuracy of subjective versus objective assessment of three-dimensional functional drained liver volume (fDLV) for clinical success after percutaneous transhepatic biliary drainage (PTBD).

Materials and Methods

This retrospective study included patients with malignant biliary obstruction and hyperbilirubinemia who underwent de novo PTBD between January 2016 and February 2017. Clinical success was defined as achieving total bilirubin level less than 1.8 mg/dL (30.8 μmol/L) within 30 days after PTBD. Seven interventional radiologists independently categorized subjective fDLV into four groups: less than 30%, 30%–50%, 51%–75%, and greater than 75% of the total liver volume. Objective fDLV was calculated …

Mechanisms Underlying Treatment-Resistant Depression: Exploring Sex-Based Biological Differences, Francisco E R Da Silva, Atakan Yucel, Antonio P M Menezes, Ana C Ruiz, Marcela C Carbajal Tamez, Tatiana Barichello, Giselli Scaini, Joao Quevedo

Faculty, Staff and Student Publications

Treatment-resistant depression (TRD) represents a severe and complex subtype of major depressive disorder (MDD), affecting approximately 30% of patients who fail to respond adequately to multiple standard antidepressant therapies. While the pathophysiology of TRD remains incompletely understood, emerging evidence suggests that sex-based biological differences might influence its onset, progression, and treatment response. Women are disproportionately affected by depression and are more likely to experience residual symptoms and treatment resistance, potentially due to hormonal fluctuations, immune system differences, and variations in brain circuitry and neuroplasticity. This narrative explores the current literature on the mechanisms underlying TRD, with a particular emphasis on …

Risk Of Second Primary Lung Cancer Among Cancer Survivors Stratified By The Site Of First Primary Cancer And The Lung Cancer Screening Eligibility Status, Sara Nofal, Edwin J Ostrin, Jianjun Zhang, Jia Wu, Paul Scheet, Mara B Antonoff, John V Heymach, Iakovos Toumazis

Faculty, Staff and Student Publications

Personal history of cancer is an independent risk factor for developing lung cancer. However, it is not considered in the current US lung cancer screening (LCS) guidelines. In this study, we assessed the risk of developing lung cancer among cancer survivors across 24 different sites of first primary cancer stratified by their LCS eligibility status. Using data from the Patient History Database at the University of Texas MD Anderson Cancer Center, we calculated and compared the cumulative incidence of second primary lung cancer, the overall and the LCS eligibility status-specific, stratified by the site of first primary cancer among cancer …

Unbound Bilirubin And Risk Of Severe Neurodevelopmental Impairment In Extremely Low Birthweight Newborns, Cody C Arnold, Ivana Maric, Ronald J Wong, Jon E Tyson, David K Stevenson

Faculty, Staff and Student Publications

Background: Unbound bilirubin (UB) was measured on day 5 ± 1 in 1101 ELBW newborns in the Aggressive vs Conservative Phototherapy randomized controlled trial. We accessed this dataset to quantify the UB-mediated risk of severe neurodevelopmental impairment (sNDI) in extremely low birthweight (ELBW) newborns.

Methods: UB levels were standardized within laboratories as z-score percentiles. A dichotomous UB exposure variable was based on sharply increased risk of sNDI at the 85th percentile (UBz>85th). Targeted maximum likelihood estimation with ensemble machine learning (TMLE + ML) and logistic regression (LR) were used to estimate sNDI risk attributable to UBz>85th.

Results: UB …

Utility Of Whole-Slide Imaging For Rapid Evaluation Of Thyroid Fna: A Multireader Prospective Study, Mohammed S Ahmed, Dianna Klippel-Almaraz, Sara E Amin, Gloria H Sura, Uma Rani Kundu, Wendong Yu, Jogn M Stewart, Qiong Gan, Savitri Krishnamurthy

Faculty, Staff and Student Publications

Background: Rapid on-site evaluation (ROSE) of thyroid fine-needle aspiration biopsy (FNAB) improves diagnostic adequacy and facilitates ancillary molecular testing. In this prospective, multireader study, the authors evaluated the feasibility of using whole-slide images (WSIs) for ROSE to determine specimen adequacy and preliminary categorization (according to The Bethesda System for Reporting Thyroid Cytopathology [Bethesda]) of image-guided thyroid FNABs compared with conventional light-microscopic (LM) examination of the same specimens in a referral cancer center.

Methods: The authors evaluated 98 ultrasound-guided thyroid FNAB cases. Smears were stained with Papanicolaou and Diff-Quik and were scanned at ×20 magnification using a Leica Aperio CS2 scanner. …

Spatial Colocalization And Molecular Crosstalk Of Myofibroblastic Cafs And Tumor Cells Shape Lymph Node Metastasis In Oral Squamous Cell Carcinoma, Ken Furudate, Shuya Kasai, Tadashi Yoshizawa, Yuya Sasaki, Kohei Fujikura, Shintaro Goto, Ryohei Ito, Koki Takagi, Tomoyuki Tanaka, Hiroshi Kijima, Kosei Kubota, Ken Itoh, Wataru Kobayashi, Koichi Takahashi

Faculty, Staff and Student Publications

Lymph node metastasis (LNM) is a critical prognostic factor for patients with oral squamous cell carcinoma (OSCC). Previous research has implicated the partial epithelial-to-mesenchymal transition of tumor cells and myofibroblastic cancer-associated fibroblasts (myCAFs) in the LNM process. However, the underlying molecular mechanisms remain poorly understood. Here, we conducted a comprehensive molecular analysis integrating original and publicly available OSCC data from bulk genome and transcriptome, single-cell transcriptome, and spatial transcriptome analyses. We found that myCAFs were quantitatively and functionally activated in LNM-positive samples and spatially colocalized with OSCC cells within the invasive tumor front (ITF), providing a niche that may facilitate …

Sex Disparities In Chlamydia And Gonorrhea Treatment In Us Adult Emergency Departments: A Systematic Review And Meta-Analysis, Rachel E Solnick, Rahi Patel, Ethan Chang, Carmen Vargas-Torres, Maaz Munawar, Carlin Pendell, Judith E Smith, Ethan Cowan, Keith E Kocher, Roland C Merchant

Faculty, Staff and Student Publications

BACKGROUND: Empiric antibiotic treatment for gonorrhea (GC) and chlamydia (CT) is common in U.S. emergency departments (EDs) due to the delayed availability of test results. Local studies have identified sex-based disparities in sexually transmitted infection (STI) care, with females potentially receiving less empiric treatment than males. This study evaluates how STI treatment aligns with laboratory-confirmed results to quantify potential overtreatment and undertreatment rates and investigates sex differences for these outcomes.

METHODS: We conducted a preregistered (PROSPERO #241429) systematic review and meta-analysis of studies published between January 2010 and January 2025 in U.S. EDs, excluding studies conducted exclusively in pediatric settings. …

Parent Needs, Recommendations, And Systemic Challenges Affecting Pediatric Hypertension Detection, Abbas H. Zaidi, Erica D. Sood, Sarah De Ferranti, Samuel Gidding, Varsha Zadokar, Jonathan M. Miller, Anne E Kazak

Department of Pediatrics Faculty Papers

Pediatric hypertension (HTN) affects 3%-5% of children in the United States, yet only 25% are diagnosed and 60% lack recommended follow-up care. Skepticism about elevated blood pressure (BP) readings and reluctance to use antihypertensive medications by parents and clinicians highlight the need for stakeholder-informed strategies to address these challenges. This study examined parents' perceived needs, their recommended strategies to improve HTN detection, and contextual health system challenges. Parents and clinicians from 10 pediatric primary care clinics participated in semi-structured qualitative interviews. Only parents of children with documented stage 2 BP readings and a HTN diagnosis, but with gaps in care …

The Potential Of 4-Methylumbelliferone To Be Repurposed For Treating Liver Fibrosis, Xi Chen, Huiqiao Li, Yanru Deng, Jieyi Meng, Shangang Zhao, Clavia Ruth Wooton-Kee, Xia Gao, Bingning Dong, Dongyin Guan, Chaodong Wu, Philipp E Scherer, Yi Zhu

Faculty, Staff and Students Publications

4-Methylumbelliferone (4-MU) is the active component of hymecromone, a choleretic and antispasmodic drug with an excellent safety profile. In rodent studies, high doses of 4-MU are also used to inhibit the production of hyaluronan (HA), a biomarker of liver fibrosis. Further, 4-MU shows excellent efficacy in inhibiting liver fibrosis of different etiologies in animal studies, eliciting interest in its repurposing for this condition. However, 4-MU's mechanism of action, and whether it inhibits liver fibrosis by impeding HA synthesis remains unclear. Using several transgenic mouse models with HA overproduction or degradation in different types of liver cells, we found that both …

A Multi-Institutional Multi-Methods Analysis Of Jeopardy Systems In Academic Hospital Medicine, Kirsten N Kangelaris, Angela Keniston, Andrew D Auerbach, Gregory Bowling, Marisha Burden, Shradha A Kulkarni, Luci K Leykum, Anne S Linker, Matthew Sakumoto, Jeffrey Schnipper, Gopi Astik

Faculty, Staff and Students Publications

Background: Hospital medicine programs use backup ("jeopardy") systems to cover unexpected staffing gaps, but little is known about their structures or optimal practices.

Objectives: To describe jeopardy structures, assess clinician perceptions, and identify potential approaches across a broad sample of hospital medicine groups.

Methods: This multi-methods study, conducted within a national hospitalist consortium, used virtual focus groups and an email survey to (1) describe the presence and structure of jeopardy systems and (2) explore features perceived as fair, equitable, and tolerable. Rapid qualitative analysis identified major themes, while descriptive methods analyzed survey data.

Results: Twenty-five individuals participated in focus groups, …

Five-Year Pivotal Trial Outcomes Of The Gore Excluder Conformable Endoprosthesis Implanted In Abdominal Aortic Aneurysms With Short Non-Angulated Infrarenal Seal Zones, Bjoern D Suckow, Gustavo S Oderich, Mahmoud W Almadani, Dai Yamanouchi, Alyssa J Pyun, Erin Moore, Patrick E Muck, Robert Y Rhee

Faculty, Staff and Students Publications

Objective: The GORE EXCLUDER Conformable Abdominal Aortic Aneurysm Endoprosthesis with Active Control System (EXCC) is approved in the United States (U.S.) for treatment of AAAs and highly angulated (≤90°) and short (≥10 mm) infrarenal aortic proximal seal zones (necks). Reported here are the 5-year outcomes of the EXCC U.S. pivotal clinical trial in the short, non-angulated cohort (SNA).

Methods: The EXCC investigational device exemption prospective pivotal trial short neck sub-study across 31 sites included patients with infrarenal necks measuring ≥10 mm length and ≤60° angulation. Five-year outcomes assessed by Core lab and adjudicated by independent review committee included patient safety …

One-Year Outcomes From The Pivotal Trial Of A Four-Branch Off-The-Shelf Solution To Treat Pararenal And Extent Iv Thoracoabdominal Aortic Aneurysms, Mark A Farber, Sukgu Han, Michel S Makaroun, Jon S Matsumura, Bernardo C Mendes, Gustavo S Oderich, Luis A Sanchez, Bjoern D Suckow, Carlos H Timaran

Faculty, Staff and Students Publications

Objective: To report 1-year primary-arm outcomes of the GORE EXCLUDER Thoracoabdominal Branch Endoprosthesis pivotal trial.

Methods: The multicenter, nonrandomized, prospective study included patients with extent IV thoracoabdominal aortic aneurysms (TAAAs) and pararenal aortic aneurysms (PRAAs). All-cause and adjudicated lesion-related mortality were assessed at 12 months. Core-lab-reported, imaging-dependent outcomes included aneurysm size, endoleaks assessed through 1-year follow-up window, and target vessel instability (defined as occlusion, stenosis, type Ic/IIIc endoleak, or reintervention) at 1 year.

Results: One hundred two patients were treated; 59 patients had an extent IV TAAA and 43 had a PRAA. The mean maximum aneurysm diameter was 59.4 ± …

Changes In Child Placement After Child Abuse Pediatrics Consultation For Suspected Physical Abuse, Kristine A Campbell, Antoinette L Laskey, Daniel M Lindberg, M Katherine Henry, Porcia Vaughn, James D Anderst, Megan M Letson, Angela N Bachim, Nancy S Harper, Carmen M Coombs, Lori D Frasier, Joanne N Wood

Faculty, Staff and Students Publications

Background: The association between child abuse pediatric (CAP) assessments and child welfare outcomes is unknown.

Objective: To determine the association between a CAP determination of the likelihood of physical abuse and change in child placement. We hypothesized that child race would be associated with CAP determination of abuse likelihood and child welfare outcomes.

Participants and setting: Children under age ten years with in-person CAP consultation and referral to child protective services for suspected physical abuse at a U.S. pediatric referral center participating in CAPNET, a CAP research network, from 02/2021 to 01/2023.

Methods: We created a series of generalized estimating …

A Phase 2 Randomized Trial Of Nbi-1065846 (Tak-041) In Patients With Anhedonia Associated With Major Depressive Disorder: Results Of The Terpsis Study, Shannon R Benedetto, Adrian Ionescu, Tingting Ge, Maura Furey, Swan Lin, Manish K Jha, Andrew Krystal, Asim A Shah, David P Walling, Neel Shah, Sakina J Rizvi, Sidney Kennedy, Antonio Laurenza, Venkatesha Murthy, Eiry Roberts, Jaskaran B Singh

Faculty, Staff and Students Publications

Background: Anhedonia is a core symptom of major depressive disorder (MDD) that may result from aberrant lateral habenula hyperactivity. Targeting G-protein coupled receptor 139 (GPR139) may improve anhedonia by modulating lateral habenula activity. NBI-1065846 is an investigational GPR139 agonist that improved anhedonia, anxiety, and depression in rodent models.

Methods: TERPSIS was a phase 2, proof-of-concept clinical study. Adults with MDD experiencing a major depressive episode with anhedonia were randomized 1:1 to NBI-1065846 or placebo for 8 weeks. The primary endpoint was the change in the Dimensional Anhedonia Rating Scale (DARS) score. Secondary endpoints were change in total Montgomery Åsberg Depression …