Medical Specialties Commons^™

Development Of An Age-Appropriate Household Dysfunction Measure And Its Concurrent Validity With Multiple Outcomes Among Middle School Adolescents In Southeast Texas, Sumaita Choudhury, Timothy J Walker, Emily T Hébert, Christine M Markham, Ross Shegog, Robert C Addy, Melissa F Peskin

Faculty, Staff and Student Publications

Existing adverse childhood experience (ACE) measures include a limited number of household dysfunction (HD) items and the use of adult-oriented language that is not always appropriate for middle schoolers. We developed an age-appropriate 10-item HD measure informed by previously validated ACE measures and tested its concurrent validity with dating violence (DV) perpetration, lifetime substance use, and mental health outcomes among middle schoolers in Southeast Texas. This cross-sectional study used the baseline data from a DV prevention intervention program for sixth graders (N = 126), Me & You Tech. Baseline data were collected from March 2023 to April 2023. To …

Comparison Of Thrombectomy Alone Versus Bridging Thrombolysis In A Us Population Using Regression Discontinuity Analysis, Youngran Kim, Sergio Salazar-Marioni, Rania Abdelkhaleq, Ananya Iyyangar, Diogo Haussen, Jonathan Grossberg, Jaydevsinh Dolia, Aqueel Pabaney, Mahmoud Mohammaden, Ameer Hassan, Wondwossen Tekle, Hamzah Saei, Mohamad Abdalkader, Piers Klein, Taha Nisar, Adeel Saleemi, Shahram Majidi, Johanna Fifi, Gabrielle Valestin, Guillermo Linares, Kara Christopher, David S Liebeskind, Mouhammad Jumaa, Syed Zaidi, Raul Nogueira, Brijesh Mehta, Joy Sessa, Juan Vivanco-Suarez, Aaron Rodriguez-Calienes, Milagros Galecio-Castillo, Santiago Ortega-Gutierrez, James Siegler, Mary Penckofer, Italo Linfante, Sunil A Sheth, Svin Registry Consortium

Faculty, Staff and Student Publications

The role of intravenous thrombolysis (IVT) in combination with endovascular thrombectomy (EVT) for the treatment of large vessel occlusion acute ischemic stroke has been evaluated exclusively outside the US, in randomized clinical trials which failed to demonstrate non-inferiority of skipping IVT. Because practice patterns and IVT dosing differ within the US, and prior observational US-based cohorts suggested improved clinical outcomes in patients who received IVT before EVT, a US-based evaluation is needed. This is a quasi-experimental study of a large US cohort using a regression discontinuity design (RDD) that enables the estimation of causal effects when randomization is not feasible. …

The Impact Of Breast Radiotherapy On The Tumor Genome And Immune Ecosystem, Aislyn Schalck, Tuan Tran, Jianzhuo Li, Emi Sei, Shanshan Bai, Min Hu, Jerome Lin, Scott J Bright, Samuel Reddick, Fei Yang, Harsh Batra, Alejandro Contreras, Maria Gabriela Raso, Michael C Stauder, Karen E Hoffman, Jay P Reddy, Kevin T Nead, Benjamin D Smith, Gabriel O Sawakuchi, Wendy A Woodward, Stephanie S Watowich, Jennifer K Litton, Isabelle Bedrosian, Elizabeth A Mittendorf, Huong Le-Petross, Nicholas E Navin, Simona F Shaitelman

Faculty, Staff and Student Publications

Radiotherapy is a pillar of breast cancer treatment; however, it remains unclear how radiotherapy modulates the tumor microenvironment. We investigated this question in a cohort of 20 patients with estrogen-receptor positive (ER+) breast tumors who received neoadjuvant radiotherapy. Tumor biopsies were collected before and 7 days postradiation. Single-cell DNA sequencing (scDNA-seq) and scRNA-seq were conducted on 8 and 11 patients, respectively, at these two time points. The scRNA data showed increased infiltration of naive-like CD4 T cells and an early, activated CD8 T cell population following radiotherapy. Radiotherapy also eliminated existing cytotoxic T cells and resulted in myeloid cell increases. …

Hand Hygiene Roles, Challenges, And Intervention Feedback From School Staff: A Qualitative Analysis, Belize, 2022-2023, Anh N Ly, Christina Craig, Dian Maheia, Yolanda Gongora, Vickie Romero, Rosalva Blanco, Allison Lino, Kelsey Mcdavid, Allison Stewart, Victoria Trinies, Alexandra Medley, Francis Morey, Russell Manzanero, Matthew Lozier, Kristy O Murray

Faculty, Staff and Students Publications

Hand hygiene (HH) in school settings can reduce the spread of infectious diseases and student absenteeism due to illness. During the COVID-19 pandemic, the World Health Organization recommended HH as a public health measure to prevent disease transmission. Understanding school staff's experiences with school-based programs is important for future program development and improvement. As part of a mixed-methods study, we conducted in-depth interviews in March 2022 with school administrators and teachers at 12 primary schools in Belize, selected based on high gaps in HH resources, to understand HH responsibilities, supplies, and challenges. An intervention was implemented to increase HH knowledge …

The Impact Of Narratives And Active Video Games Among Black And Hispanic Children With Overweight And Obesity: A Randomized Controlled Trial, Amy S Lu, Tom Baranowski, Tiago V Barreira, Amy Fleischman, Melanie C Green, Shirley Y Huang, I-Min Lee, Lynne L Levitsky, Farzad Noubary, Debbe Thompson

Children’s Nutrition Research Center Staff Publications

Background: Overweight and obesity disproportionately affect Black and Hispanic children who also play more video games. Narratives, coupled with home-based active video games (AVGs), may enhance PA and mitigate these disparities. This study tested the effect of narrative-enhanced home-based AVGs among predominantly Black and Hispanic children with overweight and obesity.

Methods: This 6-month three-group RCT recruited 135 children aged 7-14 from pediatric clinics in Boston, MA (January 2020 - May 2022) during the COVID-19 pandemic. Participants were randomized into: [Narrative + AVG], receiving an Xbox/Kinect with six AVGs interspersed with a narrative animation Ataraxia (72 episodes over six months), which …

Time To Treatment In Pediatric Patients With Repeated Episodes Of Status Epilepticus, Jennifer V Gettings, Iván Sánchez Fernández, Anne Anderson, J Nicholas Brenton, Afra Can, Justice Clark, Raquel Farias Moeller, Howard P Goodkin, Yi-Chen Lai, Mohamad A Mikati, Lindsey A Morgan, Edward Novotny, Adam P Ostendorf, Juan Piantino, James J Riviello, Kumar Sannagowdara, Robert C Tasker, Dmitry Tchapyjnikov, Mark S Wainwright, Angus Wilfong, Korwyn Williams, Bo Zhang, Tobias Loddenkemper, Marina Gaínza-Lein, Pediatric Status Epilepticus Research Group (Pserg)

Duncan NRI Faculty and Staff Publications

Objective: To compare pediatric patients who presented with repeated status epilepticus episodes to patients with a single episode of status epilepticus and identify distinguishing clinical factors.

Methods: Retrospective analysis of a multicenter, prospective observational cohort of pediatric patients with status epilepticus between 2011 and 2019.

Results: Out of 504 status epilepticus episodes in 420 patients, 50 patients (10.3%) had repeated episodes of status epilepticus. The only predictor of repeated status epilepticus was a prior diagnosis of epilepsy. There was no difference in time to treatment with the first benzodiazepine in patients presenting with their first status epilepticus episode compared to …

Steps Toward Clinical Validation Of Exhaled Volatile Organic Compound Biomarkers For Hypoglycemia In Persons With Type 1 Diabetes., Mark Woollam, Paula Angarita-Rivera, Sanskar Thakur, Ali Daneshkhah, Amanda P Siegel, Dana S Hardin, Mangilal Agarwal

Ambulatory and Primary Care Articles

Persons with type 1 diabetes (T1D) must track/control their blood glucose (BG) levels to avoid hypoglycemic events (BG <  70 mg/dL), which in the most severe cases can lead to seizures or even death. Canines may lead the way toward innovative testing solutions, as they can be trained to identify hypoglycemia simply and noninvasively by smelling exhaled volatile organic compounds (VOCs). To identify breath-based biomarkers of hypoglycemia, samples were collected during two consecutive summers at a diabetes camp (Cohort 1 and Cohort 2), and VOCs were analyzed by gas chromatography-mass spectrometry. Conserved VOCs between the two cohorts were identified, but individual VOCs alone had low accuracies for detection. Therefore, supervised multivariate statistical analysis was undertaken to identify a biosignature in the training data set (Cohort 1) that could detect hypoglycemia with higher accuracy (sensitivity = 94.8%/specificity = 95.0%). When this model was blindly tested on Cohort 2, hypoglycemia was classified with sensitivity = 90.0%/specificity = 89.9%. Ultimately, this study makes strides toward clinical validation through verifying biomarkers of hypoglycemia in hundreds of breath samples. These results may be translated to design a sensor array that could be integrated into a portable breathalyzer to increase glycemic control in persons with T1D.

A Smart Pill Bottle And Text Messaging Intervention For Promoting Medication Adherence In Patients With Chronic Myeloid Leukemia: A Pilot Study Of Txt4 Tki, Kuang-Yi Wen, Neil Palmisiano, Rita Smith, Rachel Slamon, Gina Keiffer, Christian Fidler, Margaret Kasner, Lindsay Wilde, Md

Department of Medical Oncology Faculty Papers

BACKGROUND: Patients undergoing tyrosine kinase inhibitor (TKI) therapy for chronic myeloid leukemia (CML) often face challenges with adherence, despite the efficacy of the treatment. Theory-guided and evidence-informed interventions addressing psychosocial and adherence barriers are critical for promoting adherence. Using a mixed-method approach, the pilot study developed and evaluated the feasibility and potential impact of an intervention "txt4TKI," to support medication and symptom management among CML patients undergoing TKI therapy.

METHODS: Guided by the Necessity and Concerns framework, the study comprised two phases: Phase 1 involved qualitative patient needs assessment interviews informing intervention design. Phase 2 was a single-arm pilot study …

Development And Pilot Testing Of An Addiction Clinic-Based Pre-Exposure Prophylaxis Uptake And Adherence Intervention For Women With Substance Use Disorders: Protocol For A Pilot Randomized Trial, Angela M Heads, Diane Santa Maria, Mandy J Hill, Robert Suchting, Kimberly N Evans, Zaneta Gaul, Luba Yammine, Constanza De Dios, Joy M Schmitz

Faculty, Staff and Student Publications

Background: Black and Hispanic women in the United States continue to bear disproportionate incidence of HIV related to sexual transmission and injection drug use. Specifically, women with substance use disorders (SUDs) are more likely to engage in vaginal or anal condomless sex associated with HIV transmission. Pre-exposure prophylaxis (PrEP) is a highly effective HIV prevention tool but is not widely used by racial or ethnic minority women. Effective interventions for engaging women with SUDs in HIV prevention interventions that are culturally appropriate and, therefore, more appealing to racial or ethnic minority women with SUDs are critically needed.

Objective: This 3-phased …

The Effect Of Celecoxib And Mumab911 On Strain Adaptive Bone Remodeling And Fracture Repair In Female Mice: Implications For Rapidly Progressive Osteoarthritis, Nicholas Ruggiero, Alexandra Ciuciu, Ashkan Sedigh, Ibtesam Rajpar, David Shelton, Patrice Belanger, Kathryn Gropp, John A. Collins, Theresa A. Freeman, Ryan E. Tomlinson

Department of Orthopaedic Surgery Faculty Papers

Debilitating pain is the primary clinical feature of osteoarthritis (OA) that drives the enormous healthcare costs. Osteoarthritis-related pain is often treated with non-steroidal anti-inflammatory drugs (NSAIDs), which effectively relieve pain and inflammation by inhibition of prostaglandin synthesis. Antibodies directed against nerve growth factor (NGF) were tested some time ago as an alternative potential analgesic for musculoskeletal pain, including osteoarthritis-related pain. Unfortunately, clinical development of these drugs was put on hold due to adverse outcomes - primarily rapidly progressive osteoarthritis. Both prostaglandin synthesis and NGF have been implicated as critical mediators of strain adaptive bone remodeling, which may play a role …

Personalizing Neoadjuvant Chemotherapy Regimens For Triple-Negative Breast Cancer Using A Biology-Based Digital Twin, Chase Christenson, Chengyue Wu, David A Hormuth, Jingfei Ma, Clinton Yam, Gaiane M Rauch, Thomas E Yankeelov

Faculty, Staff and Student Publications

Despite advances triple negative breast cancer treatment, ~50% of patients will not achieve a pathological complete response prior to surgery with standard of care neoadjuvant therapy (NAT). We hypothesize that personalized regimens for NAT could significantly improve patient outcomes, which we address with a patient-specific digital twin framework. This framework is established by calibrating a biology-based model to longitudinal magnetic resonance images with approximate Bayesian computation. We then apply optimal control theory to either (1) reduce the final tumor cell number with equivalent dose, or (2) reduce the total dose of NAT with equivalent response. For (1), the personalized regimens …

Untargeted Proteomics Enables Ultra-Rapid Variant Prioritisation In Mitochondrial And Other Rare Diseases, Daniella H Hock, Nikeisha J Caruana, Liana N Semcesen, Nicole J Lake, Luke E Formosa, Sumudu S C Amarasekera, Tegan Stait, Simone Tregoning, Leah E Frajman, Adam M Bournazos, David R L Robinson, Megan Ball, Boris Reljic, Bryony Ryder, Mathew J Wallis, Anand Vasudevan, Cara Beck, Heidi Peters, Joy Lee, Natalie B Tan, Mary-Louise Freckmann, Mitomdt Diagnostic Network For Genomics And Omics, Vasiliki Karlaftis, Chantal Attard, Paul Monagle, Amanda Samarasinghe, Rosie Brown, Weimin Bi, Monkol Lek, Robert Mcfarland, Robert W Taylor, Michael T Ryan, Sandra T Cooper, Zornitza Stark, John Christodoulou, Alison G Compton, David R Thorburn, David A Stroud

Faculty, Staff and Students Publications

Background: Only half of individuals with suspected rare diseases receive a genetic diagnosis following genomic testing. A genetic diagnosis allows access to appropriate care, restores reproductive confidence and reduces the number of potentially unnecessary interventions. A major barrier is the lack of disease agnostic functional tests suitable for implementation in routine diagnostics that can provide evidence supporting pathogenicity of novel variants, especially those refractory to RNA sequencing.

Methods: Focusing on mitochondrial disease, we describe an untargeted mass-spectrometry based proteomics pipeline that can quantify proteins encoded by > 50% of Mendelian disease genes and > 80% of known mitochondrial disease genes in clinically …

Multicomponent Parenteral Lipid Emulsions Do Not Prevent Liver Injury In Neonatal Pigs With Obstructive Cholestasis, Greg Guthrie, Caitlin Vonderohe, Valeria Meléndez Hebib, Barbara Stoll, Douglas Burrin

Children’s Nutrition Research Center Staff Publications

Biliary atresia (BA) is a pediatric liver disease that often necessitates parenteral nutrition (PN) to support growth due to impaired liver function. While soy-based lipid emulsions (SLE) are commonly used in PN, they may contribute to cholestatic liver injury. In contrast, mixed lipid emulsions (MLE) show promise in preventing cholestasis in infants without BA, potentially by restoring bile flow. However, their effectiveness in patients of complete bile duct obstruction, as seen in BA, remains uncertain. To explore the potential benefits of MLE in BA, we utilized a neonatal pig model of bile duct ligation (BDL). Pigs underwent either BDL or …

The Joint Association Of Diet Quality And Sleep Regularity With Incident Cardiovascular Disease In The Multi-Ethnic Study Of Atherosclerosis, Kaitlin S Potts, Claire Veldkamp, Alexis C Wood, Erin D Michos, Raymond Noordam, Tianyi Huang, Susan Redline, Heming Wang

Children’s Nutrition Research Center Staff Publications

Background/objectives: Diet quality and sleep regularity both influence cardiovascular disease (CVD) risk and may influence each other, but there is scarce evidence for their joint or interacting associations in relation to CVD. We assessed these associations in the Multi-Ethnic Study of Atherosclerosis (MESA).

Methods: Participants free of CVD with valid diet and sleep measures in 2010-2013 were included and followed through 2020 for detection of incident CVD (188 events detected over 8.8 years among 1782 participants; 55% women). Sleep timing and duration regularity were assessed via the intra-individual SD of sleep onset time and duration across 5- to 7-day actigraphy. …

Decoding Resistance To Immune Checkpoint Inhibitors In Non-Small Cell Lung Cancer: A Comprehensive Analysis Of Plasma Proteomics And Therapeutic Implications, Michal Harel, Nili Dahan, Coren Lahav, Eyal Jacob, Yehonatan Elon, Igor Puzanov, Ronan J. Kelly, Yuval Shaked, Raya Leibowitz, David P. Carbone, David R. Gandara, Adam P. Dicker

Department of Radiation Oncology Faculty Papers

BACKGROUND: Immune checkpoint inhibitors (ICIs) have shown substantial benefit for patients with advanced non-small cell lung cancer (NSCLC). However, resistance to ICIs remains a major clinical challenge. Here, we perform a comprehensive bioinformatic analysis of plasma proteomic profiles to explore the underlying biology of treatment resistance in NSCLC.

METHODS: The analysis was performed on 388 "resistance-associated proteins" (RAPs) that were previously described as pretreatment plasma proteomic predictors within the PROphet computational model designed to predict ICI clinical benefit in NSCLC. Putative tissue origins of the RAPs were explored using publicly available datasets. Enrichment analyses were performed to investigate RAP-related biological …

The Perk/Atf4 Pathway Is Required For Metabolic Reprogramming And Progressive Lung Fibrosis, Jyotsana Pandey, Jennifer L Larson-Casey, Mallikarjun H Patil, Chao He, Nisarat Pinthong, A Brent Carter

Faculty, Staff and Students Publications

Asbestosis is a prototypical type of fibrosis that is progressive and does not resolve. ER stress is increased in multiple cell types that contribute to fibrosis; however, the mechanism(s) by which ER stress in lung macrophages contributes to fibrosis is poorly understood. Here, we show that ER stress resulted in protein kinase RNA-like ER kinase (PERK; Eif2ak3) activation in humans with asbestosis. Similar results were seen in asbestos-injured mice. Mice harboring a conditional deletion of Eif2ak3 were protected from fibrosis. Lung macrophages from asbestosis individuals had evidence of metabolic reprogramming to fatty acid oxidation (FAO). Eif2ak3fl/fl mice had increased oxygen …

Identification Of Surrogate Biomarkers For Mucopolysaccharidosis Type Iva, Yasuhiko Ago, Shaukat Khan, Kimberly Klipner, Allison Bradford, Shunji Tomatsu

Department of Pediatrics Faculty Papers

Mucopolysaccharidosis type IVA (MPS IVA, Morquio A syndrome) is a rare inherited disorder characterized by skeletal dysplasia due to deficient N-acetylgalactosamine-6-sulfate sulfatase activity, resulting in glycosaminoglycan (GAG) accumulation. Identifying accurate biomarkers reflecting clinical severity and therapeutic response remains challenging. This study evaluated potential surrogate biomarkers, including N-terminal pro-C-type natriuretic peptide (NT-proCNP), collagen types I and II, mono-sulfated keratan sulfate (KS), di-sulfated KS, and chondroitin-6-sulfate (C6S), in blood and urine samples from 60 patients ranging from 1 to 62 years of age. NT-proCNP levels were significantly elevated in patients of all ages and negatively correlated with growth impairment, especially after 8 …

Global Dna Methylation Differences Involving Germline Structural Variation Impact Gene Expression In Pediatric Brain Tumors, Fengju Chen, Yiqun Zhang, Wei Li, Fritz J Sedlazeck, Lanlan Shen, Chad J Creighton

Children’s Nutrition Research Center Staff Publications

The extent of genetic variation and its influence on gene expression across multiple tissue and cellular contexts is still being characterized, with germline Structural Variants (SVs) being historically understudied. DNA methylation also represents a component of normal germline variation across individuals. Here, we combine germline SVs (by short-read sequencing) with tumor DNA methylation across 1292 pediatric brain tumor patients. For thousands of methylation probes for CpG Islands (CGIs) or enhancers, rare and common SV breakpoints upstream or downstream associate with differential methylation in tumors spanning various histologic types, a significant subset involving genes with SV-associated differential expression. Cancer predisposition genes …

In Vivo Crispr Activation Screen Identifies Acyl-Coa-Binding Protein As A Driver Of Bone Metastasis, Hongqi Teng, Qinglei Hang, Caishang Zheng, Yuelong Yan, Shaomin Liu, Yang Zhao, Yalan Deng, Litong Nie, Weiche Wu, Marisela Sheldon, Zachary Yu, Wei Shi, Jianxuan Gao, Chenling Meng, Consuelo Martinez, Jie Zhang, Fan Yao, Yutong Sun, Di Zhao, Boyi Gan, Tong Meng, Li Ma

Faculty, Staff and Student Publications

One of the most common sites of cancer metastasis is to the bone. Bone metastasis is associated with substantial morbidity and mortality, and current therapeutic interventions remain largely palliative. Metastasizing tumor cells need to reprogram their metabolic states to adapt to the nutrient environment of distant organs; however, the role and translational relevance of lipid metabolism in bone metastasis remain unclear. Here, we used an in vivo CRISPR activation screening system coupled with positive selection to identify acyl-coenzyme A (CoA) binding protein (ACBP) as a bone metastasis driver. In nonmetastatic and weakly metastatic cancer cells, overexpression of wild-type ACBP, but …

A Review Of Mirvetuximab Soravtansine-Gynx In Folate Receptor Alpha-Expressing Platinum-Resistant Ovarian Cancer, Judith A Smith, Patrick Medina, Mary Miao, Kathleen N Moore

Faculty, Staff and Student Publications

Purpose: To evaluate the pharmacology, efficacy, safety, and dosing and administration considerations (including adjusted ideal body weight [AIBW] dosing) for mirvetuximab soravtansine-gynx, a first-in-class folate receptor alpha (FRα)-directed antibody-drug conjugate for platinum-resistant ovarian cancer (PROC).

Summary: A literature search was conducted in PubMed using the terms "ovarian cancer" and "mirvetuximab soravtansine" of articles published from inception to April 16, 2024. Relevant publications, abstracts, and clinical trials were reviewed. Mirvetuximab soravtansine-gynx is dosed at 6 mg/kg AIBW every 3 weeks and comprises an FRα-binding antibody, a hydrophilic disulfide linker, and a maytansinoid DM4 payload. Mirvetuximab soravtansine-gynx binds to FRα, which induces …

Dietary Intake Of Protein By Food Source And Incident Hypertension Among Diverse Us Adults: The Mesa Study, Ji Yun Tark, Ruosha Li, Bing Yu, Alexis C Wood, Nikhil S Padhye, Marcia C De Oliveira Otto

Faculty, Staff and Student Publications

Background: Dietary guidelines recommend adequate protein intake from diverse sources for optimal blood pressure; however, its role in hypertension risk remains unclear. We examined prospective associations of protein intake and diversity, overall and by source, with hypertension risk in the MESA (Multi-Ethnic Study of Atherosclerosis) study.

Methods and results: Among 2294 participants aged 45 to 84 years without hypertension at baseline, total, animal, and plant protein intake was assessed using a 120-item food frequency questionnaire. Protein diversity was evaluated using count and the dissimilarity index. Over a 9-year median follow-up, 1356 hypertension cases were identified through blood pressure measurements and …

Ccaat/Enhancer-Binding Proteins Α And Β Regulate Ovulation And Gene Expression Via Dose- And Stage-Dependent Mechanisms, Hanxue Zhang, Rainer B Lanz, Jimmy Dhillon, Paul D Soloway, Bo Shui, Yi Athena Ren

Faculty, Staff and Students Publications

The preovulatory luteinizing hormone (LH) surge orchestrates complex cellular and molecular events leading to ovulation. CCAAT/enhancer-binding proteins α and β (C/EBPα/β) are transcription factors acutely induced by the LH surge and crucial for ovulation and granulosa cell luteinization. However, biological processes (BPs) and their regulatory mechanisms downstream of C/EBPα/β in the preovulatory ovary are not completely understood. To address this knowledge gap, we generated Cebpa/bfl/fl;Pgr-Cre mutants and compared them with Cebpa/bfl/fl;Cyp19a1-Cre mutant female mice: Cebpa/bfl/fl;Cyp19a1-Cre mutants have undetectable levels of C/EBPα/β throughout the preovulatory stages and do not ovulate, aligning with previous reports; and Cebpa/bfl/fl;Pgr-Cre mutants present gradual depletion of …

Neoadjuvant With Low-Dose Radiotherapy, Tislelizumab, Albumin-Bound Paclitaxel, And Cisplatin For Resectable Locally Advanced Head And Neck Squamous Cell Carcinoma: Phase Ii Single-Arm Trial, Zhigang Liu, Dong Wang, Guanjun Li, Muhua Yi, Zhaoyuan Zhang, Guihua Zhong, Liangfu Xu, Rong Jiang, Yannan Zheng, Linxuan Huang, Yingpeng Peng, Lizhong Liang, Jianpeng Li, Ye Liu, Jun Lai, Xianjuan Lv, Yongqiang Xu, Qiaodan Liu, Zhiqiang Wang, Zhutian Liu, Qinan Yang, Li Nie, Jiao Lei, Xiaotao Huang, Zhijie Liu, Wen Jiang

Faculty, Staff and Student Publications

Although pathological complete response (pCR) and major pathological response (MPR) rates of neoadjuvant immunotherapy combined with chemotherapy in head and neck squamous cell carcinoma (HNSCC) trials remain suboptimal, emerging evidence highlights the synergistic potential of combining low-dose radiotherapy with immunotherapy to promote the efficacy of immunotherapy. This phase II, open-label, single-arm, multicenter trial (NCT05343325) enrolled 28 patients with untreated stage III-IVB HNSCC (NeoRTPC02). Patients received neoadjuvant low-dose radiotherapy, the programmed death-1 (PD-1) inhibitor tislelizumab, albumin-bound paclitaxel, and cisplatin for two cycles, followed by radical resection ~4 weeks after treatment completion. The primary endpoint, pCR rate, was achieved in 14 of …

Tacrolimus Dosing In Liver Transplant Recipients Using Phenotypic Personalized Medicine: A Phase 2 Randomized Clinical Trial, Jeffrey Khong, Megan Lee, Curtis Warren, Un Kim, Sergio Duarte, Kenneth Andreoni, Sunaina Shrestha, Mark Johnson, Narendra Battula, Danielle Mckimmy, Thiago Beduschi, Ji-Hyun Lee, Derek Li, Chih-Ming Ho, Ali Zarrinpar

Department of Surgery Faculty Papers

Tacrolimus is the most commonly used immunosuppression drug after solid organ transplantation; however, its dosing is challenging due to substantial inter-individual variability, often resulting in blood levels that deviate from the target therapeutic range. We explored whether a dynamically customized, phenotypic-outcome-guided drug dosing method could improve maintenance of drug trough levels within pre-determined target ranges, focusing on tacrolimus immediately after liver transplantation. This single-center, partially blinded, completed clinical trial involved 62 adults undergoing liver transplantation, block randomized into parallel groups: standard-of-care (SOC) clinician-determined or Phenotypic Personalized Medicine (PPM)-guided tacrolimus dosing. The primary outcome was percentage of post-transplant days with large …

Identifying Distinct Subgroups With Severe Pain In Sickle Cell Disease: A Cluster Analysis Of The Grndad Multi-Center Registry, Martha O. Kenney, Samuel Wilson, Morgan Rosser, Sophie Lanzkron, Julie Kanter, Susan Padrino, Payal Desai, Deepa Manwani, Alice Cohen, Stephanie Guarino, Ward Hagar, Joshua Field, Jane Little

Department of Medicine Faculty Papers

Sickle cell disease (SCD) affects millions of individuals worldwide, and is characterized by both acute, episodic pain and chronic, persistent pain. Despite the significant burden of the disease, clinicians continue to face significant challenges in treating SCD pain due to variability in pain experiences. The objectives of this study were (1) to identify distinct pain subgroups based on demographic and biopsychosocial characteristics and (2) to evaluate the relationship between the subgroups and pain impact - a SCD-disease specific measure of pain interference. To achieve these objectives, we performed a hierarchical cluster analysis on a cross-sectional sample of adults with SCD …

Prevalence Of Cardiovascular-Kidney-Metabolic Stages In Us Adolescents And Relationship To Social Determinants Of Health, Carissa M. Baker-Smith, Abigail M. Gauen, Lucia C. Petito, Sadiya S. Khan, Norrina B. Allen

Department of Pediatrics Faculty Papers

BACKGROUND: Risk factors for atherosclerotic cardiovascular disease begin in youth. Knowledge of the prevalence of cardio-kidney-metabolic (CKM) syndrome in adolescents and its risk factors is critical to understanding the cause of atherosclerotic cardiovascular disease risk burden.

METHODS: We conducted a cross-sectional analysis of the 2017 to 2020 US National Health and Nutrition Examination Survey data and determined the prevalence of each CKM stage in adolescents aged 12 to 18 years. We then assessed the relationship between the family income-to-poverty ratio, health insurance, routine health care access, food security, health behaviors, and CKM stage. We quantified associations between social factors, behaviors, …

Development And Validation Of A Clinical Risk Model For Postoperative Outcome In Newly Diagnosed Glioblastoma: A Report Of The Rano Resect Group, Philipp Karschnia, Jacob S Young, Gilbert C Youssef, Antonio Dono, Levin Häni, Tommaso Sciortino, Francesco Bruno, Stephanie T Juenger, Nico Teske, Jorg Dietrich, Michael Weller, Michael A Vogelbaum, Martin Van Den Bent, Juergen Beck, Niklas Thon, Jasper K W Gerritsen, Shawn Hervey-Jumper, Daniel P Cahill, Susan M Chang, Roberta Rudà, Lorenzo Bello, Oliver Schnell, Yoshua Esquenazi, Maximilian I Ruge, Stefan J Grau, Raymond Y Huang, Patrick Y Wen, Mitchel S Berger, Annette M Molinaro, Joerg-Christian Tonn

Faculty, Staff and Student Publications

Background: Following surgery, patients with newly diagnosed glioblastoma frequently enter clinical trials. Nuanced risk assessment is warranted to reduce imbalances between study arms. Here, we aimed (I) to analyze the interactive effects of residual tumor with clinical and molecular factors on outcome and (II) to define a postoperative risk assessment tool.

Methods: The response assessment in neuro-oncology (RANO) resect group retrospectively compiled an international, seven-center training cohort of patients with newly diagnosed glioblastoma. The combined associations of residual tumor with molecular or clinical factors and survival were analyzed, and recursive partitioning analysis was performed for risk modeling. The resulting model …

Long-Term Efficacy Of Pembrolizumab And The Clinical Utility Of Ctdna In Locally Advanced Dmmr/Msi-H Solid Tumors, Michael Lapelusa, Wei Qiao, Bryan Iorgulescu, Francis San Lucas, Keyur Patel, Deepak Bhamidipati, Jane Varkey Thomas, Nancy You, Wai Chin Foo, Dipen Maru, Selvi Thirumurthi, Van Morris, Scott Kopetz, Michael Overman, Kaysia Ludford

Faculty, Staff and Student Publications

Neoadjuvant immunotherapy can induce pathologic complete response (pCR) in patients with localized deficient mismatch repair (dMMR)/microsatellite instability-high (MSI-H) tumors. The long-term outcomes of these patients are unknown, as is the clinical utility of measuring circulating tumor DNA (ctDNA). Follow-up was evaluated in patients enrolled in a phase II trial (NCT04082572) that evaluated the efficacy and safety of pembrolizumab in patients with localized dMMR/MSI-H tumors. The primary outcomes of this trial have previously been reported. 3-year EFS and OS rates were 80% (95% CI: 66% - 93%) and 94% (95% CI: 86% - 100%). Patients without detectable ctDNA after pembrolizumab had …

Developing The Mycancergene Digital Health Portal To Improve Patients' Understanding Of Germline Cancer Genetic Test Results: Development, User, And Usability Testing Study, Phillip Trieu, Dominique Fetzer, Briana Mcleod, Kathryn Schweickert, Lauren Gutstein, Brian Egleston, Susan Domchek, Linda Fleisher, Lynne Wagner, Kuang-Yi Wen, Cara Cacioppo, Jessica E. Ebrahimzadeh, Dana Falcone, Claire Langer, Elisabeth Wood, Kelsey Karpink, Shelby Posen, Enida Selmani, Angela R. Bradbury

Department of Medical Oncology Faculty Papers

BACKGROUND: The use of multigene panels has significantly increased the likelihood that genetic testing will leave patients with uncertainties regarding test interpretation, implications, and recommendations, which will change over time. Effective longitudinal care models are needed to provide patients with updated information and to obtain patient and family history updates.

OBJECTIVE: To bridge this gap, we aimed to develop a patient- and genetic provider-informed digital genetic health portal (GHP), MyCancerGene, to improve longitudinal patient understanding of and responses to genetic testing.

METHODS: We used a 5-step process to develop MyCancerGene. To better understand their interest in and willingness to use …

Immunotherapy With Nebulized Pattern Recognition Receptor Agonists Restores Severe Immune Paralysis And Improves Outcomes In Mice With Influenza-Associated Pulmonary Aspergillosis, Jezreel Pantaleón García, Sebastian Wurster, Nathaniel D Albert, Uddalak Bharadwaj, Keerthi Bhoda, Vikram K Kulkarni, Mbaya Ntita, Paris Rodríguez Carstens, Madeleine Burch-Eapen, Daniela Covarrubias López, Jania Foncerrada Lizaola, Katherine E Larsen, Lauren M Matula, Seyed J Moghaddam, Yongxing Wang, Dimitrios P Kontoyiannis, Scott E Evans

Faculty, Staff and Student Publications

Influenza-associated pulmonary aspergillosis (IAPA) is a potentially deadly superinfection in patients with influenza pneumonia, especially those with severe disease, underlying immunosuppression, corticosteroid therapy, or requiring intensive care support. Given the high mortality of IAPA, adjunct immunomodulatory strategies remain a critical unmet need. Previously, the desensitization of pattern recognition pathways has been described as a hallmark of IAPA pathogenesis and a predictor of mortality in IAPA patients. Therefore, we studied the impact of nebulized Toll-like receptor 2/6/9 agonists Pam2 CSK4 (Pam2) and CpG oligodeoxynucleotides (ODNs) on infection outcomes and pulmonary immunopathology in a corticosteroid-immunosuppressed murine IAPA model. Mice with IAPA receiving …