Digital Commons Network^™

Five-Year Follow-Up Analysis Of Zuma-5: Axicabtagene Ciloleucel In Relapsed/Refractory Indolent Non-Hodgkin Lymphoma, Sattva S Neelapu, Julio C Chavez, Alison R Sehgal, Narendranath Epperla, Matthew L Ulrickson, Emmanuel Bachy, Pashna N Munshi, Carla Casulo, David G Maloney, Sven De Vos, Ran Reshef, Lori A Leslie, Olalekan O Oluwole, Ibrahim Yakoub-Agha, Rashmi Khanal, Joseph D Rosenblatt, Jacob Wulff, Rhine R Shen, Wangshu Zhang, Soumya Poddar, Harry Miao, Olga Nikolajeva, Caron A Jacobson

Faculty, Staff and Student Publications

Axicabtagene ciloleucel (axi-cel) is an autologous anti-CD19 chimeric antigen receptor (CAR) T-cell therapy approved for relapsed/refractory (R/R) follicular lymphoma (FL). Here, we report updated clinical outcomes from ZUMA-5 in 159 enrolled patients with R/R indolent non-Hodgkin lymphoma (iNHL; 127 with FL and 31 with marginal zone lymphoma) after a median follow-up of 64.6 months. Patients underwent leukapheresis and received lymphodepleting chemotherapy and axi-cel (2 × 106 CAR T cells/kg). The overall response rate was 90% (75% complete response rate). The median duration of response was 60.4 months, and the median progression-free survival (PFS) was 62.2 months; median time to next …

Acute Myeloid Leukemia With T(10; 17)(P15; Q21)/ Zmynd11::Mbtd1: A Subtype With Minimal Differentiation, Cd7/Cd56 Expression, And Generally Poor Outcomes In Adults, Qing Wei, Naveen Pemmaraju, Sa A Wang, Shimin Hu, Courtney Dinardo, Ghayas C Issa, Carlos E Bueso-Ramos, Jie Xu, Shaoying Li, Jeffrey L Medeiros, Guilin Tang

Faculty, Staff and Student Publications

No abstract provided.

Agitation In Alzheimer’S Disease: From Assessment To Therapeutics, Antonio L Teixeira, Youngran Kim, Thiago M Cordeiro, Gabriel A De Erausquin, Natalia P Rocha

Faculty, Staff and Student Publications

Agitation is a neuropsychiatric syndrome characterized by excessive motor and/or verbal behaviors, with or without aggressive behaviors. The prevalence of agitation in Alzheimer’s disease varies from 5% to over 50%. Multiple factors have been implicated in its pathophysiology, including disease stage, comorbidity with other symptoms (e.g., psychosis, anxiety/depression), and psychosocial factors. Ruling out delirium and identifying environmental triggers are fundamental steps in the management of agitation in Alzheimer’s disease. For establishing an effective therapeutic plan, it is important to define duration, severity, and potential for harm. While non-pharmacological approaches are considered the first line of intervention, pharmacological agents …

Infection And Nonunion Rates In Open Fractures: Description Of 6,042 Fractures From The Flow And Prep-It Trials, Roman M Natoli, Lucas S Marchand, Sofia Bzovsky, Jennifer E Hagen, Mark J Gage, Christina A Stennett, Nathan N O'Hara, Kyle J Jeray, Brad Petrisor, Sheila Sprague, Gerard P Slobogean

Faculty, Staff and Student Publications

Background: Infection and nonunion are common sequelae of open fractures. Studies have shown infection and nonunion rates ranging from 2% to 52% and 12% to 17%, respectively. The present article describes the rates of surgical site infection (SSI) and delayed union/nonunion following open fractures in a large contemporary series of patients from prospective clinical trials with adjudicated outcomes.

Methods: A descriptive analysis was performed with use of patient data from the FLOW, Aqueous-PREP, and PREPARE-Open studies. These studies, published within the past 10 years, included multiple international trauma centers and shared definitions for SSI and delayed union/nonunion. SSI and delayed …

14,441 Genomics-Based Validated Automated Comprehensive Clinicopathologic Correlations For Myeloid Neoplasms., Ahmed Elsafty, Yomna Ahmed, Taher F Halawa, Shaoguang Li, Dongguang Li, Elena Agranovsky, Ahmed Soliman, Howida Talaat, Mohamed Montaser, Omar Elnady, Deyaa Elnady, Mohamed Mahmoud Moustafa, Nourhan Ibrahim, Maryana Gumenyak, Yasmin Soliman, Samah Ali, Elshaimaa Abdelrahman, Hatem M S Alahwal, Ahmed S Barefah, Ashraf Abdelghany, Sherif Ammar, Nermeen Abdel-Haleem, Osama Abdel-Kareem, Samir N Shamma, Naglaa Husein, Maha M Sakr, Heba-Allah E Abdelrhman, Menatalla Nadim, Hany Girguis, Manal Othman, Ola Soliman, Walaa H Behery, Lamis Eltoukhy, Heldez A Mohamed, Aya M Hassan, Fatma-Elzahraa A Bebers, Marwa Abdel-Zaher, Sara A Abbas, Shady Attia, Mohamed A Saada, Amira S Eid, Soha E Khorshed, Khaled Talaat, Mohamed Saad Hamed Mahmoud, Mahmoud M S Mahmoud, Ola M S Mahmoud, Abdel-Rahman O Abdel-Kareem, Ahmed K Talaat, Haitham Heneish, Ibrahim I Samaha, Mones Safwat, Mohamed K Talaat, Alaa O Abdel-Kareem, Hadeel Abdel-Monem, Ramy Abaza, Hazem Abaza, Nora Ahmad, May A Maarouf, Iman A Shaheen, Ahmed S Abdelhafiz, Amera Rabee, Yara M Montaser

Faculty, Staff and Student Publications

The dataset (Elsafty_Reports_of_Myeloid_Neoplasms_2024) consists of 14,441 comprehensive clinicopathologic correlations (CPCs) for myeloid neoplasms (MN) with corresponding laboratory results. Specialized online platform utilizing these laboratory results automatically generated the diagnostic and prognostic CPCs. These results include complete blood counts (CBC), peripheral blood smear (PBS) findings, blast/promyelocyte count with dysplasia screening by flow cytometry, and molecular results by NGS/PCR. Two Hematopathologists, who performed the CBC and PBS review, collected their 10,794 real-world reports of cases served in Egypt with molecular studies performed in the USA and Europe. These newly-diagnosed cases included 243 chronic myeloid leukemia (CML) cases with 257 mutations/aberrations; 4,567 non-CML …

Estimated Impact Of 2022–2023 Influenza Vaccines On Annual Hospital Burden In The United States, Kaiming Bi, Shraddha Ramdas Bandekar, Anass Bouchnita, Annalise Cramer, Spencer J Fox, Rebecca K Borchering, Matthew Biggerstaff, Lauren Ancel Meyers

Faculty, Staff and Student Publications

During the COVID-19 pandemic early years, infection prevention measures suppressed transmission of seasonal influenza and other respiratory viruses. The early onset and moderate severity of the US 2022-2023 influenza season may have resulted from reduced use of nonpharmaceutical interventions or lower population immunity after 2 y of limited influenza virus circulation. We used a mathematical model of influenza virus transmission that incorporates vaccine-derived protection against both infection and severe disease to estimate the impact of influenza vaccines on healthcare burden. Assuming reported levels of past vaccine effectiveness (VE) against infection and hospitalization, we estimate that influenza vaccines prevented 69,886 (95% …

Sex Differences In Atherosclerotic Coronary Artery Disease Patterns, Kazumasa Ikeda, Daniel Munhoz, Sofie Brouwers, Jeroen Sonck, Hitoshi Matsuo, Toshiro Shinke, Hirohiko Ando, Brian Ko, Simone Biscaglia, Fernando Rivero, Thomas Engstrøm, Ketina Arslani, Antonio Maria Leone, Domenico Galante, Lokien X Van Nunen, William F Fearon, Evald Høj Christiansen, Stephane Fournier, Liyew Desta, Andy Yong, Julien Adjedj, Javier Escaned, Masafumi Nakayama, Ashkan Eftekhari, Frederik M Zimmermann, Koshiro Sakai, Tatyana Storozhenko, Bruno R Da Costa, Gianluca Campo, Colin Berry, Damien Collison, Thomas Johnson, Tetsuya Amano, Divaka Perera, Allen Jeremias, Ziad Ali, Bernard De Bruyne, Frederic Bouisset, Takashi Kubo, Nobuhiro Tanaka, Kazuhiro Satomi, Nils P Johnson, Carlos Collet, Takuya Mizukami

Faculty, Staff and Student Publications

Background: Sex differences in coronary artery disease (CAD) have been increasingly recognized, as women present with distinct clinical characteristics and outcomes compared with men. This study investigated the impact of sex on pathophysiological CAD patterns (focal versus diffuse) in stable patients undergoing percutaneous coronary interventions (PCI).

Methods: We conducted a subanalysis of the PPG Global (Pullback Pressure Gradient Global Registry) study, a multicenter, prospective trial including 993 patients (236 [23.8%] women and 757 [76.2%] men) with hemodynamically significant CAD, defined as fractional flow reserve ≤0.80. The pullback pressure gradient metric categorized CAD patterns as focal or diffuse. Patient-reported outcomes were …

Ertapenem As An Antibiotic Prophylaxis For Colectomies And Laparotomies: A Systematic Review, Stephanie Martinez Ugarte, Mokunfayo O Fajemisin, Beatriz Varman, Parker C Towns, Elias A Chamely, Renee W Green, William D Rieger, Susan H Wootton, Lillian S Kao

Library Staff Publications

Introduction: Given concerns for antibiotic resistance, broader spectrum antibiotic agents such as ertapenem are being used for pre-operative prophylaxis. We hypothesize that pre-operative ertapenem prior to laparotomies and colectomies is superior at decreasing surgical site infections (SSIs) compared with other widely used antibiotic agents.

Methods: Medline, Embase, the Cochrane Library, and Web of Science were queried for studies until February 02, 2025. Studies were excluded if they did not evaluate ertapenem as a pre-operative antibiotic prophylaxis in patients undergoing laparotomy or colectomy, the outcome was not SSIs, or it represented a review of prior publications. Three reviewers independently extracted relevant …

Ertapenem As An Antibiotic Prophylaxis For Colectomies And Laparotomies: A Systematic Review, Stephanie Martinez Ugarte, Mokunfayo O Fajemisin, Beatriz Varman, Parker C Towns, Elias A Chamely, Renee W Green, William D Rieger, Susan H Wootton, Lillian S Kao

Library Staff Publications

Introduction: Given concerns for antibiotic resistance, broader spectrum antibiotic agents such as ertapenem are being used for pre-operative prophylaxis. We hypothesize that pre-operative ertapenem prior to laparotomies and colectomies is superior at decreasing surgical site infections (SSIs) compared with other widely used antibiotic agents.

Methods: Medline, Embase, the Cochrane Library, and Web of Science were queried for studies until February 02, 2025. Studies were excluded if they did not evaluate ertapenem as a pre-operative antibiotic prophylaxis in patients undergoing laparotomy or colectomy, the outcome was not SSIs, or it represented a review of prior publications. Three reviewers independently extracted relevant …

Retinol Tracing Within Murine Neural Retina Reveals Cell Type-Specific Retinol Transport And Distribution, Zachary J Engfer, Grazyna Palczewska, Samuel W Du, Jianye Zhang, Zhiqian Dong, Carolline Rodrigues Menezes, Jun Wang, Jianming Shao, Budd A Tucker, Robert F Mullins, Rui Chen, Philip D Kiser, Krzysztof Palczewski

Faculty, Staff and Students Publications

11-cis-Retinal is essential for light perception in mammalian photoreceptors (PRs), and aberrations in retinoid transformations cause severe retinal diseases. Understanding these processes is crucial for combating blinding diseases. The visual cycle, operating within PRs and the retinal pigment epithelium (RPE), regenerates 11-cis-retinal to sustain light sensitivity. Retinoids are also present in Müller glia (MG), hypothesized to supply 11-cis-retinol to cone PRs and retinal ganglion cells (RGCs). To trace retinoid movement through retinal cell types, we used cell-specific knock-in of lecithin:retinol acyltransferase (LRAT), which converts retinols into stable retinyl esters (REs). Ectopic LRAT expression in murine PRs, MG, and RGCs resulted …

Improved Technical Outcomes With Converting Thrombectomy Techniques After Failed First Pass Recanalization, Hidetoshi Matsukawa, Charles Matouk, Kazutaka Uchida, Sami Al Kasab, Mohammad-Mahdi Sowlat, Sameh Samir Elawady, Ilko Maier, Pascal Jabbour, Joon-Tae Kim, Stacey Q Wolfe, Ansaar T Rai, Robert M Starke, Marios-Nikos Psychogios, Edgar A Samaniego, Adam S Arthur, Hugo Cuellar, Brain M Howard, Daniele G Romano, Omar Tanweer, Justin R Mascitelli, Isabel Fragata, Adam Polifka, Joshua W Osbun, Roberto Javier Crosa, Min S Park, Michael R Levitt, Waleed Brinjikji, Mark Moss, Richard Williamson, Pedro Navia, Peter Kan, Reade Andrew De Leacy, Shakeel A Chowdhry, Mohamad Ezzeldin, Alejandro M Spiotta, Shinichi Yoshimura, Ali M Alawieh

Faculty, Staff and Students Publications

Background: A higher number of recanalization attempts reduces the efficacy of endovascular thrombectomy (EVT) for acute ischemic stroke secondary to large vessel occlusion (LVO). We assessed the impact of switching EVT techniques after a failed first pass on procedural and clinical outcomes.

Methods: This multicenter international study, conducted between January 2013 and December 2022, included patients undergoing EVT for anterior circulation LVO (internal carotid artery or M1 segments) with failed first pass recanalization. Propensity score matching identified a 1:1 matched cohort of patients in whom EVT technique was changed after a failed first pass and those with the same technique …

Be Faster Community Of Practice To Increase Rapid Initiation Of Antiretroviral Therapy In Houston, Texas: A Pre-Post Intervention Study, Naomi Sequeira, Bich N Dang, Melanie Goebel, Monisha Arya, Avishek Ghosh-Hajra, Kathryn Fergus, Shital M Patel

Faculty, Staff and Students Publications

Background: Rapid initiation of antiretroviral therapy (Rapid ART) is a key strategy of the Ending the HIV Epidemic (EHE) initiative. The Baylor College of Medicine Extension for Community Healthcare Outcomes (ECHO) Facilitating Antiretroviral Start Earlier (BE FASTER) program was developed to address this call-to-action. The program uses the ProjectECHO tele-mentoring model as an implementation tool in Harris County, a priority EHE jurisdiction. The authors present results on the acceptability and feasibility of the BE FASTER program.

Methods: Multidisciplinary health professionals from 5 Ryan White Part A funded agencies formed the community of practice. The BE FASTER program included 9 monthly …

Prognosis And Treatment Response Stratification According To Loss Of Proofreading (Lop), Giulia Maddalena, Fadl A Zeineddine, Saikat Chowdhury, Mohammad A Zeineddine, Abdelrahman M Yousef, Francesca Bergamo, Sara Lonardi, Timothy A Yap, Michael Geoffrey White, Michael J Overman, Scott Kopetz, John Paul Shen

Faculty, Staff and Student Publications

Background: Only a subset of polymerase epsilon (POLE) mutations is associated with hypermutant phenotype; we hypothesized that only loss-of-proofreading (LOP) POLE mutations are associated with favorable immunotherapy response.

Methods: This retrospective cohort study included a pan-cancer cohort of 69,223 patients from cBioPortal and a cohort of patients with 41 POLE mutant metastatic colorectal (CRC) treated with immunotherapy at the MD Anderson Cancer Center between January 2017 and May 2023. We evaluated prognosis according to POLE mutation functionality.

Results: In the pan-cancer cBioPortal cohort (n=69,223) POLE was mutated in 2.8% (1,965) of tumors; of these, only 7.5% (n=148) had …

Comparing Diagnostic Tools For Heart Failure With Preserved Ejection Fraction Across Community And Clinical Cohorts, Luca Monzo, Olivier Huttin, Biykem Bozkurt, Kévin Duarte, Cecilia Linde, Lars H Lund, Camilla Hage, Erwan Donal, Martin Magnusson, Peter Nilsson, Margret Leosdottir, Erwan Bozec, Guillaume Baudry, Faiez Zannad, Nicolas Girerd

Faculty, Staff and Students Publications

Background: Diagnosing heart failure with preserved ejection fraction (HFpEF) remains challenging, particularly in older adults. While the Heart Failure Association (HFA)-PEFF and H2FPEF Scores offer structured diagnostic approaches, their clinical utility is still debated. This study aims to compare the diagnostic accuracy of HFpEF Scores versus inclusion criteria used in sodium-glucose cotransporter-2 inhibitors (SGLT2i) trials, age-adjusted N-terminal pro B-type natriuretic peptide (NT-proBNP) thresholds and the universal definition of heart failure (HF).

Methods: Diagnostic tools were assessed using sex-weighted and age-weighted propensity score adjustment in individuals aged 60-80 years from two established HFpEF cohorts (MEtabolic Road to DIAstolic Heart Failure (MEDIA), …

Family Caregivers' Perspectives On Challenges And Support Needs In Hospital-Based Palliative Care For Persons Living With Dementia, Jung Kwak, Anita Chary, Sarah Stayer, Kwaku Duah Oppong, Sumin Yoon, Snehal Patel, Elizabeth A Kvale

Faculty, Staff and Students Publications

Palliative care needs of hospitalized persons living with dementia (PLWD) and their family caregivers remain poorly understood. This mixed-methods study explored caregivers' perspectives on challenges and support needs when hospitalized PLWD received specialist palliative care consultations. Thirty-two caregivers were recruited from two hospitals; 18 completed interviews and surveys, and 14 completed surveys only. Participants were racially and ethnically diverse (19% Black or African American, 34% Latino or Hispanic). Most identified as women (65%) and adult children (56%). Commonly reported challenges included managing health issues (59%), emotional distress (56%), and decision-making (47%). Thematic analysis of interviews revealed three themes: the value …

Application Of Freezetb, A Targeted Nanopore Sequencing Assay, For Identification Of Drug Resistance And Lineages Among Pulmonary Tuberculosis Cases In Alaska, Bryce Inman, Jeremy Butler, Soren George-Nichol, Ganna Kovalenko, Theresa Savidge, Yvette Vergnetti, Catherine Pongratz, Elizabeth Bee, Andrew R Dinardo, Alexander Kay, Anna Mandalakas, Eric Bortz, Tara E Ness

Faculty, Staff and Students Publications

Alaska has the highest incidence of tuberculosis (TB) in the United States, with 8% mortality while undergoing TB treatment. With a quarter of TB cases lacking sputum culture to enable drug resistance testing, FreezeTB aimed to develop tools tailored to meet the challenges in Alaska while being translatable to other settings. We designed a rapid and cost-effective laboratory workflow and software to identify drug-resistant mutations in Mycobacterium tuberculosis using targeted next-generation sequencing (tNGS). FreezeTB, a Fast, Reliable, Economical Evaluation tool to Zap Endemic Tuberculosis, amplifies 22 gene loci associated with resistance to 16 anti-tuberculosis drugs. M. tuberculosis isolates from Alaska …

Effects Of Residual Pah Exposure From Firefighters’ Skin And Turnout Gear On Biospecimen Microrna Expression, Jooyeon Hwang, Jenny R Gipson, Chao Xu, Timothy Vanwagoner, Xin Xu, Robert J Agnew, Willard M Freeman

Faculty, Staff and Student Publications

Firefighters are routinely exposed to polycyclic aromatic hydrocarbons (PAHs) during fire suppression activities, molecular biomarkers reflecting such exposure remain underexplored. Thus, we explored an integrated exposure assessment framework linking PAH contamination on turnout gear and skin to changes in microRNA (miRNA) expression in skin and blood biospecimens. Our goals are to evaluate the relationship between fire-related PAH exposure and miRNA expression profiles in firefighters, and to identify candidate miRNA biomarkers of occupational exposure. This prospective study enrolled 25 firefighters. PAHs on turnout gear and skin were quantified post-fire using gas chromatography/mass spectrometry. Concurrently, skin tape strips and blood were collected …

Comparing The Effects Of Ect And Intravenous Ketamine In Psychiatric Patients With Major Depressive Episodes, Julia Myerson, Katrina A Rufino, Sanjay J Mathew, Marie Fletcher, Neil Puri, Hyuntaek Oh

Faculty, Staff and Students Publications

Background: Electroconvulsive therapy (ECT) and intravenous (IV) ketamine are treatments used for severe depression and/or treatment-resistant depression (TRD). ECT is considered one of the most effective treatments for severe depression, although there is debate within the field regarding the effectiveness between ECT and IV ketamine in comparable TRD patient groups.

Methods: This retrospective chart review of open-label, nonrandomized treatment from a psychiatric hospital compared the effects of up to three weeks of ECT and IV ketamine in patients with major depressive episodes (MDEs). Our cohort included 146 inpatients and outpatients aged 18 to 74 years old. 94 patients received subanesthetic …

Characterizing The Metabolites Of The Tyrosine-Kinase Inhibitor Pexidartinib In Mouse Feces, Urine, Plasma, And Liver, Xuan Qin, Si Chen, John M Hakenjos, Jian Wang, Lei Guo, Ashish Dogra, Zhaoyong Hu, Kevin R Mackenzie, Feng Li

Faculty, Staff and Students Publications

Pexidartinib (PEX, TURALIO®), a tyrosine kinase inhibitor, is approved for treating tenosynovial giant cell tumor in adults. However, its potential to cause fatal liver injury has prompted the U.S. FDA to issue a black box warning, and the mechanisms underlying its hepatotoxicity remain largely unknown. As biotransformation may contribute to PEX-induced hepatotoxicity, understanding its metabolism is essential. Our previous research indicated that PEX forms reactive metabolites in human and mouse liver microsomes and in human hepatocytes. We investigated PEX metabolism and liver distribution in mice with a focus on metabolite characterization. Our data shows that PEX is mainly excreted into …

Late Morbidity And Mortality In Survivors Of Childhood Ependymoma: A Report From The Childhood Cancer Survivor Study (Ccss), Katharine R Lange, Peter De Blank, Mengqi Xing, Sedigheh Mirzaei, Deo Kumar Srivastava, Kevin Oeffinger, Joseph Neglia, Kevin Krull, Paul C Nathan, Rebecca Howell, Kirsten K Ness, Lucie M Turcotte, Wendy Leisenring, Gregory T Armstrong, Tara Brinkman, Daniel C Bowers, Mehmet Fatih Okcu

Faculty, Staff and Student Publications

Background/objectives: Treatment of childhood ependymoma evolved from 1970 to 1999 by reducing radiation volumes and incorporating chemotherapy. The impact of these changes on long-term health outcomes remains unknown. In this report, we evaluated temporal changes in all-cause and cause-specific late mortality, chronic health conditions (CHCs), and subsequent neoplasms (SNs) in the Childhood Cancer Survivor Study (CCSS) cohort of adult survivors of pediatric ependymoma, diagnosed between 1970 and 1999.

Methods: A total of 404 five-year survivors of ependymoma (47.5% female, 80.7% non-Hispanic White, median 6 (range 0-20) years at diagnosis, 22 (5-49) years from diagnosis) diagnosed between 1970 and 1999 and …

Imaging Features Of High-Grade Astrocytoma With Piloid Features: A Single Center Case Series, Heba Al Qudah, Jackson D Hamilton, Maria A Gubbiotti, Ahmed Msherghi, Hamza A Salim, Sahar Alizada, Ho-Ling Liu, Vinodh A Kumar, Max Wintermark, Rami W Eldaya

Faculty, Staff and Student Publications

High-grade astrocytoma with piloid features (HGAP) is a recently described IDH-wildtype tumor with limited literature describing its imaging features. We present our institution's experience and the largest imaging-focused cohort of HGAP reported to date, offering a comprehensive analysis of MRI features of seventeen intracranial and one spinal HGAP, while introducing novel imaging features that have not been previously described. These include focal areas of diffusion restriction, surrounding spiculated, finger-like enhancement and increased perfusion metrics. Additionally, we highlight imaging features of HGAP arising in patients with Neurofibromatosis Type 1, such as intraventricular tumor spread, unusual temporal lobe location and multifocal presentation.

First-Line Met Tyrosine Kinase Inhibitors Versus Immunotherapy ± Chemotherapy For Patients With Met Exon 14 Skipping Mutant Metastatic Nsclc, Federica Pecci, Hui Li, Alessandro Di Federico, Jia Wu, Hong Chen, Eleonora Gariazzo, Francesco Mantuano, Edoardo Garbo, Mihaela Aldea, Valentina Santo, Don Gibbons, Hai Tran, Francesco Paoloni, Guilherme Rossato De Almeida, Giulio Metro, Andrea De Giglio, Francesco Gelsomino, Xinan Wang, Marcello Tiseo, Julia Rotow, Andrea Ardizzoni, J Jack Lee, Mark M Awad, Alfredo Addeo, Lingzhi Hong, Marcelo V Negrao, Pasi A Jänne, John V Heymach, Jianjun Zhang, Biagio Ricciuti, Xiuning Le

Faculty, Staff and Student Publications

Purpose: First-line treatment options for MET exon 14 skipping-mutant metastatic non-small cell lung cancer vary because of differences in drug approvals and clinical experience. This study investigates factors influencing outcomes with first-line MET tyrosine kinase inhibitors (TKI) versus immune checkpoint inhibitors (ICI) ± chemotherapy.

Experimental design: Clinicopathologic data were collected from patients with metastatic MET exon 14 skipping-mutant non-small cell lung cancer treated with first-line MET TKI or ICI ± chemotherapy at five centers. Primary endpoints were real-world progression-free survival (rwPFS) and overall survival (OS) to first-line MET TKI versus ICI ± chemotherapy. Subgroup analyses by clinical and tumor characteristics …

A Role For Gut Mycobiome And Altered Fungal-Bacterial Interactions In Women With Endometriosis†, Chandni Talwar, Ashirbad Guria, Kristi Hoffman, Scott Biest, Patricia Jimenez, Ramakrishna Kommagani

Faculty, Staff and Students Publications

Endometriosis is a gynecological pathology prevalent in reproductive age women in which the inner uterine wall (endometrium) grows outside as ectopic lesions. The inflammation resulting from these growing implants closely associates with disease severity, causing chronic pain and infertility. Emerging studies have found altered bacterial communities in endometriosis and a causal role for gut bacteria in endometriosis. However, the role of the gut mycobiome, i.e., the fungal component of the microbiome in endometriosis is a current knowledge gap that needs to be addressed. In this study, utilizing the stool samples from women with endometriosis, we found that the gut fungal …

Vitamin D Is Glucoprotective In Aging Males But Not Females, Olivia Z B Ginnard, Maria Morales, Ji Youn Youn, Yong Xu, Stephanie R Sisley

Faculty, Staff and Students Publications

Vitamin D supplementation is linked to many beneficial health outcomes in the geriatric population, such as decreased mortality, epigenetic aging, and fracture risk. Conversely, type 2 diabetes is strongly linked to vitamin D deficiency in older adults. However, there is a discrepancy between clinical trials in adults on the efficacy of vitamin D treatment in prediabetes and diabetes. In addition, human data indicates there may be sexual dimorphism in the effect of vitamin D deficiency on dysglycemia that is more pronounced in men. These incongruities may be due to our limited understanding of the underlying mechanisms of vitamin D in …

Efficacy Of Medical-Legal Partnerships To Address Health-Harming Legal Needs: A Systematic Review Of Experimental Studies In The Field, Jemima John, Thomas Murphy, Emily Zientek, Winston Liaw, Odinakachukwu Dimgba, Thien-An Nguyen, Catherine Burnett, Mary Aitken, Shreela Sharma

Faculty, Staff and Student Publications

Background: Despite the documented success of medical-legal partnerships (MLPs), there is a dearth of robust experimental-based research on their efficacy. This review synthesizes the findings of MLP interventions and identifies opportunities for MLP expansion in vulnerable communities.

Methods: Articles were eligible if they tested the experimental effects of an MLP intervention on health-harming legal needs (HHLNs) and had full text for review. Two reviewers independently screened articles for inclusion and assessed the quality (risk of bias) of each study.

Results: Seven studies were eligible. Populations were largely women, of color, and of lower socioeconomic status. All studies demonstrated positive effects …

Culture-Independent Meta-Pangenomics Enabled By Long-Read Metagenomics Reveals Associations With Pediatric Undernutrition, Jeremiah J Minich, Nicholas Allsing, M Omar Din, Michael J Tisza, Kenneth Maleta, Daniel Mcdonald, Nolan Hartwick, Allen Mamerto, Caitriona Brennan, Lauren Hansen, Justin Shaffer, Emily R Murray, Tiffany Duong, Rob Knight, Kevin Stephenson, Mark J Manary, Todd P Michael

Faculty, Staff and Students Publications

The human gut microbiome is linked to child malnutrition, yet traditional microbiome approaches lack resolution. We hypothesized that complete metagenome-assembled genomes (cMAGs), recovered through long-read (LR) DNA sequencing, would enable pangenome and microbial genome-wide association study (GWAS) analyses to identify microbial genetic associations with child linear growth. LR methods produced 44-64× more cMAGs per gigabase pair (Gbp) than short-read methods, with PacBio (PB) yielding the most accurate and cost-effective assemblies. In a Malawian longitudinal pediatric cohort, we generated 986 cMAGs (839 circular) from 47 samples and applied this database to an expanded set of 210 samples. Machine learning identified species …

Genetic And Embryonic Transcriptome Analyses Reveal The Molecular And Developmental Basis Of Mayer-Rokitansky-Küster-Hauser Syndrome, Na Chen, Xi Cheng, Sen Zhao, Hengqiang Zhao, Chenglu Qin, Yaru Zhang, Xijuan Lin, Qing Li, Yuan Wang, Jia Kang, Jing Yu, Jianbin Guo, Qianqian Gao, Jiali Duan, Yuchen Niu, Jianzhong Su, Zhihong Wu, Terry Jianguo Zhang, Wanlu Liu, Pengfei Liu, Shan Deng, Nan Wu, Lan Zhu

Faculty, Staff and Students Publications

Background: Mayer-Rokitansky-Küster-Hauser syndrome (MRKHS) is characterised by aplasia of the uterus, cervix and upper part of the vagina. The genetic aetiology remains incompletely understood.

Methods: We performed gene-level and gene set-level burden analyses based on exome sequencing/genome sequencing data from 727 probands with MRKHS and 2504 female control individuals. Single-cell RNA sequencing (scRNA-seq) was performed on human and mouse embryonic metanephros at different developmental stages. Genetic and transcriptomic data were integrated to prioritise suboptimal genetic signals, identify relevant cell types and determine key developmental stages. Potential digenic inheritance was assessed and prioritised using coexpression patterns from scRNA-seq data.

Results: We …

A Practical Primer On How To Detect And Treat Depression In Ckd, L Parker Gregg, Lynnel Goodman, Ella Q Carroll, S Susan Hedayati

Faculty, Staff and Students Publications

Detection and management of depression have special considerations in people with kidney disease. Screening should be done every 6-12 months using a self-reported questionnaire. Clinicians should rule out symptoms from medical conditions such as dialysis inadequacy or hypothyroidism and confirm the presence of sadness or anhedonia. Sertraline has shown limited efficacy and an increased risk for adverse effects such as gastrointestinal symptoms, so cautious, gradual dose titration is warranted. Cognitive behavioral therapy has potential benefit for depressive symptoms in people with kidney disease. Current trials are evaluating behavioral activation therapy. Physical activity has many benefits and likely improves depression.

Design, Optimization, And Development Of Ripk1 Degraders With Improved Pharmacokinetic And Pharmacodynamic Properties, Dong Lu, Xin Yu, Hanfeng Lin, Ran Cheng, Bin Yang, Min Zhang, Jingjing Chen, Feng Li, Xiaoli Qi, Jin Wang

Faculty, Staff and Students Publications

Pharmacological degradation of receptor-interacting protein kinase 1 (RIPK1) offers a compelling therapeutic strategy to overcome its scaffolding role in tumor resistance and to enhance the efficacy of immune checkpoint blockade (ICB) therapies. In this study, we report the discovery of a novel RIPK1 degrader, LD5097(24b), developed through systematic optimization of its precursor compound, LD4172—specifically refining the linker, RIPK1 warhead exit vector, and VHL ligand components. LD5097(24b) exhibits potent and selective RIPK1 degradation, triggering rapid and efficient downregulation of RIPK1 and significantly enhancing TNFα-mediated apoptosis in Jurkat cells. Compared to LD4172, LD5097(24b) demonstrates markedly improved metabolic stability and pharmacokinetic properties. In …

Primary Intramedullary Spinal Melanocytomas: Case Report And Review Of Clinical Features, Diagnosis, And Management, Gil Kimchi, Samantha Varela, Juan Pablo Zuluaga-Garcia, Francisco Call-Orellana, Esteban Ramirez Ferrer, Romulo Augusto Andrade De Almeida, Maria A Gubbiotti, Isabella C Glitza, Andrew J Bishop, Jonathan D Grant, Robert Y North, Christopher A Alvarez-Breckenridge, Laurence D Rhines, Claudio E Tatsui

Faculty, Staff and Student Publications

Objective: Intramedullary melanocytomas are extremely rare spinal cord tumors with distinct histopathological and imaging characteristics. This report reviews the literature on this pathology and presents a representative case study, highlighting aspects of diagnosis and management.

Methods: A scoping review of PubMed, Web of Science, and Embase databases was conducted to identify reports on intramedullary melanocytomas, focusing on clinical presentation, imaging features, histopathology, treatment, and outcomes. Case reports and case series were included due to the rarity of these tumors.

Results: Twelve manuscripts met the inclusion criteria, including 15 patients. In the majority of patients, intramedullary melanocytomas present with progressive myelopathy …