Medical Specialties Commons^™

Large-Scale Genome-Wide Analyses Of Stuttering, Hannah G Polikowsky, Alyssa C Scartozzi, Douglas M Shaw, Dillon G Pruett, Hung-Hsin Chen, Lauren E Petty, Alexander S Petty, Emily J Lowther, Shu-Hsien Cho, Yao Yu, Sahar Mozaffari, Christy L Avery, Kathleen Mullan Harris, Reyna L Gordon, Janet M Beilby, Kathryn Z Viljoen, Robin M Jones, Chad D Huff, Heather M Highland, Shelly Jo Kraft, Jennifer E Below

Faculty, Staff and Student Publications

Developmental stuttering is a highly heritable, common speech condition characterized by prolongations, blocks and repetitions of speech. Although stuttering is highly heritable and enriched within families, the genetic architecture is largely understudied. We reasoned that there are both shared and distinct genetic variants impacting stuttering risk within sex and ancestry groups. To test this idea, we performed eight primary genome-wide association analyses of self-reported stuttering that were stratified by sex and ancestry, as well as secondary meta-analyses of more than one million individuals (99,776 cases and 1,023,243 controls), identifying 57 unique loci. We validated the genetic risk of self-reported stuttering …

Generation Of Human Induced Pluripotent Stem Cell Lines From An Age-Related Macular Degeneration Patient With Hyperreflective Foci Overlying Drusen (Rfsci002-A) And An Unaffected Sibling (Rfsci001-A), Adnin Ashrafi, Wendy Runyon, Sam Hu, Ritu Kumar, Timothy Catchpole, Ajeet Singh, Rinki Ratnapriya, Karl G Csaky, Srinivasa R Sripathi

Faculty, Staff and Students Publications

Age-related macular degeneration (AMD) is a leading cause of vision loss, driven by retinal pigment epithelium (RPE) and photoreceptor degeneration. A key feature is drusen accumulation between the RPE and Bruch's membrane. In intermediate AMD, hyperreflective foci (HRF)-bright intraretinal lesions visible on optical coherence tomography (OCT) imaging-serve as biomarkers of disease progression. To study HRF mechanisms, we generated induced pluripotent stem cell (iPSC) lines from an AMD patient with HRF overlying drusen (RFSC4) and their unaffected sibling (RFSC3). These iPSC models offer a platform to explore disease mechanisms and develop therapies for AMD.

Perioperative Durvalumab Plus Chemotherapy Plus New Agents For Resectable Non-Small-Cell Lung Cancer: The Platform Phase 2 Neocoast-2 Trial, Tina Cascone, Laura Bonanno, Florian Guisier, Amelia Insa, Moishe Liberman, Olivier Bylicki, Lorenzo Livi, Thomas Egenod, Romain Corre, Dong-Wan Kim, Maria Rosario Garcia Campelo, Mariano Provencio Pulla, Byoung Yong Shim, Giulio Metro, Jaafar Bennouna, Agata A Bielska, Alula R Yohannes, Yun He, Adam Dowson, Gozde Kar, Lara Mcgrath, Rakesh Kumar, Italia Grenga, Jonathan Spicer, Patrick M Forde

Faculty, Staff and Student Publications

In the phase II NeoCOAST-2 platform study, 202 patients with untreated, resectable stage IIA–IIIB non-small-cell lung cancer (NSCLC) were randomized to receive neoadjuvant durvalumab plus platinum-doublet chemotherapy with oleclumab, a CD73 inhibitor (Arm 1), or with monalizumab, a NKG2A inhibitor (Arm 2), or neoadjuvant durvalumab plus single-agent platinum chemotherapy with the TROP-2 antibody–drug conjugate (ADC) datopotamab deruxtecan (Arm 4), followed by surgical resection and adjuvant durvalumab with oleclumab or monalizumab (Arms 1 and 2) or durvalumab alone (Arm 4). Primary endpoints were pathological complete response (pCR) rate and safety; secondary endpoints included feasibility of surgery and major pathological response (mPR) …

A Phase 2 Trial Of Cpx-351 Combined With Venetoclax In Relapsed Or Refractory Acute Myeloid Leukemia, Tapan M Kadia, Wei-Ying Jen, Alex Bataller, Alexandre Bazinet, Gautam Borthakur, Elias Jabbour, Wei Qiao, Nicholas J Short, Koichi Takahashi, Ghayas C Issa, Courtney D Dinardo, Guillermo Montalban-Bravo, Naveen Pemmaraju, Andrew Tran, Vanthana Bharathi, Sanam Loghavi, Amin M Alousi, Uday Popat, Naval G Daver, Farhad Ravandi, Hagop M Kantarjian

Faculty, Staff and Student Publications

Outcomes in patients with relapsed/refractory (RR) AML are poor. We sought to investigate if CPX-531 in combination with venetoclax (CPX + VEN) was tolerable and effective in RR AML. This was a single institution phase 1b/2 trial of CPX + VEN. Patients aged ≥ 18 years with RR AML who were fit for intensive chemotherapy were eligible. Prior venetoclax exposure was allowed. The phase 1b portion followed a 3 + 3 design to identify the recommended phase 2 dose (RP2D) for the expansion cohort. At the starting dose level of −1, prolonged myelosuppression was observed, leading to dose level −2 …

Excellent Response Following Palliative Radiation For Locally Advanced Epidemic/Aids-Associated Kaposi Sarcoma Of The Lower Extremity: A Case Report, Anushka S Mandalapu, Alison K Yoder, Xin Wang, Devarati Mitra, Andrew J Bishop, B Ashleigh Guadagnolo, Ahsan S Farooqi

Faculty, Staff and Student Publications

No abstract provided.

Acquired Resistance In Cancer: Towards Targeted Therapeutic Strategies, Alice Soragni, Erik S Knudsen, Thomas N O'Connor, Cristina E Tognon, Jeffrey W Tyner, Beatrice Gini, Donghwa Kim, Trever G Bivona, Xingxing Zang, Agnieszka K Witkiewicz, David W Goodrich, Dadi Jiang, Seth T Gammon, Christopher D Willey, Paul C Boutros, Vlad C Sandulache, Abdullah A Osman, Jeffrey N Myers, Kamiya Mehla, Pankaj K Singh, Keith S Chan, Hongbo Gao, Himangi Marathe

Faculty, Staff and Student Publications

Development of acquired therapeutic resistance limits the efficacy of cancer treatments and accounts for therapeutic failure in most patients. How resistance arises, varies across cancer types and differs depending on therapeutic modalities is incompletely understood. Novel strategies that address and overcome the various and complex resistance mechanisms necessitate a deep understanding of the underlying dynamics. We are at a crucial time when innovative technologies applied to patient-relevant tumour models have the potential to bridge the gap between fundamental research into mechanisms and timing of acquired resistance and clinical applications that translate these findings into actionable strategies to extend therapy efficacy. …

Molecular Determinants Of Sotorasib Clinical Efficacy In Krasg12c-Mutated Non-Small-Cell Lung Cancer, Ferdinandos Skoulidis, Bob T Li, Adrianus Johannes De Langen, David S Hong, Herve Lena, Juergen Wolf, Grace K Dy, Alessandra Curioni Fontecedro, Pascale Tomasini, Vamsidhar Velcheti, Anthonie J Van Der Wekken, Christophe Dooms, Luis Paz-Ares Rodriguez, Giannis Mountzios, Adrian Sacher, Ernest Nadal, Sebastien Couraud, Sang-We Kim, Kenneth O'Byrne, Danilo Rocco, Ryo Toyozawa, Izabela Chmielewska, Colin R Lindsay, Antreas Hindoyan, Lata Mukundan, Tomasz Wilmanski, Abraham Anderson, Christine Ardito-Abraham, Amrita Pati, Anita Reddy, Bhakti Mehta, Martin Schuler

Faculty, Staff and Student Publications

Molecular determinants of KRAS(G12C)inhibitor efficacy in KRASG12C-mutated non-small-cell lung cancer (NSCLC) remain poorly characterized. Here we report one of the largest integrated analyses to date of sotorasib clinical efficacy biomarkers from the phase 2 CodeBreaK 100 and phase 3 CodeBreaK 200 studies. We reveal differential sotorasib activity and relative benefit compared to docetaxel across KRASG12C-mutated NSCLC co-mutational subsets and transcriptional subtypes. We also identify low expression of TTF1 and KEAP1 co-mutations/NRF2 activation as major determinants of sotorasib anti-tumor efficacy and adverse prognostic features. Exploratory analyses highlight potential tumor cell-extrinsic contributors to sotorasib anti-tumor activity and suggest …

Computed Tomography Radiomics-Based Cross-Sectional Detection Of Mandibular Osteoradionecrosis In Head And Neck Cancer Survivors, Serageldin Kamel, Laia Humbert-Vidan, Zaphanlene Kaffey, Sarah Mirbahaeddin, Abdulrahman Abusaif, David T A Fuentes, Kareem Wahid, Cem Dede, Mohamed A Naser, Renjie He, Ahmed W Moawad, Khaled M Elsayes, Melissa M Chen, Adegbenga O Otun, Jillian Rigert, Mark S Chambers, Andrew Hope, Erin Watson, Kristy K Brock, Katherine Hutcheson, Lisanne Van Dijk, Amy C Moreno, Stephen Y Lai, Clifton D Fuller, Abdallah S R Mohamed, Md Anderson Head And Neck Cancer Symptom Working Group

Faculty, Staff and Student Publications

Purpose: This study aims to identify radiomic features from contrast-enhanced CT (CECT) scans that differentiate osteoradionecrosis (ORN) from normal mandibular bone in head and neck cancer (HNC) patients treated with radiotherapy (RT).

Materials and methods: CECT images from 150 patients with confirmed ORN diagnosis (2008-2018) at MD Anderson Cancer Center (MDACC) were analyzed (80 % train, 20 % test). Radiomic features were extracted using PyRadiomics from manually segmented ORN regions and automated contralateral healthy mandible regions. Correlation analysis (r > 0.95) reduced features for model training. A random Forest (RF) classifier with Recursive Feature Elimination identified discriminative features. Explainability was assessed …

Characterization Of The Germline Pathogenic Mutational Landscape And Oncologic Outcomes Among 877 Patients With Invasive Lobular Carcinoma, Victoria D Huynh, Jason Mouabbi, Henry M Kuerer, Kerollos Nashat Wanis, Hiam M Abdel-Salam, Angelica M Gutierrez, Helen M Johnson, Anthony Lucci, Kelly K Hunt, Banu K Arun

Faculty, Staff and Student Publications

Purpose: There is a paucity of literature on germline pathogenic variants (gPVs) in patients with invasive lobular carcinoma (ILC). This study characterizes the landscape and compares clinicopathologic variables and treatment outcomes between those with and without gPVs.

Methods: A prospectively maintained institutional database was used to identify all patients diagnosed with nonmetastatic ILC who had germline genetic testing. Clinicopathologic characteristics and time to recurrence, contralateral cancer, and death were compared for patients with and without gPVs. Conditional hazard ratios, computed by Cox proportional hazards models, described associations between clinicopathologic factors, including gPV status, and cancer events.

Results: Of 4398 patients …

Mitophagy’S Impacts On Cancer And Neurodegenerative Diseases: Implications For Future Therapies, Jason Huang, Vincent Truong Pham, Shaozi Fu, Gang Huang, Ya-Guang Liu, Lei Zheng

Faculty, Staff and Student Publications

Substantial evidence supports an inverse relationship between cancer and neurodegenerative diseases (NDDs), but few studies investigate the biological mechanisms underlying this phenomenon. While previous explanations-such as inflammation, reactive oxygen species (ROS), genetic mutations, and cell death-remain significant, they ultimately converge on mitophagy. This review identifies mitophagy as a pivotal factor in the development of both cancer and NDDs, while also evaluating specific mechanisms and processes to clarify how mitophagy connects these opposing disease trajectories. By examining these factors, we aim to uncover the underlying mechanisms that explain the inverse relationship between cancer and NDDs, which will help develop therapeutic strategies …

Community-Engaged Medical Student Elective To Improve Knowledge And Attitudes Toward Individuals With Intellectual And Developmental Disabilities, Kathryn J Kemere, Nital Appelbaum, Priya Chandan, Elisha Acosta

Faculty, Staff and Students Publications

Individuals with intellectual and developmental disabilities (IDD) face multiple barriers to inclusion throughout life. One barrier is the medical knowledge and biases of adult healthcare providers with diagnoses traditionally associated with childhood. Medical school curricula have limited content related to IDD, and students have limited opportunities to engage with community organizations during their clinical years. Methods: We created a one-month clinical elective to address medical students' attitudes and knowledge regarding individuals with IDD using experiential learning. Students saw adult patients in our primary care clinic with a variety of IDD diagnoses and spent 30% of their time at community sites …

Standard Cardiovascular Risk Prediction Scores Underestimate Risk In Immune-Mediated Thrombotic Thrombocytopenic Purpura Survivors, Binish Javed, Jenna Brown, Jay Meade, Vijay Nambi, Ang Li, Shruti Chaturvedi, Senthil Sukumar

Faculty, Staff and Students Publications

Background: Immune-mediated thrombotic thrombocytopenic purpura (iTTP) is a rare hematologic disorder with improved survival due to advancements in treatment. However, long-term cardiovascular morbidity and mortality remain significant. Established cardiovascular risk calculators, such as the 2008 Framingham Heart Study (FHS) global cardiovascular disease (CVD) and the American College of Cardiology/American Heart Association (ACC/AHA) atherosclerotic CVD (ASCVD) risk estimators, may not adequately account for the elevated and unique cardiovascular risks in iTTP survivors.

Objectives: To evaluate the discrimination and calibration of the ACC/AHA ASCVD and FHS global CVD models in predicting major adverse cardiovascular events (MACEs) among iTTP survivors.

Methods: This retrospective …

Comparative Efficacy Of Current Topical Treatments For Dry Eye Disease: A Review Of Pivotal Clinical Trials Evaluating Corneal Staining Outcomes, Ahmad Fahmy, Masih Ahmed, Stephen Pflugfelder, Anara Serikbaeva, Fang-Wei Tsao

Faculty, Staff and Students Publications

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Outcomes Of Suprapatellar Intramedullary Nail Fixation Of Tibial Shaft Fractures In Skeletally Immature Patients, Carlos D Pargas-Colina, Tori J Coble, Sara E Davis, David D Spence, Jonathan K Rowland, Derek M Kelly, Benjamin W Sheffer

Faculty, Staff and Students Publications

Background: Tibial shaft fractures in children require individualized treatment approaches, including elastic nails, plates and screws, intramedullary rigid nails (IMN), and external fixators, with selection based on fracture characteristics and patient factors. IMN risks damaging the physis, but can provide enhanced stability and immediate weight bearing. While both infrapatellar and suprapatellar approaches exist for IMN placement, studies in adults have demonstrated that the suprapatellar approach offers higher patient satisfaction, less anterior knee pain, and lower radiation exposure. However, there is a lack of data on IMN for pediatric tibial fractures.

Methods: This single-center, retrospective cohort study analyzed patients aged 11-16 …

Insights Into The Molecular Mechanism Of Pulmonary Vein Stenosis In Pediatric Patients With Congenital Heart Disease, Alyssa B Kalustian, Pengfei Ji, Lalita Wadhwa, Christopher A Caldarone, Manish Bansal, Athar M Qureshi, Jeffrey S Heinle, Ravi K Birla

Faculty, Staff and Students Publications

Objective: Pediatric pulmonary vein stenosis (PVS) is associated with substantial morbidity and mortality for the subset of patients with recurrent or progressive disease. The molecular mechanisms underlying the development and trajectory of PVS remain unclear. This study characterizes the transcriptome of clinical and phenotypic subtypes of PVS.

Methods: Bulk RNA sequencing analysis was performed on human pulmonary vein tissue samples obtained from surgical interventions for pediatric patients with PVS. Transcriptomic profiles were compared for primary versus postrepair PVS as well as aggressive versus nonaggressive clinical phenotypes. Principal component analysis was performed, the differential gene expression quantified, and pathway analysis conducted …

High Risk Of Drug-Resistant Tuberculosis In Igra-Negative Contacts: Should Preventive Treatment Be Considered?, Thomas Theo Brehm, Niklas Köhler, Hans-Peter Grobbel, Jürgen Welling, Anna Maria Mandalakas, Vinicius Fava, Erwin Schurr, Christoph Lange

Faculty, Staff and Students Publications

Purpose: Deciding whether to provide preventive treatment to contacts of individuals with multidrug-resistant (MDR) tuberculosis is complex.

Methods: We present the diagnostic pathways, clinical course and outcome of tuberculosis treatment in eight siblings from a single family. Tuberculosis disease was diagnosed by Mycobacterium tuberculosis culture and molecular detection of M. tuberculosis-specific DNA from bronchopulmonary specimens using GeneXpert® MTB/RIF. M. tuberculosis infection was diagnosed by an interferon-gamma release assay (IGRA; QuantiFERON®-TB Gold Plus). Whole exome sequencing for genetic predisposition to mycobacterial infection was performed in one patient.

Results: Six of eight siblings aged 16-20 years from a migrant family of Somali …

Minimum Core Data Elements For Evaluation Of Thoracic Aortic Disease, Andreina Carbone, Mary J Roman, Melissa L Russo, Kathryn W Holmes, Maya Brown-Zimmerman, John Elefteriades, Catherine M Otto, Nicholas S Burris, Carlos Alberto Campello Jorge, Scott C Deroo, Maral Ouzounian, Matthew D Solomon, Jay D Humphrey, Bart Loeys, Shaine A Morris, Guillaume Jondeau, Scott A Lemaire, Sherene Shalhub, Siddharth K Prakash

Faculty, Staff and Students Publications

Thoracic aortic aneurysms predisposing to aortic dissections are rare but potentially deadly conditions that can be inherited in families. Understanding the natural history and genetic causes of thoracic aortic disease (TAD) requires international collaboration. The aim of this project is to provide core data elements that can be assessed directly and summarized efficiently in research records while developing standards to harmonize data across registries and clinical trials. Ten contemporary TAD registries were analyzed to identify significant gaps in the amount and types of data that are needed for accurate, verifiable, and reproducible studies. The set of data elements recommended by …

Ruptured Arteriovenous Malformation Mortality: Incidence, Risk Factors, And Inpatient Outcome Score, Eric Feldstein, Allison Zhong, Kevin Clare, Bridget Nolan, Smit Patel, Nir Lavi-Romer, Zehavya Stadlan, Alis Dicpinigaitis, Jose Dominguez, Haris Kamal, Steven D Shapiro, Arundhati Biswas, Omar Tanweer, Ketan Bulsara, Carrie Muh, Jared Pisapia, Simon Hanft, Stephan Mayer, Chirag D Gandhi, Fawaz Al-Mufti

Faculty, Staff and Students Publications

Background

Limited literature exists on the morbidity and mortality of AVM associated intracerebral hemorrhage (ICH) compared with non-AVM ICH.

Objective

We examine morbidity and mortality in cAVM in a large nationwide inpatient sample to create a prognostic inpatient ruptured AVM mortality score.

Methods

This retrospective cohort study from 2008 to 2014 compares outcomes in cAVM related hemorrhages and ICH utilizing the National Inpatient Sample database. Diagnostic codes for ICH and AVM underlying ICH were identified. We compared case fatality according to medical complications. Multivariate analysis was used to derive hazard ratios and 95% confidence intervals to assess odds of mortality. …

The Microrna Mir-30a Blocks Adipose Tissue Fibrosis Accumulation In Obesity, Pradip K Saha, Robert Sharp, Aaron R Cox, Rabie Habib, Michael J Bolt, Jessica B Felix, Claudia E Ramirez Bustamante, Xin Li, Sung Yun Jung, Kang Ho Kim, Kai Sun, Huaizhu Wu, Samuel Klein, Sean M Hartig

Faculty, Staff and Student Publications

White adipose tissue (WAT) fibrosis occurring in obesity contributes to the inflammatory and metabolic comorbidities of insulin resistance and type 2 diabetes, yet the mechanisms involved remain poorly understood. Here, we report a role for the broadly conserved miRNA miR-30a as a regulator of WAT fibrosis and systemic glucose metabolism. Mice modified to express miR-30a at elevated levels in adipose tissues maintain insulin sensitivity coupled with reduced fatty liver disease when fed a high-fat diet. These effects were attributable to cell-autonomous functions of miR-30a that potently increase expression of adipocyte-specific genes. Proteomic screening revealed miR-30a limits profibrotic programs in subcutaneous …

Author Correction: The Long-Term Effects Of Chemotherapy On Normal Blood Cells, Emily Mitchell, My H Pham, Anna Clay, Rashesh Sanghvi, Nicholas Williams, Sandra Pietsch, Joanne I Hsu, Nina Friesgaard Øbro, Hyunchul Jung, Aditi Vedi, Sarah Moody, Jingwei Wang, Daniel Leonganmornlert, Michael Spencer Chapman, Ellie Dunstone, Anna Santarsieri, Alex Cagan, Heather E Machado, E Joanna Baxter, George Follows, Daniel J Hodson, Ultan Mcdermott, Gary J Doherty, Inigo Martincorena, Laura Humphreys, Krishnaa Mahbubani, Kourosh Saeb Parsy, Koichi Takahashi, Margaret A Goodell, David Kent, Elisa Laurenti, Peter J Campbell, Raheleh Rahbari, Jyoti Nangalia, Michael R Stratton

Faculty, Staff and Student Publications

No abstract provided.

Evolution Of Esophageal Adenocarcinoma From Precursor Lesion Stem Cells, Wa Xian, Shan Wang, Jingzhong Xie, Yusuke Yamamoto, Melina Khorrami, Yanting Zhang, Raul Caballero Montes, Caycel Desales, Melika Khorrami, Zaal Mory, Ashley Hoffman, Amber Su, Crystal Nguyen, Peter J A Davies, Clifford Stephan, Shuang Pan, Wengen Wu, Yuxin Liu, Jeremy Siegelman, Rebecca E Waters, William A Ross, Shumei Song, Mark Metersky, David G Beer, Christopher P Crum, Alexander J Stewart, Matthew Vincent, Richard Russell, Robert A Izard, Khek Yu Ho, Jack Hung-Sen Lai, William W Bachovchin, Jaffer A Ajani, Frank D Mckeon

Faculty, Staff and Student Publications

Background & aims: Metastatic cancers arise from a decades-long succession of increasingly virulent precursor lesions, each of which represents prospective targets for therapeutic intervention. This evolutionary process has been particularly vivid in esophageal adenocarcinoma (EAC), as this cancer and associated precursor lesions, including Barrett's esophagus (BE), low-grade dysplasia (LGD), and high-grade dysplasia (HGD), coexist in an accessible, 2-dimensional pattern in esophageal mucosa. Given the durability of these precursor lesions, it is likely that they, like EAC, rely on stem cells for their regenerative growth. To assess the role of stem cells in the evolution of EAC, we apply technology that …

Experiences Of The Emergency Department Environment: A Qualitative Study With Caregivers Of People With Dementia, Anita N Chary, Michelle Suh, Annika Bhananker, Norvin Hernandez, Ana Paulina Rivera, Ed Boyer, Mark E Kunik, Manish N Shah, Christine Ritchie, Aanand D Naik, Shan W Liu, Maura Kennedy

Faculty, Staff and Students Publications

ED crowding and boarding adversely impact older patients' care and outcomes. Little is known about how ED crowding impacts persons living with dementia, a vulnerable population. This study sought to explore ED experiences of caregivers of people with dementia during a period of ED crowding and boarding. We performed semi-structured interviews with caregivers of people with dementia with an ED visit during a period of ED crowding and boarding at two public hospitals experiencing a threefold increase in boarding from pre-pandemic levels. Participants were recruited via chart review. We coded data using an inductive approach. Three themes emerged from 29 …

Notice-Ed: Nurse Or Technician Insights Into Cognitive Evaluations In The Emergency Department, Sarah J Nessen, Anita N Chary, Annika R Bhananker, K Jane Muir, Lauren T Southerland, Kyra O'Brien, Ari B Friedman

Faculty, Staff and Students Publications

Background: Several strategies have been proposed to increase chronic cognitive impairment (CI) screening in the emergency department (ED). Our goal was to assess the feasibility and acceptability of implementing specific CI screening tools and strategies in the ED from an ED registered nurse and technician perspective.

Methods: We performed a qualitative study using semi-structured interviews with a purposive sample of ED nurses and ED technicians (EDTs). Participants worked at an urban academic hospital and were interviewed between November 2023 and March 2024. Interviews assessed participants' opinions on the feasibility and acceptability of CI screening and the use of machine learning …

Incidence, Predictors, And Indications Of Permanent Pacemaker Implantation Following Orthotopic Heart Transplantation: A Single-Center Experience, Iriagbonse Rotimi Asemota, Siddharth Das, Michelle Nsahlai, Edward Graviss, Duc T Nguyen, Paul A Schurmann, Rayan Yousefzai

Faculty, Staff and Students Publications

In the modern era of orthotopic heart transplantation (OHT) with bicaval anastomosis, there is a paucity of data on permanent pacemaker implantation (PPI) in this population. This is a retrospective study describing the incidence, indication, and predictors in patients who underwent PPI after OHT. Using the transplant database from our institution between January 2016 and December 2022, 370 patients who had de-novo OHT were identified. The incidence of PPI post-OHT was 8.1% (n = 30 patients). The average time from OHT to PPI was 30.5 days. The most common indication for PPI was sinus node dysfunction, accounting for 83% …

A Simple, Interpretable Machine Learning Model Based On Clinical Factors Accurately Predicts Incident Dysplasia Or Malignancy In Barrett's Esophagus, Ashwin Rao, Jasmine Haydel, Samuel Ma, Aaron P Thrift, Theresa Nguyen-Wenker, Hashem B El-Serag

Faculty, Staff and Students Publications

Purpose: Identifying patients likely to develop dysplasia or malignancy is critical for effective surveillance in patients with Barrett's Esophagus (BE). However, current predictive models are limited. We evaluated the performance of machine learning (ML) models in predicting incident dysplasia or malignancy in a cohort of veteran patients with BE.

Methods: We analyzed data from 598 patients newly diagnosed with non-dysplastic BE (NDBE), BE indefinite for dysplasia (BE-IND), and BE with non-persistent low-grade dysplasia (LGD) at the Michael DeBakey Veterans Affairs Medical Center from November 1990 to January 2019 with follow-up through January 2024. Progressors were patients who developed persistent LGD, …

Nerve-To-Cancer Transfer Of Mitochondria During Cancer Metastasis, Gregory Hoover, Shila Gilbert, Olivia Curley, Clémence Obellianne, Mike T Lin, William Hixson, Terry W Pierce, Joel F Andrews, Mikhail F Alexeyev, Yi Ding, Ping Bu, Fariba Behbod, Daniel Medina, Jeffrey T Chang, Gustavo Ayala, Simon Grelet

Faculty, Staff and Students Publications

The nervous system has a pivotal role in cancer biology, and pathological investigations have linked intratumoural nerve density to metastasis1. However, the precise impact of cancer-associated neurons and the communication channels at the nerve–cancer interface remain poorly understood. Previous cancer denervation models in rodents and humans have highlighted robust cancer dependency on nerves, but the underlying mechanisms that drive nerve-mediated cancer aggressivity remain unknown2,3. Here we show that cancer-associated neurons enhance cancer metabolic plasticity by transferring mitochondria to cancer cells. Breast cancer denervation and nerve–cancer coculture models confirmed that neurons significantly improve tumour energetics. …

Use Of Granulocyte-Colony Stimulating Factor For Beta-Lactam Induced Neutropenia In Children With Bacterial Meningitis, Cheng Yu Yen, Sheldon L Kaplan, Debra L Palazzi, Grant Stimes

Faculty, Staff and Students Publications

Drug induced neutropenia is an uncommon but potentially serious side effect in children receiving prolonged β-lactam antibiotic therapy. Management of β-lactam induced neutropenia in children remains challenging and often requires antibiotic therapy interruption or modification. There are limited data in pediatric patients about use of granulocyte-colony stimulating factor (G-CSF) for the treatment of drug induced neutropenia. We report the use of G-CSF for β-lactam induced neutropenia in four pediatric patients between the ages of 3 months and 18 years with bacterial meningitis in this case series.

Sirt5 Inhibition Impairs Mitochondrial Metabolism And Enhances Venetoclax-Induced Elimination Of Acute Myeloid Leukemia Cells, Moran Wang, Ruiqi Zhu, Donald Small, Lan Lin, Li Li, Shengling Ma, Linghui Xia, Shanshan Luo, Wenjuan He, Jianming Yu, Junying Li, Ruowen Wei, Ao Zhang, Wei Shi, Yu Hu

Faculty, Staff and Students Publications

Metabolic reprogramming is a key focus of targeted therapies in acute myeloid leukemia (AML). The mitochondrial sirtuin SIRT5 removes succinyl groups from specific lysines and impacts cell metabolism, but its role in AML tumorigenesis has not been extensively explored. A recent study highlighted that SIRT5 regulates AML cell activity by modulating glutamine metabolism, but its molecular targets in AML remain unclear. This study aims to identify the substrates of SIRT5 in AML. It was found that a total of 83 proteins with 121 lysine (K) residues showed increased succinylation after SIRT5 knockdown, as determined by succinylome analysis of MOLM-13 cells. …

Improving Pediatric Heart Failure Outcomes Through Collaboration And Innovation: The Current Status Of The Advanced Cardiac Therapies Improving Outcomes Network (Action), Lydia K Wright, David M Peng, Joseph A Spinner, Jenna M Murray, Matthew J O'Connor, Christina J Vanderpluym, David N Rosenthal, Lauren Smyth, Angela Lorts

Faculty, Staff and Students Publications

The Advanced Cardiac Therapies Improving Outcomes Network (ACTION) was founded in 2017 as a learning health care system to bring together all stakeholders with the aim of improving outcomes for pediatric and congenital heart disease patients with heart failure. From an initial focus on the ventricular assist device (VAD) population, work in the network has expanded to encompass the scope of heart failure in these patients. Through the collection and use of real-world data, the field has gained greater understanding of best practices in care of these patients, as well as improved access to devices with pediatric labeling of devices …

Measuring The Impact Of A Delay In Care On Pediatric Otolaryngologic Surgery Completion, Geethanjeli N Mahendran, Ching Siong Tey, Mary Frances Musso, Grace Shebha Anand, Jeffrey Larson, Mitesh Mehta, Lara Reichert, Kara Prickett, Nikhila Pinnapureddy Raol

Faculty, Staff and Students Publications

Objective: To determine if postponement of elective pediatric otorhinolaryngology surgeries results in a change in overall healthcare utilization and if there is any commensurate impact on disease progression.

Methods: We identified patients ≤18 years of age whose surgeries were postponed at the onset of the COVID-19 pandemic-related shutdown. We then tracked patients' rate of and patterns of rescheduling surgery. Surveys were also sent to caregivers to better characterize his/her decision regarding moving forward with his/her child's surgery during COVID-19.

Results: A total of 1915 pediatric patients had elective surgeries canceled, of which 992 (51.8%) were rescheduled within 4 months. No …