Digital Commons Network^™

Restricting Metabolic Plasticity Enhances Stress Adaptation Through The Modulation Of Pdh And Hif1a In Trap1-Depleted Colon Cancer, Hong-Yuan Tsai, Miao-Hsueh Chen, Jihye Yun, Lisa A Lai, John F Valentine, Mary P Bronner, Teresa A Brentnall, Sheng Pan, Ru Chen

Faculty, Staff and Student Publications

Metabolic plasticity allows cancer cells to survive under adverse conditions. To investigate the role of mitochondrial chaperone tumor necrosis factor receptor-associated protein 1 (TRAP1) in this process, we used CRISPR/Cas9 mediated genetic deletion to knock out (KO) TRAP1 in colon cancer cells. Depletion of TRAP1 triggered a series of events: induced metabolic reprogramming, increased glycolytic flux, downregulation of mitochondrial complex I, and elevated ROS generation. TRAP1-deficient cells showed tolerance to Oxidative Phosphorylation (OXPHOS) inhibitors and exhibited a higher extracellular acidification rate (ECAR). Additionally, TRAP1 depletion activated hypoxia response elements (HREs) and upregulated HIF1A target genes such as GLUT1 and MCT1. …

Risk Score Roulette: A Cautionary Tale Of Polygenic Risk Score Reliability, Diane Xue, Elizabeth E Blue, Alexis C Wood, Jerome I Rotter, Alison E Fohner

Children’s Nutrition Research Center Staff Publications

Genetic risk prediction for Alzheimer's disease (AD) has high potential impact, yet few studies have assessed the reliability of various polygenic risk score (PRS) methods at the individual level. Here, we evaluated the reliability of AD PRS estimates among 6338 participants from the Multi-Ethnic Study of Atherosclerosis. We compared four PRS models that have been previously associated with dementia risk. Despite similar population-level performance metrics, inter-model reliability of individual-level risk assessment was low, even among individuals classified in the top and bottom deciles. These findings raise serious concerns about the downstream application of PRS for guiding interventions for AD.

Proteolysis-Targeting Chimeras In Cancer Therapy: Targeted Protein Degradation For Next-Generation Treatment, Yamile Abuchard, Mariana Barragan, Ricardo Pequeno Bracho, Salique H. Shaham, Debasish Bandyopadhyay, Elias George, Diane Nguyen, Manish Tripathi

School of Medicine Publications

Proteolysis-targeting chimeras (PROTACs) have the potential to revolutionize cancer treatment by specifically targeting and degrading oncogenic proteins. Using the ubiquitin-proteasome system, PROTACs allow the selective degradation of disease-causing proteins, including those traditionally deemed “undruggable” by conventional small-molecule inhibitors. By catalytically eliminating rather than inhibiting proteins, PROTACs provide sustained target suppression with lower doses and reduced toxicity. Their bifunctional design linking a protein of interest to an E3 ligase drives targeted ubiquitination and subsequent proteasomal degradation. Recent progress demonstrates promise in treating solid and hematologic malignancies, with several candidates advancing to clinical trials. This review provides a comprehensive overview of developing …

Association Of Component Strategies Of The Target Stroke Phase 3 Nationwide Quality Improvement Program With Accelerated Door-To-Puncture And Door-In-Door-Out Times For Ischemic Stroke Endovascular Thrombectomy In The United States, Brian Mac Grory, Kaiz S. Asif, Haolin Xu, Brooke Alhant, Jay Lusk, David Hasan, Soojin Park, Amelia K. Boehme, Ameer E. Hassan, Kyle M. Fargen

School of Medicine Publications

Background: The Target Stroke Phase III program is a national quality improvement initiative led by the American Heart Association, which sought to improve the quality of care for patients with acute stroke undergoing acute reperfusion therapy including endovascular thrombectomy (EVT).

Methods: A retrospective, observational cohort study was performed using data from the American Heart Association Get With The Guidelines-Stroke Program between January 1, 2017, and March 31, 2022. Three categories of patients were analyzed: (1) patients who arrived directly at the thrombectomy hospital and had EVT, (2) patients who were transferred in from a nonthrombectomy hospital and had EVT, and …

Advancements In Metastatic Spinal Cord Compression Treatment: A Narrative Review Of Innovations, Challenges, And Future Directions, Tirath Patel, Fathimathul Henna, Iman Sharif, Anaya Noor, Hafiza Tooba Siddiqui, Zarhaish Barkat-Ullah, Mahnoor Ishaque, Najia Ali Khan, Christopher Hanani, Abhishek Goyal, Nikhilesh Anand

School of Medicine Publications

Objective: To synthesize recent advancements in metastatic spinal cord compression (MSCC) treatment, evaluating their efficacy in improving neurological function, pain relief, survival, and quality of life.

Background: MSCC is an oncologic emergency caused by the progression of cancer to the spine and is prevalent in approximately 3-5% of all cancer patients, with a relatively higher incidence of breast, prostate, and lung cancers. MSCC can lead to irreversible paralysis due to loss of vital sensory and motor functions, thus requiring an immediate diagnosis and treatment.

Methods: A systematic PubMed search identified studies published over the past 5 years focusing on advancements …

Health Disparity Indices In The Assessment Of Adolescent Idiopathic Scoliosis: Are All Indices Similar?, William Woodhams, Michael Benvenuti, Jonathan Warren, George Thomas, John Anderson, Richard M. Schwend, K Aaron Shaw

Manuscripts, Articles, Book Chapters and Other Papers

BACKGROUND: Adolescent idiopathic scoliosis (AIS) is a common spinal deformity. Previous studies have demonstrated that healthcare disparities affect the initial presentation of AIS patients. However, studies have utilized various socioeconomic status (SES) indices with no previous study assessing the congruency of these indices.

METHODS: A single-center, retrospective review of adolescent patients presenting for initial evaluation of scoliosis was performed at a tertiary care pediatric hospital based in the central United States. Patient demographic data were recorded in addition to radiographic data consisting of coronal curve magnitude at presentation and skeletal maturity indices. Socioeconomic variables were collected, including geographic area of …

Parental Psychosocial Outcomes After A Positive Newborn Screen For A Lysosomal Storage Disorder., Courtney D. Berrios, Randi N. Gadea, Meghan Strenk, Twisha Nadella, Jennifer L. Gannon, Janelle R. Noel-Macdonnell Phd

Manuscripts, Articles, Book Chapters and Other Papers

PURPOSE: This study explores the psychosocial impact of a positive newborn screen (NBS) result for four lysosomal storage disorders (LSDs) (Fabry disease, Krabbe disease, Mucopolysaccharidosis Type I, Pompe disease) across confirmatory results.

METHODS: Parents whose child who had a positive NBS for one of the included LSDs were recruited for a retrospective cohort (n = 80) or prospective, longitudinal cohorts (n = 50). Surveys assessed uncertainty, anxiety, intrusive or avoidant thoughts, and perceived vulnerability of their child's health. In-depth interviews explored the NBS experience and psychosocial response.

RESULTS: Participants experienced uncertainty and anxiety during confirmatory testing that improved as parents …

Preoperative Immobilization For Pediatric Femur Fractures., Connor Mathes, Leilani Mansy, Lisa Berglund, Caleb W. Grote

Manuscripts, Articles, Book Chapters and Other Papers

Guidelines for the definitive surgical management of pediatric femoral shaft fractures have recently been established. Initial preoperative immobilization of these patients varies by age and size; limited guidelines exist to guide caregivers in appropriate preoperative care. Here, we present our recommendations based on clinical experience and literature review. We prefer temporary splints for patients younger than 5 years and Bucks boot traction for skeletally immature patients older than 5 years. In small patients, the splint should extend past the iliac crest and down to the foot to ensure proper immobilization of the femur fracture. For Bucks boot traction, proper traction …

Bilateral Pleuropulmonary Blastoma In An Infant., R Guanà, E Zambaiti, Maria Grazia Sacco Casamassima, S Garofalo, L Lonati, E Stanton, F Gennari

Manuscripts, Articles, Book Chapters and Other Papers

No abstract provided.

Zero Fluoroscopy Ablation Of Arrhythmias In Patients With Congenital Heart Disease, Shailendra Upadhyay, Jenna Schermerhorn, Whitney Fairchild, Jamie Bopp, Irfan Warsy

Manuscripts, Articles, Book Chapters and Other Papers

Aims

Radiation-free catheter ablation is feasible with modern electroanatomic mapping systems. We aimed to evaluate the feasibility, safety, and outcomes of non-fluoroscopic ablation (NFA) in patients with congenital heart disease (CHD).

Methods

We retrospectively reviewed CHD patients who underwent NFA between November 2016 and January 2025. All procedures were performed using the CARTO 3D electroanatomic mapping system. Atrial, ventricular, and aortic geometries were reconstructed as needed. Catheter navigation and sheath placement were guided without fluoroscopy; intracardiac echocardiography was used selectively.

Results

Forty-two patients (23 females) with CHD underwent NFA. The median age was 14 years (range 4–56), and median weight …

Improving Infant Continuity Of Care In An Academic Center Clinic: A Quality Improvement Project., Abiye Y. Okah, Morgen L. Govindan, Rachael D. Dameron, Kristi Williams

Manuscripts, Articles, Book Chapters and Other Papers

INTRODUCTION: Continuity of care (COC) with an identified provider is a key principle of the patient-centered medical home. COC may be impacted by other activities that providers practicing in an academic center must engage in. The disruption of care processes during the COVID-19 pandemic led to a decrease in COC for infants attending our academic center's primary care clinic. We implemented a quality improvement (QI) project to improve the rates of infant COC.

METHODS: In 2021, we implemented a QI project with the aim of increasing the percentage of 12-month-old infants who had seen the same provider for at least …

Telepsychiatry For Substance Use Disorders: Evolution From Rapid Covid-19 Pandemic Adoption To Sustainable Integration, Jack Wang

Marshall Journal of Medicine

ABSTRACT

Introduction: Prior to the COVID-19 pandemic, telepsychiatry for substance use disorder (SUD) management was generally an underutilized modality, mainly due to regulatory constraints. Through the pandemic, governmental deregulations rapidly and massively expanded their adoption, bringing out their significant potential to expand access, overcome barriers, and mitigate stigma for individuals seeking addiction care, particularly for rural and underserved populations. This narrative review consolidates the recent research on the growing adoption of telepsychiatry in the management of SUDs. It aims to explore the evidence-based benefits, identify common challenges, and underscore key considerations for its effective and equitable integration into SUD treatment …

Lyme Disease Presenting As A Dermal Hypersensitivity Reaction, William T. Snider, Ian Depew, Rebecca Hicks, Shane Cook

Marshall Journal of Medicine

Background:

Lyme disease is a well-recognized illness commonly associated with skin manifestations such as erythema migrans. However, atypical presentations can complicate diagnosis, particularly when they deviate from classic clinical and histological findings.

Methods:

We report a potential case of Lyme disease presenting as a dermal hypersensitivity reaction (DHR), with clinical findings resembling urticaria rather than urticarial vasculitis. Skin biopsy findings were reviewed, and Lyme serology testing was performed.

Results:

The biopsy did not demonstrate the characteristic superficial perivascular lymphocytic infiltrate typically seen with erythema migrans. The patient's history included prior tick exposures, but while Lyme IgM was positive, the Lyme …

Nonglomerular Hypocomplementemic Interstitial Nephritis, Tyler Hemphill, Yogesh Sanghvi

HCA Healthcare Journal of Medicine

Background

Acute interstitial nephritis (AIN) is the most common cause of acute kidney injury (AKI) with subsequent renal impairment and is often underdiagnosed. Acute interstitial nephritis presents with a decline in kidney function and is characterized by an inflammatory infiltrate in the kidney interstitium. It is most often induced by drug therapy and is sometimes followed by infections with unknown causes. In a typical presentation of AIN, there is no evidence of hypocomplementemia; low complement is associated most commonly with autoimmune etiologies. Renal biopsy serves as the most definitive test for both the diagnosis and prognosis of AIN.

Case Presentation …

Use Of Topical Hemostatic Agents In A Gynecologic Patient With Coagulopathy, Alexis O'Connell, Syeda Zainab Shah

HCA Healthcare Journal of Medicine

Introduction

The use of topical hemostatic agents has become common during surgical interventions. There is a wide variety of substances available to augment clotting, ranging from physical agents to topical thrombin combinations. Application of these agents in gynecologic surgery in patients with existing coagulopathies has not been studied.

Case Presentation

A 62-year-old woman with an inferior vena cava filter and a history of multiple deep vein thromboses presented to the clinic with pelvic pain, stress urinary incontinence, and uterovaginal prolapse. She underwent a total vaginal hysterectomy, sacral colpopexy, tension-free vaginal tape sling, and cystourethroscopy. Warfarin was cross titrated to enoxaparin …

Utilizing Femoral Metaphyseal Sleeves In Primary Total Knee Arthroplasty For Post-Traumatic Osteoarthritis: A Case Report, Zachary Sukin, Adam Dentinger, Jeremiah Earl

HCA Healthcare Journal of Medicine

Background

Total knee arthroplasty in younger patients presents a heightened risk of postoperative complications and implant failures compared to older populations, particularly in those with posttraumatic arthritis. These challenges necessitate careful consideration and specialized approaches to optimize the outcomes in this patient demographic.

Case Presentation

A 43-year-old man presented with left knee pain resulting from a traumatic lawn mower injury, causing an intraarticular distal femur, at the age of 6. The injury led to a limb-length discrepancy for which he underwent 2 limb-lengthening procedures in his early 20s. Radiographs demonstrated advanced posttraumatic osteoarthritis, and the patient elected to proceed with …

Upper Respiratory Tract Infection Leading To A New Diagnosis Of Sweet Syndrome And Monoclonal Gammopathy Of Unknown Significance, Nidhi Rawat, Meron Gebrehiwot, Jason Raw, Jeyaprakash Ramachandran

HCA Healthcare Journal of Medicine

Background

We present a rare case of Sweet syndrome with underlying monoclonal gammopathy of unknown significance (MGUS) which initially presented as upper respiratory tract infection.

Case Presentation

A 52-year-old woman presented with a complaint of sore throat for 6 days, productive cough and fever for 5 days, and red, pruritic, circular, tender rashes on face, arms and trunk for 2 days. There was a past history of similar self-limiting rashes presenting intermittently for 1.5 years. She also reported to be taking tablet ibuprofen, as required for the past 1-2 years, for cervical spondylosis. On integumentary examination, widespread, red, tender, annular …

Capacity Over Cognition: A Case Of High-Risk Disease And Homelessness, Mikalah E. Maury, Avery M. Duncan, Rebecca A. Taylor, Mary Ann Beil, Maulikkumar A. Patel

HCA Healthcare Journal of Medicine

Background

Medical decision-making in indigent patients with baseline cognitive deficits and lack of supportive resources is a difficult problem that reveals many ethical issues. Performing high-level medical procedures (eg, invasive surgery, chemotherapy, radiation therapy) on these patients without supportive resources brings into question the efficacy and necessity of treatment if it places the patient at higher risk of additional complications and mortality.

Case Presentation

In this article, we present a case of a 62-year-old indigent man with a long history of encephalopathy secondary to alcohol abuse, presenting with an aggressive head and neck cancer impacting his quality of life.

Conclusion …

Rapid Percutaneous Nephrostomy Stent Encrustation In Pregnancy: Navigating Your Stone Challenge, Victor M. Feldbaum, Roberto Morales, Shawn R. Ramsey, Michael L. Douso

HCA Healthcare Journal of Medicine

Background

Surgical management of kidney stones in pregnancy can be a serious problem for both mother and fetus.

Case Presentation

A 20-year-old woman with a second trimester pregnancy presented to the emergency room with renal calculi. She required surgical intervention and a left nephrostomy tube after consultation with urology. Five weeks later, her tube was solidified in place unbeknownst to her care team. She required several surgeries, dealt with encrustation remnants, infections, radiation exposure, persistent infection requiring antibiotic management, and, ultimately, an early delivery at 37 weeks.

Conclusion

At the time of writing, this was the first case to describe …

Rectal Fidaxomicin As Salvage Therapy In Fulminant Clostridioides Difficile Infection After Total Colectomy: A Case Report, Akankcha Alok, Mohamed Ismail, Stephanie Pino Fabara, Mohammed Al Said, Vidya Sagar Kollu

HCA Healthcare Journal of Medicine

Introduction

Clostridioides difficile infection (CDI) is a significant cause of antibiotic-associated diarrhea and colitis, ranging from mild to severe and potentially life-threatening conditions, like fulminant colitis with toxic megacolon and bowel perforation. The 2021 guidelines from the Infectious Diseases Society of America (IDSA) and Society for Healthcare Epidemiology of America (SHEA) recommend vancomycin and metronidazole for fulminant CDI (FCDI), with consideration of rectal vancomycin for cases with ileus. Fidaxomicin, though preferred for initial and recurrent CDI treatment, is not the first line for FCDI due to limited evidence. Fidaxomicin has a narrow spectrum of activity only targeting C difficile and …

Clinical Images Of Cutaneous Horns In Patients Presenting To A Family Medicine Residency Practice, Julia Fashner, Tillie Schumann

HCA Healthcare Journal of Medicine

We detail 2 cases of cutaneous horn, also referred to as cornu cutaneum, which is a hard-compacted linear outgrowth of keratin that projects above the skin. We present these images to increase awareness for all medical specialties who may see a patient with this skin lesion.

Clinical Characteristics Associated With Hospital Mortality And Length Of Stay Among Older Adults Admitted With Delirium: Retrospective Analysis, Se Won Lee, Jeff J. Kim, Cole Kretchmar, Napatkamon Ayutyanont, Mooyeon Oh-Park

HCA Healthcare Journal of Medicine

Background

Limited information exists on the characteristics of older adults admitted with delirium at risk of poor hospital outcomes. This study aims to identify risk factors present on admission that are associated with hospital mortality and length of stay (LOS) among older adults admitted with delirium.

Methods

This is a retrospective study of 5598 patients 65 years of age or older who were admitted to acute care units at 8 community hospitals with an International Statistical Classification of Diseases, Tenth Revision code of delirium.

Results

Multivariate regression analyses revealed that in-hospital mortality increase was associated with increased age, Asian race, …

Can The Combination Of White Blood Cell Count And C-Reactive Protein Rule Out Pediatric Appendicitis, A Retrospective Analysis?, Scott Gutovitz, Samantha Stoner, Jarrett Koper, Sarah Kleist

HCA Healthcare Journal of Medicine

Background

Pediatric appendicitis (PA) is the most frequent cause of pediatric emergency surgery. Standard PA scoring systems incorporate inflammatory biomarkers (white blood cell count [WBC] or C-reactive protein [CRP]); however, the individual biomarker sensitivities have not been reported beyond single-center sites. We aimed to measure the individual and combined sensitivities of WBC and CRP to rule out PA in a large multicenter hospital system.

Methods

We did a retrospective study of pediatric emergency department patients (age <18) with abdominal pain, using a deidentified electronic health database from a 175-hospital system in the United States, comparing PA versus non-PA patients. Pediatric appendicitis patients were identified by ICD-10 diagnosis codes and had advanced imaging, whereas non-PA patients had advanced imaging and were discharged home with the ICD-10 code for abdominal pain. Using matched propensity matching, we calculated receiver operator characteristics and Youden’s index to find the optimal cutpoints. Sensitivity was calculated at the optimal and traditional cutpoints for each biomarker, also combined in parallel fashion.

Results

We identified 7414 subjects (3707 PA matched to 3707 controls). The WBC in PA patients was 14.99 ± 5.00 k/mm³ versus 9.63 …

Beyond The Norm: Decoding Spontaneous Coronary Artery Dissection As An Unusual Cause Of Acute Coronary Syndrome, Holden Zimmerman, Himanshi Banker, Inder P. Kaur, Jaskaran Munjal, Vasu Gupta, Ayushi Garg, Nikita Garg, Meet Patel, Rohit Jain

HCA Healthcare Journal of Medicine

Spontaneous coronary artery dissection (SCAD) is a rare nonatherosclerotic cause of myocardial infarction among young women, particularly during pregnancy. As the name suggests, SCAD is caused by the spontaneous formation of the false lumen within the coronary artery wall, thus compromising the blood flow to the myocardium. Unlike atherosclerotic acute coronary syndromes, SCAD is not directly associated with diabetes or hypertension; moreover, underlying connective tissue defects and inflammation are considered more contributory towards its etiology. Although its pathophysiology is not well understood, multiple theories have been proposed. Clinically, SCAD has a similar presentation to acute coronary syndromes, including substernal chest …

Circulating Inflammatory Biomarkers And Endometriosis Lesion Characteristics In The Wise Consortium, Kathryn L. Terry, Amy Shafrir, Ashley Laliberte, Allison F. Vitonis, Kurtis Garbutt, Mary Depari, Christian Becker, Naoko Sasamoto, Krina T. Zondervan, Stacey A. Missmer

Health Sciences Faculty Publications

Endometriosis is a chronic inflammatory condition requiring surgical or imaging visualization for definitive diagnosis. How endometriotic lesion characteristics relate to circulating inflammatory markers remains unclear. We evaluated 11 inflammatory biomarkers, including interleukin (IL)-1β, -6, -8, -10, -16, tumor necrosis factor (TNF)-α, thymus and activation regulated chemokine (TARC), monocyte chemotactic protein (MCP)-1, -4, and Interferon gamma-induced protein (IP)-10, in 566 participants with endometriosis from the Women’s Health Study: From Adolescence to Adulthood (A2A), Endometriosis Oxford Care & Research (CaRe) study (ENDOX) and Endometriosis: Natural History, Diagnosis, and Outcome (ENDO) study to evaluate associations with endometriosis characteristics, including macrophenotype (superficial lesions only, …

Atypical Abdominal Pain: Uncovering Malignant Peritoneal Mesothelioma In Suspected Crohn's Disease: A Case Report, Catherine Loehr, Lara Boudreaux, Ann Porter Uhlhorn, Nisha Loganantharaj

School of Medicine Faculty Publications

BACKGROUND: Malignant peritoneal mesothelioma (MPM) is a rare and aggressive cancer from the serosal membranes of the abdominal cavity. In the United States, MPM accounts for about 10-15% of all mesothelioma cases, and translates into approximately 600 new cases diagnosed annually. It is typically diagnosed in Caucasian individuals, and while asbestos exposure is a well-established risk factor for pleural mesothelioma, its association with peritoneal mesothelioma remains less clear. Clinical symptoms of MPM, such as abdominal pain, bloating, and weight loss, overlap with other gastrointestinal disorders, which often leads to delayed diagnosis. This case report presents a unique instance of MPM …

Safety And Efficacy Of Liver-Directed Radiotherapy After Chemoimmunotherapy For Advanced Cholangiocarcinoma: An Early Report From A Large Tertiary Cancer Center, Abdulmoiz Asif, Abdulmoid Asif, Michael K Rooney, Enoch Chang, Felicity Namayanja, Kimana Quentin, Sunyoung Lee, Ian Hu, Vincent Bernard, Prajnan Das, Emma B Holiday, Sonal Noticewala, Grace L Smith, Albert C Koong, Ethan B Ludmir, Milind Javle, Lianchun Xiao, Eugene J Koay

Faculty, Staff and Student Publications

BACKGROUND: Recent randomized controlled trials have established chemoimmunotherapy as the standard of care for patients with advanced biliary cancers with a median overall survival (OS) of about thirteen months. No data exist to demonstrate the safety and efficacy of liver-directed radiotherapy (RT) for extrahepatic and intrahepatic cholangiocarcinoma (CCA) in the era of chemoimmunotherapy. The purpose of this study is to report our early experience treating patients with CCA using RT and chemoimmunotherapy.

METHODS: Twenty-eight patients with CCA who received chemoimmunotherapy sequentially and/or concurrently with RT were retrospectively analyzed. The median biologic equivalent dose (BED) of RT was 84.0 [interquartile range …

Urinary Vitamin D Binding Protein And Kidney Injury Molecule-1 Are Potent Predictors Of Acute Kidney Injury After Left Ventricular Assist Device Implantation, Shiyi Li, Iván Murrieta-Álvarez, Katherine V Nordick, Zachary Gray, Camila Hochman-Mendez, Alexis E Shafii, Kenneth K Liao, Carl P Walther, Nandan K Mondal

Faculty, Staff and Students Publications

Background/Objectives: Acute kidney injury (AKI) is a frequent and serious complication following left ventricular assist device (LVAD) implantation. This study aimed to predict AKI within 90 days post-LVAD by evaluating urinary levels of vitamin D binding protein (VDBP) and kidney injury molecule-1 (KIM-1).

Methods: We prospectively enrolled 29 advanced heart failure patients undergoing LVAD implantation and categorized them into four groups based on pre-LVAD kidney function and hemodynamic stability. Early-morning urine samples were collected 24 h before and 1 week after surgery. Urinary VDBP and KIM-1 levels, normalized to creatinine, were measured.

Results: Thirteen patients developed AKI …

Pediatric Non-Down Syndrome Acute Megakaryoblastic Leukemia Patients Have Dismal Outcomes Irrespective Of Allogeneic Hematopoietic Stem Cell Transplant: A Single-Center Experience, Gabriela Llaurador, Matthew Willis, Michele S Redell, M Monica Gramatges, Andrea N Marcogliese, Swati Naik, Robert Krance, Erin Doherty, Alexandra M Stevens

Faculty, Staff and Students Publications

Background: Pediatric non-Down Syndrome Acute Megakaryoblastic Leukemia (non-DS-AMKL) is a rare subtype of Acute Myeloid Leukemia (AML) arising from primitive megakaryocytes and is associated with poor outcomes. Given its high incidence of relapse, this subpopulation of children is frequently referred for allogeneic hematopoietic stem cell transplant (allo-HSCT) in first complete remission (CR1).

Objectives: The objective of this study was to describe the clinical outcomes of non-DS-AMKL pediatric patients in a large, single-institution cohort.

Methods: A retrospective review of the medical records of thirty-six patients diagnosed with non-DS-AMKL treated at Texas Children's Hospital from 2000 to 2022 was conducted.

Results: Twenty-nine …

Resolving Slc6a1 Variable Expressivity With Deep Clinical Phenotyping And Drosophila Models, Kristy L Jay, Nikhita Gogate, Paige I Hall, Kimberly M Ezell, Jonathan C Andrews, Sharayu V Jangam, Hongling Pan, Kelvin Pham, Ryan German, Vanessa Gomez, Emily Jellinek-Russo, Eric A Storch, Brain Gene Registry Consortium, Undiagnosed Diseases Network, Shinya Yamamoto, Oguz Kanca, Hugo J Bellen, Herman A Dierick, Joy D Cogan, John A Phillips, Rizwan Hamid, Thomas Cassini, Lynette Rives, Sumit Pruthi, Hua-Chang Chen, Jennifer E Posey, Michael F Wangler

Faculty, Staff and Students Publications

Variants in SLC6A1 result in a rare neurodevelopmental disorder characterized by a variable clinical presentation of symptoms including developmental delay, epilepsy, motor dysfunction, and autism spectrum disorder. SLC6A1 haploinsufficiency has been confirmed as the predominant pathway of SLC6A1-related neurodevelopmental disorder (SLC6A1-NDD); however, the molecular mechanism underlying the variable clinical presentation remains unclear. Here, through work of the Undiagnosed Diseases Network, we identify an individual with an inherited p.A334S variant of uncertain significance. To resolve this variant and better understand the variable expressivity associated with SLC6A1, we assess the phenotypes of the proband in comparison with a cohort of 13 individuals …