Medical Specialties Commons^™

Dna Damage Response Signatures Are Associated With Frontline Chemotherapy Response And Routes Of Tumor Evolution In Extensive Stage Small Cell Lung Cancer, Benjamin B Morris, Simon Heeke, Yuanxin Xi, Lixia Diao, Qi Wang, Pedro Rocha, Edurne Arriola, Myung Chang Lee, Darren R Tyson, Kyle Concannon, Kavya Ramkumar, C Allison Stewart, Robert J Cardnell, Runsheng Wang, Vito Quaranta, Jing Wang, John V Heymach, Barzin Y Nabet, David S Shames, Carl M Gay, Lauren A Byers

Faculty, Staff and Student Publications

Introduction: A hallmark of small cell lung cancer (SCLC) is its recalcitrance to therapy. While most SCLCs respond to frontline therapy, resistance inevitably develops. Identifying phenotypes potentiating chemoresistance and immune evasion is a crucial unmet need. Previous reports have linked upregulation of the DNA damage response (DDR) machinery to chemoresistance and immune evasion across cancers. However, it is unknown if SCLCs exhibit distinct DDR phenotypes.

Methods: To study SCLC DDR phenotypes, we developed a new DDR gene analysis method and applied it to SCLC clinical samples, in vitro, and in vivo model systems. We then investigated how DDR regulation is …

Sap30, A Novel Autophagy Regulatory Gene In Neuroblastoma, Anup S Pathania, Anjana Murugan, Areem Zahid, Haritha Chava, Don W Coulter, George A Calin, Kishore B Challagundla

Faculty, Staff and Student Publications

Neuroblastoma (NB), a devastating pediatric cancer originating from neural crest cells crucial for nervous system development, poses a significant therapeutic challenge. Despite chemotherapy being the primary treatment, approximately 70% of high-risk NB cases develop resistance. Autophagy is vital for neuronal development, balance, and differentiation of neural stem cells into mature neurons. However, the intricate mechanisms governing autophagy and the pivotal genes orchestrating its regulation in NB remain largely elusive. In this study, we first identified Sin3A Associated Protein 30 (SAP30) as a novel regulator of autophagy in NB. Silencing SAP30 inhibits autophagy and disrupts starvation-induced physiological autophagy in NB cells. …

Do We Need To Add The Type Of Treatment Planning System, Dose Calculation Grid Size, And Ct Density Curve To Predictive Models?, Reza Reiazi, Surendra Prajapati, Leonardo Che Fru, Dongyeon Lee, Mohammad Salehpour

Faculty, Staff and Student Publications

Background: Generalizability and domain dependency are critical challenges in developing predictive models for healthcare, particularly in medical diagnostics and radiation oncology. Predictive models designed to assess tumor recurrence rely on comprehensive and high-quality datasets, encompassing treatment planning parameters, imaging protocols, and patient-specific data. However, domain dependency, arising from variations in dose calculation algorithms, computed tomography (CT) density conversion curves, imaging modalities, and institutional protocols, can significantly undermine model reliability and clinical utility.

Methods: This study evaluated dose calculation differences in the head and neck cancer treatment plans of 19 patients using two treatment planning systems, Pinnacle 9.10 and RayStation 11, …

Evaluation And Surgical Management Of Pediatric Cutaneous Melanoma And Atypical Spitz And Non-Spitz Melanocytic Tumors (Melanocytomas): A Report From Children's Oncology Group, Michael R Sargen, Raymond L Barnhill, David E Elder, Susan M Swetter, Victor G Prieto, Jennifer S Ko, Armita Bahrami, Pedram Gerami, Arivarasan Karunamurthy, Alberto S Pappo, Lynn M Schuchter, Philip E Leboit, Iwei Yeh, John M Kirkwood, Melinda Jen, Ira J Dunkel, Megan M Durham, Emily R Christison-Lagay, Mary T Austin, Jennifer H Aldrink, Casey Mehrhoff, Elena B Hawryluk, Emily Y Chu, Klaus J Busam, Vernon Sondak, Jane Messina, Susana Puig, Andrew J Colebatch, Carrie C Coughlin, Kristen G Berrebi, Theodore W Laetsch, Sarah G Mitchell, Brittani Seynnaeve

Faculty, Staff and Student Publications

Purpose: The purpose of this study was to develop recommendations for the diagnostic evaluation and surgical management of cutaneous melanoma (CM) and atypical Spitz tumors (AST) and non-Spitz melanocytic tumors (melanocytomas) in pediatric (age 0-10 years) and adolescent (age 11-18 years) patients.

Methods: A Children's Oncology Group-led panel with external, multidisciplinary CM specialists convened to develop recommendations on the basis of available data and expertise.

Results: Thirty-three experts from multiple specialties (cutaneous/medical/surgical oncology, dermatology, and dermatopathology) established recommendations with supporting data from 87 peer-reviewed publications.

Recommendations: (1) Excisional biopsies with 1-3 mm margins should be performed when feasible for clinically …

Intraoperative Code Status: Moving From Misinformation To Respect For Patient Autonomy, Jacob Applegarth, Jacob M. Morton, Nathan M. Novotny, Ngan Nguyen, Abram Brummett

Conference Presentation Abstracts

Introduction: Intraoperative code status represents a complicated topic for patients and providers. Prior studies demonstrated a lack of understanding of intraoperative code status, specifically do not resuscitate (DNR) orders. This misunderstanding appears common despite clear professional recommendations. A recent survey of surgery residents at our institution showed variability in understanding of intraoperative code status policy despite clear institutional guidelines. Few studies utilized simulated education for surgeons and surgical residents to navigate intraoperative DNR status. This project aims to create a simulation-based program for residents to navigate intraoperative DNR status ethically and to assess its impact on learning, practice patterns and …

Assessment Of The Effect Of Classic Sports Massage On The Reduction Of Delayed Onset Muscle Soreness In The Rectus Abdominis, Dariusz Boguszewski, Cezary Kaaroud, Jakub Grzegorz Adamczyk

Baltic Journal of Health and Physical Activity

The aim of this study was to evaluate the influence of classic massage on the reduction of post-exercise pain in the rectus abdominis muscle. Twenty-eight people between 20 and 43 years of age (mean age 27.4) were qualified for the study. There were nine women and six men in Group 1 (experimental) and six women and seven men in Group 2 (control). All participants of the study qualified after in the initial interview they performed sit-ups, according to the guidelines of the International Physical Fitness Test. Group 1 was subjected to the convergence of classical sports massage (3 treatments). The …

Assessment Of The Reliability And Validity Of Simple And Complex Reaction Speed Tests In Mixed Martial Arts Athletes Using The Blazepod System, Jacek Polechoński, Jan Pilch, Alan Langer, Magdalena Prończuk, Jarosław Markowski, Adam Maszczyk

Baltic Journal of Health and Physical Activity

The main aim of the research was to evaluate the reliability and validity of measurements of simple and complex reaction speed using the BlazePod system in MMA athletes. Additionally, these motor skills for the right and left hands of the studied athletes were compared. The study involved 34 male professional MMA practitioners (training experience 7.0±4.0 years, age 26.5±5.3 years, body mass 76.9±9.8 kg, height 178.5±5.7 cm). The evaluation of reaction speed utilized the BlazePod^TM system and classic computer tests. The time from the activation of a light stimulus to the hand striking a glowing target in front of the …

Perceptions Of Cardiac Surgeons Regarding The Integration Of Artificial Intelligence In Cardiac Surgery, Nada Alguizzani, Fareed Khouqeer, Rasha Alorini, Imtenan Oberi

Journal of the Saudi Heart Association

Background: After the surge of artificial intelligence in late 2022, researchers started exploring the idea of using artificial intelligence in the medical field. Considering the endless possibilities of artificial intelligence, there is still some hesitation toward its use in the medical field. This study aims to explore the attitudes of cardiac surgeons toward involving artificial intelligence in diagnosing cardiac conditions and planning cardiac operations.

Methodology: This study surveyed cardiac surgeons on AI integration in their field using a cross-sectional design and purposive sampling. Data were collected via a structured questionnaire and analyzed in IBM SPSS 29.0.

Results: Our study included …

Seizure Freedom And Reducing The Risk Of Sudden Unexpected Death In Patients With Focal Epilepsy Treated With Cenobamate Or Other Antiseizure Medications, Michael R. Sperling, William E. Rosenfeld, John Watson, Pavel Klein

Department of Neurology Faculty Papers

People with epilepsy who have uncontrolled seizures are at increased risk of all-cause mortality, injuries, comorbidities, mood and psychosocial disorders, and diminished quality of life. For those with focal epilepsy, focal to bilateral tonic-clonic seizures (FBTCS) pose the greatest risk for sudden unexpected death in epilepsy (SUDEP), a leading cause of premature mortality in people with epilepsy. Cenobamate is a third-generation antiseizure medication with demonstrated efficacy in controlling focal seizures, including FBTCS, in people with drug-resistant epilepsy. Treatment with cenobamate in clinical trials was associated with a reduction in all-cause mortality to a rate statistically indistinguishable from that seen in …

Utility Of 3-Dimensional Echocardiography In Patients With Complex Intracardiac Connections And Ventricular Septal Defects, Aura Andrea Sanchez Mejia, Tam T Doan, Christian Lilje, Minh B Nguyen, Ricardo H Pignatelli, Shagun Sachdeva, Anitha Parthiban

Faculty, Staff and Students Publications

The surgical management of patients with complex intracardiac connections, ventricular septal defect (VSD), and 2 adequately sized ventricles is challenging. Understanding the VSD anatomy and its spatial relationships with the outflow tracts is critical to determining the suitability for biventricular repair. Transthoracic 2-dimensional echocardiography (2D-echo) is the primary cardiac imaging tool in congenital heart disease. Transthoracic 3-dimensional echocardiography (3D-echo) has an additive role over 2D-echo in the definition of the potential baffle pathway from the VSD to the semilunar valves, the anatomical characteristics of the VSD, and any substrate for systemic outflow tract obstruction postrepair. In this paper, we describe …

Novel Valve-In-Valve Transcatheter Systemic Tricuspid Valve Replacement In Congenitally Corrected Transposition Of The Great Arteries, Aamer Naofal, Riyad Yazan Kherallah, Wilson W Lam, Dhaval R Parekh

Faculty, Staff and Students Publications

A 41-year-old woman with history of situs inversus totalis, dextrocardia, congenitally corrected transposition of the great arteries, and systemic tricuspid valve replacement presented with worsening of her baseline orthopnea and exertional dyspnea caused by stenosis of the tricuspid valve. Given her high risk for surgery, valve-in-valve transcatheter tricuspid valve replacement was pursued and performed successfully, leading to resolution of her symptoms. Previous valve-in-valve tricuspid interventions are rare. This case is notable as the first systemic atrioventricular valve-in-valve replacement in a patient with dextrocardia through a septal approach.

Eco-Microbiology: Discovering Biochemical Enhancers Of Pet Biodegradation By Piscinibacter Sakaiensis, Felipe-Andrés Piedra, Miguel A Salazar, Sara Abouelniaj, Raayed Rahman, Justin C Clark, Yimo Han, Zhao Wang, Anthony Maresso

Faculty, Staff and Students Publications

The scale of plastic pollution boggles the mind. Nearly 400 megatons of virgin plastics are produced annually, with an environmental release rate of 80%, and plastic waste, including microplastics and nanoplastics, is associated with a plethora of problems. The naturally evolved abilities of plastic-degrading microbes offer a starting point for generating sustainable and eco-centric solutions to plastic pollution-a field of endeavor we term eco-microbiology. Here, we developed an iterative discovery procedure coupling faster polyethylene terephthalate (PET)-dependent bioactivity screens with longer-term PET biodegradation assays to find biochemical boosters of PET consumption by the bacterium Piscinibacter sakaiensis. We discovered multiple hits …

Editorial: Old Drugs: Confronting Recent Advancements And Challenges, Anna Wiktorowska-Owczarek, Diego Iacono, Magdalena Jasińska-Stroschein

Department of Neurology Faculty Papers

No abstract provided.

Asymmetrical Glymphatic Dysfunction In Patients With Long Covid Associated Neurocognitive Impairment- Correlation With Bbb Disruption, Joga Chaganti, Tanush Talekar, Bruce J. Brew

Department of Radiology Faculty Papers

BACKGROUND AND PURPOSE: The glymphatic system, a waste clearance pathway, has been implicated in several neurological conditions associated with neuroinflammation. COVID-19 associated neurocognitive impairment, part of the post-acute sequelae of SARS-CoV-2 infection (PASC), is strongly associated with neuroinflammation and disrupted blood-brain barrier (BBB). Several studies have implicated a synergistic interaction between the glymphatic system dysfunction and BBB disruption. In this proof-of-concept study, we investigated the role of the MRI metric diffusion along the perivascular spaces DTI (DTI-ALPS) in patients with PASC and correlated this with the BBB capillary permeability metric- K trans derived from Dynamic contrast enhanced (DCE) perfusion.

MATERIALS …

Severe Maternal Morbidity In Twin Pregnancies: The Impact Of Body Mass Index And Gestational Weight Gain, Nathan A. Keller, Frank Ian Jackson, Insaf Kouba, Luis A. Bracero, Matthew J. Blitz

Specialty Medicine Faculty Publications

Objectives: The objective of this study was to determine whether body mass index (BMI) and gestational weight gain (GWG) are associated with severe maternal morbidity (SMM) in twin gestations.
Methods: This was a retrospective cohort of all twin pregnancies delivered at seven hospitals in New York from 2019 to 2023. Multivariable logistic regression modeled the probability of SMM as a function of BMI group, adjusting for excessive GWG, race-ethnicity, and obstetric comorbidity index. A total of 1,976 twin gestations were included.
Results: The SMM rate was 14.0 % (n=276).
Conclusions: Neither pre-pregnancy BMI nor GWG was associated with SMM, both …

Mind Matters: How Anxiety And Depression Shape Low-Risk Prostate Cancer Active Surveillance Adherence In A Real-World Population, Zachariah Taylor, Kayla Meyer, Danielle Terrenzio, Ryan Wong, Sharon L. Larson, Stephanie Kjelstrom, Natalina Contoreggi, Laurence Belkoff, Ilia Zeltser

Jefferson Hospital Staff Papers and Presentations

PURPOSE: While the mental health impact of a prostate cancer diagnosis, including low-risk prostate cancer, is well-documented, the effect of pre-existing anxiety and/or depression on adherence to active surveillance protocols in low-risk prostate cancer patients remains unclear. This study assessed the association between prior anxiety and/or depression and active surveillance adherence in men with low-risk prostate cancer.

METHODS: We conducted a retrospective, multicenter study involving 426 men diagnosed with low-risk prostate cancer who were recommended active surveillance as the primary management strategy. Active surveillance adherence was defined by completion of both a prostate-specific antigen test and a prostate biopsy within …

International Expert Consensus On The Current Status And Future Prospects Of Artificial Intelligence In Metabolic And Bariatric Surgery, Mohammad Kermansaravi, Sonja Chiappetta, Shahab Shahabi Shahmiri, Julian Varas, Chetan Parmar, Yung Lee, Jerry T. Dang, Asim Shabbir, Daniel Hashimoto, Amir Hossein Davarpanah Jazi, Ozanan R. Meireles, Edo Aarts, Hazem Almomani, Aayad Alqahtani, Ali Aminian, Estuardo Behrens, Dieter Birk, Felipe J. Cantu, Ricardo V. Cohen, Maurizio De Luca, Nicola Di Lorenzo, Bruno Dillemans, Mohamad Hayssam Elfawal, Daniel Moritz Felsenreich, Michel Gagner, Hector Gabriel Galvan, Carlos Galvani, Khaled Gawdat, Omar M. Ghanem, Et Al

School of Medicine Faculty Publications

Artificial intelligence (AI) is transforming the landscape of medicine, including surgical science and practice. The evolution of AI from rule-based systems to advanced machine learning and deep learning algorithms has opened new avenues for its application in metabolic and bariatric surgery (MBS). AI has the potential to enhance various aspects of MBS, including education and training, decision-making, procedure planning, cost and time efficiency, optimization of surgical techniques, outcome and complication prediction, patient education, and access to care. However, concerns persist regarding the reliability of AI-generated decisions and associated ethical considerations. This study aims to establish a consensus on the role …

Using Ehr Reminders To Control Hypertension, Umme Kulsoom Ghous, Logan Mcculley, Danielle C. Hall, Linda Katherine Lambert, Laura Reed Dnp, Aprn, Fnp-Bc, Cne

Doctor of Nursing Practice Projects

Purpose/Background

Hypertension is a significant risk factor for cardiovascular and kidney diseases but is often under-diagnosed and poorly managed. Electronic Health Records (EHR) can help by providing automated reminders to recheck elevated blood pressure (BP) readings, ensuring accurate measurements, and guiding clinical interventions. This study aims to determine if EHR-based reminders improve BP control in adult patients aged 21 and older, focusing on hypertension diagnosis accuracy and timely management.

Methods

After a literature review, the study took place in a primary care clinic and only included patients with an existing diagnosis of hypertension. Thirty patients were included in the study. …

Diverse Ancestral Representation Improves Genetic Intolerance Metrics, Alexander L Han, Chloe F Sands, Dorota Matelska, Jessica C Butts, Vida Ravanmehr, Fengyuan Hu, Esmeralda Villavicencio Gonzalez, Nicholas Katsanis, Carlos D Bustamante, Quanli Wang, Slavé Petrovski, Dimitrios Vitsios, Ryan S Dhindsa

Duncan NRI Faculty and Staff Publications

The unprecedented scale of genomic databases has revolutionized our ability to identify regions in the human genome intolerant to variation—regions often implicated in disease. However, these datasets remain constrained by limited ancestral diversity. Here, we analyze whole-exome sequencing data from 460,551 UK Biobank and 125,748 Genome Aggregation Database (gnomAD) participants across multiple ancestries to test several key intolerance metrics, including the Residual Variance Intolerance Score (RVIS), Missense Tolerance Ratio (MTR), and Loss-of-Function Observed/Expected ratio (LOF O/E). We demonstrate that increasing ancestral representation, rather than sample size alone, critically drives their performance. Scores trained on variation observed in African and Admixed …

The Importance Of Better Natural History Studies For Duchenne Muscular Dystrophy, David J. Birnkrant

Faculty Scholarship

No abstract provided.

Dietary Effects On The Retina Of Hamsters, Nicole El-Darzi, Natalia Mast, Yong Li, Irina A. Pikuleva

Faculty Scholarship

The retina is a sensory tissue in the back of the eye, which captures visual information and relays it to the brain. The retinal pigment epithelium separates the neural retina from the choroidal (systemic) circulation and is thereby exposed to circulating lipoprotein particles. Herein, we used hamsters and conducted various retinal evaluations of animals fed either a normal diet or a Western-type diet (WTD). Prior to evaluations, hamsters were injected with indocyanine green (ICG), a fluorescent dye that binds to various proteins and lipids in the systemic circulation. The WTD increased plasma levels of total and HDL cholesterol 1.8- and …

Endovascular Re-Intervention For Recurrent Lower Limb Ischemia After Previous Endovascular Intervention, Mohamed Abdelsamie Abdelkhalek Elbahat

Journal of Medicine in Scientific Research

Background Redo endovascular interventions are increasingly employed to address recurrent lower limb ischemia following prior successful procedures. Despite their minimally invasive nature and flexibility, there is limited data on their midterm effectiveness and safety. Objective To evaluate the effectiveness and outcomes of endovascular re-intervention in managing recurrent lower limb ischemia after previous procedures. Patients and Methods This study included 40 patients with recurrent lower limb ischemia, managed at Shebin Elkoom Teaching Hospital between 2023 and 2024. Patients had previously undergone successful endovascular interventions at least 30 days before recurrence and were treated with angioplasty alone or in combination with stenting. …

A Deep Sparse Capsule Network For Non-Invasive Blood Glucose Level Estimation Using A Ppg Sensor, Narmatha Chellamani, Saleh Ali Albelwi, Manimurugan Shanmuganathan, Palanisamy Amirthalingam, Emad Muteb Alharbi, Hibah Qasem Salman Alatawi, Kousalya Prabahar, Jawhara Bader Aljabri, Anand Paul

School of Public Health Faculty Publications

Diabetes, a chronic medical condition, affects millions of people worldwide and requires consistent monitoring of blood glucose levels (BGLs). Traditional invasive methods for BGL monitoring can be challenging and painful for patients. This study introduces a non-invasive, deep learning (DL)-based approach to estimate BGL using photoplethysmography (PPG) signals. Specifically, a Deep Sparse Capsule Network (DSCNet) model is proposed to provide accurate and robust BGL monitoring. The proposed model’s workflow includes data collection, preprocessing, feature extraction, and predictions. A hardware module was designed using a PPG sensor and Raspberry Pi to collect patient data. In preprocessing, a Savitzky–Golay filter and moving …

Author Correction: Generation Of A Tree Shrew Breast Cancer Model Using Lentivirus Expressing Pik3ca-H1047r, Li Zeng, Hong-Yan Zhang, Chuan-Yu Yang, Zhuo Cheng, Qiu-Yun Jiang, Yao Luo, Yi Li, Fu-Bing Li, Ce-Shi Chen

Faculty, Staff and Students Publications

No abstract provided.

Framework For Kidney Health Follow-Up Among Neonates With Critical Cardiac Disease: A Report From The Neonatal Kidney Health Consensus Workshop, Stephen M Gorga, Tara Beck, Paulomi Chaudhry, Marissa J Defreitas, Dana Y Fuhrman, Catherine Joseph, Catherine D Krawczeski, David M Kwiatkowski, Michelle C Starr, Matthew W Harer, Jennifer R Charlton, David J Askenazi, David T Selewski, Katja M Gist

Faculty, Staff and Students Publications

Acute kidney injury is common among neonates with critical cardiac disease. Risk factors and associations with kidney-related outcomes are heterogeneous and distinct from other neonates. As survival of children with critical cardiac disease increases to adulthood, the burden of chronic kidney disease is increasing. Thirty percent to 50% of adults with congenital heart disease have impaired kidney function, even in the absence of prior kidney injury episodes. This may be related to the current standardized acute kidney injury criteria, which may not fully capture clinically meaningful kidney injury and long-term kidney health risks. An improved understanding of which neonates with …

Emerging Clostridioides Difficile Ribotypes Have Divergent Metabolic Phenotypes, Firas S Midani, Heather A Danhof, Nathanael Mathew, Colleen K Ardis, Kevin W Garey, Jennifer K Spinler, Robert A Britton

Faculty, Staff and Students Publications

Clostridioides difficile is a gram-positive spore-forming pathogen that commonly causes diarrheal infections in the developed world. Although C. difficile is a genetically diverse species, certain ribotypes are overrepresented in human infections, and it is unclear if metabolic adaptations are essential for the emergence of these epidemic ribotypes. To identify ribotype-specific metabolic differences, we therefore tested carbon substrate utilization by 88 C. difficile isolates and looked for differences in growth between 22 ribotypes. As expected, C. difficile was capable of growing on a variety of carbon substrates. Further, C. difficile strains clustered by phylogenetic relationship and displayed ribotype-specific and clade-specific …

The Autophagy Protein Atg14 Safeguards Against Unscheduled Pyroptosis Activation To Enable Embryo Transport During Early Pregnancy, Pooja Popli, Arin K Oestreich, Vineet K Maurya, Marina N Rowen, Yong Zhang, Michael J Holtzman, Ramya Masand, John P Lydon, Shizuo Akira, Kelle Moley, Ramakrishna Kommagani

Faculty, Staff and Students Publications

Recurrent pregnancy loss, characterized by two or more failed clinical pregnancies, poses a significant challenge to reproductive health. In addition to embryo quality and endometrial function, proper oviduct function is also essential for successful pregnancy establishment. Therefore, structural abnormalities or inflammation resulting from infection in the oviduct may impede the transport of embryos to the endometrium, thereby increasing the risk of miscarriage. However, our understanding of the biological processes that preserve the oviductal cellular structure and functional integrity is limited. Here, we report that autophagy-related protein ATG14 plays a crucial role in maintaining the cellular integrity of the oviduct by …

Comparing Postoperative Opioid Use In Primary And Revision Lumbar Fusion: A Propensity-Matched Analysis, Jonathan Dalton, Jarod Olson, Nicholas B. Pohl, Rajkishen Narayanan, Omar Tarawneh, Yunsoo Lee, Michael V. Carter, Gokul Karthikeyan, Logan Witt, Aayush Mehta, John J. Mangan, Mark F. Kurd, Jose A. Canseco, Alan S. Hilibrand, Alex R. Vaccaro, Gregory D. Schroeder, Christopher K. Kepler

Department of Orthopaedic Surgery Faculty Papers

OBJECTIVE: This study compared postoperative opioid use for patients undergoing short segment primary versus revision lumbar fusion.

METHODS: Patients who underwent primary or revision 1-2 level lumbar fusion (2017-2021) were included in this study. The state Prescription Drug Monitoring Program was reviewed for all patients to quantify preoperative and postoperative opioid, benzodiazepine, muscle relaxant, and gabapentin use. A 1:1 propensity match was performed to match primary lumbar fusion patients with revision lumbar fusion patients. Revision lumbar fusion patients were substratified into those with or without persistent postoperative opioid use to identify demographic differences between these patient cohorts.

RESULTS: The final …

Icos-Expressing Car-T Cells Mediate Durable Eradication Of Triple-Negative Breast Cancer And Metastasis, Shelley Herbrich, Mehdi Chaib, Padmanee Sharma

Faculty, Staff and Student Publications

Triple-negative breast cancer (TNBC) remains one of the most aggressive and therapeutically challenging breast cancer subtypes. In their recent study, Cao et al introduced a B7H3-specific chimeric antigen receptor (CAR)-T cell with constitutive inducible co-stimulator (ICOS) expression (ICOS-B7H3-CAR-T), which demonstrated eradication of TNBC, including metastases, in preclinical models. These CAR-T cells exploit the expression of ICOS ligand on TNBC cells, enhancing antitumor cytotoxicity through ICOS signaling. Compared with conventional B7H3-CAR-T cells, the ICOS-B7H3-CAR-T cells exhibited superior antitumor efficacy, increased cytokine secretion, and prolonged survival in xenograft murine models. This study highlights ICOS as a promising co-stimulatory molecule for improving CAR-T …

Guanine Nucleotide Biosynthesis Blockade Impairs Mll Complex Formation And Sensitizes Leukemias To Menin Inhibition, Xiangguo Shi, Minhua Li, Zian Liu, Jonathan Tiessen, Yuan Li, Jing Zhou, Yudan Zhu, Swetha Mahesula, Qing Ding, Lin Tan, Mengdie Feng, Yuki Kageyama, Yusuke Hara, Jacob J Tao, Xuan Luo, Kathryn A Patras, Philip L Lorenzi, Suming Huang, Alexandra M Stevens, Koichi Takahashi, Ghayas C Issa, Md Abul Hassan Samee, Michalis Agathocleous, Daisuke Nakada

Faculty, Staff and Student Publications

Targeting the dependency of MLL-rearranged (MLLr) leukemias on menin with small molecule inhibitors has opened new therapeutic strategies for these poor-prognosis diseases. However, the rapid development of menin inhibitor resistance calls for combinatory strategies to improve responses and prevent resistance. Here we show that leukemia stem cells (LSCs) of MLLr acute myeloid leukemia (AML) exhibit enhanced guanine nucleotide biosynthesis, the inhibition of which leads to myeloid differentiation and sensitization to menin inhibitors. Mechanistically, targeting inosine monophosphate dehydrogenase 2 (IMPDH2) reduces guanine nucleotides and rRNA transcription, leading to reduced protein expression of LEDGF and menin. Consequently, the formation and chromatin binding …