Digital Commons Network^™

Blood Bacterial Dna Signatures In A Prospective Cohort Of Patients With Masld Cirrhosis, Suet-Ying Kwan, Lillian I Dolapchiev, Caren I Sanchez, Tiffany L Calderone, Jessica I Sanchez, Megha B Bhongade, Ahmed El Sabagh, Darrel W Cleere, Nakul Gupta, Prasun K Jalal, David W Victor, Laura Beretta

Faculty, Staff and Student Publications

Background: Predictive biomarkers are needed to identify individuals with metabolic dysfunction-associated steatotic liver disease (MASLD), at high risk for HCC. Our study aimed to determine whether the detection of circulating bacterial DNA could be associated with HCC development in MASLD patients with liver cirrhosis.

Methods: We developed a multicenter prospective cohort of patients with cirrhosis undergoing surveillance for HCC by contrast-enhanced magnetic resonance imaging. In a nested cohort study, we performed 16S rRNA sequencing of cell-free DNA extracted from 343 longitudinal plasma samples collected from 151 MASLD patients with cirrhosis. Among the 151 patients, 25 developed HCC during follow-up.

Results: …

Technical Development And In Silico Implementation Of Syntheticmr In Head And Neck Adaptive Radiation Therapy: A Prospective R-Ideal Stage 0/1 Technology Development Report, Lucas Mccullum, Samuel L Mulder, Natalie A West, Robert Aghoghovbia, Alaa Mohamed Shawky Ali, Hayden Scott, Travis C Salzillo, Yao Ding, Alex Dresner, Ergys Subashi, Dan Ma, R Jason Stafford, Ken-Pin Hwang, Clifton D Fuller

Faculty, Staff and Student Publications

Background: SyntheticMR has the capability of generating quantitative relaxometry maps and synthetic contrast-weighted MRI images in rapid acquisition times. Recently, it has gained attention in the diagnostic community, however, no studies have investigated its feasibility on the MR-Simulation or MR-Linac systems, especially as part of the head and neck adaptive radiation oncology workflow.

Purpose: Demonstrating its feasibility will facilitate rapid quantitative biomarker extraction, which can be leveraged to guide adaptive radiation therapy decision making.

Methods: Two phantoms, two healthy volunteers, and one patient were scanned using SyntheticMR on the MR-Simulation and MR-Linac devices with scan times between 4 to 6 …

Long-Term Transfusion Independence With Luspatercept Versus Epoetin Alfa In Erythropoiesis-Stimulating Agent-Naive, Lower-Risk Myelodysplastic Syndromes In The Commands Trial, Guillermo Garcia-Manero, Valeria Santini, Amer M Zeidan, Rami S Komrokji, Veronika Pozharskaya, Shelonitda Rose, Karen Keeperman, Yinzhi Lai, Sameer Kalsekar, Barkha Aggarwal, Dimana Miteva, David Valcárcel, Pierre Fenaux, Jake Shortt, Matteo Giovanni Della Porta, Uwe Platzbecker

Faculty, Staff and Student Publications

Introduction: The efficacy of erythropoiesis-stimulating agents (ESAs) for transfusion-dependent (TD) anemia in lower-risk myelodysplastic syndromes (LR-MDS) is limited. Luspatercept achieved significantly greater rates of red blood cell (RBC) transfusion independence (TI) versus epoetin alfa (an ESA) in the phase 3 COMMANDS trial. This analysis assessed long-term RBC-TI, cumulative response, and safety with luspatercept in COMMANDS.

Methods: Eligible patients aged ≥ 18 years, with ESA-naive, RBC TD LR-MDS were randomized 1:1 to receive luspatercept (1.0 mg/kg, titration to 1.75 mg/kg permitted) or epoetin alfa (450 IU/kg, titration to 1050 IU/kg). Disease assessment was carried out at week 24 (day 169) and …

Impacts Of Radiation On Metabolism And Vascular Cell Senescence, Junichi Abe, Khanh Chau, Anahita Mojiri, Guangyu Wang, Masayoshi Oikawa, Venkata S K Samanthapudi, Abigail M Osborn, Keila C Ostos-Mendoza, Karla N Mariscal-Reyes, Tammay Mathur, Abhishek Jain, Joerg Herrmann, Syed Wamique Yusuf, Sunil Krishnan, Anita Deswal, Steven H Lin, Sivareddy Kotla, John P Cooke, Nhat-Tu Le

Faculty, Staff and Student Publications

Significance: This review investigates how radiation therapy (RT) increases the risk of delayed cardiovascular disease (CVD) in cancer survivors. Understanding the mechanisms underlying radiation-induced CVD is essential for developing targeted therapies to mitigate these effects and improve long-term outcomes for patients with cancer.

Recent Advances: Recent studies have primarily focused on metabolic alterations induced by irradiation in various cancer cell types. However, there remains a significant knowledge gap regarding the role of chronic metabolic alterations in normal cells, particularly vascular cells, in the progression of CVD after RT.

Critical Issues: This review centers on RT-induced metabolic alterations in vascular cells …

Heat Shock Induces Alternative Polyadenylation Through Dynamic Dna Methylation And Chromatin Looping, Emily E Fink, Yi Zhang, Briana Santo, Anwita Siddavatam, Rosie Ou, Vishal Nanavaty, Byron H Lee, Angela H Ting

Faculty, Staff and Student Publications

Alternative cleavage and polyadenylation (APA) is a gene regulatory mechanism used by cells under stress to upregulate proteostasis-promoting transcripts, but how cells achieve this remains poorly understood. Previously, we elucidated a DNA methylation-regulated APA mechanism, in which gene body DNA methylation enhances distal poly(A) isoform expression by blocking CCCTC-binding factor (CTCF) binding and chromatin loop formation at APA control regions. We hypothesized that DNA methylation-regulated APA is one mechanism cells employ to induce proteostasis-promoting poly(A) isoforms. At the DNAJB6 cochaperone locus, acute heat shock resulted in binding of stress response transcription factors heat shock factor 1, ATF6, and YY1 at …

Powerest: Statistical Power Estimation For Spatial Transcriptomics Experiments To Detect Differentially Expressed Genes Between Two Conditions, Lan Shui, Anirban Maitra, Ying Yuan, Ken Lau, Harsimran Kaur, Liang Li, Ziyi Li

Faculty, Staff and Student Publications

Recent advancements in spatial transcriptomics (ST) have significantly enhanced biological research in various domains. However, the high cost for current ST data generation techniques restricts the large-scale application of ST. Consequently, maximization of the use of available resources to achieve robust statistical power for ST data is a pressing need. One fundamental question in ST analysis is detection of differentially expressed genes (DEGs) under different conditions using ST data. Such DEG analyses are performed frequently, but their power calculations are rarely discussed in the literature. To address this gap, we developed PoweREST, a power estimation tool designed to support the …

Hyalinization-Based Pathologic Response And Immune Infiltration Following Neoadjuvant Radiotherapy With Or Without Immune-Checkpoint Blockade In Localized Undifferentiated Pleomorphic Sarcoma, R S Traweek, M Zoghbi, R Lazcano, B M Cope, A J Bishop, A Farooqi, D Mitra, A K Yoder, B A Guadagnolo, D R Ingram, K Wani, D Shamsutdinova, A J Lazar, W-L Wang, C P Scally, E Z Keung, K E Torres, K K Hunt, R Ratan, J A Livingston, M S Nakazawa, D M Araujo, S Patel, V Ravi, A P Conley, M A Zarzour, N Somaiah, C L Roland, E F Nassif Haddad

Faculty, Staff and Student Publications

BACKGROUND: Standard-of-care treatment of localized undifferentiated pleomorphic sarcoma (UPS) involves preoperative radiotherapy (RT) and surgery. Combination of RT with immune-checkpoint blockade (ICB) represents a promising new strategy.

METHODS: Our primary objective was to assess survival outcomes and pathologically documented response in patients receiving RT with or without ICB or chemotherapy.

RESULTS: In a retrospective cohort of 68 patients with primary or locally recurrent UPS who received neoadjuvant RT with or without ICB, the ICB group had greater tumor hyalinization than the non-ICB group (89% compared with 30%, P = 0.018). In the non-ICB group, 19/37 patients (51%) achieved hyalinization-based pathologic …

Dynamic Contrast-Enhanced Mri Processing Comparison For Distinguishing True Progression From Pseudoprogression In High-Grade Glioma, Ahmad Amer, Shehbaz Ansari, Apollo Krayyem, Suprateek Kundu, Swapnil Khose, Halyna Pokhylevych, Susana Calle, Chirag B Patel, Zixi Yang, Ho-Ling Anthony Liu, Jason M Johnson

Faculty, Staff and Student Publications

Background: Treatment-related changes may occur due to radiation and temozolomide in glioblastoma and can mimic tumor progression on conventional MRI. DCE-MRI enables quantification of the extent of blood-brain barrier (BBB) disruption, providing information about areas of suspicious postcontrast T1 enhancement. We compared DCE-MRI processing methods for distinguishing true disease progression from pseudoprogression in high-grade gliomas (HGGs).

Methods: We identified 110 patients with HGG treated with surgery and chemoradiation who underwent DCE-MRI to further interrogate areas of new/increasing enhancement. All patients had confirmatory surgery/biopsy with pathology-confirmed progression or pseudoprogression. Scans were performed at 3T and analyzed using nordicICE. The MCA, SSS, …

Kap1 Promotes Gastric Adenocarcinoma Progression By Activating Hippo/Yap1 Signaling Via Binding To Hnrnpab, Shumei Song, Yibo Fan, Gengyi Zou, Longfei Huo, Janani Kumar, Yuan Li, Ruiping Wang, Enyu Dai, Jiankang Jin, Ailing W Scott, Shan Shao, Melissa Pool Pizzi, Jody V Vykoukal, Hiroyuki Katayama, Samir Hanash, George A Calin, Xing Zhang, Min Gyu Lee, Zhenning Wang, Yuan-Hung Lo, Qiong Gan, Rebecca E Waters, Feng Yin, Linghua Wang, Xiaodong Cheng, Jaffer A Ajani, Shilpa S Dhar

Faculty, Staff and Student Publications

Gastric adenocarcinoma (GAC) remains a significant global health challenge, with over a million new cases annually. Peritoneal carcinomatosis (PC), detected in ∼20 % of cases at diagnosis and ∼45 % later, is uniformly fatal, with limited treatment options. This study investigated the role of KAP1 in GAC progression, focusing on its interaction with YAP1 and cancer stemness traits. Analysis of over 596 primary GACs and 72 PC samples revealed that high nuclear KAP1 expression correlates with poor prognosis. KAP1 knockdown reduced oncogenic activity and stemness traits in GAC cells. Mechanistically, KAP1 positively regulates YAP1 transcription by binding to its promoter …

Tumour And Microenvironment Crosstalk In Nsclc Progression And Response To Therapy, Zahraa Rahal, Roy El Darzi, Seyed Javad Moghaddam, Tina Cascone, Humam Kadara

Faculty, Staff and Student Publications

The treatment landscape of non-small-cell lung cancer (NSCLC) is evolving rapidly, driven by advances in the development of targeted agents and immunotherapies. Despite this progress, some patients have suboptimal responses to treatment, highlighting the need for new therapeutic strategies. In the past decade, the important role of the tumour microenvironment (TME) in NSCLC progression, metastatic dissemination and response to treatment has become increasingly evident. Understanding the complexity of the TME and its interactions with NSCLC can propel efforts to improve current treatment modalities, overcome resistance and develop new treatments, which will ultimately improve the outcomes of patients. In this Review, …

Semi-Automated Hippocampal Avoidance Whole-Brain Radiotherapy Planning, Dong Joo Rhee, Subha Perni, Kelly J Perrin, Kevin E Casey, Alexandra O Leone, Callistus M Nguyen, Laurence E Court, He Wang, Xin Wang, Eun Young Han

Faculty, Staff and Student Publications

Background: Hippocampal avoidance whole-brain radiotherapy (HA-WBRT) is designed to spare cognitive function by reducing radiation dose to the hippocampus during the treatment of brain metastases. Current manual planning methods can be time-consuming and may vary in quality, necessitating the development of automated approaches to streamline the process and ensure consistency.

Purpose: To automate hippocampal avoidance whole-brain radiotherapy (HA-WBRT) planning.

Methods: Our algorithm automatically contours organs-at-risk (OARs) and the hippocampal-avoidance brain target. The algorithm generates planning structures from given contours, utilizing preset beam parameters and dose constraints for optimization. If the dose constraints are unmet, "hotspot" contours will be created to …

Risk Of Early Death After Acute Leukemia Diagnosis Among Adolescents And Young Adults, Amy M Berkman, Clark R Andersen, Vidya Puthenpura, Nicholas J Short, Kelly Merriman, Mahesh Swaminathan, Branko Cuglievan, David Mccall, Courtney Dinardo, Cesar Nunez, Nitin Jain, Tapan Kadia, Ghayas Issa, Amber Gibson, Miriam B Garcia, J Andrew Livingston, Susan Parsons, Michelle A T Hildebrandt, Michael E Roth

Faculty, Staff and Student Publications

Background: Advances in care have led to improvements in survival for adolescents and young adults (AYAs) diagnosed with cancer; however, the risk of early death remains high for certain cancers, particularly acute leukemias. Risk factors for early death in AYAs diagnosed with acute leukemia have not been well studied.

Methods: The Surveillance, Epidemiology, and End Results registry was used to assess risk of early death (within 2 months of diagnosis) in AYAs diagnosed with acute leukemia (n = 16 153). Early death proportion, by year, for AYAs diagnosed between 2006 and 2020 was described. Associations between incidence of early death …

A Follow-Up Study On The Novel Use Of Contrast-Enhanced Susceptibility-Weighted Imaging For Extremity Desmoid Fibromatosis Response Assessment, Raul F Valenzuela, Elvis Duran-Sierra, Mathew Antony, Behrang Amini, Sam Lo, Keila E Torres, Ken-Pin Hwang, Jingfei Ma, R Jasson Stafford, Ravin Ratan, John E Madewell, Dejka Araujo, William A Murphy, Colleen M Costelloe

Faculty, Staff and Student Publications

Desmoid tumors are rare mesenchymal neoplasms characterized by a clonal proliferation of fibroblasts and myofibroblasts. Using the novel contrast-enhanced susceptibility-weighted imaging (CE-SWI) for characterizing desmoid tumors can enhance the separation between fibrous T2-hypointense and cellular T1-enhancing components. We aim to evaluate the effectiveness of the CE-SWI signal, volumetric, and radiomics-derived features in assessing desmoid treatment response. This IRB-approved study included 17 single-lesion extremity desmoid fibromatosis patients who underwent standard-of-care MRI, including CE-SWI, from March 2021 to February 2024. Measurements of maximum diameter, volume, and the modified Choi (m-Choi: tumor/muscle T2 ratio) were computed based on CE-SWI and T2-STIR volumetric tumor …

Cdemapper: Enhancing National Institutes Of Health Common Data Element Use With Large Language Models, Yan Wang, Jimin Huang, Huan He, Vincent Zhang, Yujia Zhou, Xubing Hao, Pritham Ram, Lingfei Qian, Qianqian Xie, Ruey-Ling Weng, Fongci Lin, Yan Hu, Licong Cui, Xiaoqian Jiang, Hua Xu, Na Hong

Faculty, Staff and Student Publications

Objective: Common Data Elements (CDEs) standardize data collection and sharing across studies, enhancing data interoperability and improving research reproducibility. However, implementing CDEs presents challenges due to the broad range and variety of data elements. This study aims to develop a CDE mapping tool to bridge the gap between local data elements and National Institutes of Health (NIH) CDEs.

Methods: We propose CDEMapper, a large language model (LLM)-powered mapping tool designed to assist in mapping local data elements to NIH CDEs. CDEMapper has 3 core modules: (1) CDE indexing and embeddings. NIH CDEs were indexed and embedded to support semantic search; …

Hernia Recurrence Risk Matters More Than Mesh Type To Patients Undergoing Ventral Hernia Repair, Stephanie Martinez Ugarte, Mokunfayo O Fajemisin, Chelsea J Guy-Frank, Dalya M Ferguson, Jonah J Stulberg, Lillian S Kao, Julie L Holihan

Faculty, Staff and Student Publications

Introduction: Patients' perceptions about synthetic mesh for ventral hernia repair (VHR) may stem from a lack of knowledge of risks. We assessed patients' threshold for accepting the risk of hernia recurrence to avoid synthetic mesh.

Methods: Patients ≥18 y old with prior or upcoming VHR viewed a one-time video decision aid describing recurrence risk with biologic versus synthetic mesh. Patients chose between these options using a probability trade-off (PTO) technique, varying hernia recurrence rate with biologic mesh. Based on randomized trials, the recurrence rate using synthetic mesh was 9%. The PTO score was the recurrence rate (0%-100%) at which patients …

Aortopexy With Plication Of Kommerell Diverticulum Is An Effective Alternative To Diverticulum Resection And Reimplantation Of The Aberrant Left Subclavian Artery For Surgical Management Of Vascular Rings In Children, Adegbemisola Aregbe Perkins, Ana-Lucia Tomescu, Christopher J Knott-Craig, Umar Boston, Thomas Spentzas, Karthik Vaidyanathan Ramakrishnan

Faculty, Staff and Student Publications

Background

Right aortic arch with an aberrant left subclavian artery arising from a Kommerell diverticulum is the most common form of vascular ring. We report the outcomes of plication and pexy of the diverticulum in addition to division of the left-sided ligamentum to treat this lesion in children.

Methods

Forty-four patients were included in the study; 22 patients underwent division of the ligamentum arteriosum alone, while the other half underwent plication and/or pexy of the Kommerell diverticulum in addition to division of the ligamentum. The primary outcome of interest was reintervention for persistent symptoms following the initial operation. The other …

Efficacy And Safety Of Mechanical Thrombectomy In Distal Medium Middle Cerebral Artery Occlusion Ischemic Stroke Patients On Low-Dose Aspirin, Hamza Adel Salim, Vivek Yedavalli, Fathi Milhem, Basel Musmar, Nimer Adeeb, Motaz Daraghma, Kareem El Naamani, Nils Henninger, Sri Hari Sundararajan, Anna Luisa Kühn, Jane Khalife, Sherief Ghozy, Luca Scarcia, Benjamin Yq Tan, Robert W Regenhardt, Jeremy J Heit, Nicole M Cancelliere, Joshua D Bernstock, Aymeric Rouchaud, Jens Fiehler, Sunil Sheth, Ajit S Puri, Christian Dyzmann, Marco Colasurdo, Leonardo Renieri, João Pedro Filipe, Pablo Harker, Răzvan Alexandru Radu, Mohamad Abdalkader, Piers Klein, Thomas R Marotta, Julian Spears, Takahiro Ota, Ashkan Mowla, Pascal Jabbour, Arundhati Biswas, Frédéric Clarençon, James E Siegler, Thanh N Nguyen, Ricardo Varela, Amanda Baker, Muhammed Amir Essibayi, David Altschul, Nestor R Gonzalez, Markus A Möhlenbruch, Vincent Costalat, Benjamin Gory, Christian Paul Stracke, Constantin Hecker, Hamza Shaikh, Christoph J Griessenauer, David S Liebeskind, Alessandro Pedicelli, Andrea M Alexandre, Illario Tancredi, Tobias D Faizy, Erwah Kalsoum, Max Wintermark, Boris Lubicz, Aman B Patel, Vitor Mendes Pereira, Adrien Guenego, Adam A Dmytriw

Faculty, Staff and Student Publications

Background: Acute ischemic stroke (AIS) from distal medium vessel occlusion (DMVO) presents unique treatment challenges. Mechanical thrombectomy (MT) is emerging as a viable option for these patients, yet the role of pre-stroke aspirin treatment is unclear. This study evaluates the impact of pre-stroke low-dose aspirin on outcomes in DMVO patients undergoing MT.

Methods: We conducted a multinational, multicenter, propensity score-weighted analysis within the Multicenter Analysis of primary Distal medium vessel occlusions: effect of Mechanical Thrombectomy (MAD-MT) registry. Patients with AIS due to DMVO, treated with MT, were included. We compared outcomes between patients on pre-stroke low-dose aspirin (75-100 mg) and …

Interconnections Of Insulin/Igf-1 Signaling And Autophagy Abnormalities In Alzheimer’S Disease, Wang Liao, Jinfeng Xuan, Woo-In Ryu, Mariana K Bormann, Yoon Lee, Haley Dion, Elizabeth Evangelista, Ruiyi Li, Lucas Trambaiolli, Jun Liu, Arthur J Siegel, Brent P Forester, Bruce M Cohen, Kai-Christian Sonntag

Faculty, Staff and Student Publications

Introduction: Impaired insulin (INS) and insulin-like growth factor 1 (IGF-1) signaling are features of both brain aging and late-onset Alzheimer's disease (LOAD). However, their exact underlying mechanisms and cause-and-effect linkages, including the downstream regulation of endocytosis and autophagy, are still not well understood.

Methods: We investigated INS/IGF-1 signaling and its connection with endocytic and autophagic processes in fibroblasts from LOAD patients and healthy young or old control individuals.

Results: Compared to control old-age cells, protein levels in the INS/IGF-1 signaling cascade were elevated in LOAD cells, but activation of AKT was reduced. The activation of the INS/IGF-1/AKT/FOXO1 or mTOR axes …

Preventing Acute Kidney Injury And Its Longer-Term Impact In The Critically Ill, Alexander Zarbock, Lui Forni, Jay L Koyner, Hernando Gómez, Neesh Pannu, Marlies Ostermann, Rinaldo Bellomo, John A Kellum, Thilo Von Groote

Faculty, Staff and Student Publications

Acute kidney injury (AKI) is a heterogeneous syndrome that not only affects short-term morbidity and mortality but also influences long-term outcomes. AKI is part of acute kidney disease (AKD) that encompasses a range of different conditions and is characterized by a kidney dysfunction lasting 90 days or less after which time the term chronic kidney disease (CKD) applies. AKD may result in irreversible loss of nephrons and may lead to CKD. In this narrative review, an update on different aspects of AKI in critically ill patients will be provided. We discuss biomarkers for early diagnosis of AKI, sub-clinical AKI, as …

Long-Term Exposure To Multiple Air Pollutants And Multi-Level Socioeconomic Status: Joint Effects On Age-Related Macular Degeneration, Subsequent Ocular Comorbidity, And Death In Middle-Aged And Older Adults, Yang Yang, Liangkai Chen, Qichen Liu, Min Mu, Jing Huang, Guangming Zhang, Qianqian Song

Faculty, Staff and Student Publications

Background: Both air pollution and socioeconomic status (SES) are recognized as significant determinants of health outcomes. However, no study has explored the combined effects of air pollutants and SES on (1) age-related macular degeneration (AMD) incidence; (2) trajectories from baseline to AMD, subsequent ocular comorbidity (OCMD), and mortality; and (3) life expectancy in middle-aged and older adults.

Methods: Using UK Biobank data, we created two composite air pollution scores (APS) and assessed SES at individual and neighborhood levels. OCMD was defined as glaucoma or cataract occurrence after AMD diagnosis. Cox proportional hazard regression models, multistate models, and life tables were …

Switching From Adalimumab Reference Product To And Among Adalimumab Biosimilars Outside The Usa: Insights For Us Clinicians, John R P Tesser, Aline Charabaty, Adelaide A Hebert

Faculty, Staff and Student Publications

Ten adalimumab biosimilars have been introduced in the United States (USA) since 2023, while adalimumab biosimilars have been available for several years in other countries. These experiences of biosimilar uptake outside the USA can inform US-based healthcare professionals on switching in real-life practice settings. Considerations include how healthcare professionals might meaningfully address patient concerns about outcomes to improve patient satisfaction. A search of the MEDLINE database was used to identify publications on switching to and among adalimumab biosimilars in an ex-US setting, with no restriction on publication language and using a time frame of 1 January 2017 through 12 December …

Endovascular Therapy For Late-Window M2-Segment Middle Cerebral Artery Occlusion: Analysis Of The Clear Study, Simon Winzer, Daniel P O Kaiser, Muhammad M Qureshi, Alicia C Castonguay, Daniel Strbian, Raul G Nogueira, Simon Nagel, Jean Raymond, Mohamad Abdalkader, Jelle Demeestere, João Pedro Marto, Hiroshi Yamagami, Kanta Tanaka, Sunil A Sheth, Anne Dusart, Patrik Michel, Marta Olive Gadea, Marc Ribo, Osama O Zaidat, Diogo C Haussen, Hilde Henon, Mahmoud H Mohammaden, Markus A Möhlenbruch, James E Siegler, Ajit S Puri, Johannes Kaesmacher, Piers Klein, Liisa Tomppo, Francois Caparros, João Nuno Ramos, Mouhammad Jumaa, Syed Zaidi, Nicolas Martinez-Majander, Stefania Nannoni, Lieselotte Vandewalle, Flavio Bellante, Milagros Galecio-Castillo, Sergio Salazar-Marioni, Pekka Virtanen, Anke Wouters, Rita Ventura, Jessica Jesser, Adnan Mujanovic, Liqi Shu, Abiya Qureshi, Zhongming Qiu, Hesham E Masoud, Manuel Requena, Mikko Sillanpää, Wei Hu, Eugene Lin, Charlotte Cordonnier, Daniel Roy, Shadi Yaghi, Davide Strambo, Urs Fischer, Santiago Ortega-Gutierrez, Robin Lemmens, Peter A Ringleb, Thanh N Nguyen, Volker Puetz

Faculty, Staff and Student Publications

Background: There is uncertainty about whether patients with M2 occlusion benefit from endovascular therapy (EVT) in the late (6-24-hour) time window. We evaluated the clinical outcomes of patients with M2 occlusion selected for EVT compared with those who received medical management (MM) in the late window.

Methods: This multinational cohort study was conducted at 66 sites across 10 countries (January 2014 to May 2022). We included consecutive patients with late-window stroke due to M2 occlusion, baseline National Institutes of Health Stroke Scale score of ≥5, and premorbid modified Rankin Scale score of ≤2 who received EVT or MM alone. The …

A Case Of Aqp4-Igg Neuromyelitis Optica Presenting With Orbital Inflammatory Syndrome, Lucy A Bailey, Roy F Riascos, Ore-Ofe O Adesina

Faculty, Staff and Student Publications

A 45-year-old healthy African-American man experienced 2 months of right-eye soreness followed by acute onset of right painful vision loss with binocular, oblique diplopia. Visual acuity was count fingers OD and 20/20 OS. He had a partial, right, pupil-involving cranial nerve III palsy with a right relative afferent pupillary defect and optic disc edema with tortuous vessels. Magnetic resonance imaging showed increased T2 signal with tortuosity and thickening of the retrobulbar right optic nerve with associated restricted diffusion and enhancement, enhancement of orbital fat adjacent to the optic nerve sheath, and relative right proptosis. Workup was positive for aquaporin-4 antibody …

Automated Mycoplasma Genitalium Molecular Macrolide Resistance Detection And Nucleic Acid Target Semi-Quantitation: Patient Demographic Considerations, Josephine Moore, Trinity Krueger, Amanda Zapp, Stephen C Lavey, Kimber L Munson, Irene A Stafford, Michael E Newcomb, Brian Mustanski, Erik Munson

Faculty, Staff and Student Publications

Recent work has optimized parameters of a real-time reverse transcriptase PCR-based laboratory-developed test on the Panther Fusion system which detects Mycoplasma genitalium-specific macrolide resistance-associated mutations LDT (MRM-LDT) from primary swab and urine specimens. In this study, MRM-LDT was applied to a large multi-demographic study set to further characterize M. genitalium resistance in the United States. A total of 2,145 primary clinical specimens testing positive for M. genitalium 16S rRNA by transcription-mediated amplification (TMA) were initially titered by the same assay using serial 10-fold dilutions to determine relative target nucleic acid burden. Specimens were then processed for MRM-LDT. Findings were stratified …

Evolving Hemodynamics In Fontan Circulation: Age-Driven Insights In Patients With Interrupted Inferior Vena Cava And Hepatoazygos Shunt, Vikas Kannojiya, Akshita Sahni, Emily Eickhoff, Neha Zacharia, Nicole St Clair, Noah Schulz, Peter E Hammer, Pedro J Del Nido, Rahul H Rathod, David M Hoganson, Vijay Govindarajan

Faculty, Staff and Student Publications

Patients with interrupted inferior vena cava (I-IVC) and azygos continuation who undergo Fontan completion via hepatoazygos shunting exhibit unique hemodynamic challenges. This study evaluates age-related shifts in systemic venous return dominance, hepatic flow distribution (HFD), power loss (PL), and flow disturbances using patient-specific computational fluid dynamics (CFD). Data analysis from 95 patients with I-IVC showed a nonlinear shift in upper-to-lower body systemic flow dominance with ratios of 2, 1, and 0.5 (correlating to ages ∼3, ∼10, and ∼20, respectively). CFD simulations for 17 selected patients revealed a trend of increasing HFD toward the right pulmonary artery, with median splits of …

Prevalence, Treatment Patterns, Burden, And Factors Related To Treatment Failure With Sodium-Glucose Cotransporter 2 Inhibitor In Adults With Type 2 Diabetes In The United States, Xi Tan, Yiwen Cao, Yan Wang, Joanna Boland, Mico Guevarra, Lin Xie, Yan Song, Min Ji Kwak

Faculty, Staff and Student Publications

Aims: To evaluate treatment failure of sodium-glucose cotransporter 2 inhibitors (SGLT2i) among adults with type 2 diabetes (T2D) and assess associated risk factors and clinical and economic outcomes in the real-world setting.

Methods: Adults with T2D who initiated SGLT2i were selected from the Komodo's Healthcare Map, an administrative claims database (2016-2024). Treatment failure was defined as discontinuation, add-on/switching, or uncontrolled glycated hemoglobin (HbA1c) without action. Risk factors, treatment patterns, and clinical and economic burden were assessed.

Results: Among 237,295 eligible adults, the overall rate of treatment failure with SGLT2i was 77.3 %, with a median time to failure of 9.14 …

Molecular Profile Of Adult Primary Leptomeningeal Gliomatosis Aligns With Glioblastoma, Idh-Wildtype, Yi Zhu, Darin D Carabenciov, Derek R Johnson, Jorge A Trejo-Lopez, Aivi T Nguyen, Aditya Raghunathan, Giuseppe Lanzino, Cristiane M Ida, Cinthya J Zepeda-Mendoza, Surendra Dasari, Emilie Russler-Germain, Sonika Dahiya, Martha Quezado, Kenneth Aldape, Caterina Giannini

2020-Current year OA Pubs

Adult primary leptomeningeal gliomatosis (PLG) is a rare, rapidly progressive and fatal disease characterized by prominent leptomeningeal infiltration by a glial tumor without an identifiable parenchymal mass. The molecular profile of adult PLG has not been well-characterized. We report the clinical, pathological, and molecular findings of six adult PLG patients (five males and one female), median age 58 years. All cases exhibited pathological leptomeningeal enhancement at presentation. Leptomeningeal biopsy was diagnostic in five (of six) cases, revealing infiltration by an astrocytic glioma with mitotic activity, lacking microvascular proliferation or necrosis. One case was diagnosed at autopsy. All tumors were IDH-wildtype, …

Oatp1b1/1b3 Deficiency Exacerbates Hyperbilirubinemia In Erythropoietic Protoporphyria, Ruizhi Gu, Fu-Ying Qin, Luxuan Wang, Jiaojiao Zhang, Jacob Emerson, Qing Ma, Jie Lu, Karl E Anderson, Junmei Wang, Xiaochao Ma

Faculty, Staff and Student Publications

Erythropoietic protoporphyria (EPP) is caused by loss-of-function mutations in ferrochelatase (FECH), leading to the accumulation of its substrate, protoporphyrin IX (PPIX). PPIX is primarily produced in the bone marrow and transported to the liver for excretion. Because PPIX is hydrophobic, its elevated levels can cause bile duct blockage, cholestatic liver injury, and even liver failure. However, the specific transporter responsible for PPIX uptake into hepatocytes remains unclear. The OATP1B1/1B3 transporters, which are expressed in hepatocytes, facilitate the uptake of coproporphyrin III, a structural analog of PPIX. Additionally, OATP1B1/1B3 mediates the uptake of bilirubin, a biomarker of liver injury, from plasma …

Outcomes And Toxicity Following 3 Or More Definitive Courses Of Thoracic Radiation Therapy For Non-Small Cell Lung Cancer, Abigael Odwuor, Percy Lee, Joe Y Chang, Saumil Gandhi, Zhongxing Liao, Steven H Lin, Aileen Chen, Quynh-Nhu Nguyen, Michael S O'Reilly, Stephen G Chun, Julianna Bronk, David Qian, Matthew S Ning

Faculty, Staff and Student Publications

Purpose: Salvage re-irradiation is increasingly utilized to manage non-small cell lung cancer (NSCLC) locoregional recurrence or new lung primaries in previously treated areas. There is sparse information on efficacy and toxicity profile. We report a large experience of patients treated with multiple courses of definitive radiation for new and recurrent NSCLC.

Methods and materials: Medical records of patients who underwent ≥ 3 definitive thoracic radiation therapy (RT) courses for new or recurrent NSCLC at our cancer center from 2012 through 2021 were retrospectively reviewed following institutional review board approval. Toxicity was graded per Common Terminology Criteria for Adverse Events (CTCAE) …

Heat Shock Induces Alternative Polyadenylation Through Dynamic Dna Methylation And Chromatin Looping, Emily E Fink, Yi Zhang, Briana Santo, Anwita Siddavatam, Rosie Ou, Vishal Nanavaty, Byron H Lee, Angela H Ting

Faculty, Staff and Student Publications

Alternative cleavage and polyadenylation (APA) is a gene regulatory mechanism used by cells under stress to upregulate proteostasis-promoting transcripts, but how cells achieve this remains poorly understood. Previously, we elucidated a DNA methylation-regulated APA mechanism, in which gene body DNA methylation enhances distal poly(A) isoform expression by blocking CCCTC-binding factor (CTCF) binding and chromatin loop formation at APA control regions. We hypothesized that DNA methylation-regulated APA is one mechanism cells employ to induce proteostasis-promoting poly(A) isoforms. At the DNAJB6 cochaperone locus, acute heat shock resulted in binding of stress response transcription factors heat shock factor 1, ATF6, and YY1 at …