Medical Specialties Commons^™

Confessions In Cases Of Child Physical Abuse-A Capnet Study, Margaret R Russell, Antoinette L Laskey, Henry T Puls, Suzanne P Starling, Joanne N Wood, Daniel M Lindberg, Nancy S Harper, Caitlin R Mcnamara, Angela N Bachim, Farah W Brink, Lori D Frasier, James D Anderst, Porcia Vaughn, Kristine A Campbell

Faculty, Staff and Students Publications

Objective: Prior research on confessions of physical abuse (PA) has explored mechanisms of injury. Little is known about conditions supporting a confession of abuse or how confessions may influence case outcomes.

Methods: This cross-sectional study of suspected PA in children aged < 10 years at 10 centers participating in CAPNET, a multicenter child PA research network, included children with in-person Child Abuse Pediatrics (CAP) consultations between February 2021 and December 2022 and excluded children without injury. Our focus was a confession of inflicted injury known to the CAP during clinical involvement. We compared child and clinical characteristics, out-of-home (OOH) placements, and arrests between cases with and without confessions. Multivariable models using generalized estimating equations (GEE) produced adjusted predicted probabilities (APP) clustering by CAPNET site.

Results: Confessions were known to CAPs in 115/4297 (2.7%) cases, with significant site variability. In a multivariable GEE model, confessions were more likely in cases with injuries with high specificity for abuse (APP 6.0% vs 1.6%, P < .001), near-fatality (APP 5.6% vs 2.3%, P < .001), and older children (APP 4.8% vs 2.5%, P = .025). OOH placements and arrests were more common in cases with confessions. CAP awareness of confessions, OOH placements, and arrests did not follow racial or ethnic patterns seen in the US child welfare system. Lower socioeconomic status was associated with OOH placements and arrests but not with CAP awareness of confessions.

Conclusions: Our findings highlight differences in case characteristics and outcomes where a confession is known to the CAP and raise questions about …

Neutrophil-Microglia Interaction Drives Motor Dysfunction In A Neuromyelitis Optica Model Induced By Subarachnoid Aqp4-Igg, Fangfang Qi, Vanda A Lennon, Shunyi Zhao, Yong Guo, Husheng Ding, Caiyun Liu, Whitney M Bartley, Tingjun Chen, Claudia F Lucchinetti, Long-Jun Wu

Faculty, Staff and Student Publications

Neutrophils and neutrophil extracellular traps (NETs) contribute to early neuromyelitis optica (NMO) histopathology initiated by IgG targeting astrocytic aquaporin-4 (AQP4) water channels. Yet, the mechanisms underlying neutrophil recruitment and their pathogenic roles in disease progression remain unclear. To investigate molecular-cellular events preceding classical complement cascade activation in a mouse NMO model, we continuously infused, via spinal subarachnoid route, a non-complement-activating mouse monoclonal AQP4-IgG. Parenchymal infiltration of netting neutrophils containing C5a ensued with microglial activation and motor impairment but no blood-brain barrier leakage. Motor impairment and neuronal dysfunction both reversed when AQP4-IgG infusion stopped. Two-photon microscopy and electron microscopy-based reconstructions revealed …

Gompertz Growth With A Shared Carrying Capacity Optimally Simulates Primary And Metastatic Tumor Growth Dynamics, Pirmin Schlicke, Preethi Korangath, Xiaoxi Pan, Caner Ercan, Kathleen Gabrielson, Lyndsey Werhane, Yinyin Yuan, Sébastien Benzekry, Robert Ivkov, Heiko Enderling

Faculty, Staff and Student Publications

Background: Cancer is a systemic disease with most deaths attributed to metastatic burden. Primary and metastatic tumors, albeit at different anatomic locations, are interconnected through multiple biological processes. Pre-clinical and clinical observations of growth acceleration of metastases after surgery, or abscopal effects outside the radiation field are widely reported, yet reliably triggering favorable and avoiding unfavorable systemic responses remains an unmet clinical need. Understanding local and systemic tumor interaction dynamics will help guide future treatments.

Methods: We analyze the data of multiple in vivo tumor models. We formalize the systemic interplay of tumors as mathematical differential equation and calibrate parameters …

Structural-Functional Analyses Of The Huntingtin/Hap40 Complex In Drosophila And Humans, Stephen M Farmer, Amanda Solbach, Shiyu Xu, Beatriz Rios, Xin Ye, Amy Gao, Daniela Covarrubias, Yue Yu, Lili Ye, Vicky Chuong, Erin Furr Stimming, Haiqing Zhao, Sheng Zhang

Faculty, Staff and Student Publications

Huntington's disease (HD) is a neurodegenerative disorder caused by an abnormal CAG expansion in the Huntingtin (HTT) gene. Given its simple genetic cause but complex pathogenic mechanisms, interest in targeting HTT for HD treatment is growing, necessitating a clear understanding of HTT regulation. HTT protein primarily exists in a core complex with HAP40, forming a highly ordered structure with two large globular domains connected by a bridge. We previously demonstrated that HAP40 is conserved in

Unraveling The Nexus: Tumor Mutational Burden, Pd-L1 Expression, And Oncogenic Alterations In Non-Small Cell Lung Cancer Cytology Specimens, Min Dai, Francis Anthony San Lucas, Hector Alvarez, Leomar Ballester, Hui Chen, Keyur P Patel, Asif Rashid, Shun Rao, Mark J Routbort, Gloria Sura, Keith Sweeney, Gokce Toruner, Peng Wei, Richard Yang, Hyvan Dang, Rajyalakshmi Luthra, Sinchita Roy-Chowdhuri

Faculty, Staff and Student Publications

Background: PD-L1 expression and tumor mutational burden (TMB) are biomarkers for immune checkpoint inhibitor (ICI) therapy in non-small cell lung cancer (NSCLC); however, patients harboring oncogenic alterations have limited benefit from ICIs. The impact of oncogenic alterations on TMB and PD-L1 tumor proportion score in lung cytology specimens is poorly understood. Herein, the association between oncogenic alterations, TMB, and PD-L1 in NSCLC cytology specimens is explored.

Methods: Next-generation sequencing results from 312 NSCLC cytology specimens were retrospectively reviewed that interrogate 610 genes and select immuno-oncology signatures. TMB and PD-L1 immunohistochemical expression across oncogenic alterations were analyzed to explore associations.

Results: …

Baseline Parp-1 Pet Imaging In Patients With Advanced Solid Tumors With Dna Damage Response Mutations, Tarek Daoud, Jiansong Chen, Peng Wei, Franklin Wong, Timothy A Yap, Lilie L Lin

Faculty, Staff and Student Publications

Purpose: Inhibitors of poly(ADP-ribose) polymerase (PARP), an enzyme with numerous roles in DNA damage response signaling, represent a class of anti-cancer drugs approved for treating solid tumors with defects in the DNA damage response. However, additional methods for identifying patients who would benefit from the use of PARP inhibitors are urgently needed. We evaluated a novel radiotracer, 18F-FluorThanatrace ([18F]-FTT), to noninvasively assess PARP activity with PET/CT before treatment and determine associations between uptake, tumor mutation status, and prior receipt of therapy including PARP inhibitors.

Methods: Fifty-two patients with solid tumors underwent whole-body (skull base to thigh) [18F]-FTT PET/CT scans before …

Confessions In Cases Of Child Physical Abuse-A Capnet Study., Margaret R. Russell, Antoinette L. Laskey, Henry T. Puls, Suzanne P. Starling, Joanne N. Wood, Daniel M. Lindberg, Nancy S. Harper, Caitlin R. Mcnamara, Angela W. Bachim, Farah W. Brink, Lori D. Frasier, James Anderst, Porcia Vaughn, Kristine A. Campbell

Manuscripts, Articles, Book Chapters and Other Papers

OBJECTIVE: Prior research on confessions of physical abuse (PA) has explored mechanisms of injury. Little is known about conditions supporting a confession of abuse or how confessions may influence case outcomes.

METHODS: This cross-sectional study of suspected PA in children aged < 10 years at 10 centers participating in CAPNET, a multicenter child PA research network, included children with in-person Child Abuse Pediatrics (CAP) consultations between February 2021 and December 2022 and excluded children without injury. Our focus was a confession of inflicted injury known to the CAP during clinical involvement. We compared child and clinical characteristics, out-of-home (OOH) placements, and arrests between cases with and without confessions. Multivariable models using generalized estimating equations (GEE) produced adjusted predicted probabilities (APP) clustering by CAPNET site.

RESULTS: Confessions were known to CAPs in 115/4297 (2.7%) cases, with significant site variability. In a multivariable GEE model, confessions were more likely in cases with injuries with high specificity for abuse (APP 6.0% vs 1.6%, P < .001), near-fatality (APP 5.6% vs 2.3%, P < .001), and older children (APP 4.8% vs 2.5%, P = .025). OOH placements and arrests were more common in cases with confessions. CAP awareness of confessions, OOH placements, and arrests did not follow racial or ethnic patterns seen in the US child welfare system. Lower socioeconomic status was associated with OOH placements and arrests but not with CAP awareness of confessions.

CONCLUSIONS: Our findings highlight differences in case characteristics and outcomes where a confession is known to the CAP and raise questions about …

Platelets Cause Microvascular Occlusion And Delayed Neurological Deficits After Subarachnoid Hemorrhage In Mice., Ari Dienel, Sung-Ha Hong, Kiara Torres, Kanako Matsumura, Jose Guzman, Peeyush Thankamani Pandit, Bibek Samal, Harveen Kaur, Samitha Nemirajaiah, Angelica Bernal, H Alex Choi, Louise D Mccullough, Spiros L Blackburn, Jaroslaw Aronowski, Devin W Mcbride

Faculty, Staff and Student Publications

After subarachnoid hemorrhage (SAH), some patients develop delayed neurological deficits (DND). Microthrombi are considered a contributing factor to DND, but clinical trials of antiplatelets had mixed results. Existing research suggests that platelets play a role in the etiology of DND, but no comprehensive study has tested causality between platelets and DND after SAH. Here we hypothesize that after SAH, platelet activation promotes microthrombi formation, occlusion of the brain microvasculature and contributes to DND, and that inhibiting platelet aggregation is a therapeutic strategy. Mice experiencing SAH were administered various interventions. The animals were subjected to stimulation of platelets, platelet depletion, or …

Initial Site Of Metastasis Influences Prognosis In Pancreatic Ductal Adenocarcinoma, Eleanor Mancheski, David Baek, Wilbur Bowne, Harish Lavu, Charles Yeo, Avinoam Nevler

Department of Surgery Faculty Papers

INTRODUCTION: Metastatic pancreatic ductal adenocarcinoma (mPDAC) is a highly aggressive malignancy. Prior studies suggest that the initial site of metastasis may impact prognosis. This study investigates whether overall survival in mPDAC patients differs between patients first presenting with lung metastases versus those presenting with liver metastases.

METHODS: This retrospective analysis utilized the multi-institutional TriNetX database, identifying patients with histologically diagnosed PDAC who initially presented with either liver or lung metastases. Demographic, histologic, and outcome data were collected and analyzed. Patients were matched 1:1 using a nearest neighbor propensity score (PS) algorithm, and Kaplan-Meier survival analyses were performed. Cox regression was …

Axillary Management After Neoadjuvant Endocrine Therapy (Net), Laura Leonard, Min Yi, Emma Wingate, Puneet Singh, Abigail Caudle, Rosa F Hwang, Isabelle Bedrosian, Vicente Valero, Jennifer Litton, Nuhad Ibrahim, Kelly K Hunt

Faculty, Staff and Student Publications

BACKGROUND: In patients with hormone receptor-positive (HR

PATIENTS AND METHODS: We performed a retrospective review of patients with clinical stage I-III, HR

RESULTS: A total of 230 patients were included; 120 (52.2%) were clinically node-negative (cN0), while 110 (47.8%) were clinically node-positive (cN+). In the cN+ group, 7.3% (8/110) had a nodal pathologic complete response (pCR). In total, 76.4% (84/110) in the cN+ group underwent axillary lymph node dissection (ALND) as the initial axillary procedure, and 90.9% (100/110) underwent ALND overall. In total, 98.3% (118/120) with cN0 disease underwent sentinel lymph node dissection (SLND), and 28 (23.7%) had positive nodes. …

Free Versus In Situ Right Internal Mammary Artery As A Conduit In Coronary Artery Bypass Surgery: A Meta-Analysis, Yuta Kikuchi, Tomoki Sakata, Tomonari Shimoda, Shinichi Fukuhara, Junichi Shimamura, Makoto Hibino, Tsuyoshi Kaneko, Hiroo Takayama, Hisato Takagi, Michel Pompeu Sa, Toshiki Kuno

Department of Medicine Faculty Papers

OBJECTIVES: There is debate regarding the optimal choice for a second conduit in coronary artery bypass grafting. The right internal mammary artery (RIMA) is commonly employed as a second conduit; however, it is unclear whether the free (fRIMA) or in situ (isRIMA) configuration yields superior outcomes. We performed a systematic review and meta-analysis to compare clinical outcomes between fRIMA and isRIMA as the second conduit.

METHODS: A comprehensive search of PubMed (MEDLINE), EMBASE, and CENTRAL was performed through May 2025 to identify studies comparing outcomes in patients undergoing coronary artery bypass grafting with either fRIMA or isRIMA as a second …

Breast Cancer-Derived Extracellular Vesicle Mir-425-5p (Mir-425) Promotes Brain Metastasis Via Activating Astrocytes Through The Novel Mir-425-Znf24-Ccl8 Signaling Axis, Grace L Wong, Munazza S Khan, Sara Manore, Shivani Bindal, Ravi Singh, Hui-Wen Lo

Faculty, Staff and Student Publications

Mechanisms underlying breast cancer brain metastasis (BCBM) are still not well understood. Here, we identified that BCBM patient serum contained extracellular vesicles (EVs) with high levels of microRNAs (miRNAs)-107 and -425. Levels of miR-107 and miR-425 were elevated in brain metastases, and the elevation was associated with poor patient prognoses. Ectopic expression of miR-107 and miR-425 promoted mammospheres; however, the inhibition of miR-425, but not miR-107, suppressed breast cancer mammosphere formation. We further observed that EVs from miR-425-overexpressing breast cancer cells strongly activated astrocytes whereas their inhibitors abrogated the effect. Conditioned media from miR-425-activated astrocytes promoted mammospheres. To elucidate how …

Gene-Agnostic Therapeutic Strategies For Inherited Retinal Diseases: Neuroprotection And Immunomodulation, Lucas W. Rowe, S. Patricia Becerra, Robert E. Maclaren, Robert L. Avery, Charles C. Wykoff, Allen C. Ho, Carl D. Regillo, Dean Eliott, Andrew Osborne, Katie M. Binley, Thomas A. Ciulla

Wills Eye Hospital Papers

Background/Objectives: Inherited retinal diseases (IRDs) represent a genetically heterogeneous group of disorders caused by mutations in over 280 genes with more than 3100 identified variants. While gene-specific replacement therapies have achieved landmark success with voretigene neparvovec (Luxturna) for biallelic RPE65-associated retinal dystrophy, developing individual therapies for each genetic subtype remains impractical. This review examines gene-agnostic therapeutic approaches utilizing neuroprotection and immunomodulation that target common pathophysiological mechanisms shared across multiple IRD genotypes. Methods: We reviewed the literature on neuroprotective and immunomodulatory gene therapy strategies for IRDs, focusing on neurotrophic factors and complement system modulation. Results: Neuroprotective approaches delivering neurotrophic factors—including pigment …

Increasing Utilization Trends Of Robotic Assistance In Orthopaedic Surgery, Anish K. Ponna, Alec Giakas, Anthony A. Khoudary, Spencer N. Uggla, Sina Ramtin, Yousef A. Soliman, Asif M. Ilyas

Department of Orthopaedic Surgery Faculty Papers

INTRODUCTION: Robotic-assisted surgeries in orthopaedics have increased, particularly in hip and knee arthroplasty and spine surgeries. This study evaluates national utilization trends of robotic-assisted orthopaedic surgeries and demographic and geographic distribution of patients undergoing these surgeries.

METHODS: A retrospective cohort study was conducted on patients who underwent total hip arthroplasty, total and partial knee arthroplasty, or spine arthrodesis from 2017 to 2023 using the TriNetX database. Relevant International Classification of Diseases, 10th Revision, and Current Procedural Terminology codes identified patients who underwent a primary surgery with a corresponding robot-assisted code on the same day. Temporal trends in procedural volume were …

Measurable Residual Disease Testing In Acute Myeloid Leukemia: Current State, Foundational Models, And Tools For Future Development, Joseph Van Galen, Stephen D. Willis, Ashish Bains, Sara H. Small

Department of Medical Oncology Faculty Papers

Acute myeloid leukemia (AML) is a lethal and rapidly progressive hematologic malignancy with high rates of relapse and treatment refractoriness. Management of AML is complicated by biological heterogeneity in a disease that is broadly defined by the clonal expansion of myeloblasts that otherwise play an important role in healthy marrow tissues. While subtypes of AML are increasingly defined by druggable driver mutations including FLT3-ITD, IDH1, IDH2, and NPM1, conventional chemotherapy and reduced intensity induction regimens (e.g., azacitidine-venetoclax) remain therapeutic backbones. One area of active development for personalization of AML treatment is the assessment of measurable residual disease (MRD). MRD testing …

A Hemorheological Perspective On Coronary Microvascular Dysfunction: Association Of Erythrocyte Parameters With Angiography-Derived Coronary Microcirculatory Resistance, Abdulrahman Alqazzaz, Yanfeng Lu, Jasmine Bao, Gary S. Mintz, Jiahao Feng, Yong Zhang, Shanshan Gao, Qiang Song, Feifei Ning, Hytham H. Al-Samawi, Mohsen Al-Manj, Mohammed Al-Asadi, Xin Huang, Ning Guo

Student Papers, Posters & Projects

BACKGROUND: Coronary microvascular dysfunction (CMD) contributes to myocardial ischemia in patients both without obstructive coronary artery disease (e.g., MINOCA/INOCA) and in those with co-existing epicardial stenosis. While its etiology includes structural and functional causes. hematologic parameters have been linked to cardiovascular outcomes. However, the relationship between red blood cell (RBC) markers and microvascular resistance remains poorly characterized. We aim to evaluate whether RBC parameters are correlated with the angiography-derived index of microcirculatory resistance (angio-IMR).

METHODS: This retrospective study evaluated the association between red blood cell (RBC) parameters and angio-IMR in patients with intermediate coronary artery disease (30%-70% stenosis). Data were …

Fasting-Based Dietary Interventions In Cancer Patients And Survivors: A Scoping Review, Kuang-Yi Wen, Julianne Freedman, Abenezer Melaku Tafese, William Kevin Kelly, Nicole L Simone

Department of Medical Oncology Faculty Papers

Background: Fasting-based interventions are increasingly investigated as adjuncts to cancer treatment for the potential to reduce therapy-related toxicities, improve metabolic health, and enhance quality of life. However, clinical evidence regarding their efficacy, tolerability, and acceptability remains limited and fragmented. This scoping review aimed to systematically map the current evidence on fasting-based interventions in cancer patients and survivors.

Methods: A literature search was conducted in PubMed, Scopus, Web of Science, and CINAHL up to 10 June 2025. Eligible interventional studies included cancer patients or survivors and evaluated fasting-based interventions, such as time-restricted eating, intermittent fasting, short-term fasting, or fasting-mimicking …

Cystic Fibrosis And Sickle Cell Disease Associated With Nonadministration Of Vte Prophylaxis In Hospitalized Adults, Kiera Caparon, Matthew J. Lankiewicz, Jessica Crow, Jennifer C. Yui, John Lindsley, Brandyn D. Lau, Michael B. Streiff, Rakhi P. Naik, Sophie Lanzkron, Lydia H. Pecker, Peggy Kraus, Elliott R. Haut, Jiangxia Wang, Kathryn E. Dane

Cardeza Foundation for Hematologic Research

Cystic fibrosis (CF) and sickle cell disease (SCD) are associated with an increased risk of venous thromboembolism (VTE), and this risk is exacerbated by hospitalization. VTE prophylaxis nonadministration is a VTE risk factor. The objective of this study was to characterize VTE prophylaxis nonadministration among patients with either CF or SCD compared with medically ill patients without CF or SCD. We conducted a single-center retrospective cohort study of hospitalized patients who were prescribed at least 2 doses of pharmacologic VTE prophylaxis. The primary outcome was the proportion of nonadministered VTE prophylaxis doses by cohort. Multivariable logistic regression was used to …

Fecal Carbohydrate-Degrading Bacteria Are Associated With Reduced Incidence Of Lower Gastrointestinal Gvhd, Christopher Fan, Tomo Hayase, Chia-Chi Chang, Israel K Glover, Ivonne I Flores, Lauren K Mcdaniel, Miriam R Ortega, Christopher A Sanchez, Rawan K El-Himri, Alexandria N Brown, Jennifer L Karmouch, Mohamed A Jamal, Saira S Ahmed, Taylor M Halsey, Yimei Jin, Wen-Bin Tsai, Rishika Prasad, Altai Enkhbayar, Aqsa Mohammed, Maren Schmiester, Ashish Damania, Nadim J Ajami, Jennifer A Wargo, Christine B Peterson, Gabriela Rondon, Taha Al-Juhaishi, Amin M Alousi, Jeffrey J Molldrem, Richard E Champlin, Elizabeth J Shpall, Eric Martens, Cesar A Arias, Robert R Jenq, Eiko Hayase

Faculty, Staff and Student Publications

Lower gastrointestinal graft-versus-host disease (LGI-GVHD) carries morbidity and mortality for patients undergoing allogeneic hematopoietic stem cell transplantation (allo-HSCT), with critical contributions from the intestinal microbiome. In a retrospective cohort of metagenomic sequencing of stool from patients with allo-HSCT (N = 90), we found that a reduction in specific Parabacteroides and Bacteroides species around the time of engraftment contributes to LGI-GVHD risk. Given the known diverse carbohydrate-degrading functionality of these bacteria, we investigated gene abundances for carbohydrate-active enzymes (CAZymes) and found that Parabacteroides merdae, P distasonis, and Bacteroides ovatus abundances were significantly correlated with CAZymes in patients who did not develop …

Fibrinogen-Bmal1 Signaling As A Therapeutic Target To Limit Aortic Dissection By Preserving Vsmc Contractility, Xiaohan Zhong, Dongjie Li, Yuanfei Zhao, Lu Dai, Jinzhang Li, Zhiqi Ji, Bojing Zuo, Hongshan Liu, Haixia Huang, Wei Wang, Haiyang Li, Yuyong Liu, Ming Gong, Xin-Liang Ma, Wenjian Jiang, Meili Wang, Hongjia Zhang

Department of Emergency Medicine Faculty Papers

Aortic dissection (AD) is a life-threatening vascular disease with a high mortality rate. Surgery is essential in the acute phase but carries significant risks, whereas elective surgery during the chronic phase yields better outcomes. However, no pharmacological therapy has been proven effective in slowing AD progression. In our recent pilot clinical study, an association between higher plasma fibrinogen levels and improved clinical outcomes was observed in AD patients, suggesting a potential protective role of fibrinogen. However, direct evidence supporting this hypothesis is lacking. In this study, a population-based analysis of nonsurgically managed patients with acute AD revealed a distinct association: …

Patient Perceptions And Knowledge Of Corticosteroid Injections: A Cross-Sectional Survey Study, Juliet Chung, Sina Ramtin, Philip Koehler, Stephen Stache, Charles Langman, Bryan Hozack, Asif M. Ilyas

Rothman Institute Papers

INTRODUCTION: Although cortisone injections are commonly used, patient understanding of cortisone is variable and often affected by misconceptions. This study explores patient perspectives, identifies misconceptions, and emphasizes the importance of improved patient education to enhance patient-centered care.

METHODS: A cross-sectional survey study was conducted from April to August 2024 among patients aged 18 and older presenting to an orthopedic physicians' office. Patients completed a novel anonymous questionnaire designed to assess their knowledge and perceptions of cortisone injections. A total of 246 patients participated, with responses collected electronically via SurveyMonkey.

RESULTS: Among 246 respondents, individuals with history of prior cortisone infections …

Polθ Activity Modulates Sensitivity To Standard Therapies In Dnmt3a-Deficient Leukemia, Bac Viet Le, Umeshkumar Vekariya, Monika M. Toma, Margaret Nieborowska-Skorska, Marie-Christine Caron, Malgorzata Gozdecka, Zayd Haydar, Martin Walsh, Jayashri Ghosh, Elaine Vaughan-Williams, Paulina Podszywalow-Bartnicka, Anna-Mariya Kukuyan, Sylwia Ziolkowska, Jessica Atkins, Emir Hadzijusufovic, Gurushankar Chandramouly, Reza Nejati, Katarzyna Piwocka, Richard T. Pomerantz, George S. Vassiliou, Brian J.P. Huntly, Peter Valent, Mariusz Wasik, Alfonso Bellacosa, Jean-Yves Masson, Gaorav P. Gupta, Grant A. Challen, Tomasz Skorski

Department of Biochemistry and Molecular Biology Faculty Papers

Myeloid malignancies carrying somatic DNMT3A mutations (DNMT3Amut) are refractory to standard therapy. DNMT3Amut leukemia cells accumulate toxic DNA double-strand breaks (DSBs) and stalled replication forks, rendering them dependent on DNA damage response (DDR). We report here that DNA polymerase theta (Polθ), a key element in DSB repair by end-joining (Polθ-mediated end-joining [TMEJ]) and in fork restarting, promotes survival and proliferation of DNMT3Amut leukemia cells. Polθ is overexpressed in DNMT3Amut leukemia cells due to abrogation of PARP1 PARylation-dependent UBE2O E3 ligase-mediated ubiquitination and proteasomal degradation of Polθ. In addition, PARP1-mediated recruitment of the SMARCAD1-MSH2/MSH3 repressive complex to DSBs is diminished in …

Radiation Doses To Cardiac Substructures Predict Elevation In High-Sensitivity Cardiac Troponin T Levels In Radiation Therapy For Lung Cancer, Xinru Chen, Xiaodong Zhang, Ting Xu, Radhe Mohan, Ruitao Lin, Mei Chen, Rachel C Maguire, Yao Zhao, Efstratios Koutroumpakis, Nicolas L Palaskas, Anita Deswal, Ali Ajdari, Joshua S Niedzielski, Sanjay S Shete, Laurence E Court, Jinzhong Yang, Zhongxing Liao

Faculty, Staff and Student Publications

Purpose: Cardiotoxicity is a major concern for patients undergoing thoracic radiation therapy. This study compared the predictive power of radiation dose-volume histogram (DVH) parameters and radiomic/dosiomic features of the whole heart (WH) and cardiac substructures for elevated circulating high-sensitivity cardiac troponin T (hs-cTnT), a biomarker for early detection of cardiac adverse events.

Methods and materials: A retrospective cohort of 160 patients with non-small cell lung cancer (NSCLC) from a completed prospective trial and a prospective cohort of 57 patients with NSCLC enrolled in an ongoing trial were analyzed. The endpoint was hs-cTnT elevation, indicated by an increase of ≥5 ng/L …

High Dietary Fiber Is Associated With Improved Outcomes In Patients With Melanoma And Sarcoma Treated With Immunotherapy Regardless Of Gut Microbiome Dysbiosis And Social Vulnerability, Brittany C Fields, Raymond S Traweek, Kai Jiang, Russell G Witt, Ashish Damania, Yi-Ju Chiang, Nadim Ajami, Elise Nassif-Haddad, Emily Z Keung, Manoj Chelvanambi, Xiaotao Zhang, Christine B Peterson, Jennifer A Wargo, Carrie R Daniel, Christina L Roland, Ashley M Holder

Faculty, Staff and Student Publications

Background: Social vulnerability, dietary fiber, and the gut microbiome have been individually implicated in clinical outcomes for melanoma and sarcoma patients. This study hypothesized that increasing social vulnerability is associated with insufficient dietary fiber intake and negatively associated with microbiome composition and clinical outcomes.

Methods: Clinicopathologic data, baseline fiber intake, and gut microbiome profiles were assessed in 153 patients with melanoma or sarcoma treated with immune checkpoint blockade (ICB) and prospectively followed. Patients' social vulnerability index (SVI) and fiber intake were evaluated for associations with microbiome composition, treatment response, and overall survival (OS).

Results: SVI percentile was 0.4 (interquartile ratio …

Pimicotinib Versus Placebo For Tenosynovial Giant Cell Tumour (Maneuver): An International, Randomised, Placebo-Controlled, Phase 3 Trial, Hairong Xu, Xiaohui Niu, Vinod Ravi, Javier Martin-Broto, Albiruni Abdul Razak, Ramy Saleh, Yong Zhou, Jingnan Shen, Tang Liu, Kamlesh Kumar Sankhala, César Serrano, Silvia Stacchiotti, Jing Wang, Giacomo G Baldi, Yi Feng, Yingqi Hua, Tao Li, Piotr Rutkowski, Xiaojing Zhang, Gabriel Tinoco, Qingping Zou, Boyao Shan, Xiangyu Zhu, Hans Gelderblom

Faculty, Staff and Student Publications

Background: Tenosynovial giant cell tumour (TGCT) is a rare, locally aggressive neoplasm that affects otherwise healthy adults. There are few systemic treatment options, highlighting an unmet need. We report the results of part 1 of the MANEUVER trial, which aimed to evaluate the efficacy and safety of pimicotinib, a highly selective, potent, colony-stimulating factor-1 receptor inhibitor, in patients with TGCT.

Methods: MANEUVER is a randomised, placebo-controlled, phase 3 study done in 40 specialised hospitals in Asia, Europe, and North America. Patients aged 18 years and older with unresectable, symptomatic TGCT (patient-reported worse stiffness or worst pain of at least 4 …

Gut Microbiota Modulation Via Repeated Donor Fecal Transplantation Improves Motor And Gastrointestinal Symptoms In Drug-Naïve Parkinson’S Disease: A Randomized Phase 2 Trial, Rui Zhang, Renyi Feng, Jiuqi Wang, Yongkang Chen, Han Liu, Qingyong Zhu, Haiyan Tian, Chi Qin, Junfang Teng, Beisha Tang, Min Wu, Jinsheng Zeng, Erxi Wu, Xuebing Ding, Xuejing Wang

Faculty, Staff and Students Publications

The gut-brain axis is increasingly recognized as a critical contributor to Parkinson's disease (PD) pathogenesis, yet the therapeutic impact of microbiota modulation remains unclear due to lack of clinical trials in drug-naïve patients. We conducted a randomized, double-blind, placebo-controlled phase 2 trial to evaluate the safety, tolerability, and efficacy of repeated donor fecal microbiota transplantation (dFMT) in de novo PD. FMT was administered for seven days (200 mL on days 1-3; 50 mL on days 4-7) per 4-week cycle. Seventy-two patients were randomized 1:1 to receive dFMT or autologous FMT (aFMT), and 66 completed the trial. At 35 weeks, the …

Cannabis Stigma And Symptom Management Considerations In Cancer Survivors: A Mixed-Methods Exploration Of Patient Perspectives, Sera Levy, Salimah Meghani, Brooke Worster, Colleen Kilanowski, Danielle Smith, Amy A. Case, Rebecca L. Ashare

Department of Medical Oncology Faculty Papers

PURPOSE: This study aims to assess for indications of stigma and attitudes toward cannabis among cancer survivors (CS) who use or consider the use of cannabis.

METHODS: This study employed a convergent, parallel mixed methods design utilizing focus group and questionnaire data to assess the presence of stigma among a sample of CS (n = 23) who use (n = 10) and do not use (n = 13) cannabis to manage symptoms. CS were recruited from a multi-site observational study in the Northeast U.S. region that assesses cannabis use among oncology patients.

RESULTS: A total of 23 CS participated in …

The Efficacy And Safety Of Serratus Anterior Plane Block In Patients Undergoing Cardiac Surgery: A Systematic Review And Meta-Analysis, Xu-Bo Cui, Ming-Zhu Cui, Qiu-Ju Yang, Yang Liu, Meng-Qi Yi, Xiao-Yang Zhang, Yun-Tai Yao

Faculty, Staff and Student Publications

Background: Serratus anterior plane block (SAPB) is a widely used fascial block that reduces postoperative pain and perioperative opioid consumption. This meta-analysis assessed the efficacy and safety of SAPB in cardiac surgery patients.

Methods: We systematically searched PubMed, Web of Science, Cochrane Library, Embase, China National Knowledge Infrastructure, and Wanfang databases on May 10, 2024. Pooled relative risks and mean differences (MD) with 95% confidence intervals (CI) were calculated for dichotomous and continuous outcomes, respectively. Heterogeneity was assessed using the I2 statistic, and publication bias was evaluated using Egger test. Subgroup analyses were stratified by study design (randomized controlled trials …

Publication Productivity Among International Medical Graduates And U.S. Medical Graduates In Neurosurgery: A Comparative Assessment Using The Arms Race Control Score, Joanna M. Roy, Omar M. M. Mansoor, Samit Sen, Aaron C. Segura, Rithvik Naga Ganti, Basel Musmar, Gilberto Perez Rodriguez Garcia, Brett Henshey, Saarang Patel, Sruthi Ranganathan, Victor Gabriel El-Hajj, Stavropoula I. Tjoumakaris, M. Reid Gooch, Robert H. Rosenwasswer, Christian Bowers, Pascal Jabbour

Department of Neurosurgery Faculty Papers

BACKGROUND AND OBJECTIVES: The Arms Race Control Score (ARCS) was developed to provide a quantitative assessment of publications among residency applicants. International medical graduates (IMGs) often have higher numbers of publications compared to U.S medical graduates (US MDs). However, there is limited knowledge of publication quality and effort among IMGs and US MDs. Our study analyzes publication productivity among IMGs and US MDs using the ARCS.

METHODS: Applicants were selected from ACGME-accredited training programs that enrolled both IMG and US MD residents over the 2018-2024 match cycle. Programs without IMG residents in a given year were excluded from the analysis. …

Interim Estimates Of 2025-26 Seasonal Influenza Vaccine Effectiveness - United States, September 2025-February 2026., Patrick Maloney, Emily L. Reeves, Kristina Wielgosz, Ashley M. Price, Karthik Natarajan, Malini B. Desilva, Kristin Dascomb, Nicola P. Klein, Sara Y. Tartof, Stephanie A. Irving, Shaun J. Grannis, Toan C. Ong, Zachary A. Weber, Jennifer E. Schuster, Danielle M. Zerr, Marian G. Michaels, Julie A. Boom, Natasha B. Halasa, Mary A. Staat, Geoffrey A. Weinberg, Stacey L. House, Elie A. Saade, Krissy Moehling Geffel, Manjusha Gaglani, Karen J. Wernli, Vel Murugan, Emily T. Martin, Natalie A B Bontrager, Marie K. Kirby, Amanda B. Payne, Fatimah S. Dawood, Ayzsa Tannis, Heidi L. Moline, Sifang Kathy Zhao, Katherine Adams, Jennifer Decuir, Samantha M. Olson, Jessie R. Chung, Nathaniel Lewis, Brendan Flannery, Carrie Reed, Shikha Garg, Sascha Ellington, Cdc Influenza Vaccine Effectiveness Collaborators

Manuscripts, Articles, Book Chapters and Other Papers

In the United States, annual influenza vaccination has been recommended for all persons aged ≥6 months, including during the 2025-26 season. Interim influenza vaccine effectiveness (VE) estimates were calculated for patients with acute respiratory illness-associated outpatient visits and hospitalizations from three U.S. respiratory virus VE networks during the 2025-26 influenza season, using a test-negative case-control design. Among children and adolescents aged < 18 years, VE was 38%-41% against influenza outpatient visits and 41% against influenza-associated hospitalization. Among adults aged ≥18 years, VE was 22%-34% against influenza outpatient visits and 30% against influenza-associated hospitalization. Among children and adolescents, VE against influenza A ranged from 37% (against outpatient visits) to 42% (against hospitalization) across settings; among adults, VE against influenza A ranged from 30% (against hospitalization) to 34% (against outpatient visits) across settings. Among children and adolescents, VE against influenza A(H3N2)-associated outpatient visits was 35% and against influenza A(H3N2)-associated hospitalization was 38%. VE against influenza B outpatient visits ranged from 45%-71% among children and adolescents and was 63% among adults. Other estimates of VE were not statistically significant or were not reportable. Although interim influenza VE is lower during the 2025-26 influenza season than it was during recent influenza seasons, these findings demonstrate that influenza vaccination still provides protection against influenza. CDC recommends influenza vaccination; U.S. influenza vaccines remain available for persons aged ≥6 months.