Medical Specialties Commons^™

Datopotamab Deruxtecan In Advanced Or Metastatic Hr+/Her2- And Triple-Negative Breast Cancer: Results From The Phase I Tropion-Pantumor01 Study, Aditya Bardia, Ian E Krop, Takahiro Kogawa, Dejan Juric, Anthony W Tolcher, Erika P Hamilton, Toru Mukohara, Aaron Lisberg, Toshio Shimizu, Alexander I Spira, Junji Tsurutani, Senthil Damodaran, Kyriakos P Papadopoulos, Jonathan Greenberg, Fumiaki Kobayashi, Hong Zebger-Gong, Rie Wong, Yui Kawasaki, Tadakatsu Nakamura, Funda Meric-Bernstam

Faculty, Staff and Student Publications

PURPOSE: Datopotamab deruxtecan (Dato-DXd) is an antibody-drug conjugate consisting of a humanized antitrophoblast cell-surface antigen 2 (TROP2) monoclonal antibody linked to a potent, exatecan-derived topoisomerase I inhibitor payload via a plasma-stable, selectively cleavable linker.

PATIENTS AND METHODS: TROPION-PanTumor01 (ClinicalTrials.gov identifier: NCT03401385) is a phase I, dose-escalation, and dose-expansion study evaluating Dato-DXd in patients with previously treated solid tumors. The primary study objective was to assess the safety and tolerability of Dato-DXd. Secondary objectives included evaluation of antitumor activity and pharmacokinetics. Results from patients with advanced/metastatic hormone receptor-positive/human epidermal growth factor receptor 2-negative (HR+/HER2-) breast cancer (BC) or triple-negative BC (TNBC) …

Randomized Placebo-Controlled, Biomarker-Stratified Phase Ib Microbiome Modulation In Melanoma: Impact Of Antibiotic Preconditioning On Microbiome And Immunity, Isabella C Glitza, Yongwoo David Seo, Christine N Spencer, Jennifer R Wortman, Elizabeth M Burton, Farah A Alayli, Christopher P Loo, Shikha Gautam, Ashish Damania, Julie Densmore, Justin Fairchild, Christopher R Cabanski, Matthew C Wong, Christine B Peterson, Brian Weiner, Nathan Hicks, John Aunins, Christopher Mcchalicher, Emily Walsh, Michael T Tetzlaff, Omid Hamid, Patrick A Ott, Genevieve M Boland, Ryan J Sullivan, Kenneth F Grossmann, Nadim J Ajami, Theresa Lavallee, Matthew R Henn, Hussein A Tawbi, Jennifer A Wargo

Faculty, Staff and Student Publications

Gut-microbiota modulation shows promise in improving immune-checkpoint blockade (ICB) response; however, precision biomarker-driven, placebo-controlled trials are lacking. We performed a multicenter, randomized placebo-controlled, biomarker-stratified phase I trial in patients with ICB-naïve metastatic melanoma using SER-401, an orally delivered Firmicutesenriched spore formulation. Fecal microbiota signatures were characterized at baseline; patients were stratified by high versus low Ruminococcaceae abundance prior to randomization to the SER-401 arm (oral vancomycin-preconditioning/SER-401 alone/nivolumab + SER-401), versus the placebo arm [placebo antibiotic/placebo microbiome modulation (PMM)/nivolumab + PMM (NCT03817125)]. Analysis of 14 accrued patients demonstrated that treatment with SER-401 + nivolumab was safe, with an overall response rate …

Change In Trust In Us Government Health Agencies For Cancer Information In The Covid-19 Era, Onyema G Chido-Amajuoyi, Rajesh Talluri, Henry K Onyeaka, Itunu Sokale, Gideon T Dosunmu, Noelle Loconte, Sanjay Shete

Faculty, Staff and Student Publications

This cross-sectional study assesses changes in levels of public trust in US government health agencies providing cancer information.

Mutation Order In Acute Myeloid Leukemia Identifies Uncommon Patterns Of Evolution And Illuminates Phenotypic Heterogeneity, Matthew Schwede, Katharina Jahn, Jack Kuipers, Linde A Miles, Robert L Bowman, Troy Robinson, Ken Furudate, Hidetaka Uryu, Tomoyuki Tanaka, Yuya Sasaki, Asiri Ediriwickrema, Brooks Benard, Andrew J Gentles, Ross Levine, Niko Beerenwinkel, Koichi Takahashi, Ravindra Majeti

Faculty, Staff and Student Publications

Acute myeloid leukemia (AML) has a poor prognosis and a heterogeneous mutation landscape. Although common mutations are well-studied, little research has characterized how the sequence of mutations relates to clinical features. Using published, single-cell DNA sequencing data from three institutions, we compared clonal evolution patterns in AML to patient characteristics, disease phenotype, and outcomes. Mutation trees, which represent the order of select mutations, were created for 207 patients from targeted panel sequencing data using 1 639 162 cells, 823 mutations, and 275 samples. In 224 distinct orderings of mutated genes, mutations related to DNA methylation typically preceded those related to …

Valine Aminoacyl-Trna Synthetase Promotes Therapy Resistance In Melanoma, Najla El-Hachem, Marine Leclercq, Miguel Susaeta Ruiz, Raphael Vanleyssem, Kateryna Shostak, Pierre-René Körner, Coralie Capron, Lorena Martin-Morales, Patrick Roncarati, Arnaud Lavergne, Arnaud Blomme, Silvia Turchetto, Eric Goffin, Palaniraja Thandapani, Ivan Tarassov, Laurent Nguyen, Bernard Pirotte, Alain Chariot, Jean-Christophe Marine, Michael Herfs, Francesca Rapino, Reuven Agami, Pierre Close

Faculty, Staff and Student Publications

Transfer RNA dynamics contribute to cancer development through regulation of codon-specific messenger RNA translation. Specific aminoacyl-tRNA synthetases can either promote or suppress tumourigenesis. Here we show that valine aminoacyl-tRNA synthetase (VARS) is a key player in the codon-biased translation reprogramming induced by resistance to targeted (MAPK) therapy in melanoma. The proteome rewiring in patient-derived MAPK therapy-resistant melanoma is biased towards the usage of valine and coincides with the upregulation of valine cognate tRNAs and of VARS expression and activity. Strikingly, VARS knockdown re-sensitizes MAPK-therapy-resistant patient-derived melanoma in vitro and in vivo. Mechanistically, VARS regulates the messenger RNA translation of valine-enriched …

Machine Learning Identifies Prognostic Subtypes Of The Tumor Microenvironment Of Nsclc, Duo Yu, Michael J Kane, Eugene J Koay, Ignacio I Wistuba, Brian P Hobbs

Faculty, Staff and Student Publications

The tumor microenvironment (TME) plays a fundamental role in tumorigenesis, tumor progression, and anti-cancer immunity potential of emerging cancer therapeutics. Understanding inter-patient TME heterogeneity, however, remains a challenge to efficient drug development. This article applies recent advances in machine learning (ML) for survival analysis to a retrospective study of NSCLC patients who received definitive surgical resection and immune pathology following surgery. ML methods are compared for their effectiveness in identifying prognostic subtypes. Six survival models, including Cox regression and five survival machine learning methods, were calibrated and applied to predict survival for NSCLC patients based on PD-L1 expression, CD3 expression, …

Combination Therapy With Novel Agents For Acute Myeloid Leukaemia: Insights Into Treatment Of A Heterogenous Disease, Wei-Ying Jen, Hagop Kantarjian, Tapan M Kadia, Courtney D Dinardo, Ghayas C Issa, Nicholas J Short, Musa Yilmaz, Gautam Borthakur, Farhad Ravandi, Naval G Daver

Faculty, Staff and Student Publications

The treatment landscape of acute myeloid leukaemia (AML) is evolving rapidly. Venetoclax in combination with intensive chemotherapy or doublets or triplets with targeted or immune therapies is the focus of numerous ongoing trials. The development of mutation-targeted therapies has greatly enhanced the treatment armamentarium, with FLT3 inhibitors and isocitrate dehydrogenase inhibitors improving outcomes in frontline and relapsed/refractory (RR) AML, and menin inhibitors showing efficacy in RR NPM1

Dynamic Stem-Loop Extension By Pol Θ And Templated Insertion During Dna Repair, Denisse Carvajal-Maldonado, Yuzhen Li, Mark Returan, April M Averill, Sylvie Doublié, Richard D Wood

Faculty, Staff and Student Publications

Theta-mediated end joining (TMEJ) is critical for survival of cancer cells when other DNA double-stranded break repair pathways are impaired. Human DNA polymerase theta (Pol θ) can extend ssDNA oligonucleotides, but little is known about preferred substrates and mechanism. We show that Pol θ can extend both ssDNA and RNA substrates by unimolecular stem-loop synthesis initiated by only two 3' terminal base pairs. Given sufficient time, Pol θ uses alternative pairing configurations that greatly expand the repertoire of sequence outcomes. Further primer-template adjustments yield low-fidelity outcomes when the nucleotide pool is imbalanced. Unimolecular stem-loop synthesis competes with bimolecular end joining, …

The Assistant Clinical Research Coordinator Program: A Pathway For Recruitment In Radiation Oncology, Michelle Aboytes, Melissa Cody, Eyiwunmi Laseinde, Jennifer Hall, Scott Soltys, Beth Beadle, Elizabeth Kidd, Yushen Qian, Albert C Koong, Daniel Chang, Quynh-Thu Le, Erqi L Pollom

Faculty, Staff and Student Publications

PURPOSE: Recruiting prospective physicians to radiation oncology can be challenging, because of limited familiarity with the field. The Assistant Clinical Research Coordinator (ACRC) program can help provide trainees early exposure to radiation oncology.

METHODS AND MATERIALS: The ACRC program involves hiring a college graduate to provide administrative and research support for faculty members. The program was developed with our institution's clinical trials office, which provided guidance on regulatory compliance and training. A structured selection process identifies top candidates, and a rigorous onboarding process ensures smooth transitions between ACRCs. We report characteristics and outcomes of ACRC employees and surveyed them to …

Cholesterol-Dependent Lxr Transcription Factor Activity Represses Pronociceptive Effects Of Estrogen In Sensory Neurons And Pain Induced By Myelin Basic Protein Fragments, Swathi K Hullugundi, Jennifer Dolkas, Andrei V Chernov, Tony L Yaksh, Kelly A Eddinger, Mila Angert, Glaucilene Ferreira Catroli, Alex Y Strongin, Patrick M Dougherty, Yan Li, Oswal Quehenberger, Aaron Armando, Veronica I Shubayev

Faculty, Staff and Student Publications

BACKGROUND: A bioactive myelin basic protein (MBP) fragment, comprising MBP

METHODS: In male and female normal and post-CCI rat sciatic nerves, we assessed: (i) cholesterol precursor and metabolite levels by lipidomics; (ii) MBP

RESULTS: CCI regulated LXRα ligand and receptor levels in nerves of both sexes, with cholesterol precursors, desmosterol and 7-DHC, and oxysterol elevated in females relative to males. MBP

CONCLUSION: The injury-released bioactive MBP fragments induce pronociceptive changes by selective inactivation of nuclear transcription factors, including LXRα. By Ncoa1 sequestration, bioactive MBP fragments render LXRα function to counteract pronociceptive activity of estrogen/ESR1 in sensory neurons. This effect of …

Evolving Horizons In Radiation Therapy Auto-Contouring: Distilling Insights, Embracing Data-Centric Frameworks, And Moving Beyond Geometric Quantification, Kareem A Wahid, Carlos E Cardenas, Barbara Marquez, Tucker J Netherton, Benjamin H Kann, Laurence E Court, Renjie He, Mohamed A Naser, Amy C Moreno, Clifton D Fuller, David Fuentes

Faculty, Staff and Student Publications

Historically, clinician-derived contouring of tumors and healthy tissues has been crucial for radiation therapy (RT) planning. In recent years, advances in artificial intelligence (AI), predominantly in deep learning (DL), have rapidly improved automated contouring for RT applications, particularly for routine organs-at-risk.1, 2, 3 Despite research efforts actively promoting its broader acceptance, clinical adoption of auto-contouring is not yet standard practice.

Notably, within several AI communities, there has been growing enthusiasm to shift from conventional “model-centric” AI approaches (ie, improving a model while keeping the data fixed), to “data-centric” AI approaches (ie, improving the data while keeping a …

A Modular Trial Of Androgen Signaling Inhibitor Combinations Testing A Risk-Adapted Strategy In Patients With Metastatic Castration-Resistant Prostate Cancer, Ana M Aparicio, Rebecca S S Tidwell, Shalini S Yadav, Jiun-Sheng Chen, Miao Zhang, Jingjing Liu, Shuai Guo, Patrick G Pilié, Yao Yu, Xingzhi Song, Haswanth Vundavilli, Sonali Jindal, Keyi Zhu, Paul V Viscuse, Justin M Lebenthal, Andrew W Hahn, Rama Soundararajan, Paul G Corn, Amado Zurita-Saavedra, Sumit K Subudhi, Jianhua Zhang, Wenyi Wang, Chad Huff, Patricia Troncoso, James P Allison, Padmanee Sharma, Christopher J Logothetis

Faculty, Staff and Student Publications

Purpose: To determine the efficacy and safety of risk-adapted combinations of androgen signaling inhibitors and inform disease classifiers for metastatic castration-resistant prostate cancers.

Patients and methods: In a modular, randomized phase II trial, 192 men were treated with 8 weeks of abiraterone acetate, prednisone, and apalutamide (AAPA; module 1) and then allocated to modules 2 or 3 based on satisfactory (≥50% PSA decline from baseline and < 5 circulating tumor cell/7.5 mL) versus unsatisfactory status. Men in the former were randomly assigned to continue AAPA alone (module 2A) or with ipilimumab (module 2B). Men in the latter group had carboplatin + cabazitaxel added to AAPA (module 3). Optional baseline biopsies were subjected to correlative studies.

Results: Median overall survival (from allocation) was 46.4 [95% confidence interval (CI), 39.2-68.2], 41.4 (95% CI, 33.3-49.9), and 18.7 (95% CI, 14.3-26.3) months in modules 2A (n = 64), 2B (n = 64), and …

Eus-Guided Hydrogel Injection To Separate Pancreatic Head Carcinoma From Duodenum For Enhanced Radiotherapy: Multi-Site Feasibility Study, Manoop S Bhutani, Amol K Narang, Kai Ding, Brenna Casey, Kumar Krishnan, Eugene J Koay, Theodore S Hong, Joseph M Herman, Kristen H Griffin, Eun Ji Shin

Faculty, Staff and Student Publications

Background and study aims The proximity of a pancreas head tumor to the duodenum often limits delivery of an ablative dose of radiation therapy. This study evaluated the feasibility and safety of using an injectable polyethylene glycol (PEG) hydrogel between the head of the pancreas and duodenum.

Patients and methods In a multi-site feasibility cohort study of patients with localized pancreatic cancer, PEG hydrogel was injected under endoscopic ultrasound guidance to temporarily position the duodenum away from the pancreas. Procedure characteristics were recorded, including hydrogel volume and space created. Patients were monitored for adverse events (AEs) and radiotherapy toxicity.

Results …

Automated Quantification Of Measurable Residual Disease In Chronic Lymphocytic Leukemia Using An Artificial Intelligence-Assisted Workflow, Alexandre Bazinet, Alan Wang, Xinmei Li, Fuli Jia, Huan Mo, Wei Wang, Sa A Wang

Faculty, Staff and Student Publications

Detection of measurable residual disease (MRD) in chronic lymphocytic leukemia (CLL) is an important prognostic marker. The most common CLL MRD method in current use is multiparameter flow cytometry, but availability is limited by the need for expert manual analysis. Automated analysis has the potential to expand access to CLL MRD testing. We evaluated the performance of an artificial intelligence (AI)-assisted multiparameter flow cytometry (MFC) workflow for CLL MRD. We randomly selected 113 CLL MRD FCS files and divided them into training and validation sets. The training set (n = 41) was gated by expert manual analysis and used to …

Α-Synuclein Seed Amplification Technology For Parkinson's Disease And Related Synucleinopathies, Claudio Soto

Faculty, Staff and Student Publications

Synucleinopathies are a group of neurodegenerative diseases (NDs) associated with cerebral accumulation of α-synuclein (αSyn) misfolded aggregates. At this time, there is no effective treatment to stop or slow down disease progression, which in part is due to the lack of an early and objective biochemical diagnosis. In the past 5 years, the seed amplification technology has emerged for highly sensitive identification of these diseases, even at the preclinical stage of the illness. Much research has been done in multiple laboratories to validate the efficacy and reproducibility of this assay. This article provides a comprehensive review of this technology, including …

Author Correction: The Evolution Of Lung Cancer And Impact Of Subclonal Selection In Tracerx, Alexander M Frankell, Michelle Dietzen, Maise Al Bakir, Emilia L Lim, Takahiro Karasaki, Sophia Ward, Selvaraju Veeriah, Emma Colliver, Ariana Huebner, Abigail Bunkum, Mark S Hill, Kristiana Grigoriadis, David A Moore, James R M Black, Wing Kin Liu, Kerstin Thol, Oriol Pich, Thomas B K Watkins, Cristina Naceur-Lombardelli, Daniel E Cook, Roberto Salgado, Gareth A Wilson, Chris Bailey, Mihaela Angelova, Robert Bentham, Carlos Martínez-Ruiz, Christopher Abbosh, Andrew G Nicholson, John Le Quesne, Dhruva Biswas, Rachel Rosenthal, Clare Puttick, Sonya Hessey, Claudia Lee, Paulina Prymas, Antonia Toncheva, Jon Smith, Wei Xing, Jerome Nicod, Gillian Price, Keith M Kerr, Babu Naidu, Gary Middleton, Kevin G Blyth, Dean A Fennell, Martin D Forster, Siow Ming Lee, Mary Falzon, Madeleine Hewish, Michael J Shackcloth, Eric Lim, Sarah Benafif, Peter Russell, Ekaterini Boleti, Matthew G Krebs, Jason F Lester, Dionysis Papadatos-Pastos, Tanya Ahmad, Ricky M Thakrar, David Lawrence, Neal Navani, Sam M Janes, Caroline Dive, Fiona H Blackhall, Yvonne Summers, Judith Cave, Teresa Marafioti, Javier Herrero, Sergio A Quezada, Karl S Peggs, Roland F Schwarz, Peter Van Loo, Daniël M Miedema, Nicolai J Birkbak, Crispin T Hiley, Allan Hackshaw, Simone Zaccaria, Tracerx Consortium, Mariam Jamal-Hanjani, Nicholas Mcgranahan, Charles Swanton

Faculty, Staff and Student Publications

No abstract provided.

Radiation Dose Attenuation Using Radpad In Cath Lab For Primary And Secondary Operators – Radar-Cath Study, Sandeepan Saha, Aditya Kapoor, Kamlesh Raut, Arpita Katheria, Harshit Khare, Ankit Sahu, Roopali Khanna, Sudeep Kumar, Naveen Garg, Satyendra Tewari

Faculty, Staff and Student Publications

BACKGROUND: Radiation injury is an important concern for interventional cardiologists and needs to be addressed. RADPAD is a radiation protection drape that has been shown to reduce the radiation exposure of the primary operator (PO). While Indian data on radiation exposure of the PO in the cath lab are scarce, the exposure of the secondary operator (SO) is even less well studied.

AIMS: The aim of this study was to evaluate the efficacy of RADPAD drapes in reducing radiation doses in the cath lab for the primary as well as the secondary operator.

METHODS: A total of 160 patients (40 …

Plasmacytoid Dendritic Cells Control Homeostasis Of Megakaryopoiesis, Florian Gaertner, Hellen Ishikawa-Ankerhold, Susanne Stutte, Wenwen Fu, Jutta Weitz, Anne Dueck, Bhavishya Nelakuditi, Valeria Fumagalli, Dominic Van Den Heuvel, Larissa Belz, Gulnoza Sobirova, Zhe Zhang, Anna Titova, Alejandro Martinez Navarro, Kami Pekayvaz, Michael Lorenz, Louisa Von Baumgarten, Jan Kranich, Tobias Straub, Bastian Popper, Vanessa Zheden, Walter Anton Kaufmann, Chenglong Guo, Guido Piontek, Saskia Von Stillfried, Peter Boor, Marco Colonna, Sebastian Clauß, Christian Schulz, Thomas Brocker, Barbara Walzog, Christoph Scheiermann, William C Aird, Claus Nerlov, Konstantin Stark, Tobias Petzold, Stefan Engelhardt, Michael Sixt, Robert Hauschild, Martina Rudelius, Robert A J Oostendorp, Matteo Iannacone, Matthias Heinig, Steffen Massberg

Faculty, Staff and Student Publications

Platelet homeostasis is essential for vascular integrity and immune defence1,2. Although the process of platelet formation by fragmenting megakaryocytes (MKs; thrombopoiesis) has been extensively studied, the cellular and molecular mechanisms required to constantly replenish the pool of MKs by their progenitor cells (megakaryopoiesis) remains unclear3,4. Here we use intravital imaging to track the cellular dynamics of megakaryopoiesis over days. We identify plasmacytoid dendritic cells (pDCs) as homeostatic sensors that monitor the bone marrow for apoptotic MKs and deliver IFNα to the MK niche triggering local on-demand proliferation and maturation of MK progenitors. This pDC-dependent feedback loop is crucial for MK …

Data-Driven Gated Positron Emission Tomography/Computed Tomography For Radiotherapy, Tinsu Pan, Dershan Luo

Faculty, Staff and Student Publications

PURPOSE: Software-based data-driven gated (DDG) positron emission tomography/computed tomography (PET/CT) has replaced hardware-based 4D PET/CT. The purpose of this article was to review DDG PET/CT, which could improve the accuracy of treatment response assessment, tumor motion evaluation, and target tumor contouring with whole-body (WB) PET/CT for radiotherapy (RT).

MATERIAL AND METHODS: This review covered the topics of 4D PET/CT with hardware gating, advancements in PET instrumentation, DDG PET, DDG CT, and DDG PET/CT based on a systematic literature review. It included a discussion of the large axial field-of-view (AFOV) PET detector and a review of the clinical results of DDG …

At-Risk Tackling Techniques And Effectiveness In English Premiership Rugby, Brady P Moore, Dakota Doucet, Bobby Dow, Sree M Vemu, Takashi Hirase, Rex A W Marco

Faculty, Staff and Student Publications

Background: Head-down tackling has been associated with higher rates of head and neck injuries and less successful tackles compared with head-up tackling in American football. In rugby, head and neck injuries have been associated with tackling, with the tackler's head positioned in front of the ball carrier.

Purpose: To assess the success and risks of tackling techniques used in the English Rugby Premiership matches.

Study design: Cross-sectional study; Level of evidence, 3.

Methods: Three reviewers analyzed 1000 consecutive solo defensive tackling attempts during the 2022 to 2023 season in 6 English Rugby Premiership matches. Slow-motion replays were used to analyze …

Long-Term Weight Loss Effects Of Semaglutide In Obesity Without Diabetes In The Select Trial, Donna H Ryan, Ildiko Lingvay, John Deanfield, Steven E Kahn, Eric Barros, Bartolome Burguera, Helen M Colhoun, Cintia Cercato, Dror Dicker, Deborah B Horn, G Kees Hovingh, Ole Kleist Jeppesen, Alexander Kokkinos, A Michael Lincoff, Sebastian M Meyhöfer, Tugce Kalayci Oral, Jorge Plutzky, André P Van Beek, John P H Wilding, Robert F Kushner

Faculty, Staff and Student Publications

In the SELECT cardiovascular outcomes trial, semaglutide showed a 20% reduction in major adverse cardiovascular events in 17,604 adults with preexisting cardiovascular disease, overweight or obesity, without diabetes. Here in this prespecified analysis, we examined effects of semaglutide on weight and anthropometric outcomes, safety and tolerability by baseline body mass index (BMI). In patients treated with semaglutide, weight loss continued over 65 weeks and was sustained for up to 4 years. At 208 weeks, semaglutide was associated with mean reduction in weight (-10.2%), waist circumference (-7.7 cm) and waist-to-height ratio (-6.9%) versus placebo (-1.5%, -1.3 cm and -1.0%, respectively; P < 0.0001 for all comparisons versus placebo). Clinically meaningful weight loss occurred in both sexes and all races, body sizes and regions. Semaglutide was associated with fewer serious adverse events. For each BMI category (

The Time-Dependent Association Between Irritable Bowel Syndrome And All-Cause And Cause-Specific Mortality: A Prospective Cohort Study Within The Uk Biobank, Fangyu Li, Yukiko Yano, Lola Étiévant, Carrie R Daniel, Shreela V Sharma, Eric L Brown, Ruosha Li, Erikka Loftfield, Qing Lan, Rashmi Sinha, Baharak Moshiree, Maki Inoue-Choi, Emily Vogtmann

Faculty, Staff and Student Publications

Introduction: Irritable bowel syndrome (IBS) is one of the most common functional gastrointestinal disorders, but few studies have evaluated mortality risks among individuals with IBS. We explored the association between IBS and all-cause and cause-specific mortality in the UK Biobank.

Methods: We included 502,369 participants from the UK Biobank with mortality data through 2022. IBS was defined using baseline self-report and linkage to primary care or hospital admission data. We estimated hazard ratios (HRs) and 95% confidence intervals (CIs) for all-cause and cause-specific mortality using multivariable Cox proportional hazards regression models within partitioned follow-up time categories (0-5, >5-10, and >10 …

Expanded-Access Use Of Elamipretide In A Patient With Membrane Protein-Associated Neurodegeneration, Jorge Patino, Anna Haertling Clearman, Lindsey Miller, Mary Kay Koenig

Faculty, Staff and Student Publications

This case report presents a progressively declining 17-year-old patient with membrane protein-associated neurodegeneration who demonstrated symptomatic improvements in her dysarthria, dysphagia, and gait, and objective improvements in her 6-minute walk test and 5 times sit-to-stand test during elamipretide treatment.

The Role Of Occipital Condyle And Atlas Anomalies On Occipital Cervical Fusion Outcomes In Chiari Malformation Type I With Syringomyelia: A Study From The Park-Reeves Syringomyelia Research Consortium, Alexander T Yahanda, Joyce Koueik, Laurie L Ackerman, P David Adelson, Gregory W Albert, Philipp R Aldana, Tord D Alden, Richard C E Anderson, David F Bauer, Tammy Bethel-Anderson, Karin Bierbrauer, Douglas L Brockmeyer, Joshua J Chern, Daniel E Couture, David J Daniels, Brian J Dlouhy, Susan R Durham, Richard G Ellenbogen, Ramin Eskandari, Herbert E Fuchs, Gerald A Grant, Patrick C Graupman, Stephanie Greene, Jeffrey P Greenfield, Naina L Gross, Daniel J Guillaume, Todd C Hankinson, Gregory G Heuer, Mark Iantosca, Bermans J Iskandar, Eric M Jackson, George I Jallo, James M Johnston, Bruce A Kaufman, Robert F Keating, Nickalus R Khan, Mark D Krieger, Jeffrey R Leonard, Cormac O Maher, Francesco T Mangano, Jonathan Martin, J Gordon Mccomb, Sean D Mcevoy, Thanda Meehan, Arnold H Menezes, Michael S Muhlbauer, Brent R O'Neill, Greg Olavarria, John Ragheb, Nathan R Selden, Manish N Shah, Chevis N Shannon, Joshua S Shimony, Matthew D Smyth, Scellig S D Stone, Jennifer M Strahle, Mandeep S Tamber, James C Torner, Gerald F Tuite, Elizabeth C Tyler-Kabara, Scott D Wait, John C Wellons, William E Whitehead, Tae Sung Park, David D Limbrick, Raheel Ahmed

Faculty, Staff and Student Publications

Objective: Congenital anomalies of the atlanto-occipital articulation may be present in patients with Chiari malformation type I (CM-I). However, it is unclear how these anomalies affect the biomechanical stability of the craniovertebral junction (CVJ) and whether they are associated with an increased incidence of occipitocervical fusion (OCF) following posterior fossa decompression (PFD). The objective of this study was to determine the prevalence of condylar hypoplasia and atlas anomalies in children with CM-I and syringomyelia. The authors also investigated the predictive contribution of these anomalies to the occurrence of OCF following PFD (PFD+OCF).

Methods: The authors analyzed the prevalence of condylar …

The Impact Of Hearing Impairment On Patient Care And Autonomy, Savannah Baimbridge, Julie Neil, Gabriel M Aisenberg

Faculty, Staff and Student Publications

Sensory deficits, including hypoacusis, can cause a barrier to communication between healthcare providers and patients, which in turn can lead to misdiagnosis and loss of patient autonomy. Such deficits are frequently overlooked in clinical encounters. We present a 92-year-old Spanish-speaking female who presented twice to the Emergency Department for complications of a diabetic foot infection. Limited evaluation, documentation, and accommodations regarding the patient's hypoacusis led to a misinterpretation of her mental status and a transfer of decision-making to surrogates. A two-toe amputation, mechanical intubation, and intensive care unit stay were followed. It was only after these events that the caregivers …

Reproducibility Of Quantitative Myocardial Perfusion And Coronary Flow Capacity By Positron Emission Tomography: 3d Digital Silicon Photomultiplier Solid State Vs Legacy 2d Analogue Systems For Clinical Practice And Trials, Amanda Roby, Lindsey Harmon, Kelly Sander, Linh Bui, Danai Kitkungvan, Monica Patel, Jagat Narula, Nils P Johnson, K Lance Gould

Faculty, Staff and Student Publications

Aims: Quantitative rest-stress myocardial perfusion in millilitres per minute per gram among multiple 2D and 3D positron emission tomography-computed tomography (PET-CT) scanners is essential for personalized cardiac management and clinical trials. Accordingly, this study reports the accuracy and precision of quantitative rest-stress millilitres per minute per gram and coronary flow capacity among 2D and two different digital 3D silicon photomultiplier (SiPM) PET-CT scanners for quantifying the severity of coronary pathophysiology for clinical trials or guiding interventions vs. medical treatment.

Methods and results: One hundred seventy-one participants underwent 748 paired serial rest or stress PET perfusion imaging in the same person …

Use Of Ipsc-Derived Smooth Muscle Cells To Model Physiology And Pathology, Callie S Kwartler, Jose Emiliano Esparza Pinelo

Faculty, Staff and Student Publications

The implementation of human induced pluripotent stem cell (hiPSC) models has introduced an additional tool for identifying molecular mechanisms of disease that complement animal models. Patient-derived or CRISPR/Cas9-edited induced pluripotent stem cells differentiated into smooth muscle cells (SMCs) have been leveraged to discover novel mechanisms, screen potential therapeutic strategies, and model in vivo development. The field has evolved over almost 15 years of research using hiPSC-SMCs and has made significant strides toward overcoming initial challenges such as the lineage specificity of SMC phenotypes. However, challenges both specific (eg, the lack of specific markers to thoroughly validate hiPSC-SMCs) and general (eg, …

Endovascular Versus Medical Therapy In Posterior Cerebral Artery Stroke: Role Of Baseline Nihss Score And Occlusion Site, Davide Strambo, Patrik Michel, Thanh N Nguyen, Mohamad Abdalkader, Muhammad M Qureshi, Daniel Strbian, Christian Herweh, Markus A Möhlenbruch, Silja Räty, Marta Olivé-Gadea, Marc Ribo, Marios Psychogios, Urs Fischer, Anh Nguyen, Joji B Kuramatsu, David Haupenthal, Martin Köhrmann, Cornelius Deuschl, Jordi Kühne Escolà, Jelle Demeestere, Robin Lemmens, Lieselotte Vandewalle, Shadi Yaghi, Liqi Shu, Volker Puetz, Daniel P O Kaiser, Johannes Kaesmacher, Adnan Mujanovic, Dominique Cornelius Marterstock, Tobias Engelhorn, Manuel Requena, Hormuzdiyar H Dasenbrock, Piers Klein, Diogo C Haussen, Mahmoud H Mohammaden, Hend Abdelhamid, Lorena Souza Viana, Bruno Cunha, Isabel Fragata, Michele Romoli, Francesco Diana, Wei Hu, Chao Zhang, Pekka Virtanen, Riikka Lauha, Jessica Jesser, Judith Clark, Stavros Matsoukas, Johanna T Fifi, Sunil A Sheth, Sergio Salazar-Marioni, João Pedro Marto, João Nuno Ramos, Milena Miszczuk, Christoph Riegler, Sven Poli, Khouloud Poli, Ashutosh P Jadhav, Shashvat M Desai, Volker Maus, Maximilian Kaeder, Adnan H Siddiqui, Andre Monteiro, Hesham E Masoud, Neil Suryadareva, Maxim Mokin, Shail Thanki, Kemal Alpay, Pauli Ylikotila, James E Siegler, Italo Linfante, Guilherme Dabus, Negar Asdaghi, Vasu Saini, Christian H Nolte, Eberhard Siebert, Bettina L Serrallach, Charlotte S Weyland, Uta Hanning, Lukas Meyer, Anne Berberich, Peter A Ringleb, Raul G Nogueira, Simon Nagel

Faculty, Staff and Student Publications

Background: Acute ischemic stroke with isolated posterior cerebral artery occlusion (iPCAO) lacks management evidence from randomized trials. We aimed to evaluate whether the association between endovascular treatment (EVT) and outcomes in iPCAO acute ischemic stroke is modified by initial stroke severity (baseline National Institutes of Health Stroke Scale [NIHSS]) and arterial occlusion site.

Methods: Based on the multicenter, retrospective, case-control study of consecutive iPCAO acute ischemic stroke patients (PLATO study [Posterior Cerebral Artery Occlusion Stroke]), we assessed the heterogeneity of EVT outcomes compared with medical management (MM) for iPCAO, according to baseline NIHSS score (≤6 versus >6) and occlusion site …

Behavioral Therapies Targeting Reward Mechanisms In Substance Use Disorders, Margaret C Wardle, Heather E Webber, Jin H Yoon, Angela M Heads, Angela L Stotts, Scott D Lane, Joy M Schmitz

Faculty, Staff and Student Publications

Behavioral therapies are considered best practices in the treatment of substance use disorders (SUD) and used as first-line approaches for SUDs without FDA-approved pharmacotherapies. Decades of research on the neuroscience of drug reward and addiction have informed the development of current leading behavioral therapies that, while differing in focus and technique, have in common the overarching goal of shifting reward responding away from drug and toward natural non-drug rewards. This review begins by describing key neurobiological processes of reward in addiction, followed by a description of how various behavioral therapies address specific reward processes. Based on this review, a conceptual …

High-Dimensional Multivariate Analysis Of Variance Via Geometric Median And Bootstrapping, Guanghui Cheng, Ruitao Lin, Liuhua Peng

Faculty, Staff and Student Publications

The geometric median, which is applicable to high-dimensional data, can be viewed as a generalization of the univariate median used in 1-dimensional data. It can be used as a robust estimator for identifying the location of multi-dimensional data and has a wide range of applications in real-world scenarios. This paper explores the problem of high-dimensional multivariate analysis of variance (MANOVA) using the geometric median. A maximum-type statistic that relies on the differences between the geometric medians among various groups is introduced. The distribution of the new test statistic is derived under the null hypothesis using Gaussian approximations, and its consistency …