Medical Specialties Commons^™

Mycophenolate Mofetil Is Associated With Inferior Overall Survival In Cytomegalovirus-Seropositive Patients With Acute Myeloid Leukemia Undergoing Hematopoietic Cell Transplantation, Rima M Saliba, Stephanie J Lee, Paul A Carpenter, Geoffrey R Hill, Catherine J Lee, Amin Alousi, May Daher, George Chen, Richard E Champlin, Katayoun Rezvani, Elizabeth J Shpall, Rohtesh S Mehta

Faculty, Staff and Student Publications

No abstract provided.

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 …

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) …

Reliable Detection Of Generalized Convulsive Seizures Using An Off-The-Shelf Digital Watch: A Multisite Phase 2 Study, Yash Shashank Vakilna, Xiaojin Li, Jaison S Hampson, Yan Huang, John C Mosher, Yuri Dabaghian, Xi Luo, Blanca Talavera, Sandipan Pati, Masel Todd, Ryan Hays, Charles Akos Szabo, Guo-Qiang Zhang, Samden D Lhatoo

Faculty, Staff and Student Publications

Objective: The aim of this study was to develop a machine learning algorithm using an off-the-shelf digital watch, the Samsung watch (SM-R800), and evaluate its effectiveness for the detection of generalized convulsive seizures (GCS) in persons with epilepsy.

Methods: This multisite epilepsy monitoring unit (EMU) phase 2 study included 36 adult patients. Each patient wore a Samsung watch that contained accelerometer, gyroscope, and photoplethysmographic sensors. Sixty-eight time and frequency domain features were extracted from the sensor data and were used to train a random forest algorithm. A testing framework was developed that would better reflect the EMU setting, consisting of …

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 …

Effects Of Vitamin D Supplementation On A Deep Learning-Based Mammographic Evaluation In Swog S0812, Julia E Mcguinness, Garnet L Anderson, Simukayi Mutasa, Dawn L Hershman, Mary Beth Terry, Parisa Tehranifar, Danika L Lew, Monica Yee, Eric A Brown, Sebastien S Kairouz, Nafisa Kuwajerwala, Therese B Bevers, John E Doster, Corrine Zarwan, Laura Kruper, Lori M Minasian, Leslie Ford, Banu Arun, Marian L Neuhouser, Gary E Goodman, Powel H Brown, Richard Ha, Katherine D Crew

Faculty, Staff and Student Publications

Deep learning-based mammographic evaluations could noninvasively assess response to breast cancer chemoprevention. We evaluated change in a convolutional neural network-based breast cancer risk model applied to mammograms among women enrolled in SWOG S0812, which randomly assigned 208 premenopausal high-risk women to receive oral vitamin D3 20 000 IU weekly or placebo for 12 months. We applied the convolutional neural network model to mammograms collected at baseline (n = 109), 12 months (n = 97), and 24 months (n = 67) and compared changes in convolutional neural network-based risk score between treatment groups. Change in convolutional neural network-based risk score was …

Emerging Cell And Molecular Targets For Treating Mucus Hypersecretion In Asthma, Ana M Jaramillo, Eszter K Vladar, Fernando Holguin, Burton F Dickey, Christopher M Evans

Faculty, Staff and Student Publications

Mucus provides a protective barrier that is crucial for host defense in the lungs. However, excessive or abnormal mucus can have pathophysiological consequences in many pulmonary diseases, including asthma. Patients with asthma are treated with agents that relax airway smooth muscle and reduce airway inflammation, but responses are often inadequate. In part, this is due to the inability of existing therapeutic agents to directly target mucus. Accordingly, there is a critical need to better understand how mucus hypersecretion and airway plugging are affected by the epithelial cells that synthesize, secrete, and transport mucus components. This review highlights recent advances in …

Corrigendum To "The Use Of Mr-Guided Radiation Therapy For Head And Neck Cancer And Recommended Reporting Guidance" Seminars In Radiation Oncology Volume 34 (2024) 69-83, Brigid A Mcdonald, Riccardo Dal Bello, Clifton D Fuller, Panagiotis Balermpas

Faculty, Staff and Student Publications

No abstract provided.

Lacrimal Gland Adenocarcinoma Clinicopathologic Features And Outcomes Compared With Those Of Lacrimal Gland Adenoid Cystic Carcinoma, Hila Goldberg, Xinyang Jiang, Janet Fan, Jiawei Zhao, Jing Ning, Michelle Williams, Steven Frank, Amy Moreno, Brandon Gunn, Renata Ferrarotto, Bita Esmaeli

Faculty, Staff and Student Publications

Purpose: Lacrimal gland (LG) adenocarcinomas (ACs) are rare, with limited data. We compared clinicopathologic features and local recurrence, distant metastasis, and survival rates between LG AC and LG adenoid cystic carcinoma (ACC).

Methods: The records of LG AC patients treated from 2008 to 2022 and LG ACC patients treated from 1998 to 2022 at the same center were retrospectively reviewed.

Results: The study included 20 patients with AC; 10 de-novo AC, 10 ex-pleomorphic AC; and 51 ACC patients. The median age at diagnosis was 61 years for de-novo AC, 54 years for ex-pleomorphic AC, and 45 years for ACC. All …

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 …

Tumor-Immune Signatures Of Treatment Resistance To Brentuximab Vedotin With Ipilimumab And/Or Nivolumab In Hodgkin Lymphoma, Edgar Gonzalez-Kozlova, Hsin-Hui Huang, Opeyemi A Jagede, Kevin Tuballes, Diane M Del Valle, Geoffrey Kelly, Manishkumar Patel, Hui Xie, Jocelyn Harris, Kimberly Argueta, Kai Nie, Vanessa Barcessat, Radim Moravec, Jennifer Altreuter, Dzifa Y Duose, Brad S Kahl, Stephen M Ansell, Joyce Yu, Ethan Cerami, James R Lindsay, Ignacio I Wistuba, Seunghee Kim-Schulze, Catherine S Diefenbach, Sacha Gnjatic

Faculty, Staff and Student Publications

To investigate the cellular and molecular mechanisms associated with targeting CD30-expressing Hodgkin lymphoma (HL) and immune checkpoint modulation induced by combination therapies of CTLA4 and PD1, we leveraged Phase 1/2 multicenter open-label trial NCT01896999 that enrolled patients with refractory or relapsed HL (R/R HL). Using peripheral blood, we assessed soluble proteins, cell composition, T-cell clonality, and tumor antigen-specific antibodies in 54 patients enrolled in the phase 1 component of the trial. NCT01896999 reported high (>75%) overall objective response rates with brentuximab vedotin (BV) in combination with ipilimumab (I) and/or nivolumab (N) in patients with R/R HL. We observed a …

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 …

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 …

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 …

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 (

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 …

Polatuzumab Vedotin, Venetoclax, And An Anti-Cd20 Monoclonal Antibody In Relapsed/Refractory B-Cell Non-Hodgkin Lymphoma, Sam Yuen, Tycel J Phillips, Rajat Bannerji, Paula Marlton, Giuseppe Gritti, John F Seymour, Anna Johnston, Christopher Arthur, Anna Dodero, Sunil Sharma, Jamie Hirata, Lisa Musick, Christopher R Flowers

Faculty, Staff and Student Publications

The Phase 2 portion of this study evaluated safety and efficacy of polatuzumab vedotin 1.8 mg/kg and venetoclax 800 mg, plus fixed-dose obinutuzumab 1000 mg or rituximab 375 mg/m2 in patients with relapsed/refractory (R/R) follicular lymphoma (FL) or diffuse large B-cell lymphoma (DLBCL), respectively. Patients with complete response (CR) or partial response (PR)/stable disease (FL) or CR/PR (DLBCL) at end of induction (EOI; six 21-day cycles) received post-induction therapy with venetoclax and obinutuzumab or rituximab, respectively. Primary endpoint was CR rate at EOI. Safety-evaluable populations included 74 patients (FL cohort; median age 64 years; progression of disease within 24 months …

Cone-Beam Ct With A Noncircular (Sine-On-Sphere) Orbit: Imaging Performance Of A Clinical System For Image-Guided Interventions, A Kyle Jones, Moiz Ahmad, Shaan M Raza, Stephen R Chen, Jeffrey H Siewerdsen

Faculty, Staff and Student Publications

Purpose: We aim to compare the imaging performance of a cone-beam CT (CBCT) imaging system with noncircular scan protocols (sine-on-sphere) to a conventional circular orbit.

Approach: A biplane C-arm system (ARTIS Icono; Siemens Healthineers) capable of circular and noncircular CBCT acquisition was used, with the latter orbit (sine-on-sphere, "Sine Spin") executing a sinusoidal motion with ±10deg tilt amplitude over the half-scan orbit. A test phantom was used for the characterization of image uniformity, noise, noise-power spectrum (NPS), spatial resolution [modulation transfer function (MTF) in axial and oblique directions], and cone-beam artifacts. Findings were interpreted using an anthropomorphic head phantom with …

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 …

Oar-Weighted Dice Score: A Spatially Aware, Radiosensitivity Aware Metric For Target Structure Contour Quality Assessment, Lucas Mccullum, Kareem A Wahid, Barbara Marquez, Clifton D Fuller

Faculty, Staff and Student Publications

The Dice Similarity Coefficient (DSC) is the current de facto standard to determine agreement between a reference segmentation and one generated by manual / auto-contouring approaches. This metric is useful for non-spatially important images; however, radiation therapy requires consideration of nearby Organs-at-Risk (OARs) and their radiosensitivity which are currently unaccounted for with the traditional DSC. In this work, we introduce the OAR-DSC which accounts for nearby OARs and their radiosensitivity when computing the DSC. We illustrate the importance of this through cases where two proposed contours have similar DSC, but lower OAR-DSC when one contour expands closer to the surrounding …

Apoptosis Pathway-Associated Proteins Are Frequently Expressed In Melanoma: A Study Of 32 Cases With Focus On Acral Lentiginous Melanoma, Debora A Ledesma, Mario L Marques-Piubelli, Elsa Li-Ning-Tapia, Courtney Hudgens, Jun Gu, Rossana Lazcano, Sandro Casavilca-Zambrano, Miluska Castillo, Michael A Davies, Wen-Jen Hwu, Phyu P Aung, Alessio Giubellino, Jonathan L Curry, Carlos Torres-Cabala

Faculty, Staff and Student Publications

Acral lentiginous melanoma (ALM) is an aggressive type of cutaneous melanoma (CM) that arises on palms, soles, and nail units. ALM is rare in White population, but it is relatively more frequent in dark-skinned populations. There is an unmet need to develop new personalized and more effective treatments strategies for ALM. Increased expression of antiapoptotic proteins (ie, BCL2, MCL1) has been shown to contribute to tumorigenesis and therapeutic resistance in multiple tumor types and has been observed in a subset of ALM and mucosal melanoma cell lines in vivo and in vitro. However, little is known about their expression and …

Progressive Thrombocytopenia, Splenomegaly, And Abnormal Tone In An Infant With Growth Faltering, Gal Barak, Gail Demmler-Harrison, Linda Rossetti, Venée N Tubman, Ameya S Walimbe, Rathi Asaithambi

Faculty, Staff and Students Publications

A 4-month-old full-term female presented with growth faltering associated with progressive feeding difficulty, rash, abdominal distension, and developmental delays. She was found to have disconjugate gaze, abnormal visual tracking, mixed tone, bruising, and splenomegaly on examination. Initial workup was notable for thrombocytopenia and positive cytomegalovirus (CMV) immunoglobulin G and immunoglobulin M antibodies. She initially presented to the infectious diseases CMV clinic, where she was noted to have severe malnutrition, prompting referral to the emergency department for hospital admission to optimize nutrition with nasogastric tube feeding and facilitate additional evaluation. An active CMV infection with viruria and viremia was confirmed, but …

More Than Just Teeth: How Oral Health Can Affect The Heart, Steven Hopkins, Saivaroon Gajagowni, Yusuf Qadeer, Zhen Wang, Salim S Virani, Jukka H Meurman, Roman Leischik, Carl J Lavie, Markus Strauss, Chayakrit Krittanawong

Faculty, Staff and Students Publications

Epidemiological evidence has revealed a potential relationship between periodontal disease and cardiovascular disease (CVD). Consensus regarding a link between these pathologies remains elusive, however, largely secondary to the considerable overlap between risk factors and comorbidities common to both disease processes. This review article aims to update the evidence for an association by summarizing the evidence for causality between periodontitis and comorbidities linked to CVD, including endocarditis, hypertension (HTN), atrial fibrillation (AF), coronary artery disease (CAD), diabetes mellitus (DM) and hyperlipidemia (HLD). This article additionally discusses the role for periodontal therapy to improved management of the comorbidities, with the larger goal …

Pregnancy Outcomes Of Nifedipine Compared With Labetalol For Oral Treatment Of Mild Chronic Hypertension, Ayodeji A Sanusi, Justin Leach, Kim Boggess, Lorraine Dugoff, Baha Sibai, Kirsten Lawrence, Brenna L Hughes, Joseph Bell, Kjersti Aagaard, Rodney K Edwards, Kelly S Gibson, David M Haas, Lauren Plante, Torri D Metz, Brian Casey, Sean Esplin, Sherri Longo, Matthew K Hoffman, George R Saade, Kara K Hoppe, Janelle Foroutan, Methodius Tuuli, Michelle Y Owens, Hyagriv N Simhan, Heather Frey, Todd Rosen, Anna Palatnik, Susan Baker, Phyllis August, Uma M Reddy, Emily J Su, Iris Krishna, Nguyet A Nguyen, Mary E Norton, Daniel Skupski, Yasser Y El-Sayed, Dotun Ogunyemi, Zorina S Galis, Lorie Harper, Namasivayam Ambalavanan, Nancy L Geller, Hui-Chien Kuo, Rachel G Sinkey, Ronald Librizzi, Leonardo Pereira, Everett F Magann, Mounira Habli, Shauna Williams, Giancarlo Mari, Gabriella Pridjian, David S Mckenna, Marc Parrish, Eugene Chang, Sarah Osmundson, Joanne Quinones, Jeff M Szychowski, Alan T N Tita

Faculty, Staff and Students Publications

Objective: To evaluate maternal and neonatal outcomes by type of antihypertensive used in participants of the CHAP (Chronic Hypertension in Pregnancy) trial.

Methods: We conducted a planned secondary analysis of CHAP, an open-label, multicenter, randomized trial of antihypertensive treatment compared with standard care (no treatment unless severe hypertension developed) in pregnant patients with mild chronic hypertension (blood pressure 140-159/90-104 mm Hg before 20 weeks of gestation) and singleton pregnancies. We performed three comparisons based on medications prescribed at enrollment: labetalol compared with standard care, nifedipine compared with standard care, and labetalol compared with nifedipine. Although active compared with standard care …

Early And Late Complications Of Mandibulectomy Free Flap Reconstruction: Does The Selective Use Of Soft Tissue Only Flaps Reduce Complications?, Dylan B Mcbee, Michael J Dileo, Caroline C Keehn, Andrew T Huang, Angela D Haskins, David J Hernandez

Faculty, Staff and Students Publications

Purpose: This study aims to evaluate the factors most associated with early and late complications following microvascular free tissue transfer (MVFTT) after mandibulectomy.

Methods: A retrospective review of patients undergoing MVFTT after segmental mandibulectomy from September 2016 to February 2021 was performed across a single academic institution. Surgical variables were collected, including the location of the resultant mandibular defect (anterior vs posterior) and flap type (osseous or non-osseous). The primary outcome variables included postoperative complications (early, < 90 days; and late, >90 days) and the patients' functional status (return to oral intake). Descriptive statistics, chi-square test, Fischer's exact test, and 2-sample t tests were used …

Epigenetic Activation Of Sox11 Is Associated With Recurrence And Progression Of Ductal Carcinoma In Situ To Invasive Breast Cancer, Warapen Treekitkarnmongkol, Vandna Shah, Kazuharu Kai, Hiroshi Katayama, Justin Wong, Farah A Ladha, Tristian Nguyen, Brian Menegaz, Wei Lu, Fei Yang, Barbara Mino, Ximing Tang, Mihai Gagea, Harsh Batra, Maria Gabriela Raso, Ignacio I Wistuba, Savitri Krishnamurthy, Sarah E Pinder, Elinor J Sawyer, Alastair M Thompson, Subrata Sen

Faculty, Staff and Student Publications

Background: Risk of recurrence and progression of ductal carcinoma in situ (DCIS) to invasive cancer remains uncertain, emphasizing the need for developing predictive biomarkers of aggressive DCIS.

Methods: Human cell lines and mouse models of disease progression were analyzed for candidate risk predictive biomarkers identified and validated in two independent DCIS cohorts.

Results: RNA profiling of normal mammary and DCIS tissues (n = 48) revealed that elevated SOX11 expression correlates with MKI67, EZH2, and DCIS recurrence score. The 21T human cell line model of DCIS progression to invasive cancer and two mouse models developing mammary intraepithelial neoplasia confirmed the findings. …

Nfatc1 Is Required For Vitamin D- And Phosphate-Mediated Regulation Of Osteocyte Lacuno-Canalicular Remodeling, Supriya Jagga, Ashleigh Hughes, Niusha Manoochehri Arash, Melissa Sorsby, Daniel J Brooks, Paola Divieti Pajevic, Eva S Liu

Staff and Researcher Publications

Osteocytes are embedded in lacunae and connected by canaliculi (lacuno-canalicular network, LCN). Bones from mice with X-linked hypophosphatemia (Hyp), which have impaired production of 1,25 dihydroxyvitamin D (1,25D) and hypophosphatemia, have abnormal LCN structure that is improved by treatment with 1,25D or an anti-FGF23 targeting antibody, supporting roles for 1,25D and phosphate in regulating LCN remodeling. Bones from mice lacking the vitamin D receptor (VDR) in osteocytes (Vdrf/f;Dmp1Cre+) and mice lacking the sodium phosphate transporter 2a (Npt2aKO), which have low serum phosphate with high serum 1,25D, have impaired LCN organization, demonstrating that osteocyte-specific actions of 1,25D and hypophosphatemia regulate LCN …

The Saga Of Covid-19 In Chronic Lung Disease: History Repeats Itself, Amir Sharafkhaneh, Javad Razjouyan

Faculty, Staff and Students Publications

No abstract provided.