Medical Specialties Commons^™

Contemporary Approach To The Diagnosis And Classification Of Myelodysplastic Neoplasms/Syndromes-Recommendations From The International Consortium For Myelodysplastic Neoplasms/Syndromes (Mds [Icmds]), Fnu Aakash, Savanah D Gisriel, Amer M Zeidan, John M Bennett, Rafael Bejar, Jan Philipp Bewersdorf, Uma M Borate, Jacqueline Boultwood, Andrew M Brunner, Rena Buckstein, Hetty E Carraway, Jane E Churpek, Naval G Daver, Amy E Dezern, Fabio Efficace, Pierre Fenaux, Maria E Figueroa, Guillermo Garcia-Manero, Steven D Gore, Peter L Greenberg, Elizabeth A Griffiths, Stephanie Halene, Christopher S Hourigan, Tae Kon Kim, Nina Kim, Rami S Komrokji, Vijay K Kutchroo, Alan F List, Richard F Little, Ravindra Majeti, Aziz Nazha, Stephen D Nimer, Olatoyosi Odenike, Eric Padron, Mrinal M Patnaik, Uwe Platzbecker, Matteo G Della Porta, Gail J Roboz, David A Sallman, Valeria Santini, Guillermo Sanz, Michael R Savona, Mikkael A Sekeres, Maximilian Stahl, Daniel T Starczynowski, David P Steensma, Justin Taylor, Omar Abdel-Wahab, Andrew H Wei, Zhuoer Xie, Mina L Xu, Robert P Hasserjian, Sanam Loghavi

Faculty, Staff and Student Publications

Myelodysplastic neoplasms/syndromes (MDS) are a heterogeneous group of biologically distinct entities characterized by variable degrees of ineffective hematopoiesis. Recently, 2 classification systems (the 5th edition of the World Health Organization Classification of Haematolymphoid tTumours and the International Consensus Classification) further subcharacterized MDS into morphologically and genetically defined groups. Accurate diagnosis and subclassification of MDS require a multistep systemic approach. The International Consortium for MDS (icMDS) summarizes a contemporary, practical, and multimodal approach to MDS diagnosis and classification.

Early-Stage Extranodal Nk/T-Cell Lymphoma, Nasal Type: A Role For Elective Nodal Irradiation?, Penny Fang, Sonal S Noticewala, Susan Y Wu, Jillian R Gunther, Ethan B Ludmir, L Jeffrey Medeiros, Paolo Strati, Ranjit Nair, Chijioke Nze, Loretta J Nastoupil, Sairah Ahmed, Luis Malpica Castillo, Luis Fayad, Jason Westin, Sattva Neelapu, Christopher Flowers, Auris Huen, Swaminathan P Iyer, Bouthaina Dabaja, Chelsea C Pinnix

Faculty, Staff and Student Publications

Purpose: Extranodal NK/T-cell lymphoma (ENKTCL) is rare in the Western Hemisphere and is commonly treated with combined modality therapy (CMT).

Methods and materials: We retrospectively reviewed 35 patients treated with Ann Arbor stage I/II ENKTCL between 1994 and 2015 at a large academic cancer center in the United States.

Results: With 11.6 years median follow-up, median overall survival and progression-free survival were 13.5 and 7.5 years, respectively. Eighteen (51%) patients experienced disease relapse, with 5 regional nodal relapses, of which 2 experienced combined regional and distant relapses. All 5 regional nodal relapses occurred exclusively among patients not treated with elective …

Individual Dynamic Prediction For Cure And Survival Based On Longitudinal Biomarkers, Can Xie, Xuelin Huang, Ruosha Li, Alexander Tsodikov, Kapil Bhalla

Faculty, Staff and Student Publications

To optimize personalized treatment strategies and extend patients' survival times, it is critical to accurately predict patients' prognoses at all stages, from disease diagnosis to follow-up visits. The longitudinal biomarker measurements during visits are essential for this prediction purpose. Patients' ultimate concerns are cure and survival. However, in many situations, there is no clear biomarker indicator for cure. We propose a comprehensive joint model of longitudinal and survival data and a landmark cure model, incorporating proportions of potentially cured patients. The survival distributions in the joint and landmark models are specified through flexible hazard functions with the proportional hazards as …

Brain Gray Matter Changes In Children At Risk For Sudden Unexpected Death In Epilepsy, Bhaswati Roy, Jennifer A Ogren, Luke A Allen, Beate Diehl, Raman Sankar, Samden D Lhatoo, Rajesh Kumar, Ronald M Harper

Faculty, Staff and Student Publications

Background: Potential failing adult brain sites, stratified by risk, mediating Sudden Unexpected Death in Epilepsy (SUDEP) have been described, but are unknown in children.

Methods: We examined regional brain volumes using T1-weighted MRI images in 21 children with epilepsy at high SUDEP risk and 62 healthy children, together with SUDEP risk scores, calculated from focal seizure frequency. Gray matter tissue type was partitioned, maps normalized, smoothed, and compared between groups (SPM12; ANCOVA; covariates, age, sex, and BMI). Partial correlations between regional volumes and seizure frequency were examined (SPM12, covariates, age, sex, and BMI); 67% were at high risk for SUDEP. …

Occluder Device Removal And Total Septation Of "Swiss-Cheese" Ventricular Septal Defects, Andrew K Morse, Julija Dobrila, Damien J Lapar, Jorge D Salazar

Faculty, Staff and Student Publications

"Swiss-cheese" ventricular septal defects present complex treatment challenges. Despite difficult defect visualization and closure, complete septation is the treatment of choice. We present the case of a 2-year-old with residual apical "Swiss-cheese" ventricular septal defects after failed percutaneous device closure with 2 occluder devices. Surgical removal of 1 device and primary closure of the defects via right apical ventriculotomy resulted in successful complete septation.

Mortality Risks Associated With Depression In Men With Prostate Cancer, Casey Crump, Pär Stattin, James D Brooks, Jan Sundquist, Weiva Sieh, Kristina Sundquist

Faculty, Staff and Student Publications

Background: Men diagnosed with prostate cancer (PC) have an increased risk of depression; however, it is unclear to what extent depression affects long-term survival. A better understanding of such effects is needed to improve long-term care and outcomes for men with PC.

Objective: To determine the associations between major depression and mortality in a national cohort of men with PC.

Design, setting, and participants: A national cohort study was conducted of all 180 189 men diagnosed with PC in Sweden during 1998-2017. Subsequent diagnoses of major depression were ascertained from nationwide outpatient and inpatient records through 2018.

Outcome measurements and …

Adjuvant Rituximab And Elevated Intratumoural Cd8 Expression Are Associated With Sustained Disease Control After Radiotherapy In A Randomised Trial Of Systemic Therapy In Early-Stage Follicular Lymphoma, Michael P Macmanus, John F Seymour, Hennes Tsang, Richard Fisher, Colm Keane, Muhammed B Sabdia, Soi C Law, Jay Gunawardana, Karthik Nath, Stephen H Kazakoff, Mario L Marques-Piubelli, Daniela E Duenas, Michael R Green, Daniel Roos, Peter O'Brien, Andrew Mccann, Richard Tsang, Sidney Davis, David Christie, Chan Cheah, Benhur Amanuel, Tara Cochrane, Jason Butler, Anna Johnston, Mohamed Shanavas, Li Li, Claire Vajdic, Robert Kridel, Victoria Shelton, Samantha Hershenfield, Tara Baetz, David Lebrun, Nathalie Johnson, Marianne Brodtkorb, Maja Ludvigsen, Francesco D'Amore, Ella R Thompson, Piers Blombery, Maher K Gandhi, Joshua W D Tobin

Faculty, Staff and Student Publications

Background: We report extended follow-up of TROG99.03, a randomised phase III trial in early-stage follicular lymphoma (ESFL) including new information on the role of adjuvant rituximab and translational studies.

Methods: Patients with ESFL were randomised to involved field radiotherapy (IFRT) or IFRT plus 6-cycles cyclophosphamide/vincristine/prednisolone (IFRT + CVP). From 2006 rituximab was added to IFRT + CVP (IFRT + R-CVP). Clinical and multi-omic parameters were evaluated. Findings were validated in two independent ESFL cohorts (99 and 60 patients respectively).

Findings: Between 2000 and 2012, 150 (75 per arm) patients were recruited. 48% were positron emission tomography (PET)-staged. By protocol, at …

The Prognostic Impact Of Tumor Deposits In Colorectal Cancer: More Than Just N1c, Neal Bhutiani, Oliver Peacock, Abhineet Uppal, Chung-Yuan Hu, Brian K Bednarski, Melissa W Taggart, Arvind Dasari, Van K Morris, Harmeet Kaur, Scott Kopetz, Emma B Holliday, Prajnan Das, Y Nancy You, George J Chang

Faculty, Staff and Student Publications

Background: The identification of tumor deposits (TD) currently plays a limited role in staging for colorectal cancer (CRC) aside from N1c lymph node designation. The objective of this study was to determine the prognostic impact, beyond American Joint Committee on Cancer N1c designation, of TDs among patients with primary CRC.

Methods: Patients who had resected stage I-III primary CRC diagnosed between 2010 and 2019 were identified from the National Cancer Institute's Surveillance, Epidemiology, and End Results database. Cancer-specific survival (CSS) stratified by TD status and lymph node (N) status was calculated using the Kaplan-Meier method and multivariable Cox proportional hazards …

Mimosa: A Resource Consisting Of Improved Methylome Prediction Models Increases Power To Identify Dna Methylation-Phenotype Associations, Hunter J Melton, Zichen Zhang, Hong-Wen Deng, Lang Wu, Chong Wu

Faculty, Staff and Student Publications

Although DNA methylation (DNAm) has been implicated in the pathogenesis of numerous complex diseases, from cancer to cardiovascular disease to autoimmune disease, the exact methylation sites that play key roles in these processes remain elusive. One strategy to identify putative causal CpG sites and enhance disease etiology understanding is to conduct methylome-wide association studies (MWASs), in which predicted DNA methylation that is associated with complex diseases can be identified. However, current MWAS models are primarily trained using the data from single studies, thereby limiting the methylation prediction accuracy and the power of subsequent association studies. Here, we introduce a new …

Normal Breast Tissues Harbour Rare Populations Of Aneuploid Epithelial Cells, Yiyun Lin, Junke Wang, Kaile Wang, Shanshan Bai, Aatish Thennavan, Runmin Wei, Yun Yan, Jianzhuo Li, Heba Elgamal, Emi Sei, Anna Casasent, Mitchell Rao, Chenling Tang, Asha S Multani, Jin Ma, Jessica Montalvan, Chandandeep Nagi, Sebastian Winocour, Bora Lim, Alastair Thompson, Nicholas Navin

Faculty, Staff and Student Publications

Aneuploid epithelial cells are common in breast cancer

Wirelessly Actuated Microfluidic Pump And Valve For Controlled Liquid Delivery In Dental Implants, Yilan Xu, Honglu Lin, Boyang Xiao, Hutomo Tanoto, Joel Berinstein, Alend Khoshnaw, Simon Young, Yuxiao Zhou, Xiaoguang Dong

Faculty, Staff and Student Publications

Enabling minimally invasive and precise control of liquid release in dental implants is crucial for therapeutic functions such as delivering antibiotics to prevent biofilm formation, infusing stem cells to promote osseointegration, and administering other biomedicines. However, achieving controllable liquid cargo release in dental implants remains challenging due to the lack of wireless and miniaturized fluidic control mechanisms. Here wireless miniature pumps and valves that allow remote activation of liquid cargo delivery in dental implants, actuated and controlled by external magnetic fields (< 65 mT), are reported. A magnet-screw mechanism in a fluidic channel to function as a piston pump, alongside a flexible magnetic valve designed to open and close the fluidic channel, is proposed. The mechanisms are showcased by storing and releasing of liquid up to 52 µL in a dental implant. The liquid cargos are delivered directly to the implant-bone interface, a region traditionally difficult to access. On-demand liquid delivery is further showed by a metal implant inside both dental phantoms and porcine jawbones. The mechanisms are promising for controllable liquid release after implant placement with minimal invasion, paving the way for implantable devices that enable long-term and targeted delivery of therapeutic agents in various bioengineering applications.

Engineering Immunity: Bacterial Delivery Of Cancer Neoantigen Vaccines, Christopher D Johnston, Jennifer A Wargo

Faculty, Staff and Student Publications

In the battle against cancer, researchers are exploring the use of engineered bacteria as living medicines. Redenti and colleagues demonstrate that Escherichia coli Nissle 1917 (EcN) can be engineered to deliver cancer neoantigen payloads, stimulating antigen-specific CD4+ and CD8+ T cells and mediating antitumor immunity in preclinical models of colorectal cancer and melanoma.

Neurocognitive Functioning Of Patients With Sinonasal And Nasopharyngeal Cancers Treated With Multimodality Therapy, Dan Yaniv, Lindsay M Niccolai, Jeffrey S Wefel, Catherine M Sullaway, Jack Phan, Clifton David Fuller, Kareem B Haroun, Ehab Y Hanna, Shirley Y Su

Faculty, Staff and Student Publications

Importance Few recent studies have examined neurocognitive functioning (NCF) in patients with sinonasal and nasopharyngeal cancers (NPCs) prior to and following multimodality therapy or the potential differences in NCF by disease variables such as disease site.

Objective The objective of this study is to determine rates of NCF impairments prior to and following multimodality therapy, declines in NCF following radiotherapy (RT), and possible differences in NCF by the disease site.

Design, Setting, and Participants We conducted a retrospective chart review of 39 patients with sinonasal and NPCs who underwent comprehensive neuropsychological evaluations. Twenty patients were evaluated prior to RT, of …

The Life And Discoveries Of Yellapragada Subbarow, Nikhil R, Varuni Pragya, Subramanian Ramaswamy, Shiva Prasad B N, Mahabaleshwar Mamadapur

Digital Journal of Clinical Medicine

Dr. Yellapragada Subbarow was a researcher, teacher, and a wizard of wonder drugs who constantly made efforts in the discoveries/ inventions such as vitamins, anti-vitamins, antibiotics, and many more by disentangling the mysteries of nature for the betterment of the people. He inspired the youngsters to take up the challenges and to stand up above mediocrity. The reward for his achievement was delayed. The article describes a true humanist's journey, discoveries, and his achievements that are largely unknown to date.

Prevalence, Diagnostic Features, And Medical Outcomes Of Females With Turner Syndrome With A Trisomy X Cell Line (45, X/47, Xxx): Results From The Insights Registry, Natalia Klamut, Samantha Bothwell, Alexandra E Carl, Vaneeta Bamba, Jennifer R Law, Wendy J Brickman, Karen O Klein, Roopa Kanakatti Shankar, Catherina T Pinnaro, Patricia Y Fechner, Siddharth K Prakash, Iris Gutmark-Little, Susan Howell, Nicole Tartaglia, Marybel Good, Kelly C Ranallo, Shanlee M Davis

Faculty, Staff and Student Publications

Turner syndrome (TS) is defined by partial or complete absence of a sex chromosome. Little is known about the phenotype of individuals with TS mosaic with trisomy X (45,X/47,XXX or 45,X/46,XX/47,XXX) (~3% of TS). We compared the diagnostic, perinatal, medical, and neurodevelopmental comorbidities of mosaic 45,X/47,XXX (n = 35, 9.4%) with nonmosaic 45,X (n = 142) and mosaic 45,X/46,XX (n = 66). Females with 45,X/47,XXX had fewer neonatal concerns and lower prevalence of several TS-related diagnoses compared with 45,X; however the prevalence of neurodevelopmental and psychiatric diagnoses were not different. Compared to females with 45,X/46,XX, the 45,X/47,XXX group was significantly …

Vitamin D In Patients With Low Tumor-Burden Indolent Non-Hodgkin Lymphoma Treated With Rituximab Therapy (Ilyad): A Randomized, Phase 3 Clinical Trial, Jonathan W Friedberg, Michael T Brady, Myla Strawderman, Brad S Kahl, Izidore S Lossos, Jonathon B Cohen, Patrick M Reagan, Carla Casulo, Barbara L Averill, Andrea Baran, Grerk Sutamtewagul, Paul M Barr, John P Leonard, John M Ashton, John G Strang, Francisco Vega, Derick R Peterson, Loretta J Nastoupil

Faculty, Staff and Student Publications

Background: There is a significant association between low vitamin D levels at diagnosis of indolent B-cell lymphomas and inferior overall survival (OS). To determine whether supplemental vitamin D improves event-free survival (EFS) in these patients, we conducted a comparative double-blind study of vitamin D3 vs. placebo.

Methods: In this phase 3, randomized, double-blind, placebo-controlled trial, patients with low tumor burden follicular, marginal zone or small lymphocytic lymphoma, age 18 or older, with stage two or greater disease and no prior systemic treatment were enrolled at 7 academic cancer centers. Patients were stratified by histology and FLIPI (Follicular Lymphoma International Prognostic …

Antiangiogenic Therapy Combined With Immune Checkpoint Blockade In Urothelial Cancer: Systematic Review And Meta-Analysis, Mohammad Jad Moussa, Iuliia Kovalenko, Emanuele Crupi, Ekaterina Proskuriakova, Yimin Geng, Giuseppe Fallara, Raed Benkhadra, Daniele Raggi, Matthew T Campbell, Pavlos Msaouel, Omar Alhalabi

Faculty, Staff and Student Publications

Background: Antiangiogenic therapy had been tested in urothelial cancer (UC) without reaching the clinic.

Objective: We provide a systematic review and meta-analysis of trials to assess efficacy of immune checkpoint inhibitors (ICI) combined with antiangiogenic agents in UC.

Methods: Following PRISMA guidelines, we searched for trials with at least one arm of patients with UC treated with ICI plus antiangiogenics. Data were analyzed with the "meta" package from R using a one-staged frequentist meta-analysis.

Results: After screening 13,708 titles and abstracts, 9 studies were selected for analysis with 14 identified cohorts comprising 621 patients: 448 were ICI-naïve (ICI-N) and 173 …

Early-Stage Extranodal Nk/T-Cell Lymphoma, Nasal Type: A Role For Elective Nodal Irradiation?, Penny Fang, Sonal S Noticewala, Susan Y Wu, Jillian R Gunther, Ethan B Ludmir, L Jeffrey Medeiros, Paolo Strati, Ranjit Nair, Chijioke Nze, Loretta J Nastoupil, Sairah Ahmed, Luis Malpica Castillo, Luis Fayad, Jason Westin, Sattva Neelapu, Christopher Flowers, Auris Huen, Swaminathan P Iyer, Bouthaina Dabaja, Chelsea C Pinnix

Faculty, Staff and Student Publications

Purpose: Extranodal NK/T-cell lymphoma (ENKTCL) is rare in the Western Hemisphere and is commonly treated with combined modality therapy (CMT).

Methods and materials: We retrospectively reviewed 35 patients treated with Ann Arbor stage I/II ENKTCL between 1994 and 2015 at a large academic cancer center in the United States.

Results: With 11.6 years median follow-up, median overall survival and progression-free survival were 13.5 and 7.5 years, respectively. Eighteen (51%) patients experienced disease relapse, with 5 regional nodal relapses, of which 2 experienced combined regional and distant relapses. All 5 regional nodal relapses occurred exclusively among patients not treated with elective …

Low Intensity Mechanical Signals Promote Proliferation In A Cell-Specific Manner: Tailoring A Non-Drug Strategy To Enhance Biomanufacturing Yields, M Ete Chan, Christopher Ashdown, Lia Strait, Sishir Pasumarthy, Abdullah Hassan, Steven Crimarco, Chanpreet Singh, Vihitaben S Patel, Gabriel Pagnotti, Omor Khan, Gunes Uzer, Clinton T Rubin

Faculty, Staff and Student Publications

Biomanufacturing relies on living cells to produce biotechnology-based therapeutics, tissue engineering constructs, vaccines, and a vast range of agricultural and industrial products. With the escalating demand for these bio-based products, any process that could improve yields and shorten outcome timelines by accelerating cell proliferation would have a significant impact across the discipline. While these goals are primarily achieved using biological or chemical strategies, harnessing cell mechanosensitivity represents a promising - albeit less studied - physical pathway to promote bioprocessing endpoints, yet identifying which mechanical parameters influence cell activities has remained elusive. We tested the hypothesis that mechanical signals, delivered non-invasively …

Constructing Phylogenetic Trees For Microbiome Data Analysis: A Mini-Review, Ruitao Liu, Xi Qiao, Yushu Shi, Christine B Peterson, William S Bush, Fabio Cominelli, Ming Wang, Liangliang Zhang

Faculty, Staff and Student Publications

As next-generation sequencing technologies advance rapidly and the cost of metagenomic sequencing continues to decrease, researchers now face an unprecedented volume of microbiome data. This surge has stimulated the development of scalable microbiome data analysis methods and necessitated the incorporation of phylogenetic information into microbiome analysis for improved accuracy. Tools for constructing phylogenetic trees from 16S rRNA sequencing data are well-established, as the highly conserved regions of the 16S gene are limited, simplifying the identification of marker genes. In contrast, metagenomic and whole genome shotgun (WGS) sequencing involve sequencing from random fragments of the entire gene, making identification of consistent …

Healthcare Disparities, Screening, And Molecular Testing In The Changing Landscape Of Non-Small Cell Lung Cancer In The United States: A Review, Razelle Kurzrock, Aadel A Chaudhuri, David Feller-Kopman, Narjust Florez, Jed Gorden, Ignacio I Wistuba

Faculty, Staff and Student Publications

Inequitable access to care continues to hinder improvements in diagnosis and treatment of lung cancer. This review describes healthcare disparities in the changing landscape of non-small cell lung cancer (NSCLC) in the United States, focusing on racial, ethnic, sex-based, and socioeconomic trends. Furthermore, strategies to address disparities, overcome challenges, and improve patient outcomes are proposed. Barriers exist across lung cancer screening, diagnosis, and treatment regimens, varying by sex, age, race and ethnicity, geography, and socioeconomic status. Incidence and mortality rates of lung cancer are higher among Black men than White men, and incidences in young women are substantially greater than …

Artificial Intelligence Uncertainty Quantification In Radiotherapy Applications – A Scoping Review, Kareem A Wahid, Zaphanlene Y Kaffey, David P Farris, Laia Humbert-Vidan, Amy C Moreno, Mathis Rasmussen, Jintao Ren, Mohamed A Naser, Tucker J Netherton, Stine Korreman, Guha Balakrishnan, Clifton D Fuller, David Fuentes, Michael J Dohopolski

Faculty, Staff and Student Publications

Background/purpose: The use of artificial intelligence (AI) in radiotherapy (RT) is expanding rapidly. However, there exists a notable lack of clinician trust in AI models, underscoring the need for effective uncertainty quantification (UQ) methods. The purpose of this study was to scope existing literature related to UQ in RT, identify areas of improvement, and determine future directions.

Methods: We followed the PRISMA-ScR scoping review reporting guidelines. We utilized the population (human cancer patients), concept (utilization of AI UQ), context (radiotherapy applications) framework to structure our search and screening process. We conducted a systematic search spanning seven databases, supplemented by manual …

Systemic Sirolimus Therapy Is Associated With Reduced Intervention Frequency In Pulmonary Vein Stenosis, Alyssa B Kalustian, Joseph L Hagan, Paige E Brlecic, Ionela Iacobas, Rachel D Vanderlaan, Joseph Burns, Thao T Wu, Ravi Birla, Sharada Gowda, Manish Bansal, Srinath T Gowda, Lindsay F Eilers, Asra Khan, Juan Pablo Sandoval-Jones, Michiaki Imamura, Yishay Orr, Christopher A Caldarone, Athar M Qureshi

Faculty, Staff and Students Publications

BACKGROUND: Early clinical outcomes data for adjunctive systemic sirolimus therapy (SST) for moderate to severe pediatric pulmonary vein stenosis (PVS) are promising but limited.

OBJECTIVES: The authors aimed to characterize a cohort of patients treated with SST to determine if SST was associated with a reduction in frequency of PVS interventions.

METHODS: Medical records of 45 patients with PVS treated with SST for ≥1 month from 2015 to 2022 were retrospectively reviewed. PVS intervention rates pre-SST and on-SST were compared using generalized Poisson mixed models, accounting for paired intervals within each patient. In addition to an unadjusted model, an adjusted …

Lenvatinib Plus Ifosfamide And Etoposide In Children And Young Adults With Relapsed Osteosarcoma: A Phase 2 Randomized Clinical Trial, Nathalie Gaspar, Giun-Yi Hung, Sandra J Strauss, Quentin Campbell-Hewson, Filemon S Dela Cruz, Julia L Glade Bender, Kyung-Nam Koh, Sarah B Whittle, Godfrey Chi-Fung Chan, Nicolas U Gerber, Sauli Palmu, Daniel A Morgenstern, Alessandra Longhi, Fredrik Baecklund, Jun Ah Lee, Franco Locatelli, Catalina Márquez Vega, Katherine A Janeway, Geoffrey Mccowage, Martin G Mccabe, Behzad Bidadi, Jie Huang, Jodi Mckenzie, Chinyere E Okpara, Francisco Bautista, Olie Study Investigators

Faculty, Staff and Students Publications

IMPORTANCE: The combination of ifosfamide and etoposide (IE) is commonly used to treat relapsed or refractory osteosarcoma; however, second-line treatment recommendations vary across guidelines.

OBJECTIVE: To evaluate whether the addition of lenvatinib to IE (LEN-IE) improves outcomes in children and young adults with relapsed or refractory osteosarcoma.

DESIGN, SETTING, AND PARTICIPANTS: The OLIE phase II, open-label, randomized clinical trial was conducted globally across Europe, Asia and the Pacific, and North America. From March 22, 2020, through November 11, 2021, the trial enrolled patients aged 2 to 25 years with high-grade osteosarcoma, measurable or evaluable disease per Response Evaluation Criteria in …

Aging-Associated Mechanisms Of Atrial Fibrillation Progression And Their Therapeutic Potential, Shuai Zhao, Aaron M Johnston, Chi Him Kendrick Yiu, Lucia M Moreira, Svetlana Reilly, Xander H T Wehrens

Faculty, Staff and Students Publications

Atrial fibrillation (AF) is the most common sustained arrhythmia, with a particularly high prevalence in the elderly. As the global aging population rapidly expands, it is increasingly important to examine how alterations to the aging heart contribute to an increased AF susceptibility. This work critically reviews the key molecular mechanisms that may underpin the complex association between aging and AF. Moreover, we identify emerging novel opportunities for therapeutic intervention that may be able to prevent and/or improve the current treatment paradigms for age-related AF. This review contributes to a holistic understanding of the intricate relationship between aging and AF.

Improved Robustness For Deep Learning-Based Segmentation Of Multi-Center Myocardial Perfusion Cardiovascular Mri Datasets Using Data-Adaptive Uncertainty-Guided Space-Time Analysis., Dilek M Yalcinkaya, Khalid Youssef, Bobak Heydari, Janet Wei, C Noel Bairey Merz, Robert Judd, Rohan Dharmakumar, Orlando P Simonetti, Jonathan W Weinsaft, Subha V Raman, Behzad Sharif

Heart and Vascular Articles

BACKGROUND: Fully automatic analysis of myocardial perfusion cardiovascular magnetic resonance imaging datasets enables rapid and objective reporting of stress/rest studies in patients with suspected ischemic heart disease. Developing deep learning techniques that can analyze multi-center datasets despite limited training data and variations in software (pulse sequence) and hardware (scanner vendor) is an ongoing challenge.

METHODS: Datasets from three medical centers acquired at 3T (n = 150 subjects; 21,150 first-pass images) were included: an internal dataset (inD; n = 95) and two external datasets (exDs; n = 55) used for evaluating the robustness of the trained deep neural network (DNN) models …

Microbiota-Gut-Brain Axis In Psychiatry: Focus On Depressive Disorders, I-Ching Wang, Shelly A Buffington, Ramiro Salas

Faculty, Staff and Students Publications

Purpose of review: Gut microbiota contribute to several physiological processes in the host. The composition of the gut microbiome is associated with different neurological and neurodevelopmental diseases. In psychiatric disease, stress may be a major factor leading to gut microbiota alterations. Depressive disorders are the most prevalent mental health issues worldwide and patients often report gastrointestinal symptoms. Accordingly, evidence of gut microbial alterations in depressive disorders has been growing. Here we review current literature revealing links between the gut microbiome and brain function in the context of depression.

Recent findings: The gut-brain axis could impact the behavioral manifestation of depression …

Excellent Registry: A Prospective, Multicenter, Global Registry Of Endovascular Stroke Treatment With The Embotrap Device., Raul G Nogueira, Tommy Andersson, Diogo C Haussen, Albert J Yoo, Ricardo A Hanel, Osama O Zaidat, Werner Hacke, Tudor G Jovin, Jens Fiehler, Simon F De Meyer, Waleed Brinjikji, Karen M Doyle, David F Kallmes, David S Liebeskind, Renu Virmani, Malgosia A Kokoszka, Violiza Inoa, William Humphries, Keith B Woodward, Pascal M Jabbour, Olivier François, Elad I Levy, Hormozd Bozorgchami, Stephan Boor, Jose E Cohen, Shervin R Dashti, Muhammad A Taqi, Ronald F Budzik, Clemens M Schirmer, M Shazam Hussain, Laurent Estrade, Reade A De Leacy, Ajit S Puri, Rohan V Chitale, Caspar Brekenfeld, Adnan H Siddiqui

Neuroscience Articles

BACKGROUND: The EXCELLENT registry aimed to evaluate the effectiveness of the EMBOTRAP Revascularization Device in an all-comer population in a real-world setting, with a focus on the composition of retrieved clots.

METHODS: EXCELLENT is a prospective, global registry of patients with acute ischemic stroke treated with EMBOTRAP as the first-line mechanical thrombectomy device conducted at 34 sites (25 sites contributing clot) from September 2018 to March 2021, utilizing core imaging and central histology laboratories blinded to clinical data, independent 90-day modified Rankin Scale assessment and Clinical Events Committee.

RESULTS: After screening 3799 patients, a total of 997 subjects (mean age, …

Immunopeptidomic Mhc-I Profiling And Immunogenicity Testing Identifies Tcj2 As A New Chagas Disease Mrna Vaccine Candidate, Leroy Versteeg, Rakesh Adhikari, Gonteria Robinson, Jungsoon Lee, Junfei Wei, Nelufa Islam, Brian Keegan, William K Russell, Cristina Poveda, Maria Jose Villar, Kathryn Jones, Maria Elena Bottazzi, Peter Hotez, Edwin Tijhaar, Jeroen Pollet

Faculty, Staff and Students Publications

Trypanosoma cruzi is a protozoan parasite that causes Chagas disease. Globally 6 to 7 million people are infected by this parasite of which 20-30% will progress to develop Chronic Chagasic Cardiomyopathy (CCC). Despite its high disease burden, no clinically approved vaccine exists for the prevention or treatment of CCC. Developing vaccines that can stimulate T. cruzi-specific CD8+ cytotoxic T cells and eliminate infected cells requires targeting parasitic antigens presented on major histocompatibility complex-I (MHC-I) molecules. We utilized mass spectrometry-based immunopeptidomics to investigate which parasitic peptides are displayed on MHC-I of T. cruzi infected cells. Through duplicate experiments, we identified an …

Families’ Experiences Accessing Care After Genomic Sequencing In The Pediatric Cancer Context: “It’S Just Been A Big Juggle”, Blake Vuocolo, Amanda M Gutierrez, Jill O Robinson, Alva M Recinos, Lauren R Desrosiers, Mary A Majumder, Juan Carlos Bernini, Jonathan Gill, Timothy Griffin, Gail E Tomlinson, Kelly Vallance, Amy L Mcguire, D Williams Parsons, Sharon E Plon, Sarah Scollon

Faculty, Staff and Students Publications

Access to genomic sequencing (GS) and resulting recommendations have not been well described in pediatric oncology. GS results may provide a cancer predisposition syndrome (CPS) diagnosis that warrants screening and specialist visits beyond cancer treatment, including testing or surveillance for family members. The Texas KidsCanSeq (KCS) Study evaluated implementation of GS in a diverse pediatric oncology population. We conducted semi-structured interviews (n = 20) to explore experiences of KCS patients' families around learning about a CPS diagnosis and following up on recommended care. We used qualitative content analysis to develop themes and subthemes across families' descriptions of their experiences accessing …