Medicine and Health Sciences Commons^™

Clinical Relevance Of Myc/Bcl2 Expression And Cell Of Origin In Patients With Diffuse Large B-Cell Lymphoma Treated With Autologous Transplant, Taha Al-Juhaishi, Yingjun Wang, Denái R Milton, Zijun Y Xu-Monette, Elias Jabbour, May Daher, Jin S Im, Qaiser Bashir, Swaminathan P Iyer, David Marin, Amanda L Olson, Uday Popat, Muzaffar Qazilbash, Gabriela Rondon, Alison M Gulbis, Richard E Champlin, Ken H Young, Issa F Khouri

Faculty, Staff and Student Publications

Dual expression of MYC and BCL2 proteins (double-expressor lymphoma [DEL]) as well as cell of origin (COO) are important prognostic factors in patients with diffuse large B-cell lymphoma (DLBCL) after conventional chemotherapy. We studied the prognostic impact of DEL and COO in patients with relapsed DLBCL treated with autologous stem cell transplant (ASCT). Three-hundred and three patients with stored tissue samples were identified. Classification was successful in 267 patients: 161 (60%) were DEL/non-double hit (DHL), 98 (37%) were non-DEL/non-DHL, and 8 (3%) were DEL/DHL. Compared to non-DEL/non-DHL, DEL/DHL had worse overall survival while DEL/non-DHL did not significantly differ in overall …

Gut Oncomicrobiome Signatures (Goms) As Next-Generation Biomarkers For Cancer Immunotherapy, Andrew Maltez Thomas, Marine Fidelle, Bertrand Routy, Guido Kroemer, Jennifer A Wargo, Nicola Segata, Laurence Zitvogel

Faculty, Staff and Student Publications

Oncogenesis is associated with intestinal dysbiosis, and stool shotgun metagenomic sequencing in individuals with this condition might constitute a non-invasive approach for the early diagnosis of several cancer types. The prognostic relevance of antibiotic intake and gut microbiota composition urged investigators to develop tools for the detection of intestinal dysbiosis to enable patient stratification and microbiota-centred clinical interventions. Moreover, since the advent of immune-checkpoint inhibitors (ICIs) in oncology, the identification of biomarkers for predicting their efficacy before starting treatment has been an unmet medical need. Many previous studies addressing this question, including a meta-analysis described herein, have led to the …

Efficacy Of Immune Checkpoint Inhibitors For The Treatment Of Advanced Melanoma In Patients With Concomitant Chronic Lymphocytic Leukemia, S H Cass, J W D Tobin, Y D Seo, G Gener-Ricos, E Z Keung, E M Burton, M A Davies, J L Mcquade, A J Lazar, R Mason, M Millward, S Sandhu, C Khoo, L Warburton, V Guerra, A Haydon, H Dearden, A M Menzies, M S Carlino, J L Smith, P Mollee, M Burgess, S Mapp, C Keane, V Atkinson, S A Parikh, S N Markovic, W Ding, T G Call, P J Hampel, G V Long, J A Wargo, A Ferrajoli

Faculty, Staff and Student Publications

BACKGROUND: Immune checkpoint inhibitors (ICIs) have revolutionized the management of advanced melanoma (AM). However, data on ICI effectiveness have largely been restricted to clinical trials, thereby excluding patients with co-existing malignancies. Chronic lymphocytic leukemia (CLL) is the most prevalent adult leukemia and is associated with increased risk of melanoma. CLL alters systemic immunity and can induce T-cell exhaustion, which may limit the efficacy of ICIs in patients with CLL. We, therefore, sought to examine the efficacy of ICI in patients with these co-occurring diagnoses.

PATIENTS AND METHODS: In this international multicenter study, a retrospective review of clinical databases identified patients …

Cell Entry And Release Of Quasi-Enveloped Human Hepatitis Viruses, Anshuman Das, Efraín E Rivera-Serrano, Xin Yin, Christopher M Walker, Zongdi Feng, Stanley M Lemon

Faculty, Staff and Student Publications

Infectious hepatitis type A and type E are caused by phylogenetically distinct single-stranded, positive-sense RNA viruses that were once considered to be non-enveloped. However, studies show that both are released nonlytically from hepatocytes as 'quasi-enveloped' virions cloaked in host membranes. These virion types predominate in the blood of infected individuals and mediate virus spread within the liver. They lack virally encoded proteins on their surface and are resistant to neutralizing anti-capsid antibodies induced by infection, yet they efficiently enter cells and initiate new rounds of virus replication. In this Review, we discuss the mechanisms by which specific peptide sequences in …

Time For Bugs: The Immune Microenvironment And Microbes In Precancer, Mikayla Borthwick Bowen, Beth A Helmink, Jennifer A Wargo, Melinda S Yates

Faculty, Staff and Student Publications

Major advances in our understanding of the tumor immune microenvironment (TIME) in established cancer have been made, including the influence of host-intrinsic (host genomics) and -extrinsic factors (such as diet and the microbiome) on treatment response. Nonetheless, the immune and microbiome milieu across the spectrum of precancerous tissue and early neoplasia is a growing area of interest. There are emerging data describing the contribution of the immune microenvironment and microbiota on benign and premalignant tissues, with opportunities to target these factors in cancer prevention and interception. Throughout this review, we provide rationale for not only the critical need to further …

A Transformer-Based Hierarchical Registration Framework For Multimodality Deformable Image Registration, Yao Zhao, Xinru Chen, Brigid Mcdonald, Cenji Yu, Abdalah S R Mohamed, Clifton D Fuller, Laurence E Court, Tinsu Pan, He Wang, Xin Wang, Jack Phan, Jinzhong Yang

Faculty, Staff and Student Publications

Deformable image registration (DIR) between daily and reference images is fundamentally important for adaptive radiotherapy. In the last decade, deep learning-based image registration methods have been developed with faster computation time and improved robustness compared to traditional methods. However, the registration performance is often degraded in extra-cranial sites with large volume containing multiple anatomic regions, such as Computed Tomography (CT)/Magnetic Resonance (MR) images used in head and neck (HN) radiotherapy. In this study, we developed a hierarchical deformable image registration (DIR) framework, Patch-based Registration Network (Patch-RegNet), to improve the accuracy and speed of CT-MR and MR-MR registration for head-and-neck MR-Linac …

Bayesian Hierarchical Quantile Regression With Application To Characterizing The Immune Architecture Of Lung Cancer, Priyam Das, Christine B Peterson, Yang Ni, Alexandre Reuben, Jiexin Zhang, Jianjun Zhang, Kim-Anh Do, Veerabhadran Baladandayuthapani

Faculty, Staff and Student Publications

The successful development and implementation of precision immuno-oncology therapies requires a deeper understanding of the immune architecture at a patient level. T-cell receptor (TCR) repertoire sequencing is a relatively new technology that enables monitoring of T-cells, a subset of immune cells that play a central role in modulating immune response. These immunologic relationships are complex and are governed by various distributional aspects of an individual patient's tumor profile. We propose Bayesian QUANTIle regression for hierarchical COvariates (QUANTICO) that allows simultaneous modeling of hierarchical relationships between multilevel covariates, conducts explicit variable selection, estimates quantile and patient-specific coefficient effects, to induce individualized …

Spatially-Aware Clustering Improves Ajcc-8 Risk Stratification Performance In Oropharyngeal Carcinomas, Guadalupe Canahuate, Andrew Wentzel, Abdallah S R Mohamed, Lisanne V Van Dijk, David M Vock, Baher Elgohari, Hesham Elhalawani, Clifton D Fuller, G Elisabeta Marai

Faculty, Staff and Student Publications

OBJECTIVE: Evaluate the effectiveness of machine learning tools that incorporate spatial information such as disease location and lymph node metastatic patterns-of-spread, for prediction of survival and toxicity in HPV+ oropharyngeal cancer (OPC).

MATERIALS & METHODS: 675 HPV+ OPC patients that were treated at MD Anderson Cancer Center between 2005 and 2013 with curative intent IMRT were retrospectively collected under IRB approval. Risk stratifications incorporating patient radiometric data and lymph node metastasis patterns via an anatomically-adjacent representation with hierarchical clustering were identified. These clusterings were combined into a 3-level patient stratification and included along with other known clinical features in a …

Interleukin-10 In Cancer Immunotherapy: From Bench To Bedside, Mohamad Adham Salkeni, Aung Naing

Faculty, Staff and Student Publications

Interleukin (IL)-10 was one of the first cytokines to be recognized. However, its functionality in promoting antitumor immunity was described more recently. Context- and concentration-dependent biological effects are the hallmarks of the pleiotropic role of IL-10. Despite reducing tumor-promoting inflammation, IL-10 may have a role in rejuvenating exhausted tumor-resident T cells. Contrary to the assumption that IL-10 produces an immunosuppressive tumor microenvironment (TME), it promotes activation of tumor-resident CD8+ T cells, which aids tumor rejection. Emerging data from published early-Phase trials have shown mixed results in different tumor types. In this review, we summarize the biological effects of IL-10 and …

Emotional Distress And Cardiovascular Disease Risk Among Participants Enrolled In The Glycemia Reduction Approaches In Diabetes: A Comparative Effectiveness (Grade) Study, Gladys Crespo-Ramos, Ionut Bebu, Heidi Krause-Steinrauf, Claire J Hoogendoorn, Ran Fang, Dominic Ehrmann, Caroline Presley, Aanand D Naik, Aimee Katona, Elizabeth A Walker, Andrea Cherrington, Jeffrey S Gonzalez

Faculty, Staff and Student Publications

AIMS: People with type 2 diabetes (T2DM) have an increased risk of cardiovascular disease (CVD). We examined depressive symptoms (DS) and diabetes distress (DD) in relation to the estimated 10-year risk of CVD in adults with T2DM enrolled in the GRADE Emotional Distress Substudy.

METHODS: Linear regression models examined the associations of baseline DS and DD with estimated 10-year risk of CVD using the Atherosclerotic Cardiovascular Disease (ASCVD) risk score, adjusting for age, sex, race/ethnicity, education, income, diabetes duration, diabetes-related complications, and HbA1c.

RESULTS: A total of 1,605 GRADE participants were included: 54% Non-Latino (NL) White, 18% Latino, 19% NL-Black, …

Prediagnostic Glycoprotein Acetyl Levels And Incident And Recurrent Flare Risk Accounting For Serum Urate Levels: A Population-Based, Prospective Study And Mendelian Randomization Analysis, Amit D Joshi, Natalie Mccormick, Chio Yokose, Bing Yu, Adrienne Tin, Robert Terkeltaub, Tony R Merriman, A Heather Eliassen, Gary C Curhan, Laura M Raffield, Hyon K Choi

Faculty, Staff and Student Publications

OBJECTIVE: To prospectively investigate population-based metabolomics for incident gout and reproduce the findings for recurrent flares, accounting for serum urate.

METHODS: We conducted a prediagnostic metabolome-wide analysis among 105,615 UK Biobank participants with nuclear magnetic resonance metabolomic profiling data (168 total metabolites) from baseline blood samples collected 2006-2010 in those without history of gout. We calculated hazard ratios (HRs) for incident gout, adjusted for gout risk factors, excluding and including serum urate levels, overall and according to fasting duration before sample collection. Potential causal effects were tested with 2-sample Mendelian randomization. Poisson regression was used to calculate rate ratios (RRs) …

Exceptional Responses To Selpercatinib In Ret-Fusion Driven Metastatic Pancreatic Cancer, Deepak Bhamidipati, Sireesha Yedururi, Jason Huse, Sri Veda Chinapuvvula, Jie Wu, Vivek Subbiah

Faculty, Staff and Student Publications

No abstract provided.

Ras Gtpases And Interleaflet Coupling In The Plasma Membrane, Junchen Liu, Neha Arora, Yong Zhou

Faculty, Staff and Student Publications

RAS genes are frequently mutated in cancer. The primary signaling compartment of wild-type and constitutively active oncogenic mutant RAS proteins is the inner leaflet of the plasma membrane (PM). Thus, a better understanding of the unique environment of the PM inner leaflet is important to shed further light on RAS function. Over the past few decades, an integrated approach of superresolution imaging, molecular dynamic simulations, and biophysical assays has yielded new insights into the capacity of RAS proteins to sort lipids with specific headgroups and acyl chains, to assemble signaling nanoclusters on the inner PM. RAS proteins also sense and …

Epigenome-Wide Dna Methylation Association Study Of Circulating Ige Levels Identifies Novel Targets For Asthma, Kathryn Recto, Priyadarshini Kachroo, Tianxiao Huan, David Van Den Berg, Gha Young Lee, Helena Bui, Dong Heon Lee, Jessica Gereige, Chen Yao, Shih-Jen Hwang, Roby Joehanes, Scott T Weiss, George T O'Connor, Daniel Levy, Dawn L Demeo

Faculty, Staff and Student Publications

BACKGROUND: Identifying novel epigenetic signatures associated with serum immunoglobulin E (IgE) may improve our understanding of molecular mechanisms underlying asthma and IgE-mediated diseases.

METHODS: We performed an epigenome-wide association study using whole blood from Framingham Heart Study (FHS; n = 3,471, 46% females) participants and validated results using the Childhood Asthma Management Program (CAMP; n = 674, 39% females) and the Genetic Epidemiology of Asthma in Costa Rica Study (CRA; n = 787, 41% females). Using the closest gene to each IgE-associated CpG, we highlighted biologically plausible pathways underlying IgE regulation and analyzed the transcription patterns linked to IgE-associated CpGs …

Multivariate Genetic Analysis Of Personality And Cognitive Traits Reveals Abundant Pleiotropy, Guy Hindley, Alexey A Shadrin, Dennis Van Der Meer, Nadine Parker, Weiqiu Cheng, Kevin S O'Connell, Shahram Bahrami, Aihua Lin, Naz Karadag, Børge Holen, Thomas Bjella, Ian J Deary, Gail Davies, W David Hill, Jan Bressler, Sudha Seshadri, Chun Chieh Fan, Torill Ueland, Srdjan Djurovic, Olav B Smeland, Oleksandr Frei, Anders M Dale, Ole A Andreassen

Faculty, Staff and Student Publications

Personality and cognitive function are heritable mental traits whose genetic foundations may be distributed across interconnected brain functions. Previous studies have typically treated these complex mental traits as distinct constructs. We applied the 'pleiotropy-informed' multivariate omnibus statistical test to genome-wide association studies of 35 measures of neuroticism and cognitive function from the UK Biobank (n = 336,993). We identified 431 significantly associated genetic loci with evidence of abundant shared genetic associations, across personality and cognitive function domains. Functional characterization implicated genes with significant tissue-specific expression in all tested brain tissues and brain-specific gene sets. We conditioned independent genome-wide association studies …

An Unusual Case Of Acute Scrotal Pain, Thomas Damrow, Ryan Bellinger, Judy Lin, Jennifer A Walker

Faculty, Staff and Student Publications

Patients frequently present to the emergency department with complaints of scrotal or testicular pain. Generally, there is an algorithmic approach to workup, which includes assessment for torsion, infection, or vascular causes, and musculoskeletal causes of pain are also sometimes considered. Spinal cord pathology, however, is less often explored as a cause of testicular pain. Here, we present a case of a 45-year-old man with end-stage renal disease and hypertension who presented with acute testicular pain. After a comprehensive workup, however, the source of pain was not initially found. Progression of the patient's symptoms led to the diagnosis of spontaneous spinal …

Tepotinib Treatment In Patients With Met Exon 14-Skipping Non-Small Cell Lung Cancer: Long-Term Follow-Up Of The Vision Phase 2 Nonrandomized Clinical Trial, Julien Mazieres, Paul K Paik, Marina C Garassino, Xiuning Le, Hiroshi Sakai, Remi Veillon, Egbert F Smit, Alexis B Cortot, Jo Raskin, Santiago Viteri, Yi-Long Wu, James C H Yang, Myung-Ju Ahn, Rui Ma, Jun Zhao, Aurora O'Brate, Karin Berghoff, Rolf Bruns, Gordon Otto, Andreas Johne, Enriqueta Felip, Michael Thomas

Faculty, Staff and Student Publications

Importance: MET inhibitors have recently demonstrated clinical activity in patients with MET exon 14 (METex14)-skipping non-small cell lung cancer (NSCLC); however, data with longer follow-up and in larger populations are needed to further optimize therapeutic approaches.

Objective: To assess the long-term efficacy and safety of tepotinib, a potent and highly selective MET inhibitor, in patients with METex14-skipping NSCLC in the VISION study.

Design, setting, and participants: The VISION phase 2 nonrandomized clinical trial was a multicohort, open-label, multicenter study that enrolled patients with METex14-skipping advanced/metastatic NSCLC (cohorts A and C) from September 2016 to May 2021. Cohort C (>18 …

Microfluidic Paper-Based Device Coupled With 3d Printed Imaging Box For Colorimetric Detection In Resource-Limited Settings, Vijay Vaishampayan, Oinam Robita Chanu, Balasubramanian Sivasamy, Muthamilselvi Ponnuchamy, Varshini Karthik, Ambar Pendharkar, Lohith Srinivas Thotakura, Aryan Prabhu, Venkatesan Dhananjeyan, Ashish Kapoor

Faculty, Staff and Student Publications

Rapid and effective methods for the detection of analytes such as water contaminants, food adulterants and biomolecules are essential for the protection of public health and environmental protection. Most of the currently established analytical techniques need sophisticated equipment, centralized testing facilities, costly operations, and trained personnel. Such limitations make them inaccessible to the general populace, particularly in regions with limited resources. The emergence of microfluidic devices offers a promising alternative to overcome several such constraints. This work describes a protocol for fabricating a low-cost, open-source paper-based microfluidic device using easily available tools and materials for colorimetric detection of analytes. The …

Identifying Brain Hierarchical Structures Associated With Alzheimer’S Disease Using A Regularized Regression Method With Tree Predictors, Yi Zhao, Bingkai Wang, Chin-Fu Liu, Andreia V Faria, Michael I Miller, Brian S Caffo, Xi Luo

Faculty, Staff and Student Publications

Brain segmentation at different levels is generally represented as hierarchical trees. Brain regional atrophy at specific levels was found to be marginally associated with Alzheimer's disease outcomes. In this study, we propose an ℓ1 -type regularization for predictors that follow a hierarchical tree structure. Considering a tree as a directed acyclic graph, we interpret the model parameters from a path analysis perspective. Under this concept, the proposed penalty regulates the total effect of each predictor on the outcome. With regularity conditions, it is shown that under the proposed regularization, the estimator of the model coefficient is consistent in ℓ2 -norm …

Examining Readiness For Implementing Practice Changes In Federally Qualified Health Centers: A Rapid Qualitative Study, Emanuelle M Dias, Timothy J Walker, Derek W Craig, Robert Gibson, Jacob Szeszulski, Heather M Brandt, Hiluv Johnson, Andrea Lamont, Abraham Wandersman, Maria E Fernandez

Faculty, Staff and Student Publications

Implementing evidence-based interventions remains slow in federally qualified health centers (FQHCs). The purpose of this study is to qualitatively examine the R = MC2 (Readiness = motivation × innovation specific capacity × general capacity) heuristic subcomponents in the context of implementing general and colorectal cancer screening (CRCS)-related practice changes in FQHCs. We conducted 17 interviews with FQHC employees to examine (1) experiences with successful or unsuccessful practice change efforts, (2) using approaches to promote CRCS, and (3) opinions about R = MC2 subcomponents. We conducted a rapid qualitative analysis to examine the frequency, depth, and spontaneity of subcomponents. Priority, compatibility, …

Significant Improvement Of Fidelity For Encoded Quantum Bell Pairs At Long And Short-Distance Communication Along With Generalized Circuit, Syed Emad Uddin Shubha, Md Saifur Rahman, M R C Mahdy

Faculty, Staff and Student Publications

Quantum entanglement is a unique criterion of the quantum realm and an essential tool to secure quantum communication. Ensuring high-fidelity entanglement has always been a challenging task owing to interaction with the hostile channel environment created due to quantum noise and decoherence. Though several methods have been proposed, correcting almost all arbitrary errors is still a gigantic task. As one of the main contributions of this work, a new model for 'large distance communication' has been proposed, which may correct all bit flip errors or other errors quite extensively if proper encoding and subspace measurements are used. To achieve this …

Medical Students' Attitudes And Beliefs Toward Psilocybin: Does Terminology And Personal Experience With Psychedelics Matter?, Antonio F Pagán, Claudia Lex, Jair C Soares, Thomas D Meyer

Faculty, Staff and Student Publications

BACKGROUND: Psilocybin and psychedelic-assisted therapy (PAT) have gained renewed interest due to recent findings that PAT can enhance therapeutic outcomes. In 2019, the U.S. Food & Drug Administration (FDA) approved breakthrough therapy status to psilocybin for the treatment of depression, but PAT has yet to be approved as a therapeutic treatment for mental health disorders. Should the FDA approve PAT, medical students will serve as gatekeepers to PAT.

METHODS: Medical students (

RESULTS: Regardless of the terminology utilized, medical students held overall positive attitudes but their attitudes were significantly more positive when the term "psilocybin" was used. Furthermore, experience with …

Innate Immune Activation And White Matter Injury In A Rat Model Of Neonatal Intraventricular Hemorrhage Are Dependent On Developmental Stage, Miriam Zamorano, Scott D Olson, Candice Haase, Juan J Herrera, Shuning Huang, David J Sequeira, Charles S Cox, Brandon A Miller

Faculty, Staff and Student Publications

Background: Inflammation and white matter injury are consequences of neonatal intraventricular hemorrhage (IVH). Both white matter and the neuroimmune system are developing during the time which IVH occurs and its consequences develop. IVH has been studied in many different animal models; however, the effects of IVH occurring at different developmental time points in the same model have not been examined. Understanding how the timing of IVH affects outcome may provide important insights into both IVH pathophysiology and innate immune development.

Methods: We used intraventricular injection of lysed whole blood to model neonatal IVH in postnatal day (P)2 and P5 rats. …

Implant Survival In Tissue-Engineered Mandibular Reconstruction-Early Experiences, Victoria A Mañón, Nicholas Oda, Emeric Boudreaux, Huy Tran, Simon Young, James C Melville

Faculty, Staff and Student Publications

Study design: This article is to evaluate the early outcomes of dental implants placed in bone generated with tissueengineering techniques, specifically recombinant human bone morphogenic protein-2 (rhBMP-2), allogeneicbone particulate, and bone marrow aspirate concentrate (BMAC) in patients with resection of benignpathology.

Objective: To evaluate the long-term prognosis of dental implants placed in tissue engineered mandibular reconstruction.

Methods: We retrospectively evaluated 12 patient records, all of whom underwent segmental mandibular resection of benign pathology and reconstruction with a combination of BMAC, rhBMP-2, and allogeneic bone. Collecteddata points included the patient's age, gender, medical and social histories, implant site and placement date, …

Dependence Motives And Use Contexts That Predicted Smoking Cessation And Vaping Cessation: A Two-Year Longitudinal Study With 13 Waves, Joon Kyung Nam, Megan E Piper, Zhaoxue Tong, Runze Li, James J Yang, Douglas E Jorenby, Anne Buu

Faculty, Staff and Student Publications

INTRODUCTION: Prior studies examining the impact of e-cigarette use, dependence, cessation motivation/goals, and environmental restriction on smoking cessation were based on cross-sectional or shorter-term longitudinal data with binary outcomes. There is also a critical knowledge gap in corresponding impact on vaping cessation. This study aims to fill in these gaps by investigating these factors' effects on speed of progression to smoking and vaping cessation.

METHODS: This study conducted secondary analysis of data from 13 waves of assessment of adult cigarette users in Wisconsin from October 2015 through July 2019. Cox regression was employed to examine baseline predictors' effects on speed …

Patient Shielding During Dentomaxillofacial Radiography: Recommendations From The American Academy Of Oral And Maxillofacial Radiology, Erika Benavides, Avni Bhula, Anita Gohel, Alan G Lurie, Sanjay M Mallya, Aruna Ramesh, Donald A Tyndall

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BACKGROUND: The American Academy of Oral and Maxillofacial Radiology established an ad hoc committee to draft evidence-based recommendations and clinical guidance for the application of patient contact shielding during dentomaxillofacial imaging.

TYPES OF STUDIES REVIEWED: The committee reviewed monographs and reports from radiation protection organizations and studies that reported radiation dose to gonads, breasts, and thyroid gland from dentomaxillofacial imaging.

RESULTS: Considering the absence of radiation-induced heritable effects in humans and the negligible dose to the gonads and fetus from dentomaxillofacial imaging, the committee recommends discontinuing shielding of the gonads, pelvic structures, and fetuses during all dentomaxillofacial radiographic imaging procedures. …

The Burden Of Antimicrobial Resistance In The Americas In 2019: A Cross-Country Systematic Analysis, Antimicrobial Resistance Collaborators

Faculty, Staff and Student Publications

BACKGROUND: Antimicrobial resistance (AMR) is an urgent global health challenge and a critical threat to modern health care. Quantifying its burden in the WHO Region of the Americas has been elusive-despite the region's long history of resistance surveillance. This study provides comprehensive estimates of AMR burden in the Americas to assess this growing health threat.

METHODS: We estimated deaths and disability-adjusted life-years (DALYs) attributable to and associated with AMR for 23 bacterial pathogens and 88 pathogen-drug combinations for countries in the WHO Region of the Americas in 2019. We obtained data from mortality registries, surveillance systems, hospital systems, systematic literature …

Feasibility And Clinical Acceptability Of Automation-Assisted 3d Conformal Radiotherapy Planning For Patients With Cervical Cancer In A Resource-Constrained Setting, Sikudhani Muya, Jerry Ndumbalo, Sarah Kutika Nyagabona, Shaid Yusuf, Dong Joo Rhee, Beatrice Paul Mushi, Benjamin Li, Li Zhang, Surbhi Grover, Mary Feng, I-Chow Hsu, Elia Mmbaga, Katherine Van Loon, Laurence Court, Melody Xu

Faculty, Staff and Student Publications

Purpose: The Ocean Road Cancer Institute (ORCI) in Tanzania began offering 3D conformal radiation therapy (3DCRT) in 2018. Steep learning curves, high patient volume, and a limited workforce resulted in long radiation therapy (RT) planning workflows. We aimed to establish the feasibility of implementing an automation-assisted cervical cancer 3DCRT planning system.

Materials and methods: We performed chart abstractions on 30 patients with cervical cancer treated with 3DCRT at ORCI. The Radiation Planning Assistant (RPA) generated a new automated set of contours and plans on the basis of anonymized computed tomography images. Each were assessed for edit time requirements, dose-volume safety …

Evaluation Of The Prognostic Role Of Liver Metastases On Patient Outcomes: Systematic Review And Meta-Analysis, Jessica J Waninger, Vincent T Ma, Zoey Chopra, Ashley N Pearson, Michael D Green

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The liver is a common site of metastasis for many primary malignancies, but the quantitative impact on survival is unknown. We performed a systematic review and meta-analysis of 83 studies (604,853 patients) assessing the overall hazard associated with liver metastases by primary tumor type and treatment regimen. The pooled overall survival hazard ratio (HR) for all included studies was 1.77 (95% confidence interval [CI], 1.62-1.93). Patients with breast cancer primaries fared the worst (HR, 2.37; 95% CI, 1.64-3.44), as did patients treated with immunotherapies (HR, 1.86; 95% CI, 1.42-2.42). Liver metastases negatively impact survival, necessitating new approaches to disease management.

Immune Checkpoint Inhibitors Suppress Hepatitis C Virus Replication In Infected Patients With Solid Tumors, Marcel Yibirin, Khalis Mustafayev, Jeff Hosry, Pooja Pundhir, Joseph Klingen, Eduardo Yepez Guevara, Bruno P Granwehr, Ahmed Kaseb, Aung Naing, Sapna Patel, Amishi Y Shah, Ferdinandos Skoulidis, Hussein A Tawbi, Lan Wang, Ethan Miller, Hao Chi Zhang, Amado Zurita-Saavedra, Harrys A Torres

Faculty, Staff and Student Publications

Introduction: Data are scarce regarding the virologic impact and safety of immune checkpoint inhibitors (ICI) in patients with chronic hepatitis C virus (HCV) infection. We examined the virologic impact of ICI in HCV-infected patients with solid tumors and their safety.

Methods: HCV-infected patients with solid tumor treated with ICI at our institution between April 26, 2016, and January 5, 2022, were enrolled in a prospective observational study. The primary outcomes were ICI-induced changes in HCV viremia (HCV inhibition and HCV reactivation) and safety of ICI.

Results: We enrolled 52 consecutive patients with solid tumors treated with ICI. Most were men …