Medical Specialties Commons^™

Risk Factors For Overweight And Obesity After Childhood Acute Lymphoblastic Leukemia In North America And Switzerland: A Comparison Of Two Cohort Studies, Fabiën N Belle, Christina Schindera, Marc Ansari, Gregory T Armstrong, Maja Beck-Popovic, Rebecca Howell, Wendy M Leisenring, Lillian R Meacham, Jochen Rössler, Ben D Spycher, Emily Tonorezos, Nicolas X Von Der Weid, Yutaka Yasui, Kevin C Oeffinger, Claudia E Kuehni

Faculty, Staff and Student Publications

Background: After childhood acute lymphoblastic leukemia (ALL), sequelae include overweight and obesity, yet with conflicting evidence. We compared the prevalence of overweight and obesity between ≥5-year ALL survivors from the North American Childhood Cancer Survivor Study (CCSS) and the Swiss Childhood Cancer Survivor Study (SCCSS) and described risk factors.

Methods: We included adult childhood ALL survivors diagnosed between 1976 and 1999. We matched CCSS participants (3:1) to SCCSS participants by sex and attained age. We calculated body mass index (BMI) from self-reported height and weight for 1287 CCSS and 429 SCCSS participants; we then compared those with siblings (2034) in …

Kras G12c In Advanced Nsclc: Prevalence, Co-Mutations, And Testing, Tony Kiat Hon Lim, Ferdinandos Skoulidis, Keith M Kerr, Myung-Ju Ahn, Joshua R Kapp, Fernando A Soares, Yasushi Yatabe

Faculty, Staff and Student Publications

KRAS is the most commonly mutated oncogene in advanced, non-squamous, non-small cell lung cancer (NSCLC) in Western countries. Of the various KRAS mutants, KRAS G12C is the most common variant (~40%), representing 10-13% of advanced non-squamous NSCLC. Recent regulatory approvals of the KRASG12C-selective inhibitors sotorasib and adagrasib for patients with advanced or metastatic NSCLC harboring KRASG12C have transformed KRAS into a druggable target. In this review, we explore the evolving role of KRAS from a prognostic to a predictive biomarker in advanced NSCLC, discussing KRAS G12C biology, real-world prevalence, clinical relevance of co-mutations, and approaches to molecular testing. Real-world evidence …

International Association For The Study Of Lung Cancer Study Of Reproducibility In Assessment Of Pathologic Response In Resected Lung Cancers After Neoadjuvant Therapy, Sanja Dacic, William Travis, Mary Redman, Anjali Saqi, Wendy A Cooper, Alain Borczuk, Jin-Haeng Chung, Carolyn Glass, Javier Martin Lopez, Anja C Roden, Lynette Sholl, Annikka Weissferdt, Juan Posadas, Angela Walker, Hu Zhu, Manuja T Wijeratne, Casey Connolly, Murry Wynes, Neus Bota-Rabassedas, Beatriz Sanchez-Espiridion, J Jack Lee, Sabina Berezowska, Teh-Ying Chou, Keith Kerr, Andrew Nicholson, Claudia Poleri, Kurt A Schalper, Ming-Sound Tsao, David P Carbone, Neal Ready, Tina Cascone, John Heymach, Boris Sepesi, Catherine Shu, Naiyer Rizvi, Josuha Sonett, Nasser Altorki, Mariano Provencio, Paul A Bunn, Mark G Kris, Chandra P Belani, Karen Kelly, Ignacio Wistuba

Faculty, Staff and Student Publications

Introduction: Pathologic response has been proposed as an early clinical trial end point of survival after neoadjuvant treatment in clinical trials of NSCLC. The International Association for the Study of Lung Cancer (IASLC) published recommendations for pathologic evaluation of resected lung cancers after neoadjuvant therapy. The aim of this study was to assess pathologic response interobserver reproducibility using IASLC criteria.

Methods: An international panel of 11 pulmonary pathologists reviewed hematoxylin and eosin-stained slides from the lung tumors of resected NSCLC from 84 patients who received neoadjuvant immune checkpoint inhibitors in six clinical trials. Pathologic response was assessed for percent viable …

Renal Cell Carcinoma Of Variant Histology: Biology And Therapies, Pavlos Msaouel, Giannicola Genovese, Nizar M Tannir

Faculty, Staff and Student Publications

The term variant histology renal cell carcinomas (vhRCCs), also known as non-clear cell RCCs, refers to a diverse group of malignancies with distinct biologic and therapeutic considerations. The management of vhRCC subtypes is often based on extrapolating results from the more common clear cell RCC studies or basket trials that are not specific to each histology. The unique management of each vhRCC subtype necessitates accurate pathologic diagnosis and dedicated research efforts. Herein, we discuss tailored recommendations for each vhRCC histology informed by ongoing research and clinical experience.

Cytosolic Dna Accumulation Promotes Breast Cancer Immunogenicity Via A Sting-Independent Pathway, Jing Zhang, Hui Dai, Lei Huo, Jared K Burks, Daniel J Mcgrail, Shiaw-Yih Lin

Faculty, Staff and Student Publications

BACKGROUND: Immune checkpoint blockade (ICB) has revolutionized cancer treatment. However, ICB alone has demonstrated only benefit in a small subset of patients with breast cancer. Recent studies have shown that agents targeting DNA damage response improve the efficacy of ICB and promote cytosolic DNA accumulation. However, recent clinical trials have shown that these agents are associated with hematological toxicities. More effective therapeutic strategies are urgently needed.

METHODS: Primary triple negative breast cancer tumors were stained for cytosolic single-stranded DNA (ssDNA) using multiplex immunohistochemical staining. To increase cytosolic ssDNA, we genetically silenced TREX1. The role of tumor cytosolic ssDNA in promoting …

Basic: A Bayesian Adaptive Synthetic-Control Design For Phase Ii Clinical Trials, Liyun Jiang, Peter F Thall, Fangrong Yan, Scott Kopetz, Ying Yuan

Faculty, Staff and Student Publications

Background: Randomized controlled trials are considered the gold standard for evaluating experimental treatments but often require large sample sizes. Single-arm trials require smaller sample sizes but are subject to bias when using historical control data for comparative inferences. This article presents a Bayesian adaptive synthetic-control design that exploits historical control data to create a hybrid of a single-arm trial and a randomized controlled trial.

Methods: The Bayesian adaptive synthetic control design has two stages. In stage 1, a prespecified number of patients are enrolled in a single arm given the experimental treatment. Based on the stage 1 data, applying propensity …

A Translational Blueprint For Developing Intraoperative Imaging Agents Via Radiopharmaceutical-Guided Drug Design, Teresa E Sullivan, Servando Hernandez Vargas, Sukhen C Ghosh, Solmaz Aghaamiri, Naruhiko Ikoma, Ali Azhdarinia

Faculty, Staff and Student Publications

Cancer imaging is a rapidly evolving field due to the discovery of novel molecular targets and the availability of corresponding techniques to detect them with high precision, accuracy, and sensitivity. Nuclear medicine is the most widely used molecular imaging modality and has a growing toolkit of clinically used radiopharmaceuticals that enable whole-body tumor visualization, staging, and treatment monitoring for a variety of tumors in a non-invasive manner. The need for similar imaging capabilities in the operating room has led to the emergence of fluorescence-guided surgery (FGS) as a powerful technique that gives surgeons unprecedented ability to distinguish tumors from healthy …

Pd-1 Blockade In Combination With Dasatinib Potentiates Induction Of Anti-Acute Lymphocytic Leukemia Immunity, Paul Koller, Natalia Baran, Karine Harutyunyan, Antonio Cavazos, Saradhi Mallampati, Renee L Chin, Zhou Jiang, Xian Sun, Heng-Huan Lee, Jennifer L Hsu, Patrick Williams, Xuelin Huang, Michael A Curran, Mien-Chie Hung, Marina Konopleva

Faculty, Staff and Student Publications

Immunotherapy, in the form of hematopoietic stem cell transplantation (HSCT), has been part of the standard of care in the treatment of acute leukemia for over 40 years. Trials evaluating novel immunotherapeutic approaches, such as targeting the programmed death-1 (PD-1) pathway, have unfortunately not yielded comparable results to those seen in solid tumors. Major histocompatibility complex (MHC) proteins are cell surface proteins essential for the adaptive immune system to recognize self versus non-self. MHC typing is used to determine donor compatibility when evaluating patients for HSCT. Recently, loss of MHC class II (MHC II) was shown to be a mechanism …

Rare Variants Found In Clinical Gene Panels Illuminate The Genetic And Allelic Architecture Of Orofacial Clefting, Kimberly K Diaz Perez, Sarah W Curtis, Alba Sanchis-Juan, Xuefang Zhao, Taylor Head, Samantha Ho, Bridget Carter, Toby Mchenry, Madison R Bishop, Luz C Valencia-Ramirez, Claudia Restrepo, Jacqueline T Hecht, Lina M Uribe, George Wehby, Seth M Weinberg, Terri H Beaty, Jeffrey C Murray, Eleanor Feingold, Mary L Marazita, David J Cutler, Michael P Epstein, Harrison Brand, Elizabeth J Leslie

Faculty, Staff and Student Publications

PURPOSE: Orofacial clefts (OFCs) are common birth defects including cleft lip, cleft lip and palate, and cleft palate. OFCs have heterogeneous etiologies, complicating clinical diagnostics because it is not always apparent if the cause is Mendelian, environmental, or multifactorial. Sequencing is not currently performed for isolated or sporadic OFCs; therefore, we estimated the diagnostic yield for 418 genes in 841 cases and 294 controls.

METHODS: We evaluated 418 genes using genome sequencing and curated variants to assess their pathogenicity using American College of Medical Genetics criteria.

RESULTS: 9.04% of cases and 1.02% of controls had "likely pathogenic" variants (P < .0001), which was almost exclusively driven by heterozygous variants in autosomal genes. Cleft palate (17.6%) and cleft lip and palate (9.09%) cases had the highest yield, whereas cleft lip cases had a 2.80% yield. Out of 39 genes with likely pathogenic variants, 9 genes, including CTNND1 and IRF6, accounted for more than half of the yield (4.64% of cases). Most variants (61.8%) were "variants of uncertain significance", occurring more frequently in cases (P = .004), but no individual gene showed a significant excess of variants of uncertain significance.

CONCLUSION: …

Preclinical Development Of 1b7/Cd3, A Novel Anti-Tslpr Bispecific Antibody That Targets Crlf2-Rearranged Ph-Like B-All, Ze Tian, Chunhua Shi, Guojun Yang, Jason K Allen, Qing Shi, Amin Al-Shami, Jill Wardell Olson, Melinda G Smith, Qing Chang, Jasbir Kaur, Junping You, Timothy E Lofton, Michelle A Gonzalez, Qi Zhang, Dongxing Zha, Sarah K Tasian, Nitin Jain, Marina Y Konopleva, Timothy Heffernan, Jeffrey J Molldrem

Faculty, Staff and Student Publications

Patients harboring CRLF2-rearranged B-lineage acute lymphocytic leukemia (B-ALL) face a 5-year survival rate as low as 20%. While significant gains have been made to position targeted therapies for B-ALL treatment, continued efforts are needed to develop therapeutic options with improved duration of response. Here, first we have demonstrated that patients with CRLF2-rearranged Ph-like ALL harbor elevated thymic stromal lymphopoietin receptor (TSLPR) expression, which is comparable with CD19. Then we present and evaluate the anti-tumor characteristics of 1B7/CD3, a novel CD3-redirecting bispecific antibody (BsAb) that co-targets TSLPR. In vitro, 1B7/CD3 exhibits optimal binding to both human and cynomolgus CD3 and TSLPR. …

Can Craniosynostosis Be Diagnosed On Physical Examination? A Retrospective Review, Carmen A Zavala, Laura A Zima, Matthew R Greives, Stephen A Fletcher, Manish N Shah, Brandon A Miller, David I Sandberg, Phuong D Nguyen

Faculty, Staff and Student Publications

Craniosynostosis is a developmental craniofacial defect in which one or more sutures of the skull fuse together prematurely. Uncorrected craniosynostosis may have serious complications including elevated intracranial pressure, developmental delay, and blindness. Proper diagnosis of craniosynostosis requires a physical examination of the head with assessment for symmetry and palpation of sutures for prominence. Often, if craniosynostosis is suspected, computed tomography (CT) imaging will be obtained. Recent literature has posited that this is unnecessary. This study aims to address whether physical examination alone is sufficient for the diagnosis and treatment planning of single suture craniosynostosis. Between 2015 and 2022, the Divisions …

Characteristics And Outcomes Of Patients With Chronic Myeloid Leukemia And T315i Mutation Treated In The Pre- And Post-Ponatinib Era, Fadi G Haddad, Koji Sasaki, Aram Bidikian, Ghayas C Issa, Tapan Kadia, Nitin Jain, Yesid Alvarado, Nicholas J Short, Naveen Pemmaraju, Sanam Loghavi, Keyur P Patel, Rashmi Kanagal-Shamanna, Musa Yilmaz, Lucia Masarova, Elias Jabbour, Hagop Kantarjian

Faculty, Staff and Student Publications

Patients with chronic myeloid leukemia (CML) and T315I mutation generally have a poor prognosis. Their outcome in the post-ponatinib era remains unclear. We reviewed patients with CML in chronic (CP) or accelerated phase (AP) who developed a T315I mutation between March 15, 2004, and July 26, 2022. Patients were divided into CP, AP, or blastic phase (BP) at the time of mutation detection. Overall survival (OS) was defined from the time of mutation detection to the date of death or last follow-up. We identified a total of 107 patients: 54 (51%) in CP, 14 (13%) in AP, and 39 (36%) …

Comparisons Of Medical Cost Trajectories Between Non-Hispanic Black And Non-Hispanic White Patients With Newly Diagnosed Localized Prostate Cancer, Yu Liu, Shikun Wang, Liang Li, Ying Xu, Yu Shen, Ya-Chen Tina Shih

Faculty, Staff and Student Publications

Objectives: This study applied a recently developed statistical method to compare the mean cost trajectories between non-Hispanic White (NHW) and non-Hispanic Black (NHB) patients with localized prostate cancer conditioning on patients' survival.

Methods: In this observational study, we modeled cost trajectories of NHW and NHB patients with localized prostate cancer for 3 survival durations: 24, 48, and 72 months. We also compared the cost trajectories between NHW and NHB, stratified by comorbidities scores.

Results: We find that the mean cost trajectories of NHB were significantly higher than the trajectories of NHW in the last 12 months before death, regardless of …

Local Continual Reassessment Methods For Dose Finding And Optimization In Drug-Combination Trials, Jingyi Zhang, Fangrong Yan, Nolan A Wages, Ruitao Lin

Faculty, Staff and Student Publications

Due to the limited sample size and large dose exploration space, obtaining a desirable dose combination is a challenging task in the early development of combination treatments for cancer patients. Most existing designs for optimizing the dose combination are model-based, requiring significant efforts to elicit parameters or prior distributions. Model-based designs also rely on intensive model calibration and may yield unstable performance in the case of model misspecification or sparse data. We propose to employ local, underparameterized models for dose exploration to reduce the hurdle of model calibration and enhance the design robustness. Building upon the framework of the partial …

Lurbinectedin In Patients With Pretreated Endometrial Cancer: Results From A Phase 2 Basket Clinical Trial And Exploratory Translational Study, Rebecca Kristeleit, Alexandra Leary, Jean Pierre Delord, Victor Moreno, Ana Oaknin, Daniel Castellano, Geoffrey I Shappiro, Cristian Fernández, Carmen Kahatt, Vicente Alfaro, Mariano Siguero, Daniel Rueda, Ali Zeaiter, Ahmad Awada, Ana Santaballa, Khalil Zaman, Jalid Sehouli, Vivek Subbiah

Faculty, Staff and Student Publications

Second-line treatment of endometrial cancer is an unmet medical need. Lurbinectedin showed promising antitumor activity in a phase I study in combination with doxorubicin in advanced endometrial cancer. This phase 2 Basket trial evaluated lurbinectedin 3.2 mg/m2 1-h intravenous infusion every 3 weeks in a cohort of 73 patients with pretreated endometrial cancer. The primary endpoint was overall response rate (ORR) according to RECIST v1.1. Secondary endpoints included duration of response (DoR), progression-free survival (PFS), overall survival (OS), safety and an exploratory translational study. Confirmed complete (CR) and partial response (PR) was reported in two and six patients, respectively (ORR …

Diagnosis Of Chronic Pancreatitis Using Semi-Quantitative Mri Features Of The Pancreatic Parenchyma: Results From The Multi-Institutional Minimap Study, Temel Tirkes, Dhiraj Yadav, Darwin L Conwell, Paul R Territo, Xuandong Zhao, Scott A Persohn, Anil K Dasyam, Zarine K Shah, Sudhakar K Venkatesh, Naoki Takahashi, Ashley Wachsman, Liang Li, Yan Li, Stephen J Pandol, Walter G Park, Santhi Swaroop Vege, Phil A Hart, Mark Topazian, Dana K Andersen, Evan L Fogel, Consortium For The Study Of Chronic Pancreatitis, Diabetes, Pancreatic Cancer (Cpdpc)

Faculty, Staff and Student Publications

Purpose: To determine the diagnostic performance of parenchymal MRI features differentiating CP from controls.

Methods: This prospective study performed abdominal MRI scans at seven institutions, using 1.5 T Siemens and GE scanners, in 50 control and 51 definite CP participants, from February 2019 to May 2021. MRI parameters included the T1-weighted signal intensity ratio of the pancreas (T1 score), arterial-to-venous enhancement ratio (AVR) during venous and delayed phases, pancreas volume, and diameter. We evaluated the diagnostic performance of these parameters individually and two semi-quantitative MRI scores derived using logistic regression: SQ-MRI Model A (T1 score, AVR venous, and tail diameter) …

Circulating Short Chain Fatty Acids And Fatigue In Patients With Head And Neck Cancer: A Longitudinal Prospective Study, Canhua Xiao, Veronika Fedirko, Henry Claussen, H Richard Johnston, Gang Peng, Sudeshna Paul, Kristal M Maner-Smith, Kristin A Higgins, Dong M Shin, Nabil F Saba, Evanthia C Wommack, Deborah W Bruner, Andrew H Miller

Faculty, Staff and Student Publications

Fatigue among patients with head and neck cancer (HNC) has been associated with higher inflammation. Short-chain fatty acids (SCFAs) have been shown to have anti-inflammatory and immunoregulatory effects. Therefore, this study aimed to examine the association between SCFAs and fatigue among patients with HNC undergoing treatment with radiotherapy with or without concurrent chemotherapy. Plasma SCFAs and the Multidimensional Fatigue Inventory-20 were collected prior to and one month after the completion of treatment in 59 HNC patients. The genome-wide gene expression profile was obtained from blood leukocytes prior to treatment. Lower butyrate concentrations were significantly associated with higher fatigue (p = …

Quantitative Multiplexed Imaging Technologies For Single-Cell Analysis To Assess Predictive Markers For Immunotherapy In Thoracic Immuno-Oncology: Promises And Challenges, Edwin Roger Parra, Marius Ilié, Ignacio I Wistuba, Paul Hofman

Faculty, Staff and Student Publications

The past decade has witnessed a revolution in cancer treatment by the shift from conventional drugs (chemotherapies) towards targeted molecular therapies and immune-based therapies, in particular the immune-checkpoint inhibitors (ICIs). These immunotherapies selectively release the host immune system against the tumour and have shown unprecedented durable remission for patients with cancers that were thought incurable such as advanced non-small cell lung cancer (aNSCLC). The prediction of therapy response is based since the first anti-PD-1/PD-L1 molecules FDA and EMA approvals on the level of PD-L1 tumour cells expression evaluated by immunohistochemistry, and recently more or less on tumour mutation burden in …

Mortality, Outcomes, Costs, And Use Of Medicines Following A First Heart Failure Hospitalization: Evolution Hf, Biykem Bozkurt, Gianluigi Savarese, Samuel Adamsson Eryd, Johan Bodegård, John G F Cleland, Cindy Khordoc, Takuya Kishi, Marcus Thuresson, Orly Vardeny, Ruiqi Zhang, Lars H Lund

Faculty, Staff and Students Publications

Background: There are few contemporary data on outcomes, costs, and treatment following a hospitalization for heart failure (hHF) in epidemiologically representative cohorts.

Objectives: This study sought to describe rehospitalizations, hospitalization costs, use of guideline-directed medical therapy (GDMT) (renin-angiotensin system inhibitors, sacubitril/valsartan, beta-blockers, mineralocorticoid receptor antagonists, and sodium-glucose cotransporter-2 inhibitors), and mortality after hHF.

Methods: EVOLUTION HF (Utilization of Dapagliflozin and Other Guideline Directed Medical Therapies in Heart Failure Patients: A Multinational Observational Study Based on Secondary Data) is an observational, longitudinal cohort study using data from electronic health records or claims data sources in Japan, Sweden, the United Kingdom, and …

Review Of Toxocariasis At A Children's Hospital Prompting Need For Public Health Interventions, Mary B Fortini, Timothy A Erickson, Lauren M Leining, Karina M Robinson, Megan N Carey, Sarah J Smith, Brendan Sullivan, Alisa R Nelson, Sarah M Gunter, Jill E Weatherhead

Faculty, Staff and Students Publications

BACKGROUND: Toxocariasis, caused the by dog and cat roundworm, is one of the most common zoonotic helminth infections in the United States and can lead to severe lifelong morbidity in children. Although historical seroprevalence studies have identified a high frequency of toxocariasis regionally in the United States, there are few studies linking epidemiology and clinical disease in children. The study objective was to examine the contemporary epidemiology of pediatric toxocariasis within an endemic US region.

METHODS: We conducted an epidemiologic study analyzing children diagnosed with toxocariasis presenting to a tertiary pediatric hospital in Texas from 2010 to 2021. We examined …

The Interaction Between Autophagy, Helicobacter Pylori, And Gut Microbiota In Gastric Carcinogenesis, Ali Nabavi-Rad, Abbas Yadegar, Amir Sadeghi, Hamid Asadzadeh Aghdaei, Mohammad Reza Zali, Daniel J Klionsky, Yoshio Yamaoka

Faculty, Staff and Students Publications

Chronic infection with Helicobacter pylori is the primary risk factor for the development of gastric cancer. Hindering our ability to comprehend the precise role of autophagy during H. pylori infection is the complexity of context-dependent autophagy signaling pathways. Recent and ongoing progress in understanding H. pylori virulence allows new frontiers of research for the crosstalk between autophagy and H. pylori. Novel approaches toward discovering autophagy signaling networks have further revealed their critical influence on the structure of gut microbiota and the metabolome. Here we intend to present a holistic view of the perplexing role of autophagy in H. pylori pathogenesis …

The Improving Medication Adherence In Adolescents And Young Adults Following Liver Transplantation (Imalt) Multisite Trial: Design And Trial Implementation Considerations, Eyal Shemesh, Sarah Duncan-Park, George Mazariegos, Rachel Annunziato, Ravinder Anand, Miguel Reyes-Mugica, Jeff Mitchell, Benjamin L Shneider

Faculty, Staff and Students Publications

Background/aims: Medication non-adherence is a leading cause of transplant rejection, organ loss, and death; yet no rigorous controlled study to date has shown compelling clinical benefits from an adherence-improving intervention. Non-adherent patients are less likely to participate in trials, and therefore, most studies enroll a majority of adherent patients who do not stand to benefit from the intervention, as they do not have the condition (non-adherence) under investigation. The improving Medication Adherence in adolescent Liver Transplant recipients trial specifically targets non-adherent patients to investigate whether a remote intervention to improve adherence results in reduced incidence of biopsy-confirmed rejection.

Methods: Improving …

Quality Improvement Initiative To Improve Time And Adherence To Revaccination After Hematopoietic Cell Transplantation: Implementation Of A Revaccination Clinic Within The Transplantation Program, Caitlin Elgarten, Anne Wohlschlaeger, Ellen Levy, Katharine Tadley, Lei Wang, Megan Atkinson, Houston Roberson, Timothy Olson, Nancy Bunin, Jennifer Heimall, Brian Fisher, Stephan Grupp, Jason Freedman

Faculty, Staff and Students Publications

Background:

Revaccination after hematopoietic cell transplantation (HCT) is critical to prevent morbidity and mortality from vaccine preventable illnesses. While earlier re-vaccination after HCT is desirable, they may be ineffective if deployed before partial reconstitution of adaptive immunity. Increasingly, personalized approaches to re-vaccination after HCT have replaced time-based protocols in order to minimize unvaccinated time and enhance vaccine effectiveness. Furthermore, for revaccination to be maximally beneficial, compliance with, and timely delivery of the complete revaccination schedule is imperative, but rare, and there is little data on strategies to optimize vaccine delivery.

Objectives:

The global aim of our quality improvement initiative was …

Bioimpedance Analysis Predicts The Etiology Of Cirrhosis In A Prospective Cohort Study, Hashem B El-Serag, Ghida Akhdar, Aaron P Thrift, Michelle Luster, Saira Khaderi, Abeer Alsarraj, Hao Duong, Fasiha Kanwal

Faculty, Staff and Students Publications

BACKGROUND: Obesity is associated with an increased risk of developing cirrhosis. However, body mass index (BMI) and waist-to-hip ratio (WHR) may not be indicative of body composition parameters that predispose to cirrhosis. Bioimpedance analysis (BIA) is a noninvasive cost-efficient method for more detailed estimation of body composition.

METHODS: We examined patients with cirrhosis who underwent BIA as part of enrollment into a prospective cohort study. We examined the correlation between BIA variables, BMI, and WHR. We performed sex-adjusted and race-adjusted and race-specific multivariable logistic regression analyses to examine the association between anthropometric variables and risk factors [NAFLD, alcohol-associated liver disease …

Fatigue In Patients Receiving Maintenance Hemodialysis: A Review, Maurizio Bossola, S Susan Hedayati, Astrid D H Brys, L Parker Gregg

Faculty, Staff and Students Publications

Fatigue surrounding hemodialysis treatments is a common and often debilitating symptom that impacts patients' quality of life. Intradialytic fatigue develops or worsens immediately before hemodialysis and persists through the dialysis treatment. Little is known about associated risk factors or pathophysiology, although it may relate to a classic conditioning response. Postdialysis fatigue (PDF) develops or worsens after hemodialysis and may persist for hours. There is no consensus on how to measure PDF. Estimates for the prevalence of PDF range from 20%-86%, likely due to variation in methods of ascertainment and participant characteristics. Several hypotheses seek to explain the pathophysiology of PDF, …

The Pre-Adaptation Of A Stroke-Specific Self-Management Program Among Older Adults, Timothy Reistetter, Kimberly Hreha, Julianna M Dean, Monique R Pappadis, Rachel R Deer, Chih-Ying Li, Ickpyo Hong, Annalisa Na, Sara Nowakowski, Hashem M Shaltoni, Suresh K Bhavnani

Faculty, Staff and Students Publications

Objectives:

Managing multimorbidity as aging stroke patients is complex; standard self-management programs necessitate adaptations. We used visual analytics to examine complex relationships among aging stroke survivors’ comorbidities. These findings informed pre-adaptation of a component of the Chronic Disease Self-Management Program.

Methods:

Secondary analysis of 2013–2014 Medicare claims with stroke as an index condition, hospital readmission within 90 days (n=42,938), and 72 comorbidities. Visual analytics identified patient subgroups and co-occurring comorbidities. Guided by the framework for reporting adaptations and modifications to evidence-based interventions (FRAME), an interdisciplinary team developed vignettes that highlighted multimorbidity to customize the self-management program.

Results:

There were five …

Obesity Paradox Or Hypoxia Preconditioning: How Obstructive Sleep Apnea Modifies The Obesity-Mi Relationship, Amir Sharafkhaneh, Ritwick Agrawal, Vijay Nambi, Ahmed Bahammam, Javad Razjouyan

Faculty, Staff and Students Publications

OBJECTIVES: The objective of this study was to evaluate the interaction between obesity and obstructive sleep apnea on acute MI in hospital mortality.

METHODS: This retrospective cohort study utilized Veterans Health Administration data from years 1999-2020. Participants were categorized according to their body mass index (BMI) to non-obese (BMI

RESULTS: Among 72,036 veterans with acute-MI hospitalization, individuals with obesity and obstructive sleep apnea (OB-SA) had the lowest in-hospital mortality rate (1.0%) compared to those without obesity and obstructive sleep apnea (nOB-nSA, 2.8%), with obesity but without obstructive sleep apnea (OB-nSA, 2.4%), and with obesity and obstructive sleep apnea (nOB-SA, 1.4%). …

Gwas Meta-Analysis Of Suicide Attempt: Identification Of 12 Genome-Wide Significant Loci And Implication Of Genetic Risks For Specific Health Factors, Anna R Docherty, Niamh Mullins, Allison E Ashley-Koch, Xuejun Qin, Jonathan R I Coleman, Andrey Shabalin, Jooeun Kang, Balasz Murnyak, Frank Wendt, Mark Adams, Adrian I Campos, Emily Diblasi, Janice M Fullerton, Henry R Kranzler, Amanda V Bakian, Eric T Monson, Miguel E Rentería, Consuelo Walss-Bass, Ole A Andreassen, Chittaranjan Behera, Cynthia M Bulik, Howard J Edenberg, Ronald C Kessler, J John Mann, John I Nurnberger, Giorgio Pistis, Fabian Streit, Robert J Ursano, Renato Polimanti, Michelle Dennis, Melanie Garrett, Lauren Hair, Philip Harvey, Elizabeth R Hauser, Michael A Hauser, Jennifer Huffman, Daniel Jacobson, Ravi Madduri, Benjamin Mcmahon, David W Oslin, Jodie Trafton, Swapnil Awasthi, Wade H Berrettini, Martin Bohus, Xiao Chang, Hsi-Chung Chen, Wei J Chen, Erik D Christensen, Scott Crow, Philibert Duriez, Alexis C Edwards, Fernando Fernández-Aranda, Hanga Galfalvy, Michael Gandal, Philip Gorwood, Yiran Guo, Jonathan D Hafferty, Hakon Hakonarson, Katherine A Halmi, Akitoyo Hishimoto, Sonia Jain, Stéphane Jamain, Susana Jiménez-Murcia, Craig Johnson, Allan S Kaplan, Walter H Kaye, Pamela K Keel, James L Kennedy, Minsoo Kim, Kelly L Klump, Daniel F Levey, Dong Li, Shih-Cheng Liao, Klaus Lieb, Lisa Lilenfeld, Christian R Marshall, James E Mitchell, Satoshi Okazaki, Ikuo Otsuka, Dalila Pinto, Abigail Powers, Nicolas Ramoz, Stephan Ripke, Stefan Roepke, Vsevolod Rozanov, Stephen W Scherer, Christian Schmahl, Marcus Sokolowski, Anna Starnawska, Michael Strober, Mei-Hsin Su, Laura M Thornton, Janet Treasure, Erin B Ware, Hunna J Watson, Stephanie H Witt, D Blake Woodside, Zeynep Yilmaz, Lea Zillich, Rolf Adolfsson, Ingrid Agartz, Martin Alda, Lars Alfredsson, Vivek Appadurai, María Soler Artigas, Sandra Van Der Auwera, M Helena Azevedo, Nicholas Bass, Claiton H D Bau, Bernhard T Baune, Frank Bellivier, Klaus Berger, Joanna M Biernacka, Tim B Bigdeli, Elisabeth B Binder, Michael Boehnke, Marco P Boks, David L Braff, Richard Bryant, Monika Budde, Enda M Byrne, Wiepke Cahn, Enrique Castelao, Jorge A Cervilla, Boris Chaumette, Aiden Corvin, Nicholas Craddock, Srdjan Djurovic, Jerome C Foo, Andreas J Forstner, Mark Frye, Justine M Gatt, Ina Giegling, Hans J Grabe, Melissa J Green, Eugenio H Grevet, Maria Grigoroiu-Serbanescu, Blanca Gutierrez, Jose Guzman-Parra, Marian L Hamshere, Annette M Hartmann, Joanna Hauser, Stefanie Heilmann-Heimbach, Per Hoffmann, Marcus Ising, Ian Jones, Lisa A Jones, Lina Jonsson, René S Kahn, John R Kelsoe, Kenneth S Kendler, Stefan Kloiber, Karestan C Koenen, Manolis Kogevinas, Marie-Odile Krebs, Mikael Landén, Marion Leboyer, Phil H Lee, Douglas F Levinson, Calwing Liao, Jolanta Lissowska, Fermin Mayoral, Susan L Mcelroy, Patrick Mcgrath, Peter Mcguffin, Andrew Mcquillin, Divya Mehta, Ingrid Melle, Philip B Mitchell, Esther Molina, Gunnar Morken, Caroline Nievergelt, Markus M Nöthen, Michael C O'Donovan, Roel A Ophoff, Michael J Owen, Carlos Pato, Michele T Pato, Brenda W J H Penninx, James B Potash, Robert A Power, Martin Preisig, Digby Quested, Josep Antoni Ramos-Quiroga, Andreas Reif, Marta Ribasés, Vanesa Richarte, Marcella Rietschel, Margarita Rivera, Andrea Roberts, Gloria Roberts, Guy A Rouleau, Diego L Rovaris, Alan R Sanders, Peter R Schofield, Thomas G Schulze, Laura J Scott, Alessandro Serretti, Jianxin Shi, Lea Sirignano, Pamela Sklar, Olav B Smeland, Jordan W Smoller, Edmund J S Sonuga-Barke, Maciej Trzaskowski, Ming T Tsuang, Gustavo Turecki, Laura Vilar-Ribó, John B Vincent, Henry Völzke, James T R Walters, Cynthia Shannon Weickert, Thomas W Weickert, Myrna M Weissman, Leanne M Williams, Naomi R Wray, Clement C Zai, Esben Agerbo, Anders D Børglum, Gerome Breen, Ditte Demontis, Annette Erlangsen, Joel Gelernter, Stephen J Glatt, David M Hougaard, Hai-Gwo Hwu, Po-Hsiu Kuo, Cathryn M Lewis, Qingqin S Li, Chih-Min Liu, Nicholas G Martin, Andrew M Mcintosh, Sarah E Medland, Ole Mors, Merete Nordentoft, Catherine M Olsen, David Porteous, Daniel J Smith, Eli A Stahl, Murray B Stein, Danuta Wasserman, Thomas Werge, David C Whiteman, Virginia Willour, Hilary Coon, Jean C Beckham, Nathan A Kimbrel, Douglas M Ruderfer

Faculty, Staff and Student Publications

OBJECTIVE: Suicidal behavior is heritable and is a major cause of death worldwide. Two large-scale genome-wide association studies (GWASs) recently discovered and cross-validated genome-wide significant (GWS) loci for suicide attempt (SA). The present study leveraged the genetic cohorts from both studies to conduct the largest GWAS meta-analysis of SA to date. Multi-ancestry and admixture-specific meta-analyses were conducted within groups of significant African, East Asian, and European ancestry admixtures.

METHODS: This study comprised 22 cohorts, including 43,871 SA cases and 915,025 ancestry-matched controls. Analytical methods across multi-ancestry and individual ancestry admixtures included inverse variance-weighted fixed-effects meta-analyses, followed by gene, gene-set, tissue-set, …

Electrophysiological Responses To Emotional And Cocaine Cues Reveal Individual Neuroaffective Profiles In Cocaine Users, Heather E Webber, Constanza De Dios, Margaret C Wardle, Robert Suchting, Charles E Green, Joy M Schmitz, Scott D Lane, Francesco Versace

Faculty, Staff and Student Publications

Smokers with stronger neuroaffective responses to drug-related cues compared to non-drug-related pleasant images (C>P) are more vulnerable to compulsive smoking than individuals with the opposite brain reactivity profile (P>C). However, it is unknown if these neurobehavioral profiles exist in individuals abusing other drugs. We tested whether individuals with cocaine use disorder (CUD) show similar neuroaffective profiles to smokers. We also monitored eye movements to assess attentional bias toward cues and we further performed exploratory analyses on demographics, personality, and drug use between profiles. Participants with CUD (n=43) viewed pleasant, unpleasant, cocaine, and neutral images while we recorded electroencephalogram. …

Baseline Psychosocial, Environmental, Health, And Behavioral Correlates Of 1- And 3-Year Weight Loss After Bariatric Surgery, Ming Ji, Sonya L Negriff, Jeff M Slezak, Brianna L Taylor, Silvia R Paz, Bhumi B Bhakta, Mayra Macias, David E Arterburn, Cecelia L Crawford, Adam Drewnowski, Kristina H Lewis, Darren D Moore, Sameer B Murali, Deborah R Young, Karen J Coleman

Faculty, Staff and Student Publications

PURPOSE: Weight loss surgery is an effective, long-term treatment for severe obesity but individual response to surgery varies widely. The purpose of this study was to test a comprehensive theoretical model of factors that may be correlated with the greatest surgical weight loss at 1-3 years following surgery. Such a model would help determine what predictive factors to measure when patients are preparing for surgery that may ensure the best weight outcomes.

MATERIALS AND METHODS: The Bariatric Experience Long Term (BELONG) study collected self-reported and medical record-based baseline information as correlates of 1- and 3-year % total weight loss (TWL) …