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Dietary Habits, Meal Timing, And Meal Frequency In Kuwaiti Adults: Analysis Of The Kuwait National Nutrition Surveillance Data, Fatema Alkhulaifi, Suad Al-Hooti, Sameer Al-Zenki, Husam Alomirah, Charles Darkoh

Faculty, Staff and Student Publications

Dietary habits, including meal frequency, meal timing, and skipping meals, have been extensively studied due to their association with the development of noncommunicable diseases (NCDs). This study describes dietary habits, meal timing, frequency, skipping meals, and late-night eating in Kuwaiti adults. Kuwait National Nutrition Surveillance System data were utilized to reach the objectives of this study. The findings reveal that approximately 54% of the adults in Kuwait eat after 10 p.m., 29% skip breakfast, and 9.8% skip dinner. Furthermore, adults in Kuwait consume 4.4 meals per day on average. Women skip breakfast more often and have more extended night fasting …

Targeted Therapy With Nanatinostat And Valganciclovir In Recurrent Ebv-Positive Lymphoid Malignancies: A Phase 1b/2 Study, Bradley Haverkos, Onder Alpdogan, Robert Baiocchi, Jonathan E. Brammer, Tatyana A. Feldman, Marcelo Capra, Elizabeth A. Brem, Santosh Nair, Phillip Scheinberg, Juliana Pereira, Leyla Shune, Erel Joffe, Patricia Young, Susan Spruill, Afton Katkov, Robert Mcrae, Ivor Royston, Douglas V. Faller, Lisa Rojkjaer, Pierluigi Porcu

Department of Medical Oncology Faculty Papers

Lymphomas are not infrequently associated with the Epstein-Barr virus (EBV), and EBV positivity is linked to worse outcomes in several subtypes. Nanatinostat is a class-I selective oral histone deacetylase inhibitor that induces the expression of lytic EBV BGLF4 protein kinase in EBV+ tumor cells, activating ganciclovir via phosphorylation, resulting in tumor cell apoptosis. This phase 1b/2 study investigated the combination of nanatinostat with valganciclovir in patients aged ≥18 years with EBV+ lymphomas relapsed/refractory to ≥1 prior systemic therapy with no viable curative treatment options. In the phase 1b part, 25 patients were enrolled into 5 dose escalation cohorts to determine …

Identification Of Dual Strn-Ntrk2 Rearrangements In A High Grade Sarcoma, With Good Clinical Response To First-Line Larotrectinib Therapy, Ruihe Lin, Atrayee Basu Mallick, Zi-Xuan Wang, Phd, Scot Andrew Brown, Bo Lu, Md, Wei Jiang

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

BACKGROUND: Among the three NTRK genes, NTRK2 possesses a tremendous structural complexity and involves tumorigenesis of several types of tumors. To date, only STRN and RBPMS are identified in the fusion with NTRK2 in adult soft tissue tumors. More recently, the highly selective Trk tyrosine kinases inhibitors, including larotrectinib and entrectinib, have shown significant efficacy for treating tumors harboring NTRK fusions and were approved by FDA.

CASE PRESENTATION: We report a case of sarcoma in a 35-year-old female harboring two STRN-NTRK2 gene fusions, with a good clinical response to first-line larotrectinib treatment. Core biopsy of the 16.5 cm gluteal mass …

Early Resveratrol Treatment Mitigates Joint Degeneration And Dampens Pain In A Mouse Model Of Pseudoachondroplasia (Psach), Jacqueline T Hecht, Alka C Veerisetty, Debabrata Patra, Mohammad G Hossain, Frankie Chiu, Claire Mobed, Francis H Gannon, Karen L Posey

Faculty, Staff and Student Publications

Pseudoachondroplasia (PSACH), a severe dwarfing condition associated with early-onset joint degeneration and lifelong joint pain, is caused by mutations in cartilage oligomeric matrix protein (COMP). The mechanisms underlying the mutant-COMP pathology have been defined using the MT-COMP mouse model of PSACH that has the common D469del mutation. Mutant-COMP protein does not fold properly, and it is retained in the rough endoplasmic reticulum (rER) of chondrocytes rather than being exported to the extracellular matrix (ECM), driving ER stress that stimulates oxidative stress and inflammation, driving a self-perpetuating cycle. CHOP (ER stress signaling protein) and TNFα inflammation drive high levels of mTORC1 …

Investigating Associations Of Omega-3 Fatty Acids, Lung Function Decline, And Airway Obstruction, Bonnie K Patchen, Pallavi Balte, Traci M Bartz, R Graham Barr, Myriam Fornage, Mariaelisa Graff, David R Jacobs, Ravi Kalhan, Rozenn N Lemaitre, George O'Connor, Bruce Psaty, Jungkyun Seo, Michael Y Tsai, Alexis C Wood, Hanfei Xu, Jingwen Zhang, Sina A Gharib, Ani Manichaikul, Kari North, Lyn M Steffen, Josée Dupuis, Elizabeth Oelsner, Dana B Hancock, Patricia A Cassano

Faculty, Staff and Student Publications

Rationale: Inflammation contributes to lung function decline and the development of chronic obstructive pulmonary disease. Omega-3 fatty acids have antiinflammatory properties and may benefit lung health.

Objectives: To investigate associations of omega-3 fatty acids with lung function decline and incident airway obstruction in a diverse sample of adults from general-population cohorts.

Methods: Complementary study designs: 1) longitudinal study of plasma phospholipid omega-3 fatty acids and repeated FEV1 and FVC measures in the NHLBI Pooled Cohorts Study and 2) two-sample Mendelian randomization (MR) study of genetically predicted omega-3 fatty acids and lung function parameters.

Measurements and Main Results: The …

A Comparison Of Adult Black And White Male Killers' Behaviors, Their Motives For Murder, And What They Do With Their Victims' Bodies, Tracy Sargent

Doctoral Dissertations and Projects

Studies involving murder are often focused on one offender group or a specific victim type. Due to focused research on this topic, there is a need to explore homicidal research between two offender groups in order to compare deviant behaviors of persons who commit murder. The comparison of adult black male offenders and adult white male offenders, their motivations for murder, and what offenders do with their victims’ bodies is explored in the study. A total of 300 solved homicide cases, which consists primarily of adult male and female victims, and several child murders was collected. Such murder motivations of …

Complete Loss Of Tp53 And Rb1 Is Associated With Complex Genome And Low Immune Infiltrate In Pleomorphic Rhabdomyosarcoma, Hannah C Beird, Chia-Chin Wu, Michael Nakazawa, Davis Ingram, Joseph R Daniele, Rossana Lazcano, Latasha Little, Christopher Davies, Najat C Daw, Khalida Wani, Wei-Lien Wang, Xingzhi Song, Curtis Gumbs, Jianhua Zhang, Brian Rubin, Anthony Conley, Adrienne M Flanagan, Alexander J Lazar, P Andrew Futreal

Faculty, Staff and Student Publications

Rhabdomyosarcoma accounts for roughly 1% of adult sarcomas, with pleomorphic rhabdomyosarcoma (PRMS) as the most common subtype. Survival outcomes remain poor for patients with PRMS, and little is known about the molecular drivers of this disease. To better characterize PRMS, we performed a broad array of genomic and immunostaining analyses on 25 patient samples. In terms of gene expression and methylation, PRMS clustered more closely with other complex karyotype sarcomas than with pediatric alveolar and embryonal rhabdomyosarcoma. Immune infiltrate levels in PRMS were among the highest observed in multiple sarcoma types and contrasted with low levels in other rhabdomyosarcoma subtypes. …

Immune-Depleted Tumor Microenvironment Is Associated With Poor Outcomes And Btk Inhibitor Resistance In Mantle Cell Lymphoma, Preetesh Jain, Krystle Nomie, Nikita Kotlov, Vitaiy Segodin, Holly Hill, Chi Young Ok, Ahmed Fetooh, Rashmi Kanagal-Shamanna, Francisco Vega, Alexander Bagaev, Nathan Fowler, Christopher R Flowers, Michael Wang

Faculty, Staff and Student Publications

Mantle cell lymphoma (MCL) is a generally aggressive B cell non-Hodgkin lymphoma (B-NHL). Outcomes of patients have improved in the era of Bruton’s tyrosine kinase inhibitors (BTKi). However, MCL patients can develop resistance to BTKi over time and can progress [1]. Ibrutinib resistance in MCL is correlated with an overexpression of OXPHOS, MYC and PI3K/AKT/m-TOR pathways. Somatic mutations in TP53, KMT2D, NSD2, SMARCA4, CCND1, TRAF2, NFKBIE genes are reported with ibrutinib resistance [2]. A few reports have also demonstrated that a decrease in T cell numbers [3, 4] or a downregulation of effector/cytotoxic …

A Proof-Of-Concept Pilot Test Of A Behavioral Intervention To Improve Adherence To Dietary Recommendations For Cancer Prevention, Meghan Butryn, Charlotte Hagerman, Nicole Crane, Marny Ehmann, Evan Forman, Brandy-Joe Milliron, Nicole L. Simone

Department of Radiation Oncology Faculty Papers

OBJECTIVES: Prevention programs that can help adults improve the quality of their diets to reduce cancer risk are needed. This Phase IIa study prospectively tested a mHealth intervention designed to improve adherence to dietary quality guidelines for cancer prevention.

METHODS: All participants (N = 62) received nutrition education and a self-regulation skills curriculum, with a primary target of changing grocery shopping behavior. Using a randomized, factorial design, the study varied whether each of the following 4 components were added to the 20-week intervention: (1) location-triggered app messaging, delivered when individuals arrived at grocery stores, (2) reflections on benefits of change, …

First-In-Human, Phase I Dose-Escalation And Dose-Expansion Study Of Trophoblast Cell-Surface Antigen 2-Directed Antibody-Drug Conjugate Datopotamab Deruxtecan In Non-Small-Cell Lung Cancer: Tropion-Pantumor01, Toshio Shimizu, Jacob Sands, Kiyotaka Yoh, Alexander Spira, Edward B Garon, Satoru Kitazono, Melissa L Johnson, Funda Meric-Bernstam, Anthony W Tolcher, Noboru Yamamoto, Jon Greenberg, Yui Kawasaki, Hong Zebger-Gong, Fumiaki Kobayashi, Penny Phillips, Aaron E Lisberg, Rebecca S Heist

Faculty, Staff and Student Publications

PURPOSE: This first-in-human, dose-escalation and dose-expansion study evaluated the safety, tolerability, and antitumor activity of datopotamab deruxtecan (Dato-DXd), a novel trophoblast cell-surface antigen 2 (TROP2)-directed antibody-drug conjugate in solid tumors, including advanced non-small-cell lung cancer (NSCLC).

PATIENTS AND METHODS: Adults with locally advanced/metastatic NSCLC received 0.27-10 mg/kg Dato-DXd once every 3 weeks during escalation or 4, 6, or 8 mg/kg Dato-DXd once every 3 weeks during expansion. Primary end points were safety and tolerability. Secondary end points included objective response rate (ORR), survival, and pharmacokinetics.

RESULTS: Two hundred ten patients received Dato-DXd, including 180 in the 4-8 mg/kg dose-expansion cohorts. …

Nasal Iodophor Antiseptic Vs Nasal Mupirocin Antibiotic In The Setting Of Chlorhexidine Bathing To Prevent Infections In Adult Icus: A Randomized Clinical Trial, Susan S Huang, Edward J Septimus, Ken Kleinman, Lauren T Heim, Julia A Moody, Taliser R Avery, Laura Mclean, Syma Rashid, Katherine Haffenreffer, Lauren Shimelman, Whitney Staub-Juergens, Caren Spencer-Smith, Selsebil Sljivo, Ed Rosen, Russell E Poland, Micaela H Coady, Chi Hyun Lee, Eunice J Blanchard, Kimberly Reddish, Mary K Hayden, Robert A Weinstein, Brandon Carver, Kimberly Smith, Jason Hickok, Karen Lolans, Nadia Khan, S Gwynn Sturdevant, Sujan C Reddy, John A Jernigan, Kenneth E Sands, Jonathan B Perlin, Richard Platt

Faculty, Staff and Student Publications

IMPORTANCE: Universal nasal mupirocin plus chlorhexidine gluconate (CHG) bathing in intensive care units (ICUs) prevents methicillin-resistant Staphylococcus aureus (MRSA) infections and all-cause bloodstream infections. Antibiotic resistance to mupirocin has raised questions about whether an antiseptic could be advantageous for ICU decolonization.

OBJECTIVE: To compare the effectiveness of iodophor vs mupirocin for universal ICU nasal decolonization in combination with CHG bathing.

DESIGN, SETTING, AND PARTICIPANTS: Two-group noninferiority, pragmatic, cluster-randomized trial conducted in US community hospitals, all of which used mupirocin-CHG for universal decolonization in ICUs at baseline. Adult ICU patients in 137 randomized hospitals during baseline (May 1, 2015-April 30, 2017) …

Ccdc50 Promotes Tumor Growth Through Regulation Of Lysosome Homeostasis, Penghui Jia, Tian Tian, Zibo Li, Yicheng Wang, Yuxin Lin, Weijie Zeng, Yu Ye, Miao He, Xiangrong Ni, Ji'an Pan, Xiaonan Dong, Jian Huang, Chun-Mei Li, Deyin Guo, Panpan Hou

Faculty, Staff and Student Publications

The maintenance of lysosome homeostasis is crucial for cell growth. Lysosome-dependent degradation and metabolism sustain tumor cell survival. Here, we demonstrate that CCDC50 serves as a lysophagy receptor, promoting tumor progression and invasion by controlling lysosomal integrity and renewal. CCDC50 monitors lysosomal damage, recognizes galectin-3 and K63-linked polyubiquitination on damaged lysosomes, and specifically targets them for autophagy-dependent degradation. CCDC50 deficiency causes the accumulation of ruptured lysosomes, impaired autophagic flux, and superfluous reactive oxygen species, consequently leading to cell death and tumor suppression. CCDC50 expression is associated with malignancy, progression to metastasis, and poor overall survival in human melanoma. Targeting CCDC50 …

Pls3 Missense Variants Affecting The Actin-Binding Domains Cause X-Linked Congenital Diaphragmatic Hernia And Body-Wall Defects, Florence Petit, Mauro Longoni, Julie Wells, Richard S Maser, Eric L Bogenschutz, Matthew J Dysart, Hannah T M Contreras, Frederic Frénois, Barbara R Pober, Robin D Clark, Philip F Giampietro, Hilger H Ropers, Hao Hu, Maria Loscertales, Richard Wagner, Xingbin Ai, Harrison Brand, Anne-Sophie Jourdain, Marie-Ange Delrue, Brigitte Gilbert-Dussardier, Louise Devisme, Boris Keren, David J Mcculley, Lu Qiao, Rebecca Hernan, Julia Wynn, Tiana M Scott, Daniel G Calame, Zeynep Coban-Akdemir, Patricia Hernandez, Andres Hernandez-Garcia, Hagith Yonath, James R Lupski, Yufeng Shen, Wendy K Chung, Daryl A Scott, Carol J Bult, Patricia K Donahoe, Frances A High

Faculty, Staff and Student Publications

Congenital diaphragmatic hernia (CDH) is a relatively common and genetically heterogeneous structural birth defect associated with high mortality and morbidity. We describe eight unrelated families with an X-linked condition characterized by diaphragm defects, variable anterior body-wall anomalies, and/or facial dysmorphism. Using linkage analysis and exome or genome sequencing, we found that missense variants in plastin 3 (PLS3), a gene encoding an actin bundling protein, co-segregate with disease in all families. Loss-of-function variants in PLS3 have been previously associated with X-linked osteoporosis (MIM: 300910), so we used in silico protein modeling and a mouse model to address these seemingly disparate clinical …

Safety And Tolerability Of A Novel Anti-Her2 Antibody-Drug Conjugate (Pf-06804103) In Patients With Her2-Expressing Solid Tumors: A Phase 1 Dose-Escalation Study, Funda Meric-Bernstam, Emiliano Calvo, Keun Seok Lee, Victor Moreno, Yeon Hee Park, Sun Young Rha, Pavani Chalasani, Wei Zhong, Li Zhou, Steven Pirie-Shepherd, Abraham C F Leung, Giuseppe Curigliano

Faculty, Staff and Student Publications

PF-06804103 is an anti-HER2 antibody–drug conjugate with auristatin payload. We evaluated its safety, tolerability, and antitumor activity in patients with advanced/unresectable or metastatic breast and gastric cancers. This multicenter, open-label, first-in-human, phase 1 study (NCT03284723) comprised dose escalation (P1) and dose expansion (P2). In P1, adults with HER2+ breast or gastric cancer received PF-06804103 0.15–5.0 mg/kg intravenously once/21 days (Q3W); in P2, patients with HER2+ or HER2-low (IHC 1+ or IHC 2+/ISH−) breast cancer received 3.0 or 4.0 mg/kg Q3W. The primary endpoints were dose-limiting toxicities (DLT) and safety (P1), and objective response rate (ORR) assessed using RECIST v1.1 (P2). …

Diagnostic Criteria For Identifying Individuals At High Risk Of Progression From Mild Or Moderate To Severe Alcohol Use Disorder, Alex P Miller, Emma C Johnson, Rebecca Tillman, Vivia V Mccutcheon, Kathleen K Bucholz, Arpana Agrawal, Et Al.

2020-Current year OA Pubs

IMPORTANCE: Current Diagnostic and Statistical Manual of Mental Disorders (Fifth Edition) (DSM-5) diagnoses of substance use disorders rely on criterion count-based approaches, disregarding severity grading indexed by individual criteria.

OBJECTIVE: To examine correlates of alcohol use disorder (AUD) across count-based severity groups (ie, mild, moderate, mild-to-moderate, severe), identify specific diagnostic criteria indicative of greater severity, and evaluate whether specific criteria within mild-to-moderate AUD differentiate across relevant correlates and manifest in greater hazards of severe AUD development.

DESIGN, SETTING, AND PARTICIPANTS: This cohort study involved 2 cohorts from the family-based Collaborative Study on the Genetics of Alcoholism (COGA) with 7 sites …

Associations Between Covid-19 Therapies And Inpatient Gastrointestinal Bleeding: A Multisite Retrospective Study., Noah A. Wiedel, Harlan Sayles, Jessica Larson, Jana L. Wardian Phd, Alexander Hewlett, James C. Mcclay, Jin Ge, Alfred J. Anzalone, N3c Consortium

Journal Articles: Hospital Medicine

Little data is available regarding the incidence of gastrointestinal bleeding in adults hospitalized with COVID-19 infection and the influence of patient comorbidities and demographics, COVID-19 therapies, and typical medications used. In this retrospective study, we utilized the National COVID Cohort Collaborative to investigate the primary outcome of the development of gastrointestinal bleeding in 512 467 hospitalized US adults (age >18 years) within 14 days of a COVID-19 infection and the influence of demographics, comorbidities, and selected medications. Gastrointestinal bleeding developed in 0.44% of patients hospitalized with COVID-19. Comorbidities associated with gastrointestinal bleeding include peptic ulcer disease (adjusted odds ratio [aOR] …

First-In-Human Phase I/Ib Study Of Niz985, A Recombinant Heterodimer Of Il-15 And Il-15rα, As A Single Agent And In Combination With Spartalizumab In Patients With Advanced And Metastatic Solid Tumors, Rom Leidner, Kevin Conlon, Douglas G Mcneel, Andrea Wang-Gillam, Sumati Gupta, Robert Wesolowski, Monica Chaudhari, Nadia Hassounah, Jong Bong Lee, Lang Ho Lee, Jessica A O'Keeffe, Nancy Lewis, George N Pavlakis, John A Thompson

2020-Current year OA Pubs

BACKGROUND: Preclinically, interleukin-15 (IL-15) monotherapy promotes antitumor immune responses, which are enhanced when IL-15 is used in combination with immune checkpoint inhibitors (ICIs). This first-in-human study investigated NIZ985, a recombinant heterodimer comprising physiologically active IL-15 and IL-15 receptor α, as monotherapy and in combination with spartalizumab, an anti-programmed cell death protein-1 (anti-PD-1) monoclonal antibody, in patients with advanced solid tumors.

METHODS: This phase I/Ib study had two dose-escalation arms: single-agent NIZ985 administered subcutaneously thrice weekly (TIW, 2 weeks on/2 weeks off) or once weekly (QW, 3 weeks on/1 week off), and NIZ985 TIW or QW administered subcutaneously plus spartalizumab (400 …

Metabolomic Signatures Of Sedentary Behavior And Cardiometabolic Traits In Us Hispanics/Latinos: Results From Hchs/Sol, Jee-Young Moon, Jin Choul Chai, Bing Yu, Rebecca J Song, Guo-Chong Chen, Mariaelisa Graff, Martha L Daviglus, Queenie Chan, Bharat Thyagarajan, Sheila F Castaneda, Megan L Grove, Jianwen Cai, Xiaonan Xue, Yasmin Mossavar-Rahmani, Ramachandran S Vasan, Eric Boerwinkle, Robert C Kaplan, Qibin Qi

Faculty, Staff and Student Publications

PURPOSE: The aim of this study was to understand the serum metabolomic signatures of moderate-to-vigorous physical activity (MVPA) and sedentary behavior, and further associate their metabolomic signatures with incident cardiometabolic diseases.

METHODS: This analysis included 2711 US Hispanics/Latinos from the Hispanic Community Health Study/Study of Latinos (HCHS/SOL) aged 18-74 yr (2008-2011). An untargeted, liquid chromatography-mass spectrometry was used to profile the serum metabolome. The associations of metabolites with accelerometer-measured MVPA and sedentary time were examined using survey linear regressions adjusting for covariates. The weighted correlation network analysis identified modules of correlated metabolites in relation to sedentary time, and the modules …

Polygenic Risk And Chemotherapy-Related Subsequent Malignancies In Childhood Cancer Survivors: A Childhood Cancer Survivor Study And St Jude Lifetime Cohort Study Report, Cindy Im, Noha Sharafeldin, Yan Yuan, Zhaoming Wang, Yadav Sapkota, Zhanni Lu, Logan G Spector, Rebecca M Howell, Michael A Arnold, Melissa M Hudson, Kirsten K Ness, Leslie L Robison, Smita Bhatia, Gregory T Armstrong, Joseph P Neglia, Yutaka Yasui, Lucie M Turcotte

Faculty, Staff and Student Publications

Purpose: Chemotherapeutic exposures are associated with subsequent malignant neoplasm (SMN) risk. The role of genetic susceptibility in chemotherapy-related SMNs should be defined as use of radiation therapy (RT) decreases.

Patients and methods: SMNs among long-term childhood cancer survivors of European (EUR; N = 9,895) and African (AFR; N = 718) genetic ancestry from the Childhood Cancer Survivor Study and St Jude Lifetime Cohort Study were evaluated. An externally validated 179-variant polygenic risk score (PRS) associated with pleiotropic adult cancer risk from the UK Biobank Study (N > 400,000) was computed for each survivor. SMN cumulative incidence comparing top and bottom PRS …

Neighborhood Disadvantage And Neural Correlates Of Threat And Reward Processing In Survivors Of Recent Trauma, E. Kate Webb, Timothy D. Ely, Grace E. Rowland, Lauren A.M. Lebois, Sanne J.H. Van Rooij, Steven E. Bruce, Tanja Jovanovic, Stacey L. House, Francesca L. Beaudoin, Xinming An, Thomas C. Neylan, Gari D. Clifford, Sarah D. Linnstaedt, Laura T. Germine, Kenneth A. Bollen, Scott L. Rauch, John P. Haran, Alan B. Storrow, Christopher Lewandowski, Paul I. Musey, Phyllis L. Hendry, Sophia Sheikh, Christopher W. Jones, Brittany E. Punches, Robert A. Swor, Jose L. Pascual, Mark J. Seamon, Elizabeth M. Datner, Claire Pearson, David A. Peak, Roland C. Merchant, Robert M. Domeier, Niels K. Rathlev, Paulina Sergot, Leon D. Sanchez, Ronald C. Kessler, Karestan C. Koenen, Samuel A. Mclean, Jennifer S. Stevens, Kerry J. Ressler, Nathaniel G. Harnett

Department of Emergency Medicine Faculty Papers

IMPORTANCE: Differences in neighborhood socioeconomic characteristics are important considerations in understanding differences in risk vs resilience in mental health. Neighborhood disadvantage is associated with alterations in the function and structure of threat neurocircuitry.

OBJECTIVE: To investigate associations of neighborhood disadvantage with white and gray matter and neural reactivity to positive and negative stimuli in the context of trauma exposure.

DESIGN, SETTING, AND PARTICIPANTS: In this cross-sectional study, survivors of trauma who completed sociodemographic and posttraumatic symptom assessments and neuroimaging were recruited as part of the Advancing Understanding of Recovery After Trauma (AURORA) study between September 2017 and June 2021. Data …

The Impact Of Insomnia Symptoms On Obesity Among Mexicans Aged 50 And Older, Kanwal N Momin, Connor Sheehan, Rafael Samper-Ternent, David S López, Rebeca Wong, Sadaf Arefi Milani

Faculty, Staff and Student Publications

OBJECTIVE: To examine the association between insomnia and obesity in Mexican adults aged 50 and older.

MATERIALS AND METHODS: We used data from the Mexican Health and Aging Study (2015-2018). Self-reported insomnia was measured using the modified insomnia severity index with scores ranging from zero to six. Obesity was categorized using body mass index (BMI ≥ 30 kg/m2). We used generalized estimating equations to assess the association between insomnia and obesity over three years.

RESULTS: Insomnia was associated with obesity (odds ratio [OR]: 1.06, 95% confidence interval [CI]: 1.01,1.11), among those with no obesity at baseline. Among those with obesity, …

Neurocognitive Outcomes In Adult Survivors Of Neuroblastoma: A Report From The Childhood Cancer Survivor Study, Caroline Hesko, Wei Liu, Deo K Srivastava, Tara M Brinkman, Lisa Diller, Todd M Gibson, Kevin C Oeffinger, Wendy M Leisenring, Rebecca Howell, Gregory T Armstrong, Kevin R Krull, Tara O Henderson

Faculty, Staff and Student Publications

Background: Despite survival improvements, there is a paucity of data on neurocognitive outcomes in neuroblastoma survivors. This study addresses this literature gap.

Methods: Neurocognitive impairments in survivors were compared to sibling controls from the Childhood Cancer Survivor Study (CCSS) using the CCSS Neurocognitive Questionnaire. Impaired emotional regulation, organization, task efficiency, and memory defined as scores ≥90th percentile of sibling norms. Modified Poisson regression models evaluated associations with treatment exposures, era of diagnosis, and chronic conditions. Analyses were stratified by age at diagnosis (≤1 and >1 year) as proxy for lower versus higher risk disease.

Results: Survivors (N = 837; median …

Stereotactic Ablative Radiotherapy With Or Without Immunotherapy For Early-Stage Or Isolated Lung Parenchymal Recurrent Node-Negative Non-Small-Cell Lung Cancer: An Open-Label, Randomised, Phase 2 Trial, Joe Y Chang, Steven H Lin, Wenli Dong, Zhongxing Liao, Saumil J Gandhi, Carl M Gay, Jianjun Zhang, Stephen G Chun, Yasir Y Elamin, Frank V Fossella, George Blumenschein, Tina Cascone, Xiuning Le, Jenny V Pozadzides, Anne Tsao, Vivek Verma, James W Welsh, Aileen B Chen, Mehmet Altan, Reza J Mehran, Ara A Vaporciyan, Stephen G Swisher, Peter A Balter, Junya Fujimoto, Ignacio I Wistuba, Lei Feng, J Jack Lee, John V Heymach

Faculty, Staff and Student Publications

BACKGROUND: Stereotactic ablative radiotherapy (SABR) is the standard treatment for medically inoperable early-stage non-small-cell lung cancer (NSCLC), but regional or distant relapses, or both, are common. Immunotherapy reduces recurrence and improves survival in people with stage III NSCLC after chemoradiotherapy, but its utility in stage I and II cases is unclear. We therefore conducted a randomised phase 2 trial of SABR alone compared with SABR with immunotherapy (I-SABR) for people with early-stage NSCLC.

METHODS: We did an open-label, randomised, phase 2 trial comparing SABR to I-SABR, conducted at three different hospitals in TX, USA. People aged 18 years or older …

Atezolizumab For Advanced Alveolar Soft Part Sarcoma, Alice P Chen, Brian A Van Tine, Et Al.

2020-Current year OA Pubs

BACKGROUND: Alveolar soft part sarcoma (ASPS) is a rare soft-tissue sarcoma with a poor prognosis and no established therapy. Recently, encouraging responses to immune checkpoint inhibitors have been reported.

METHODS: We conducted an investigator-initiated, multicenter, single-group, phase 2 study of the anti-programmed death ligand 1 (PD-L1) agent atezolizumab in adult and pediatric patients with advanced ASPS. Atezolizumab was administered intravenously at a dose of 1200 mg (in patients ≥18 years of age) or 15 mg per kilogram of body weight with a 1200-mg cap (in patients <18 years of age) once every 21 days. Study end points included objective response, duration of response, and progression-free survival according to Response Evaluation Criteria in Solid Tumors (RECIST), version 1.1, as well as pharmacodynamic biomarkers of multistep drug action.

RESULTS: A total of 52 patients were evaluated. An objective response was observed in …

Neighborhood Disadvantage And Neural Correlates Of Threat And Reward Processing In Survivors Of Recent Trauma, E. Kate Webb, Timothy D. Ely, Grace E. Rowland, Lauren A. M Lebois, Sanne J. H Van Rooij, Steven E. Bruce, Tanja Jovanovic, Stacey L. House, Francesca L. Beaudoin, Xinming An, Thomas C. Neylan, Gari D. Clifford, Sarah D. Linnstaedt, Laura T. Germine, Kenneth A. Bollen, Scott L. Rauch, John P. Haran, Alan B. Storrow, Christopher A. Lewandowski, Paul I. Musey, Phyllis L. Hendry, Sophia Sheikh, Christopher W. Jones, Brittany E. Punches, Robert A. Swor, Jose L. Pascual, Mark J. Seamon, Elizabeth M. Datner, Claire Pearson, David A. Peak, Roland C. Merchant, Robert M. Domeier, Niels K. Rathlev, Paulina Sergot, Leon D. Sanchez, Ronald C. Kessler, Karestan C. Koenen, Samuel A. Mclean, Jennifer S. Stevens, Kerry J. Ressler, Nathaniel G. Harnett

Emergency Medicine Articles

IMPORTANCE: Differences in neighborhood socioeconomic characteristics are important considerations in understanding differences in risk vs resilience in mental health. Neighborhood disadvantage is associated with alterations in the function and structure of threat neurocircuitry.

OBJECTIVE: To investigate associations of neighborhood disadvantage with white and gray matter and neural reactivity to positive and negative stimuli in the context of trauma exposure.

DESIGN, SETTING, AND PARTICIPANTS: In this cross-sectional study, survivors of trauma who completed sociodemographic and posttraumatic symptom assessments and neuroimaging were recruited as part of the Advancing Understanding of Recovery After Trauma (AURORA) study between September 2017 and June 2021. Data …

Neighborhood Disadvantage And Neural Correlates Of Threat And Reward Processing In Survivors Of Recent Trauma, E Kate Webb, Stacey L House, Et Al.

2020-Current year OA Pubs

IMPORTANCE: Differences in neighborhood socioeconomic characteristics are important considerations in understanding differences in risk vs resilience in mental health. Neighborhood disadvantage is associated with alterations in the function and structure of threat neurocircuitry.

OBJECTIVE: To investigate associations of neighborhood disadvantage with white and gray matter and neural reactivity to positive and negative stimuli in the context of trauma exposure.

DESIGN, SETTING, AND PARTICIPANTS: In this cross-sectional study, survivors of trauma who completed sociodemographic and posttraumatic symptom assessments and neuroimaging were recruited as part of the Advancing Understanding of Recovery After Trauma (AURORA) study between September 2017 and June 2021. Data …

Surgical Management Of Congenital Malrotation Presenting In Adulthood., Jacob Holzemer, Krishna Patel, Oscar Ruiz, Jodi Oostra

Surgery Articles

Intestinal malrotation is characterised by positional and congenital fixation abnormalities resulting from a failure in embryonic development in the normal 270° rotation around the axis of the superior mesenteric artery. Intestinal malrotation is primarily thought to affect neonates with an incidence of 1 in 500, however, only 1 in 6000 live births are symptomatic, and these usually present within the first month of life in 40% of cases and within the first year in over 5% of cases as an obstructive pathology or volvulus. In adults, however, the incidence has been documented at 0.2%. These patients usually present with postprandial …

Childhood Exposure To Parental Threatening Behaviors And Anxiety In Emerging Adulthood: Indirect Effects Of Perceived Stress, Erika S Trent, Andres G Viana, Elizabeth M Raines, Haley E Conroy Busch, Karina Silva, Eric A Storch, Michael J Zvolensky

Center for Medical Ethics and Health Policy Staff Publications

Background: Although childhood exposure to parental threatening behaviors is associated with elevated anxiety in emerging adulthood, the underlying mechanisms remain unexplored. Perceived stress-a subjective experience comprised of feelings of helplessness (being unable to cope or exert control) and poor self-efficacy (confidence in one's ability to manage stressors)-is one candidate mechanism. The present investigation examined the underlying role of perceived stress in the association between childhood exposure to parental threatening behaviors and anxiety symptom severity in a sample of emerging adults.

Methods: Participants (N = 855; Mage = 18.75 years, SD = 1.05, range 18-24; 70.8% female) were recruited from a …

Dynamics Of Inflammatory Responses After Sars-Cov-2 Infection By Vaccination Status In The Usa: A Prospective Cohort Study, Xianming Zhu, Kelly A Gebo, Alison G Abraham, Feben Habtehyimer, Eshan U Patel, Oliver Laeyendecker, Thomas J Gniadek, Reinaldo E Fernandez, Owen R Baker, Malathi Ram, Edward R Cachay, Judith S Currier, Yuriko Fukuta, Jonathan M Gerber, Sonya L Heath, Barry Meisenberg, Moises A Huaman, Adam C Levine, Aarthi Shenoy, Shweta Anjan, Janis E Blair, Daniel Cruser, Donald N Forthal, Laura L Hammitt, Seble Kassaye, Giselle S Mosnaim, Bela Patel, James H Paxton, Jay S Raval, Catherine G Sutcliffe, Matthew Abinante, Patrick Broderick, Valerie Cluzet, Marie Elena Cordisco, Benjamin Greenblatt, Joann Petrini, William Rausch, David Shade, Karen Lane, Amy L Gawad, Sabra L Klein, Andrew Pekosz, Shmuel Shoham, Arturo Casadevall, Evan M Bloch, Daniel Hanley, David J Sullivan, Aaron A R Tobian

Faculty, Staff and Student Publications

BACKGROUND: Cytokines and chemokines play a critical role in the response to infection and vaccination. We aimed to assess the longitudinal association of COVID-19 vaccination with cytokine and chemokine concentrations and trajectories among people with SARS-CoV-2 infection.

METHODS: In this longitudinal, prospective cohort study, blood samples were used from participants enrolled in a multi-centre randomised trial assessing the efficacy of convalescent plasma therapy for ambulatory COVID-19. The trial was conducted in 23 outpatient sites in the USA. In this study, participants (aged ≥18 years) were restricted to those with COVID-19 before vaccination or with breakthrough infections who had blood samples …

Evaluation Of Field Sobriety Tests For Identifying Drivers Under The Influence Of Cannabis: A Randomized Clinical Trial, Thomas D Marcotte, Anya Umlauf, David J Grelotti, Emily G Sones, Kyle F Mastropietro, Raymond T Suhandynata, Marilyn A. Huestis, Igor Grant, Robert L Fitzgerald

Institute of Emerging Health Professions Faculty Papers

IMPORTANCE: With increasing medicinal and recreational cannabis legalization, there is a public health need for effective and unbiased evaluations for determining whether a driver is impaired due to Δ9-tetrahydrocannabinol (THC) exposure. Field sobriety tests (FSTs) are a key component of the gold standard law enforcement officer-based evaluations, yet controlled studies are inconclusive regarding their efficacy in detecting whether a person is under the influence of THC.

OBJECTIVE: To examine the classification accuracy of FSTs with respect to cannabis exposure and driving impairment (as determined via a driving simulation).

DESIGN, SETTING, AND PARTICIPANTS: This double-blind, placebo-controlled parallel randomized clinical trial was …