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2022

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Implementing Educational And Systems-Level Changes To Improve Cancer Screening Rates Among State Employees In Missouri, Misty A Phillips, Sarah Chavez, Maggie Grotefendt, Xarria Lewis, Melanie Gowdy, Jane A Mcelroy, Jean S Wang, Sandra Hentges Dec 2022

Implementing Educational And Systems-Level Changes To Improve Cancer Screening Rates Among State Employees In Missouri, Misty A Phillips, Sarah Chavez, Maggie Grotefendt, Xarria Lewis, Melanie Gowdy, Jane A Mcelroy, Jean S Wang, Sandra Hentges

2020-Current year OA Pubs

As of 2022, only 51% of active eligible state employees in Missouri have been screened for colorectal cancer and 67% for breast cancer, despite having state-sponsored health insurance. In fall 2020, the Missouri Department of Health and Senior Services Comprehensive Cancer Program partnered with the Missouri Cancer Consortium to create a strategy to improve cancer screening rates among state employees. The project was designed to include 3 phases: 1) a colorectal cancer education phase, 2) an expanded education phase that included additional cancers, and 3) a proposed intervention phase that will include screening events. In the first phase, in 2020, …


Approaches To Healthcare Personnel Exemption Requests From Coronavirus Disease 2019 (Covid-19) Vaccination: Results Of A National Survey, Thomas R Talbot, Susan E Beekmann, Hilary M Babcock, Philip M Polgreen Dec 2022

Approaches To Healthcare Personnel Exemption Requests From Coronavirus Disease 2019 (Covid-19) Vaccination: Results Of A National Survey, Thomas R Talbot, Susan E Beekmann, Hilary M Babcock, Philip M Polgreen

2020-Current year OA Pubs

OBJECTIVE: Although a growing number of healthcare facilities are implementing healthcare personnel (HCP) coronavirus disease 2019 (COVID-19) vaccination requirements, vaccine exemption request management as a part of such programs is not well described.

DESIGN: Cross-sectional survey.

PARTICIPANTS: Infectious disease (ID) physician members of the Emerging Infections Network with infection prevention or hospital epidemiology responsibilities.

METHODS: Eligible persons were sent a web-based survey focused on hospital plans and practices around exemption allowances from HCP COVID-19 vaccine requirements.

RESULTS: Of the 695 ID physicians surveyed, 263 (38%) responded. Overall, 160 respondent institutions (92%) allowed medical exemptions, whereas 132 (76%) allowed religious exemptions. …


Transferability Of Alzheimer Disease Polygenic Risk Score Across Populations And Its Association With Alzheimer Disease-Related Phenotypes, Sang-Hyuk Jung, Carlos Cruchaga, Et Al. Dec 2022

Transferability Of Alzheimer Disease Polygenic Risk Score Across Populations And Its Association With Alzheimer Disease-Related Phenotypes, Sang-Hyuk Jung, Carlos Cruchaga, Et Al.

2020-Current year OA Pubs

IMPORTANCE: Polygenic risk scores (PRSs), which aggregate the genetic effects of single-nucleotide variants identified in genome-wide association studies (GWASs), can help distinguish individuals at a high genetic risk for Alzheimer disease (AD). However, genetic studies have predominantly focused on populations of European ancestry.

OBJECTIVE: To evaluate the transferability of a PRS for AD in the Korean population using summary statistics from a prior GWAS of European populations.

DESIGN, SETTING, AND PARTICIPANTS: This cohort study developed a PRS based on the summary statistics of a large-scale GWAS of a European population (the International Genomics of Alzheimer Project; 21 982 AD cases …


Derivation And Validation Of A Clinical Prediction Rule For Upper Limb Functional Outcomes After Traumatic Cervical Spinal Cord Injury, Saad Javeed, Jacob K Greenberg, Justin K Zhang, Christopher F Dibble, Jawad M Khalifeh, Ying Liu, Thomas J Wilson, Lynda J Yang, Yikyung Park, Wilson Z Ray Dec 2022

Derivation And Validation Of A Clinical Prediction Rule For Upper Limb Functional Outcomes After Traumatic Cervical Spinal Cord Injury, Saad Javeed, Jacob K Greenberg, Justin K Zhang, Christopher F Dibble, Jawad M Khalifeh, Ying Liu, Thomas J Wilson, Lynda J Yang, Yikyung Park, Wilson Z Ray

2020-Current year OA Pubs

IMPORTANCE: Traumatic cervical spinal cord injury (SCI) can result in debilitating paralysis. Following cervical SCI, accurate early prediction of upper limb recovery can serve an important role in guiding the appropriateness and timing of reconstructive therapies.

OBJECTIVE: To develop a clinical prediction rule to prognosticate upper limb functional recovery after cervical SCI.

DESIGN, SETTING, AND PARTICIPANTS: This prognostic study was a retrospective review of a longitudinal cohort study including patients enrolled in the National SCI model systems (SCIMS) database in US. Eligible patients were 15 years or older with tetraplegia (neurological level of injury C1-C8, American Spinal Cord Injury Association …


Opensep: A Generalizable Open Source Pipeline For Sofa Score Calculation And Sepsis-3 Classification, Mackenzie R Hofford, Sean C Yu, Alistair E W Johnson, Albert M Lai, Philip R O Payne, Andrew P Michelson Dec 2022

Opensep: A Generalizable Open Source Pipeline For Sofa Score Calculation And Sepsis-3 Classification, Mackenzie R Hofford, Sean C Yu, Alistair E W Johnson, Albert M Lai, Philip R O Payne, Andrew P Michelson

2020-Current year OA Pubs

EHR-based sepsis research often uses heterogeneous definitions of sepsis leading to poor generalizability and difficulty in comparing studies to each other. We have developed OpenSep, an open-source pipeline for sepsis phenotyping according to the Sepsis-3 definition, as well as determination of time of sepsis onset and SOFA scores. The Minimal Sepsis Data Model was developed alongside the pipeline to enable the execution of the pipeline to diverse sources of electronic health record data. The pipeline's accuracy was validated by applying it to the MIMIC-IV version 1.0 data and comparing sepsis onset and SOFA scores to those produced by the pipeline …


Outcomes In Participants With Failure Of Initial Antibacterial Therapy For Hospital-Acquired/Ventilator-Associated Bacterial Pneumonia Prior To Enrollment In The Randomized, Controlled Phase 3 Aspect-Np Trial Of Ceftolozane/Tazobactam Versus Meropenem, Marin H Kollef, Jean-François Timsit, Ignacio Martin-Loeches, Richard G Wunderink, Jennifer A Huntington, Erin H Jensen, Brian Yu, Christopher J Bruno Dec 2022

Outcomes In Participants With Failure Of Initial Antibacterial Therapy For Hospital-Acquired/Ventilator-Associated Bacterial Pneumonia Prior To Enrollment In The Randomized, Controlled Phase 3 Aspect-Np Trial Of Ceftolozane/Tazobactam Versus Meropenem, Marin H Kollef, Jean-François Timsit, Ignacio Martin-Loeches, Richard G Wunderink, Jennifer A Huntington, Erin H Jensen, Brian Yu, Christopher J Bruno

2020-Current year OA Pubs

BACKGROUND: Ceftolozane/tazobactam, a combination antibacterial agent comprising an anti-pseudomonal cephalosporin and β-lactamase inhibitor, is approved for the treatment of hospital-acquired/ventilator-associated bacterial pneumonia (HABP/VABP) in adults. Participants in the ASPECT-NP trial received ceftolozane/tazobactam (3 g [2 g ceftolozane/1 g tazobactam] every 8 h) or meropenem (1 g every 8 h). Participants failing prior antibacterial therapy for the current HABP/VABP episode at study entry had lower 28-day all-cause mortality (ACM) rates with ceftolozane/tazobactam versus meropenem treatment. Here, we report a post hoc analysis examining this result.

METHODS: The phase 3, randomized, controlled, double-blind, multicenter, noninferiority trial compared ceftolozane/tazobactam versus meropenem for treatment …


Basal Bodies Bend In Response To Ciliary Forces, Anthony D Junker, Louis G Woodhams, Adam W J Soh, Eileen T O'Toole, Philip V Bayly, Chad G Pearson Dec 2022

Basal Bodies Bend In Response To Ciliary Forces, Anthony D Junker, Louis G Woodhams, Adam W J Soh, Eileen T O'Toole, Philip V Bayly, Chad G Pearson

2020-Current year OA Pubs

Motile cilia beat with an asymmetric waveform consisting of a power stroke that generates a propulsive force and a recovery stroke that returns the cilium back to the start. Cilia are anchored to the cell cortex by basal bodies (BBs) that are directly coupled to the ciliary doublet microtubules (MTs). We find that, consistent with ciliary forces imposing on BBs, bending patterns in BB triplet MTs are responsive to ciliary beating. BB bending varies as environmental conditions change the ciliary waveform. Bending occurs where striated fibers (SFs) attach to BBs and mutants with short SFs that fail to connect to …


An Open-Label Multi-Center Phase 1 Safety Study Of Bxq-350 In Children And Young Adults With Relapsed Solid Tumors, Including Recurrent Malignant Brain Tumors, Mohamed S Abdelbaki, Mariko Dawn Dewire Schottmiller, Timothy P Cripe, Richard C Curry, Charles A Cruze, Leah Her, Suzanne Demko, Denise Casey, Bhuvana Setty Dec 2022

An Open-Label Multi-Center Phase 1 Safety Study Of Bxq-350 In Children And Young Adults With Relapsed Solid Tumors, Including Recurrent Malignant Brain Tumors, Mohamed S Abdelbaki, Mariko Dawn Dewire Schottmiller, Timothy P Cripe, Richard C Curry, Charles A Cruze, Leah Her, Suzanne Demko, Denise Casey, Bhuvana Setty

2020-Current year OA Pubs

BACKGROUND: BXQ-350 is a novel anti-neoplastic agent composed of saposin C (SapC) and phospholipid dioleoylphosphatidyl-serine sodium (DOPS) that selectively binds tumor cell phosphatidylserine (PS), inducing apoptosis. BXQ-350 has demonstrated preclinical antitumor effects in high-grade gliomas (HGG) and clinical activity in adult patients with recurrent HGG.

METHODS: A phase 1 study was conducted in pediatric patients with relapsed/refractory solid tumors, including recurrent brain tumors. Primary objectives were to characterize safety and determine maximum tolerated dose (MTD) and preliminary antitumor activity. Sequential dose cohorts were assessed up to 3.2 mg/kg using an accelerated titration design. Each cycle was 28 days; dosing occurred …


Controversies In Spine Research: Organ Culture Versus In Vivo Models For Studies Of The Intervertebral Disc, Shirley N Tang, Andres F Bonilla, Nadeen O Chahine, Aimee C Colbath, Jeremiah T Easley, Sibylle Grad, Lisbet Haglund, Christine L Le Maitre, Victor Leung, Annette M Mccoy, Devina Purmessur, Simon Y Tang, Stephan Zeiter, Lachlan J Smith Dec 2022

Controversies In Spine Research: Organ Culture Versus In Vivo Models For Studies Of The Intervertebral Disc, Shirley N Tang, Andres F Bonilla, Nadeen O Chahine, Aimee C Colbath, Jeremiah T Easley, Sibylle Grad, Lisbet Haglund, Christine L Le Maitre, Victor Leung, Annette M Mccoy, Devina Purmessur, Simon Y Tang, Stephan Zeiter, Lachlan J Smith

2020-Current year OA Pubs

Intervertebral disc degeneration is a common cause of low back pain, the leading cause of disability worldwide. Appropriate preclinical models for intervertebral disc research are essential to achieving a better understanding of underlying pathophysiology and for the development, evaluation, and translation of more effective treatments. To this end, in vivo animal and ex vivo organ culture models are both widely used by spine researchers; however, the relative strengths and weaknesses of these two approaches are a source of ongoing controversy. In this article, members from the Spine and Preclinical Models Sections of the Orthopedic Research Society, including experts in both …


Community Prevalence Of Helicobacter Pylori And Dyspepsia And Efficacy Of Triple Therapy In A Rural District Of Eastern Uganda, Yang Jae Lee, Ibrahim Ssekalo, Rauben Kazungu, Timothy S Blackwell Jr, Peter Muwereza, Yuefeng Wu, José B Sáenz Dec 2022

Community Prevalence Of Helicobacter Pylori And Dyspepsia And Efficacy Of Triple Therapy In A Rural District Of Eastern Uganda, Yang Jae Lee, Ibrahim Ssekalo, Rauben Kazungu, Timothy S Blackwell Jr, Peter Muwereza, Yuefeng Wu, José B Sáenz

2020-Current year OA Pubs

BACKGROUND:

OBJECTIVES: We determined the prevalence of

METHODS: Of 400 randomly selected adult residents in eastern Uganda, 376 were administered a validated, chronic dyspepsia questionnaire and provided a stool sample for

RESULTS:

CONCLUSIONS: In our study population, chronic dyspepsia did not predict


Community Access To Primary Care Is An Important Geographic Disparity Among Ovarian Cancer Patients Undergoing Cytoreductive Surgery, Abigail S Zamorano, Angela L Mazul, Christine Marx, Mary M Mullen, Molly Greenwade, L Stewart Massad, Carolyn K Mccourt, Andrea R Hagemann, Premal H Thaker, Katherine C Fuh, Matthew A Powell, David G Mutch, Dineo Khabele, Lindsay M Kuroki Dec 2022

Community Access To Primary Care Is An Important Geographic Disparity Among Ovarian Cancer Patients Undergoing Cytoreductive Surgery, Abigail S Zamorano, Angela L Mazul, Christine Marx, Mary M Mullen, Molly Greenwade, L Stewart Massad, Carolyn K Mccourt, Andrea R Hagemann, Premal H Thaker, Katherine C Fuh, Matthew A Powell, David G Mutch, Dineo Khabele, Lindsay M Kuroki

2020-Current year OA Pubs

OBJECTIVE: Given the importance of understanding neighborhood context and geographic access to care on individual health outcomes, we sought to investigate the association of community primary care (PC) access on postoperative outcomes and survival in ovarian cancer patients.

METHODS: This was a retrospective cohort study of Stage III-IV ovarian cancer patients who underwent surgery at a single academic, tertiary care hospital between 2012 and 2015. PC access was determined using a Health Resources and Services Administration designation. Outcomes included 30-day surgical and medical complications, extended hospital stay, ICU admission, hospital readmission, progression-free and overall survival. Descriptive statistics and chi-squared analyses …


Leflunomide-Induced And Paraneoplastic Ulcers In A Rheumatoid Arthritis Patient, Michael R Vittori, Jonathan Z Tang, William H Mccoy Iv Dec 2022

Leflunomide-Induced And Paraneoplastic Ulcers In A Rheumatoid Arthritis Patient, Michael R Vittori, Jonathan Z Tang, William H Mccoy Iv

2020-Current year OA Pubs

No abstract provided.


Delayed Diagnosis And Recovery Of Fulminant Immune Checkpoint Inhibitor-Associated Myocarditis On Va-Ecmo Support, Tarun Ramayya, Joshua D Mitchell, Justin C Hartupee, Kory Lavine, Clare H Ridley, Kunal D Kotkar, Jesus Jimenez, Chieh-Yu Lin, Jose A Alvarez-Cardona, Ronald K Krone, Courtney M Campbell Dec 2022

Delayed Diagnosis And Recovery Of Fulminant Immune Checkpoint Inhibitor-Associated Myocarditis On Va-Ecmo Support, Tarun Ramayya, Joshua D Mitchell, Justin C Hartupee, Kory Lavine, Clare H Ridley, Kunal D Kotkar, Jesus Jimenez, Chieh-Yu Lin, Jose A Alvarez-Cardona, Ronald K Krone, Courtney M Campbell

2020-Current year OA Pubs

No abstract provided.


Axillary Artery Fibromuscular Dysplasia In A Symptomatic Type B Aortic Dissection Causing Acute Limb Ischemia, Brian Sullivan, Nathan Droz, Vipul Khetarpaul Dec 2022

Axillary Artery Fibromuscular Dysplasia In A Symptomatic Type B Aortic Dissection Causing Acute Limb Ischemia, Brian Sullivan, Nathan Droz, Vipul Khetarpaul

2020-Current year OA Pubs

Fibromuscular dysplasia (FMD) can manifest outside of its classic presentation with unusual pathology. In the present report, we have described a case of an older male patient with aortic degeneration related to acute type B dissection who had required emergent left carotid-subclavian transposition and aortic stenting. Intraoperatively, his axillary artery FMD led to acute upper extremity ischemia. The patient was treated with classic maneuvers, including balloon angioplasty, reflecting the best practices in vascular surgery. We have also discussed the diagnosis, classification, and management of FMD.


Prolonged Dexamethasone Exposure Enhances Zebrafish Lateral-Line Regeneration But Disrupts Mitochondrial Homeostasis And Hair Cell Function, Allison L Saettele, Hiu-Tung C Wong, Katie S Kindt, Mark E Warchol, Lavinia Sheets Dec 2022

Prolonged Dexamethasone Exposure Enhances Zebrafish Lateral-Line Regeneration But Disrupts Mitochondrial Homeostasis And Hair Cell Function, Allison L Saettele, Hiu-Tung C Wong, Katie S Kindt, Mark E Warchol, Lavinia Sheets

2020-Current year OA Pubs

The synthetic glucocorticoid dexamethasone is commonly used to treat inner ear disorders. Previous work in larval zebrafish has shown that dexamethasone treatment enhances hair cell regeneration, yet dexamethasone has also been shown to inhibit regeneration of peripheral nerves after lesion. We therefore used the zebrafish model to determine the impact of dexamethasone treatment on lateral-line hair cells and primary afferents. To explore dexamethasone in the context of regeneration, we used copper sulfate (CuSO


Infections In The First Year Of Life And Development Of Beta Cell Autoimmunity And Clinical Type 1 Diabetes In High-Risk Individuals: The Trigr Cohort, Olga Kordonouri, David Cuthbertson, Malin Belteky, Bärbel Aschemeier-Fuchs, Neil H White, Elisabeth Cummings, Mikael Knip, Johnny Ludvigsson Dec 2022

Infections In The First Year Of Life And Development Of Beta Cell Autoimmunity And Clinical Type 1 Diabetes In High-Risk Individuals: The Trigr Cohort, Olga Kordonouri, David Cuthbertson, Malin Belteky, Bärbel Aschemeier-Fuchs, Neil H White, Elisabeth Cummings, Mikael Knip, Johnny Ludvigsson

2020-Current year OA Pubs

AIMS/HYPOTHESIS: Accumulated data suggest that infections in early life contribute to the development of type 1 diabetes. Using data from the Trial to Reduce IDDM in the Genetically at Risk (TRIGR), we set out to assess whether children who later developed diabetes-related autoantibodies and/or clinical type 1 diabetes had different exposure to infections early in life compared with those who did not.

METHODS: A cohort of 2159 children with an affected first-degree relative and HLA-conferred susceptibility to type 1 diabetes were recruited between 2002 and 2007 and followed until 2017. Infections were registered prospectively. The relationship between infections in the …


Glycemia And Β-Cell Function Before And After Elexacaftor/Tezacaftor/Ivacaftor In Youth And Adults With Cystic Fibrosis, Christine L Chan, Andrea Granados, Amir Moheet, Sachinkumar Singh, Timothy Vigers, Ana Maria Arbeláez, Yaling Yi, Shanming Hu, Andrew W Norris, Katie Larson Ode Dec 2022

Glycemia And Β-Cell Function Before And After Elexacaftor/Tezacaftor/Ivacaftor In Youth And Adults With Cystic Fibrosis, Christine L Chan, Andrea Granados, Amir Moheet, Sachinkumar Singh, Timothy Vigers, Ana Maria Arbeláez, Yaling Yi, Shanming Hu, Andrew W Norris, Katie Larson Ode

2020-Current year OA Pubs

BACKGROUND: Diabetes is prevalent among people with CF (PwCF) and associated with worse clinical outcomes. CFTR modulators are highly effective in improving the disease course of CF. However, the effects of elexacaftor/tezacaftor/ivacaftor (ETI) on glucose metabolism in PwCF are unclear.

METHODS: Twenty youth and adults with CF underwent frequently sampled oral glucose tolerance tests (fsOGTT) before and after ETI initiation. Glucose, insulin, and C-peptide were collected at 0, 10, 30, 60, 90, and 120 min after 1.75 g/kg (max 75 g) of dextrose. HbA1c and continuous glucose monitoring (CGM) were collected in a subset. Estimates of insulin secretion (C-peptide index), …


Practice Patterns Of Induction Therapy In Severe Anti-Neutrophil Cytoplasmic Autoantibody-Associated Vasculitis, Faten Aqeel, Lillian Xu, Ojaswi Tomar, Jessica Duchen, Tingting Li, Duvuru Geetha Dec 2022

Practice Patterns Of Induction Therapy In Severe Anti-Neutrophil Cytoplasmic Autoantibody-Associated Vasculitis, Faten Aqeel, Lillian Xu, Ojaswi Tomar, Jessica Duchen, Tingting Li, Duvuru Geetha

2020-Current year OA Pubs

No abstract provided.


G Protein Gamma Subunit, A Hidden Master Regulator Of Gpcr Signaling, Dinesh Kankanamge, Mithila Tennakoon, Ajith Karunarathne, N Gautam Dec 2022

G Protein Gamma Subunit, A Hidden Master Regulator Of Gpcr Signaling, Dinesh Kankanamge, Mithila Tennakoon, Ajith Karunarathne, N Gautam

2020-Current year OA Pubs

Heterotrimeric G proteins (αβγ subunits) that are activated by G protein-coupled receptors (GPCRs) mediate the biological responses of eukaryotic cells to extracellular signals. The α subunits and the tightly bound βγ subunit complex of G proteins have been extensively studied and shown to control the activity of effector molecules. In contrast, the potential roles of the large family of γ subunits have been less studied. In this review, we focus on present knowledge about these proteins. Induced loss of individual γ subunit types in animal and plant models result in strikingly distinct phenotypes indicating that γ subtypes play important and …


Identification Of Patients With Ovarian Cancer Experiencing The Highest Benefit From Bevacizumab In The First-Line Setting On The Basis Of Their Tumor-Intrinsic Chemosensitivity (Kelim): The Gog-0218 Validation Study, Benoit You, David Mutch, Et Al. Dec 2022

Identification Of Patients With Ovarian Cancer Experiencing The Highest Benefit From Bevacizumab In The First-Line Setting On The Basis Of Their Tumor-Intrinsic Chemosensitivity (Kelim): The Gog-0218 Validation Study, Benoit You, David Mutch, Et Al.

2020-Current year OA Pubs

PURPOSE: In patients with high-grade ovarian cancer, predictors of bevacizumab efficacy in first-line setting are needed. In the ICON-7 trial, a poor tumor intrinsic chemosensitivity (defined by unfavorable modeled cancer antigen-125 [CA-125] ELIMination rate constant K [KELIM] score) was a predictive biomarker. Only the patients with high-risk disease (suboptimally resected stage III, or stage IV) exhibiting unfavorable KELIM score < 1.0 had overall survival (OS) benefit from bevacizumab (median: 29.7

METHODS: In GOG-0218, 1,873 patients were treated with carboplatin-paclitaxel ± concurrent-maintenance bevacizumab/placebo. Patient KELIM values were calculated with CA-125 kinetics during the first 100 chemotherapy days by the Lyon University team. The association between KELIM score (favorable ≥ 1.0, or unfavorable …


Association Of Leukocyte Telomere Length With Perceived Physical Fatigability, Rain Katz, Emma L Gay, Allison L Kuipers, Joseph H Lee, Lawrence S Honig, Kaare Christensen, Mary F Feitosa, Mary K Wojczynski, Nancy W Glynn, Llfs Research Group Dec 2022

Association Of Leukocyte Telomere Length With Perceived Physical Fatigability, Rain Katz, Emma L Gay, Allison L Kuipers, Joseph H Lee, Lawrence S Honig, Kaare Christensen, Mary F Feitosa, Mary K Wojczynski, Nancy W Glynn, Llfs Research Group

2020-Current year OA Pubs

BACKGROUND: Leukocyte telomere length (LTL) is a potential genomic marker of biological aging, but its relation to fatigability, a prognostic indicator of phenotypic aging (e.g., functional decline) is unknown. We hypothesized shorter LTL would predict greater perceived physical fatigability, but that this association would be attenuated by adjusting for chronological age.

METHODS: Two generations of participants (N = 1997; 309 probands, 1688 offspring) were from the Long Life Family Study (age = 73.7 ± 10.4, range 60-108, 54.4 % women), a longitudinal cohort study of aging. LTL was assayed at baseline. Perceived physical fatigability was measured 8.0 ± 1.1 years …


Benefits Of Early Treatment With Natalizumab: A Real-World Study, Daniel Ontaneda, Ellen M Mowry, Scott D Newsome, Robert T Naismith, Jacqueline Nicholas, Elizabeth Fisher, Carl De Moor, Justin Bohn, Pei-Ran Ho, Al Sandrock, Richard Rudick, James R Williams Dec 2022

Benefits Of Early Treatment With Natalizumab: A Real-World Study, Daniel Ontaneda, Ellen M Mowry, Scott D Newsome, Robert T Naismith, Jacqueline Nicholas, Elizabeth Fisher, Carl De Moor, Justin Bohn, Pei-Ran Ho, Al Sandrock, Richard Rudick, James R Williams

2020-Current year OA Pubs

BACKGROUND: The impact of early versus later high-efficacy disease-modifying therapy (DMT) in patients with multiple sclerosis (MS) is uncertain. This study reported the association of early versus later natalizumab treatment with real-world clinical outcomes in MS patients.

METHODS: The study included 661 participants diagnosed with MS in 1994 or later from 7 US centers participating in the MS Partners Advancing Technology for Health Solutions (MS PATHS) network. Time to natalizumab treatment between diagnosis and first infusion (TTNT) was determined from the Tysabri Outreach: Unified Commitment to Health (TOUCH) registry. Clinical outcomes were defined using neuroperformance tests included in the Multiple …


Bone Metabolism And Incretin Hormones Following Glucose Ingestion In Young Adults With Pancreatic Insufficient Cystic Fibrosis, Wang Shin Lei, Marissa J Kilberg, Babette S Zemel, Ronald C Rubenstein, Clea Harris, Saba Sheikh, Andrea Kelly, Joseph M Kindler Dec 2022

Bone Metabolism And Incretin Hormones Following Glucose Ingestion In Young Adults With Pancreatic Insufficient Cystic Fibrosis, Wang Shin Lei, Marissa J Kilberg, Babette S Zemel, Ronald C Rubenstein, Clea Harris, Saba Sheikh, Andrea Kelly, Joseph M Kindler

2020-Current year OA Pubs

BACKGROUND: Gut-derived incretin hormones, including glucose-dependent insulinotropic peptide (GIP) and glucagon-like peptide 1 (GLP-1), regulate post-prandial glucose metabolism by promoting insulin production. GIP, GLP-1, and insulin contribute to the acute bone anti-resorptive effect of macronutrient ingestion by modifying bone turnover. Cystic fibrosis (CF) is associated with exocrine pancreatic insufficiency (PI), which perturbs the incretin response. Cross-talk between the gut and bone ("gut-bone axis") has not yet been studied in PI-CF. The objectives of this study were to assess changes in biomarkers of bone metabolism during oral glucose tolerance testing (OGTT) and to test associations between incretins and biomarkers of bone …


Cognition And The Single Neuron: How Cell Types Construct The Dynamic Computations Of Frontal Cortex, Amelia J Christensen, Torben Ott, Adam Kepecs Dec 2022

Cognition And The Single Neuron: How Cell Types Construct The Dynamic Computations Of Frontal Cortex, Amelia J Christensen, Torben Ott, Adam Kepecs

2020-Current year OA Pubs

Frontal cortex is thought to underlie many advanced cognitive capacities, from self-control to long term planning. Reflecting these diverse demands, frontal neural activity is notoriously idiosyncratic, with tuning properties that are correlated with endless numbers of behavioral and task features. This menagerie of tuning has made it difficult to extract organizing principles that govern frontal neural activity. Here, we contrast two successful yet seemingly incompatible approaches that have begun to address this challenge. Inspired by the indecipherability of single-neuron tuning, the first approach casts frontal computations as dynamical trajectories traversed by arbitrary mixtures of neurons. The second approach, by contrast, …


Public Interest In Hyaluronic Acid Injections For Knee Osteoarthritis In The United States And Europe: An International Google Trends Analysis, Samuel A Cohen, Robert H Brophy, Antonia F Chen, Karl C Roberts, Robert H Quinn, Kevin G Shea Dec 2022

Public Interest In Hyaluronic Acid Injections For Knee Osteoarthritis In The United States And Europe: An International Google Trends Analysis, Samuel A Cohen, Robert H Brophy, Antonia F Chen, Karl C Roberts, Robert H Quinn, Kevin G Shea

2020-Current year OA Pubs

BACKGROUND: Hyaluronic acid injections remain a common nonsurgical alternative for the treatment of knee osteoarthritis despite limited clinical evidence and varying global recommendations regarding its use. We used the Google Trends tool to provide a quantitative analysis of public interest in hyaluronic acid injections for knee osteoarthritis in the United States and Europe.

METHODS: We customized Google Trends parameters to obtain search data from January 2009 to December 2019 in both the United States and Europe. Combinations of "arthritis", "osteoarthritis", "hyaluronic acid", "knee arthritis", "knee osteoarthritis", and "knee injection" were entered into the Google Trends tool, and trend analyses were …


The Genetic Risk Factor Cel-Hyb1 Causes Proteotoxicity And Chronic Pancreatitis In Mice, Karianne Fjeld, Steven J Wilhelm, Jianguo Lin, Xunjun Xiao, Mark E Lowe, Et Al. Dec 2022

The Genetic Risk Factor Cel-Hyb1 Causes Proteotoxicity And Chronic Pancreatitis In Mice, Karianne Fjeld, Steven J Wilhelm, Jianguo Lin, Xunjun Xiao, Mark E Lowe, Et Al.

2020-Current year OA Pubs

BACKGROUND & AIMS: The CEL gene encodes the digestive enzyme carboxyl ester lipase. CEL-HYB1, a hybrid allele of CEL and its adjacent pseudogene CELP, is a genetic variant suggested to increase the risk of chronic pancreatitis (CP). Our aim was to develop a mouse model for CEL-HYB1 that enables studies of pancreatic disease mechanisms.

METHODS: We established a knock-in mouse strain where the variable number of tandem repeat (VNTR) region of the endogenous mouse Cel gene was substituted with the mutated VNTR of the human CEL-HYB1 allele. Heterozygous and homozygous Cel-HYB1 mice and littermate wildtype controls were characterized with respect …


X-Linked Hypophosphatemia Caused By The Prevailing North American Phex Variant C.*231a>G; Exon 13–15 Duplication Is Often Misdiagnosed As Ankylosing Spondylitis And Manifests In Both Men And Women, Kathryn Mccrystal Dahir, Margo Black, Gary S Gottesman, Erik A Imel, Steven Mumm, Cindy M Nichols, Michael P Whyte Dec 2022

X-Linked Hypophosphatemia Caused By The Prevailing North American Phex Variant C.*231a>G; Exon 13–15 Duplication Is Often Misdiagnosed As Ankylosing Spondylitis And Manifests In Both Men And Women, Kathryn Mccrystal Dahir, Margo Black, Gary S Gottesman, Erik A Imel, Steven Mumm, Cindy M Nichols, Michael P Whyte

2020-Current year OA Pubs

Inactivating mutations of the gene coding for phosphate-regulating endopeptidase homolog X-linked (PHEX) cause X-linked hypophosphatemia (XLH). A novel


Vascular Endothelial-Cadherin As A Marker Of Endothelial Injury In Preclinical Alzheimer Disease, Rawan Tarawneh, Rachel S Kasper, Jessie Sanford, Chia-Ling Phuah, Jason Hassenstab, Carlos Cruchaga Dec 2022

Vascular Endothelial-Cadherin As A Marker Of Endothelial Injury In Preclinical Alzheimer Disease, Rawan Tarawneh, Rachel S Kasper, Jessie Sanford, Chia-Ling Phuah, Jason Hassenstab, Carlos Cruchaga

2020-Current year OA Pubs

OBJECTIVE: Endothelial dysfunction is an early and prevalent pathology in Alzheimer disease (AD). We here investigate the value of vascular endothelial-cadherin (VEC) as a cerebrospinal fluid (CSF) marker of endothelial injury in preclinical AD.

METHODS: Cognitively normal participants (Clinical Dementia Rating [CDR] 0) from the Knight Washington University-ADRC were included in this study (n = 700). Preclinical Alzheimer's Cognitive Composite (PACC) scores, CSF VEC, tau, p-tau181, Aβ42/Aβ40, neurofilament light-chain (NFL) levels, and magnetic resonance imaging (MRI) assessments of white matter injury (WMI) were obtained from all participants. A subset of participants underwent brain amyloid imaging using positron emission tomography (amyloid-PET) …


Multicenter Randomized Clinical Trial Of A Mailed Outreach Strategy For Hepatocellular Carcinoma Surveillance, Amit G Singal, Sarah Reddy, Himani Radadiya Aka Patel, Deyaun Villarreal, Aisha Khan, Yan Liu, Vanessa Cerda, Nicole E Rich, Caitlin C Murphy, Jasmin A Tiro, Jennifer R Kramer, Ruben Hernaez Dec 2022

Multicenter Randomized Clinical Trial Of A Mailed Outreach Strategy For Hepatocellular Carcinoma Surveillance, Amit G Singal, Sarah Reddy, Himani Radadiya Aka Patel, Deyaun Villarreal, Aisha Khan, Yan Liu, Vanessa Cerda, Nicole E Rich, Caitlin C Murphy, Jasmin A Tiro, Jennifer R Kramer, Ruben Hernaez

Faculty, Staff and Students Publications

BACKGROUND: The effectiveness of hepatocellular carcinoma (HCC) surveillance is mitigated by underuse in clinical practice, highlighting a need for interventions. We evaluated the effectiveness of mailed HCC surveillance outreach to promote HCC surveillance in patients with cirrhosis.

METHODS: We conducted a multicenter pragmatic randomized clinical trial comparing mailed outreach for surveillance ultrasound (n = 1436) and usual care with visit-based surveillance (n = 1436) among patients with cirrhosis at 3 health systems (tertiary care referral center, safety net health system, and Veterans Affairs medical center) from April 2018 to December 2019. The primary outcome of this interim analysis was guideline …


A Phase I/Ii Trial Of Nivolumab Plus Ipilimumab In Children And Young Adults With Relapsed/Refractory Solid Tumors: A Children's Oncology Group Study Advl1412, Kara L Davis, Elizabeth Fox, Emasenyie Isikwei, Joel M Reid, Xiaowei Liu, Charles G Minard, Stephan Voss, Stacey L Berg, Brenda J Weigel, Crystal L Mackall Dec 2022

A Phase I/Ii Trial Of Nivolumab Plus Ipilimumab In Children And Young Adults With Relapsed/Refractory Solid Tumors: A Children's Oncology Group Study Advl1412, Kara L Davis, Elizabeth Fox, Emasenyie Isikwei, Joel M Reid, Xiaowei Liu, Charles G Minard, Stephan Voss, Stacey L Berg, Brenda J Weigel, Crystal L Mackall

Faculty, Staff and Students Publications

PURPOSE: In many cancers, nivolumab in combination with ipilimumab improves response rates compared with either agent alone, but the combination has not been evaluated in childhood cancer. We conducted a phase I/II trial of nivolumab plus ipilimumab in children and young adults with recurrent/refractory solid tumors.

PATIENTS AND METHODS: ADVL1412, Part C assessed safety of nivolumab plus ipilimumab at two dose levels (DL): DL1 1 mg/kg of each drug and DL2 3 mg/kg nivolumab plus 1 mg/kg ipilimumab. Part D evaluated response at the recommended phase II dose (RP2D) in Ewing sarcoma, rhabdomyosarcoma, and osteosarcoma. Part E tested DL3 (1 …