Medicine and Health Sciences Commons^™

Characterization Of Copy-Number Variants In A Large Cohort Of Patients With Von Willebrand Disease Reveals A Relationship Between Disrupted Regions And Disease Type, Brooke Sadler, Pamela A Christopherson, Crystal L Perry, Daniel B Bellissimo, Sandra L Haberichter, Gabe Haller, Lilian Antunes, Veronica H Flood, Jorge Di Paola, Robert R Montgomery, Zimmerman Program Investigators

2020-Current year OA Pubs

BACKGROUND: Genetic analysis for von Willebrand disease (VWD) commonly utilizes DNA sequencing to identify variants in the von Willebrand factor (

OBJECTIVES: This study aimed to characterize CNVs in a large sample of VWF mutation-negative VWD patients.

METHODS: To determine the role of CNVs in VWD, a VWF high-resolution comparative genomic hybridization array was custom-designed to avoid multiple sequence variations, repeated sequences, and the

RESULTS: Among the 204 patients, 7 unique CNVs were found, with a total of 24 CNVs (12%). Of the 7 unique CNVs, 1 was novel, 1 was found in a VWF database, and 5 were previously …

Blocking The Functional Domain Of Tip1 By Antibodies Sensitizes Cancer To Radiation Therapy, Abhay K Singh, David Ya Dadey, Michael J Rau, James Fitzpatrick, Harendra K Shah, Minakshi Saikia, Reid Townsend, Dinesh Thotala, Dennis E Hallahan, Vaishali Kapoor

2020-Current year OA Pubs

Non-small-cell lung cancer (NSCLC) and glioblastoma (GB) have poor prognoses. Discovery of new molecular targets is needed to improve therapy. Tax interacting protein 1 (TIP1), which plays a role in cancer progression, is overexpressed and radiation-inducible in NSCLC and GB. We evaluated the effect of an anti-TIP1 antibody alone and in combination with ionizing radiation (XRT) on NSCLC and GB in vitro and in vivo. NSCLC and GB cells were treated with anti-TIP1 antibodies and evaluated for proliferation, colony formation, endocytosis, and cell death. The efficacy of anti-TIP1 antibodies in combination with XRT on tumor growth was measured in mouse …

Management Of Severe Tricuspid Valve Regurgitation Due To Ruptured Papillary Muscle In A Patient With Mediastinitis Early After Heart Transplant, Erin M Schumer, Kunal D Kotkar, M Faraz Masood, Tsuyoshi Kaneko, Ralph J Damiano, Amit Pawale

2020-Current year OA Pubs

OBJECTIVE: Even though severe tricuspid regurgitation is not uncommon after cardiac transplantation, primary severe tricuspid regurgitation is rare. We present such a case with additional complexities.

METHODS: The patient was 44-year-old man with a HeartWare durable left ventricular assist device (Heartware Inc) who received a temporary right ventricular assist device (RVAD) with a ProtekDuo cannula (LivaNova Inc USA) for refractory ventricular fibrillation and underwent a heart transplant as United Network for Organ Sharing Status 1, in the presence of partially compensated cardiogenic shock, renal failure. Given complex re-operative surgery in a volume-overloaded patient with unknown pulmonary vascular resistance, an RVAD …

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 …

Development Of A Comprehensive Cardiac Atlas On A 1.5 Tesla Magnetic Resonance Linear Accelerator, Aronne M Schottstaedt, Eric S Paulson, Jason C Rubenstein, Xinfeng Chen, Eenas A Omari, X Allen Li, Chris J Schultz, Lindsay L Puckett, Clifford G Robinson, Filippo Alongi, Elizabeth M Gore, William A Hall

2020-Current year OA Pubs

BACKGROUND AND PURPOSE: The 1.5 Tesla (T) Magnetic Resonance Linear Accelerator (MRL) provides an innovative modality for improved cardiac imaging when planning radiation treatment. No MRL based cardiac atlases currently exist, thus, we sought to comprehensively characterize cardiac substructures, including the conduction system, from cardiac images acquired using a 1.5 T MRL and provide contouring guidelines.

MATERIALS AND METHODS: Five volunteers were enrolled in a prospective protocol (NCT03500081) and were imaged on the 1.5 T MRL with Half Fourier Single-Shot Turbo Spin-Echo (HASTE) and 3D Balanced Steady-State Free Precession (bSSFP) sequences in axial, short axis, and vertical long axis. Cardiac …

Immune Adjuvant Therapy With Interleukin-7 In A Lymphopenic Patient With Aplastic Anemia And Mucormycosis, Zachary D. Crees, Dilan A. Patel, Alexandra Dram, Miriam Kim, Michael D. Bern, Allison R. Eberly, Kristan Augustin, Richard S. Hotchkiss, John F. Dipersio

2020-Current year OA Pubs

BACKGROUND: We report the case of a patient with aplastic anemia and pancytopenia on immune-suppressive therapy who developed invasive pulmonary infection with mucormycosis and was treated with immune adjuvant therapy.

CASE SUMMARY: Given the patient's profound lymphopenia and progressive invasive mucor despite dual antifungal drug therapy, interleukin (IL)-7, a cytokine that induces lymphocyte activation and proliferation, was instituted and resulted in normalization of absolute lymphocyte counts and was temporally associated with clearance of fungal pathogens and resolution of clinical symptoms.

CONCLUSION: Patients with life-threatening fungal infections are frequently immune suppressed and immune adjuvant therapies should be considered in patients who …

In Silico Trial Of Simulation-Free Hippocampal-Avoidance Whole Brain Adaptive Radiotherapy, Alex T Price, Kylie H Kang, Francisco J Reynoso, Eric Laugeman, Christopher D Abraham, Jiayi Huang, Jessica Hilliard, Nels C Knutson, Lauren E Henke

2020-Current year OA Pubs

BACKGROUND AND PURPOSE: Hippocampal-avoidance whole brain radiotherapy (HA-WBRT) can be a time-consuming process compared to conventional whole brain techniques, thus potentially limiting widespread utilization. Therefore, we evaluated the

MATERIALS AND METHODS: Ten patients previously treated for central nervous system cancers with cone-beam computed tomography (CBCT) imaging were included in this study. The CBCT was the adaptive image-of-the-day to simulate first fraction on-board imaging. Initial contours defined on the MRI were rigidly matched to the CBCT. Online ART was used to create treatment plans at first fraction. Dose-volume metrics of these simulation-free plans were compared to standard-workflow HA-WBRT plans on each …

Good Manufacturing Practice Production Of Cd34+ Progenitor-Derived Nk Cells For Adoptive Immunotherapy In Acute Myeloid Leukemia, P K J D De Jonge, P M M Van Hauten, L D Janssen, A L De Goede, M M Berrien-Elliott, J M R Van Der Meer, C M Mousset, M W H Roeven, M Foster, N Blijlevens, W Hobo, T A Fehniger, J H Jansen, N P M Schaap, H Dolstra

2020-Current year OA Pubs

Allogeneic natural killer (NK) cell-based immunotherapy is a promising, well-tolerated adjuvant therapeutic approach for acute myeloid leukemia (AML). For reproducible NK cell immunotherapy, a homogenous, pure and scalable NK cell product is preferred. Therefore, we developed a good manufacturing practice (GMP)-compliant, cytokine-based ex vivo manufacturing process for generating NK cells from CD34

Sustained Antidepressant Effect Of Ketamine Through Nmdar Trapping In The Lhb, Shuangshuang Ma, Christopher J Lingle, Et Al.

2020-Current year OA Pubs

Ketamine, an N-methyl-D-aspartate receptor (NMDAR) antagonist

Introduction To A Compendium Of Strategies To Prevent Healthcare-Associated Infections In Acute-Care Hospitals: 2022 Updates, Deborah S Yokoe, Hilary M Babcock, Erik R Dubberke, Jonas Marschall, Et Al.

2020-Current year OA Pubs

Since the initial publication of

Derivation, Validation, And Clinical Relevance Of A Pediatric Sepsis Phenotype With Persistent Hypoxemia, Encephalopathy, And Shock, L. Nelson Sanchez-Pinto, Tellen D. Bennett, Emily K. Stroup, Yuan Luo, Mihir Atreya, Juliane Bubeck-Wardenburg, Grace Chong, Alon Geva, E. Vincent S. Faustino, Reid W. Farris, Mark W. Hall, Colin Rogerson, Sareen S. Shah, Scott L. Weiss, Robinder G. Khemani

2020-Current year OA Pubs

OBJECTIVES: Untangling the heterogeneity of sepsis in children and identifying clinically relevant phenotypes could lead to the development of targeted therapies. Our aim was to analyze the organ dysfunction trajectories of children with sepsis-associated multiple organ dysfunction syndrome (MODS) to identify reproducible and clinically relevant sepsis phenotypes and determine if they are associated with heterogeneity of treatment effect (HTE) to common therapies.

DESIGN: Multicenter observational cohort study.

SETTING: Thirteen PICUs in the United States.

PATIENTS: Patients admitted with suspected infections to the PICU between 2012 and 2018.

INTERVENTIONS: None.

MEASUREMENTS AND MAIN RESULTS: We used subgraph-augmented nonnegative matrix factorization to …

Investigating Weekend Effect In The Management Of Upper And Lower Extremity Degloving Injuries, Kaamya Varagur, Janessa Sullivan, Sarah N. Chiang, Gary B. Skolnick, Justin M. Sacks, Joani M. Christensen

2020-Current year OA Pubs

BACKGROUND: Weekend presentation has been associated with adverse outcomes in emergent conditions, including stroke, myocardial infarction, and critical limb ischemia. We examine whether a weekend effect exists in the management of and outcomes after extremity degloving injuries.

METHODS: The cohort included adults presenting with open extremity degloving injuries to a tertiary level one trauma center between June 2018 and May 2022. We collected demographics, comorbidities, injury information, interventions, and complications. Propensity score weighting was used to minimize confounding differences between those presenting on weekends (Sat-Sun) versus weekdays (Mon-Fri). Weighted regressions were used to examine differences in interventions by day of …

Pancreatic Tail Cancer In The Setting Of Pancreatitis With A Review Of The Literature: A Case Report, Shinji Rho, Sooyoung Martin, Zack Nigogosyan, Vladimir Kushnir, Aaron J Mintz, Zishuo Ian Hu

2020-Current year OA Pubs

Environmental risk factors for pancreatic cancer include acute and chronic pancreatitis, obesity, and tobacco use. Differentiating a pancreatic neoplasm in a patient with pancreatitis can be challenging due to their similar presentations. A 57-year-old African American man with a history of congestive heart failure, pancreatitis, and incomplete pancreas divisum presented with an epigastric abdominal pain that radiated to his back. Imaging showed necrotizing pancreatitis, a developing splenic infarct, and a mass at the pancreas tail. The patient was discharged with pain medications and was recommended follow-up imaging after resolution of his pancreatitis. He was readmitted to the emergency department 2 …

Knowledge, Beliefs, And Practices Related To Coronavirus Disease 2019 (Covid-19) Infection And Vaccination In Healthcare Personnel Working At Nonacute Care Facilities, Armaghan-E-Rehman Mansoor, Caroline A O'Neil, David Mcdonald, Victoria J Fraser, Hilary M Babcock, Jennie H Kwon, Cdc Prevention Epicenters Program

2020-Current year OA Pubs

OBJECTIVE: To characterize experiences, beliefs, and perceptions of risk related to coronavirus disease 2019 (COVID-19), infection prevention practices, and COVID-19 vaccination among healthcare personnel (HCP) at nonacute care facilities.

DESIGN: Anonymous survey.

SETTING: Three non-acute-care facilities in St. Louis, Missouri.

PARTICIPANTS: In total, 156 HCP responded to the survey, for a 25.6% participation rate). Among them, 32% had direct patient-care roles.

METHODS: Anonymous surveys were distributed between April-May 2021. Data were collected on demographics, work experience, COVID-19 exposure, knowledge, and beliefs about infection prevention, personal protective equipment (PPE) use, COVID-19 vaccination, and the impact of COVID-19.

RESULTS: Nearly all respondents …

Is Retention Of The Acetabular Component At Revision Surgery A Long-Term Solution?, Elizabeth Lieberman, Lee Sasala, Tanner Thornton, Robert Barrack, Ryan Nunley, Susan Thapa, John Clohisy

2020-Current year OA Pubs

BACKGROUND: Acetabular retention in revision total hip arthroplasty (THA) may be advantageous, yet long-term survival data is limited. Thus, we investigated long-term survivorship of retained acetabular components in revision THA with analysis of rerevision rate, instability risk, and clinical outcomes.

METHODS: We reviewed 98 hips with polyethylene wear and/or osteolysis that were revised with retained acetabular components. Acetabular inclination and anteversion were measured from prerevision radiographs. A retrospective chart review was performed, collecting outcomes of interest including Harris hip score, instability events, and rerevision surgery. Kaplan-Meier analysis was used to calculate the risk of revision over time. Predictors of survival …

Leveraging Cd4 Cell Count At Entry Into Care To Monitor Success Of Human Immunodeficiency Virus Prevention, Treatment, And Public Health Programming In The Greater St Louis Area Between 2017 And 2020, Lindsey M Filiatreau, Aaloke Mody, Daniel Vo, Cory Bradley, Aditi Ramakrishnan, Julia López, Jane O'Halloran, Anne Trolard, William G Powderly, Elvin H Geng

2020-Current year OA Pubs

CD4 cell count at entry into human immunodeficiency virus (HIV) care is a useful indicator of success of multiple steps in HIV public health programming. We demonstrate that CD4 cell count at care initiation was stable in St Louis between 2017 and 2019 but declined in 2020. Missouri efforts in the Ending the HIV Epidemic plan should focus on rapidly identifying individuals with undiagnosed HIV infection.

Factors Associated With Shorter-Interval Cervical Cancer Screening For Young Women In Three United States Healthcare Systems, Anne Marie Mccarthy, Jasmin A Tiro, Ellen Hu, Sarah Ehsan, Jessica Chubak, Aruna Kamineni, Sarah Feldman, Steven J Atlas, Michelle I Silver, Sarah Kobrin, Jennifer S Haas

2020-Current year OA Pubs

Frequently changing cervical cancer screening guidelines over the past two decades have been inconsistently adopted in the United States. Current guidelines set the recommended screening interval to three years for average-risk women aged 21-29 years. Few studies have evaluated how patient and provider factors are associated with implementation of cervical cancer screening intervals among younger women. This study evaluated multilevel factors associated with screening interval length among 69,939 women aged 21-29 years with an initial negative Pap screen between 2010 and 2015 across three large health systems in the U.S. Shorter-interval screening was defined as a second screening Pap within …

Peripheral Nodular Enhancement In Adrenal And Renal Hematomas: A Report Of 3 Cases, Gentry Russell, Pooja Navale, Daniel R Ludwig, Benjamin S Strnad, Malak Itani

2020-Current year OA Pubs

There are a wide range of benign and malignant pathologies that the radiologist may encounter in the adrenal glands and kidneys, often incidentally when imaging is performed for other indications. Many imaging modalities including CT, MR, and US are often used in an attempt to characterize these lesions. A definitive radiological diagnosis, however, is not always possible. This is at times due to atypical presentations of typical lesions which may be mistaken for more aggressive or concerning pathologic conditions. Adrenal lesions that do not demonstrate characteristic benign imaging features might require surgical excision. Similarly, cystic renal lesions that demonstrate nodular …

The Impact Of Adding Cost Information To A Conversation Aid To Support Shared Decision Making About Low-Risk Prostate Cancer Treatment: Results Of A Stepped-Wedge Cluster Randomised Trial, Mary C Politi, Rachel C Forcino, Katelyn Parrish, Marie-Anne Durand, A James O'Malley, Rachel Moses, Krista Cooksey, Glyn Elwyn

2020-Current year OA Pubs

BACKGROUND: Decision aids help patients consider the benefits and drawbacks of care options but rarely include cost information. We assessed the impact of a conversation-based decision aid containing information about low-risk prostate cancer management options and their relative costs.

METHODS: We conducted a stepped-wedge cluster randomised trial in outpatient urology practices within a US-based academic medical center. We randomised five clinicians to four intervention sequences and enroled patients newly diagnosed with low-risk prostate cancer. Primary patient-reported outcomes collected postvisit included the frequency of cost conversations and referrals to address costs. Other patient-reported outcomes included: decisional conflict postvisit and at 3 …

Identifying Contributors To Disparities In Patient Access Of Online Medical Records: Examining The Role Of Clinician Encouragement, Bryan A Sisk, Sunny Lin, Joyce Joy E Balls-Berry, Argentina E Servin, Jennifer W Mack

2020-Current year OA Pubs

OBJECTIVE: The aim of this study was to understand the influence of clinician encouragement and sociodemographic factors on whether patients access online electronic medical records (EMR).

MATERIALS AND METHODS: We analyzed 3279 responses from the Health Information National Trends Survey 5 cycle 4 survey, a cross-sectional, nationally representative survey administered by the National Cancer Institute. Frequencies and weighted proportions were calculated to compare clinical encouragement and access to their online EMR. Using multivariate logistic regression, we identified factors associated with online EMR use and clinician encouragement.

RESULTS: In 2020, an estimated 42% of US adults accessed their online EMR and …

Allogeneic Hematopoietic Cell Transplantation Improves Outcome In Myelodysplastic Syndrome Across High-Risk Genetic Subgroups: Genetic Analysis Of The Blood And Marrow Transplant Clinical Trials Network 1102 Study, Jurjen Versluis, Peter Westervelt, Et Al.

2020-Current year OA Pubs

PURPOSE: Allogeneic hematopoietic cell transplantation (HCT) in patients with myelodysplastic syndrome (MDS) improves overall survival (OS). We evaluated the impact of MDS genetics on the benefit of HCT in a biological assignment (donor

METHODS: We performed targeted sequencing in 309 patients age 50-75 years with International Prognostic Scoring System (IPSS) intermediate-2 or high-risk MDS, enrolled in the Blood and Marrow Transplant Clinical Trials Network 1102 study and assessed the association of gene mutations with OS. Patients with

RESULTS: The distribution of gene mutations was similar in the donor and no donor arms, with

CONCLUSION: HCT improved OS compared with non-HCT …

Non-Small Cell Lung Cancer Epigenomes Exhibit Altered Dna Methylation In Smokers And Never-Smokers, Jennifer A Karlow, Erica C Pehrsson, Xiaoyun Xing, Mark Watson, Siddhartha Devarakonda, Ramaswamy Govindan, Ting Wang

2020-Current year OA Pubs

Epigenetic alterations are widespread in cancer and can complement genetic alterations to influence cancer progression and treatment outcome. To determine the potential contribution of DNAmethylation alterations to tumor phenotype in non-small cell lung cancer (NSCLC) in both smoker and never-smoker patients, we performed genome-wide profiling of DNA methylation in 17 primary NSCLC tumors and 10 matched normal lung samples using the complementary assays, methylated DNA immunoprecipitation sequencing (MeDIP-seq) and methylation sensitive restriction enzyme sequencing (MRE-seq). We reported recurrent methylation changes in the promoters of several genes, many previously implicated in cancer, including FAM83A and SEPT9 (hypomethylation), as well as PCDH7, …

Identifying And Addressing Barriers To Implementing Core Electronic Health Record Use Metrics For Ambulatory Care: Virtual Consensus Conference Proceedings, Deborah R. Levy, Amanda J. Moy, Nate Apathy, Julia Adler-Milstein, Lisa Rotenstein, Bidisha Nath, S. Trent Rosenbloom, Thomas Kannampallil, Rebecca G. Mishuris, Aram Alexanian, Amber Sieja, Michelle R. Hribar, Jigar S. Patel, Christine A. Sinsky, Edward R. Melnick

2020-Current year OA Pubs

Precise, reliable, valid metrics that are cost-effective and require reasonable implementation time and effort are needed to drive electronic health record (EHR) improvements and decrease EHR burden. Differences exist between research and vendor definitions of metrics. PROCESS:  We convened three stakeholder groups (health system informatics leaders, EHR vendor representatives, and researchers) in a virtual workshop series to achieve consensus on barriers, solutions, and next steps to implementing the core EHR use metrics in ambulatory care. CONCLUSION:  Actionable solutions identified to address core categories of EHR metric implementation challenges include: (1) maintaining broad stakeholder engagement, (2) reaching agreement on standardized measure …

Intra-Individual Variability Adaptively Increases Following Inhibition Training During Middle Childhood, Roser Cañigueral, Keertana Ganesan, Claire R Smid, Abigail Thompson, Nico U F Dosenbach, Nikolaus Steinbeis

2020-Current year OA Pubs

There is ongoing debate on the relationship between intra-individual variability (IIV) of cognitive processes and task performance. While psychological research has traditionally assumed that lower intra-individual variability (IIV) aids consistent task performance, some studies suggest that greater IIV can also be adaptive, especially when flexible responding is required. Here we selectively manipulate inhibitory control (Stopping) and response speed (Going) by means of a training paradigm to 1) assess how this manipulation impacts Stopping IIV and its relationship to task performance, and 2) replicate previous findings showing that reductions in Going IIV are adaptive. A group of 208 6-13-year-old children were …

The Vcam1-Apoe Pathway Directs Microglial Chemotaxis And Alleviates Alzheimer's Disease Pathology, Shun-Fat Lau, Wei Wu, Hiu Yi Wong, Li Ouyang, Yi Qiao, Jiahui Xu, Jessica Hiu-Yan Lau, Carlton Wong, Yuanbing Jiang, David M Holtzman, Amy K Y Fu, Nancy Y Ip

2020-Current year OA Pubs

In Alzheimer's disease (AD), sensome receptor dysfunction impairs microglial danger-associated molecular pattern (DAMP) clearance and exacerbates disease pathology. Although extrinsic signals, including interleukin-33 (IL-33), can restore microglial DAMP clearance, it remains largely unclear how the sensome receptor is regulated and interacts with DAMP during phagocytic clearance. Here, we show that IL-33 induces VCAM1 in microglia, which promotes microglial chemotaxis toward amyloid-beta (Aβ) plaque-associated ApoE, and leads to Aβ clearance. We show that IL-33 stimulates a chemotactic state in microglia, characterized by Aβ-directed migration. Functional screening identified that VCAM1 directs microglial Aβ chemotaxis by sensing Aβ plaque-associated ApoE. Moreover, we found …

Antibody Response To Sars-Cov-2 Vaccines In Patients With Relapsing Multiple Sclerosis Treated With Evobrutinib: A Bruton's Tyrosine Kinase Inhibitor, Amit Bar-Or, Anne H Cross, Anthony L Cunningham, Yann Hyvert, Andrea Seitzinger, Hans Gühring, Elise E Drouin, Nektaria Alexandri, Davorka Tomic, Xavier Montalban

2020-Current year OA Pubs

BACKGROUND: Evobrutinib is an oral, central nervous system (CNS)-penetrant and highly selective covalent Bruton's tyrosine kinase inhibitor under clinical development for patients with relapsing multiple sclerosis (RMS).

OBJECTIVE: To investigate the effect of evobrutinib on immune responses in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccinated patients with RMS from a Phase II trial (NCT02975349).

METHODS: A

RESULTS: In the vaccinated subgroup, mean/minimum evobrutinib exposure pre-vaccination was 105.2/88.7 weeks. In total, 43 of 45 patients developed/increased S1/S2 IgG antibody levels post-vaccination; one patient's antibody response remained negative post-vaccination and the other had antibody levels above the upper limit of detection, …

Clinical Classification Of Variants In The Valosin-Containing Protein Gene Associated With Multisystem Proteinopathy, Marianela Schiava, Jil Daw, Conrad Chris Weihl, Et Al.

2020-Current year OA Pubs

BACKGROUND AND OBJECTIVES: Pathogenic variants in the valosin-containing protein (

METHODS: A 6-item clinical score was developed to evaluate the phenotypic level of evidence to support the pathogenicity of the novel variants. Each item is allocated a value, a score ranging from 0.5 to 5.5 points. A receiver-operating characteristic curve was used to identify a cutoff value of 3 to consider a variant as high likelihood disease associated. The scoring system results were confronted with results of in vitro ATPase activity assays and with in silico analysis.

RESULTS: All variants were missense, except for one small deletion-insertion, 18 led to …

Racial And Ethnic Disparities In Cervical Cancer Screening From Three U.S. Healthcare Settings, Jennifer C Spencer, Jane J Kim, Jasmin A Tiro, Sarah J Feldman, Sarah C Kobrin, Celette Sugg Skinner, Lei Wang, Anne Marie Mccarthy, Steve J Atlas, Sandi L Pruitt, Michelle I Silver, Jennifer S Haas

2020-Current year OA Pubs

INTRODUCTION: This study sought to characterize racial and ethnic disparities in cervical cancer screening and follow-up of abnormal findings across 3 U.S. healthcare settings.

METHODS: Data were from 2016 to 2019 and were analyzed in 2022, reflecting sites within the Multi-level Optimization of the Cervical Cancer Screening Process in Diverse Settings & Populations Research Center, part of the Population-based Research to Optimize the Screening Process consortium, including a safety-net system in the southwestern U.S., a northwestern mixed-model system, and a northeastern integrated healthcare system. Screening uptake was evaluated among average-risk patients (i.e., no previous abnormalities) by race and ethnicity as …

Neratinib + Fulvestrant + Trastuzumab For Hr-Positive, Her2-Negative, Her2-Mutant Metastatic Breast Cancer: Outcomes And Biomarker Analysis From The Summit Trial, K Jhaveri, H Park, C Ma, R Bose, L Peterson, Et Al.

2020-Current year OA Pubs

BACKGROUND: HER2 mutations are targetable alterations in patients with hormone receptor-positive (HR+) metastatic breast cancer (MBC). In the SUMMIT basket study, patients with HER2-mutant MBC received neratinib monotherapy, neratinib + fulvestrant, or neratinib + fulvestrant + trastuzumab (N + F + T). We report results from 71 patients with HR+, HER2-mutant MBC, including 21 (seven in each arm) from a randomized substudy of fulvestrant versus fulvestrant + trastuzumab (F + T) versus N + F + T.

PATIENTS AND METHODS: Patients with HR+ HER2-negative MBC with activating HER2 mutation(s) and prior cyclin-dependent kinase 4/6 inhibitor (CDK4/6i) therapy received N + …

Optimizing The Utility Of Anorectal Manometry For Diagnosis And Therapy: A Roundtable Review And Recommendations, Satish S C Rao, Gregory S Sayuk, Et Al.

2020-Current year OA Pubs

BACKGROUND & AIMS: Anorectal manometry (ARM) is a comprehensive diagnostic tool for evaluating patients with constipation, fecal incontinence, or anorectal pain; however, it is not widely utilized for reasons that remain unclear. The aim of this roundtable discussion was to critically examine the current clinical practices of ARM and biofeedback therapy by physicians and surgeons in both academic and community settings.

METHODS: Leaders in medical and surgical gastroenterology and physical therapy with interest in anorectal disorders were surveyed regarding practice patterns and utilization of these technologies. Subsequently, a roundtable was held to discuss survey results, explore current diagnostic and therapeutic …