Medicine and Health Sciences Commons^™

A Site-Wise Reliability Analysis Of The Abcd Diffusion Fractional Anisotropy And Cortical Thickness: Impact Of Scanner Platforms, Yezhi Pan, L Elliot Hong, Ashley Acheson, Paul M Thompson, Neda Jahanshad, Alyssa H Zhu, Jiaao Yu, Chixiang Chen, Tianzhou Ma, Ho-Ling Liu, Jelle Veraart, Els Fieremans, Nicole R Karcher, Peter Kochunov, Shuo Chen

2020-Current year OA Pubs

The Adolescent Brain and Cognitive Development (ABCD) project is the largest study of adolescent brain development. ABCD longitudinally tracks 11,868 participants aged 9-10 years from 21 sites using standardized protocols for multi-site MRI data collection and analysis. While the multi-site and multi-scanner study design enhances the robustness and generalizability of analysis results, it may also introduce nonbiological variances including scanner-related variations, subject motion, and deviations from protocols. ABCD imaging data were collected biennially within a period of ongoing maturation in cortical thickness and integrity of cerebral white matter. These changes can bias the classical test-retest methodologies, such as intraclass correlation …

Extrapolative Validity Evidence Of The Anastomosis Objective Structured Assessment Of Technical Skill (A-Osats) For Robotic Ileocolic Anastomosis, Tiffany K Brocke, Cory Fox, Julie M Clanahan, Coen L Klos, William C Chapman Jr, Paul E Wise, Michael M Awad, Kerri A Ohman

2020-Current year OA Pubs

OBJECTIVE: To collect validity evidence for the use of the Anastomosis Objective Structured Assessment of Technical Skills (A-OSATS) instrument, which has been developed to evaluate performance of a minimally invasive side-to-side bowel anastomosis with hand-sewn common enterotomy.

DESIGN: Residents performed a robotic ileocolic anastomosis simulation on an ex vivo porcine model. Faculty scored each resident with the A-OSATS and performed a provocative leak test on the completed anastomoses. Residents were reassessed on the sewing sub-score 1 month later. Data were compared with parametric and nonparametric analysis.

SETTING: Single academic general surgery residency PARTICIPANTS: PGY-4 and -5 general surgery residents (n …

The Post-Transplant Lymphoproliferative Disorders-Metagenomic Shotgun Microbial Sequencing (Ptld-Msms) Study Methods And Protocol, Vikas R. Dharnidharka, Kristine M. Wylie, Todd N. Wylie, Marianna B. Ruzinova, Charles W. Goss, Gregory A. Storch, Neha Mehta-Shah, Derek Byers, Leslie Walther, Lujain Jaza, Hongjie Gu, Mansi Agarwal, Et Al.

2020-Current year OA Pubs

Post-transplant lymphoproliferative disorders (PTLDs) remain a feared complication of transplantation, with significant morbidity and mortality. The oncogenic Epstein-Barr virus (EBV) is a key pathogenic driver in 50%-80% of cases. Numerous prognostic indices, comprising multiple clinical, epidemiological and tumor characteristics, including EBV tumor positivity, do not consistently associate with worse patient survival, suggesting a potential role for EBV genome variants in determining outcome. However, the precision medicine tools for determining if a viral genome variant is pathogenic are very limited compared with human genome variants. Further, targeted studies have not implicated a specific viral etiological agent in EBV-negative PTLD. Using novel …

Evidence Of Human Bourbon Virus Infections, North Carolina, Usa, Diana L Zychowski, Gayan Bamunuarachchi, Scott P Commins, Ross M Boyce, Adrianus C M Boon

2020-Current year OA Pubs

Bourbon virus is a tickborne virus that can cause human disease. Cases have been reported in Kansas, Oklahoma, and Missouri, USA. We identified Bourbon virus-specific neutralizing antibodies in patients from North Carolina. Bourbon virus infections are likely more common than previously thought, highlighting the need for improved diagnostics and surveillance.

Concurrent Optogenetic Motor Mapping Of Multiple Limbs In Awake Mice Reveals Cortical Organization Of Coordinated Movements, Nischal Khanal, Jonah A Padawer-Curry, Trevor Voss, Kevin A Schulte, Annie R Bice, Adam Q Bauer

2020-Current year OA Pubs

BACKGROUND: Motor mapping allows for determining the macroscopic organization of motor circuits and corresponding motor movement representations on the cortex. Techniques such as intracortical microstimulation (ICMS) are robust, but can be time consuming and invasive, making them non-ideal for cortex-wide mapping or longitudinal studies. In contrast, optogenetic motor mapping offers a rapid and minimally invasive technique, enabling mapping with high spatiotemporal resolution. However, motor mapping has seen limited use in tracking 3-dimensonal, multi-limb movements in awake animals. This gap has left open questions regarding the underlying organizational principles of motor control of coordinated, ethologically-relevant movements involving multiple limbs.

OBJECTIVE: Our …

Distinct Patterns Of Smooth Muscle Phenotypic Modulation In Thoracic And Abdominal Aortic Aneurysms, Chien-Jung Lin, Campbell Keating, Robyn Roth, Yasar Caliskan, Mustafa Nazzal, Vernat Exil, Richard Dipaolo, Divya Ratan Verma, Kishore Harjai, Mohamed Zayed, Chieh-Yu Lin, Robert P Mecham, Ajay K Jain

2020-Current year OA Pubs

Thoracic and abdominal aortic aneurysms (TAAs and AAAs, respectively) share morphological features but have distinct clinical and hereditary characteristics. Studies using bulk RNA comparisons revealed distinct patterns of gene expression in human TAA and AAA tissues. However, given the summative nature of bulk RNA studies, these findings represent the totality of gene expression without regards to the differences in cellular composition. Single-cell RNA sequencing provides an opportunity to interrogate cell-type-specific transcriptomes. Single cell RNA sequencing datasets from mouse TAA (GSE153534) and AAA (GSE164678 and GSE152583) with respective controls were obtained from the Gene Expression Omnibus. Bioinformatic analysis was performed with …

A Phase 1 First-In-Human Study Of The Mcl-1 Inhibitor Azd5991 In Patients With Relapsed/Refractory Hematologic Malignancies, Pinkal Desai, Amanda Cashen, Et Al.

2020-Current year OA Pubs

PURPOSE: AZD5991, a human MCL-1 inhibitor, was assessed for safety, tolerability, pharmacokinetics, and antitumor activity as monotherapy and in combination with venetoclax in patients with relapsed or refractory hematologic malignancies.

PATIENTS AND METHODS: In the monotherapy cohort (n = 61), patients with hematologic malignancies received AZD5991 intravenously in escalating doses either once or twice weekly, following intrapatient dose escalation, during a 3-week cycle. In the combination cohort (n = 17), patients with acute myeloid leukemia and myelodysplastic syndrome received escalating doses of AZD5991 and venetoclax during either a 3- or 4-week cycle. Primary objectives were safety and maximum tolerated dose; …

Cohort Expansion And Genotype-Phenotype Analysis Of Rab11a-Associated Neurodevelopmental Disorder, Maria Carla Borroto, Jorge L Granadillo, Et Al.

2020-Current year OA Pubs

BACKGROUND: GTPases of the Rab family are important orchestrators of membrane trafficking, and their dysregulation has been linked to a variety of neuropathologies. In 2017, we established a causal link between RAB11A variants and developmental and epileptic encephalopathy. In this study, we expand the phenotype of RAB11A-associated neurodevelopmental disorder and explore genotype-phenotype correlations.

METHODS: We assessed 16 patients with pathogenic or likely pathogenic RAB11A variants, generally de novo, heterozygous missense variants. One individual had a homozygous nonsense variant, although concomitant with a pathogenic LAMA2 variant, which made their respective contributions to the phenotype difficult to discriminate.

RESULTS: We reinforce the …

Impact Of Artificial Intelligence-Based Autosegmentation Of Organs At Risk In Low- And Middle-Income Countries, Solomon Kibudde, Awusi Kavuma, Yao Hao, Tianyu Zhao, Hiram Gay, Jacaranda Van Rheenen, Pavan Mukesh Jhaveri, Minjmaa Minjgee, Enkhsetseg Vanchinbazar, Urdenekhuu Nansalmaa, Baozhou Sun

2020-Current year OA Pubs

PURPOSE: Radiation therapy (RT) processes require significant human resources and expertise, creating a barrier to rapid RT deployment in low- and middle-income countries (LMICs). Accurate segmentation of tumor targets and organs at risk (OARs) is crucial for optimal RT. This study assessed the impact of artificial intelligence (AI)-based autosegmentation of OARs in 2 LMICs.

METHODS AND MATERIALS: Ten patients, comprising 5 head and neck (HN) cancer patients and 5 prostate cancer patients, were randomly selected. Planning computed tomography images were subjected to autosegmentation using an Food and Drug Administration-approved AI software tool and manual segmentation by experienced radiation oncologists from …

Precision Functional Mapping To Advance Developmental Psychiatry Research, Alyssa K Labonte, M Catalina Camacho, Julia Moser, Sanju Koirala, Timothy O Laumann, Scott Marek, Damien Fair, Chad M Sylvester

2020-Current year OA Pubs

Many psychiatric conditions have their roots in early development. Individual differences in prenatal brain function (which is influenced by a combination of genetic risk and the prenatal environment) likely interact with individual differences in postnatal experience, resulting in substantial variation in brain functional organization and development in infancy. Neuroimaging has been a powerful tool for understanding typical and atypical brain function and holds promise for uncovering the neurodevelopmental basis of psychiatric illness; however, its clinical utility has been relatively limited thus far. A substantial challenge in this endeavor is the traditional approach of averaging brain data across groups despite individuals …

Attention-Based Cnn-Bilstm For Sleep State Classification Of Spatiotemporal Wide-Field Calcium Imaging Data, Xiaohui Zhang, Eric C Landsness, Hanyang Miao, Wei Chen, Michelle J Tang, Lindsey M Brier, Joseph P Culver, Jin-Moo Lee, Mark A Anastasio

2020-Current year OA Pubs

BACKGROUND: Wide-field calcium imaging (WFCI) with genetically encoded calcium indicators allows for spatiotemporal recordings of neuronal activity in mice. When applied to the study of sleep, WFCI data are manually scored into the sleep states of wakefulness, non-REM (NREM) and REM by use of adjunct EEG and EMG recordings. However, this process is time-consuming, invasive and often suffers from low inter- and intra-rater reliability. Therefore, an automated sleep state classification method that operates on spatiotemporal WFCI data is desired.

NEW METHOD: A hybrid network architecture consisting of a convolutional neural network (CNN) to extract spatial features of image frames and …

Effect Of Surgical Fixation Timing On In-Hospital Mortality And Morbidity Of Distal Femur Fractures, Joseph T Gutbrod, Dustin Stwalley, Anna N Miller

2020-Current year OA Pubs

INTRODUCTION: The literature lacks a large-scale study investigating the effect of surgical fixation timing on early mortality and morbidity outcomes in distal femur fractures. The aims of this study were to determine the effect of fixation timing on in-hospital mortality and morbidity outcomes for operatively treated distal femur fractures retrospectively using large database data.

METHODS: This study is a retrospective analysis using data from the National Trauma Data Bank. Patients were stratified into a fragility cohort (age ≥ 60, ISS < 16) and polytrauma cohort (age < 60, ISS ≥16), with both cohorts analyzed separately. Within each cohort, patients were split into three fixation timing groups: within 24 h, between 24 and 48 h, and greater than 48 h from presentation to the hospital. Fixation-timing groups were compared based on the primary outcome of in-hospital mortality rate. Secondary outcomes included hospital length of stay (LOS), ICU length of stay (ICU LOS), days on a ventilator, and complications.

RESULTS: The fragility and polytrauma cohorts included 22,045 and 5,905 patients, respectively. The in-hospital mortality rate was 1.23 % in …

Can Acetabular Dysplasia Be Measured On Axial Ct? A Measurement For Trauma Surgeons, Ravi R Agrawal, Eric R Barnard, Helena F Barber, Anna N Miller

2020-Current year OA Pubs

BACKGROUND: Acetabular dysplasia has been theorized as a risk factor instability amongst common acetabular fractures, such as posterior wall (PW) fractures. However, common radiographic measurements often cannot be acquired in trauma patients. We evaluated axial computed tomography (CT) scans to identify novel, easily-obtained measurements that correlate with acetabular dysplasia for use in surgical indications and planning.

METHODS: Patients with known acetabular dysplasia undergoing elective periacetabular osteotomy were selected. A different group of patients without pelvic ring or acetabular fractures from an institutional trauma registry were selected as a comparison group. Standard indices of dysplasia were collected, such as center-edge angle …

Influence Of Physical Activity Measurement On The Association Between Life's Essential 8 And Incident Cardiovascular Disease In Older Women, Eric T Hyde, Steve Nguyen, Michael J Lamonte, Chongzhi Di, John Bellettiere, Lesley F Tinker, Randi E Foraker, Hilary A Tindle, Marcia L Stefanick, Andrea Z Lacroix

2020-Current year OA Pubs

OBJECTIVE: The American Heart Association's Life's Essential 8 (LE8) metric includes self-reported physical activity as one of the metrics for assessing cardiovascular health. Self-reported physical activity is prone to misclassification, whereas accelerometer measures are less biased. We examined associations of LE8 and incident cardiovascular disease (CVD) using self-reported and accelerometer-measured physical activity.

METHODS: Participants in the Women's Health Initiative (WHI) Objective Physical Activity and Cardiovascular Health Study (n = 4,243; mean age = 79 ± 7 years) with no CVD history completed the WHI physical activity questionnaire and the Community Healthy Activities Model Program for Seniors (CHAMPS) questionnaire prior to …

Differential Chromatin Accessibility And Transcriptional Dynamics Define Breast Cancer Subtypes And Their Lineages, Michael D Iglesia, Reyka G Jayasinghe, Siqi Chen, Nadezhda V Terekhanova, John M Herndon, Erik Storrs, Alla Karpova, Daniel Cui Zhou, Nataly Naser Al Deen, Andrew T Shinkle, Rita Jui-Hsien Lu, Wagma Caravan, Andrew Houston, Yanyan Zhao, Kazuhito Sato, Preet Lal, Cherease Street, Fernanda Martins Rodrigues, Austin N Southard-Smith, André Luiz N Targino Da Costa, Houxiang Zhu, Chia-Kuei Mo, Lisa Crowson, Robert S Fulton, Matthew A Wyczalkowski, Catrina C Fronick, Lucinda A Fulton, Hua Sun, Sherri R Davies, Elizabeth L Appelbaum, Sara E Chasnoff, Madelyn Carmody, Candace Brooks, Ruiyang Liu, Michael C Wendl, Clara Oh, Diane Bender, Carlos Cruchaga, Oscar Harari, Andrea Bredemeyer, Kory Lavine, Ron Bose, Julie Margenthaler, Jason M Held, Samuel Achilefu, Foluso Ademuyiwa, Rebecca Aft, Cynthia Ma, Graham A Colditz, Stephen T Oh, James Fitzpatrick, Kooresh I Shoghi, Milan G Chheda, Deborah J Veis, Feng Chen, Ryan C Fields, William E Gillanders, Li Ding, Et Al.

2020-Current year OA Pubs

Breast cancer (BC) is defined by distinct molecular subtypes with different cells of origin. The transcriptional networks that characterize the subtype-specific tumor-normal lineages are not established. In this work, we applied bulk, single-cell and single-nucleus multi-omic techniques as well as spatial transcriptomics and multiplex imaging on 61 samples from 37 patients with BC to show characteristic links in gene expression and chromatin accessibility between BC subtypes and their putative cells of origin. Regulatory network analysis of transcription factors underscored the importance of BHLHE40 in luminal BC and luminal mature cells and KLF5 in basal-like tumors and luminal progenitor cells. Furthermore, …

Posttreatment Surveillance Intensity And Overall Survival In Prostate Cancer Survivors (Aft-30), Ronald C Chen, Ramsankar Basak, Stacie Dusetzina, Deborah S Usinger, Zahed Mohammed, Aaron D Falchook, Jessica R Schumacher, Amanda B Francescatti, Amanda Cuddy, George J Chang, Benjamin D Kozower, Caprice C Greenberg, Anne K Barber, Aaron J Katz

2020-Current year OA Pubs

BACKGROUND: Posttreatment surveillance affects millions of cancer survivors, but empiric data to guide clinical practice are lacking. This study assessed whether the intensity of surveillance testing after radical prostatectomy or radiation therapy for localized prostate cancer is associated with overall survival.

METHODS: Men diagnosed with localized prostate cancer between 2005 and 2010 who underwent radical prostatectomy or radiation therapy at a Commission on Cancer-accredited facility were randomly sampled. Primary data collected from 10 147 patients sampled across 1007 facilities were linked with existing data from the National Cancer Database. Analysis examined whether intensity of surveillance measured as the number of …

Iglon5 Frequency In Idiopathic Rem Sleep Behavior Disorder: A Multicenter Study, Ronald Postuma, Jennifer Mcleland, Albert A. Davis, Yo-El S. Ju, Et Al.

2020-Current year OA Pubs

BACKGROUND AND OBJECTIVES: Idiopathic/isolated REM sleep behavior disorder (iRBD) has been strongly linked to neurodegenerative synucleinopathies such as Parkinson disease, dementia with Lewy bodies, and multiple system atrophy. However, there have been increasing reports of RBD as a presenting feature of serious and treatable autoimmune syndromes, particularly IGLON5. This study's objective was to investigate the frequency of autoantibodies in a large cohort of participants with iRBD.

METHODS: Participants were enrolled in the North American Prodromal Synucleinopathy cohort with polysomnography-confirmed iRBD, free of parkinsonism and dementia. Plasma samples were systematically screened for the autoantibodies IGLON5, DPPX, LGI1, and CASPR2 using plasma …

Adjuvant Trastuzumab Emtansine Versus Paclitaxel Plus Trastuzumab For Stage I Human Epidermal Growth Factor Receptor 2-Positive Breast Cancer: 5-Year Results And Correlative Analyses From Atempt, Paolo Tarantino, Ron Bose, Et Al.

2020-Current year OA Pubs

PURPOSE: Long-term outcomes of patients with stage I human epidermal growth factor receptor 2 (HER2)-positive breast cancer receiving adjuvant trastuzumab emtansine (T-DM1) remain undefined, and prognostic predictors represent an unmet need.

METHODS: In the ATEMPT phase II trial, patients with stage I centrally confirmed HER2-positive breast cancer were randomly assigned 3:1 to adjuvant T-DM1 for 1 year or paclitaxel plus trastuzumab (TH). Coprimary objectives were to compare the incidence of clinically relevant toxicities between arms and to evaluate invasive disease-free survival (iDFS) with T-DM1. Correlative analyses included the HER2DX genomic tool, multiomic evaluations of HER2 heterogeneity, and predictors of thrombocytopenia. …

Clinical Validation Of A Cell-Free Dna Fragmentome Assay For Augmentation Of Lung Cancer Early Detection, Peter J Mazzone, David Gierada, Et Al.

2020-Current year OA Pubs

Lung cancer screening via annual low-dose computed tomography has poor adoption. We conducted a prospective case-control study among 958 individuals eligible for lung cancer screening to develop a blood-based lung cancer detection test that when positive is followed by a low-dose computed tomography. Changes in genome-wide cell-free DNA fragmentation profiles (fragmentomes) in peripheral blood reflected genomic and chromatin characteristics of lung cancer. We applied machine learning to fragmentome features to identify individuals who were more or less likely to have lung cancer. We trained the classifier using 576 cases and controls from study samples and validated it in a held-out …

Il-10r Inhibition Reprograms Tumor-Associated Macrophages And Reverses Drug Resistance In Multiple Myeloma, Jennifer Sun, Monica Shokeen, Barbara Muz, Kinan Alhallak, Chaelee Park, Berit Lubben, Yixuan Chen, Ola Adebayo, Hannah Bash, Sarah Kelley, Mark Fiala, Diane E Bender, Ravi Vij, Abdel Kareem Azab, Et Al.

2020-Current year OA Pubs

Multiple myeloma (MM) is the cancer of plasma cells within the bone marrow and remains incurable. Tumor-associated macrophages (TAMs) within the tumor microenvironment often display a pro-tumor phenotype and correlate with tumor proliferation, survival, and therapy resistance. IL-10 is a key immunosuppressive cytokine that leads to recruitment and development of TAMs. In this study, we investigated the role of IL-10 in MM TAM development as well as the therapeutic application of IL-10/IL-10R/STAT3 signaling inhibition. We demonstrated that IL-10 is overexpressed in MM BM and mediates M2-like polarization of TAMs in patient BM, 3D co-cultures in vitro, and mouse models. In …

Multiomic Profiling Identifies Predictors Of Survival In African American Patients With Acute Myeloid Leukemia, Andrew Stiff, Geoffrey L Uy, Et Al.

2020-Current year OA Pubs

Genomic profiles and prognostic biomarkers in patients with acute myeloid leukemia (AML) from ancestry-diverse populations are underexplored. We analyzed the exomes and transcriptomes of 100 patients with AML with genomically confirmed African ancestry (Black; Alliance) and compared their somatic mutation frequencies with those of 323 self-reported white patients with AML, 55% of whom had genomically confirmed European ancestry (white; BeatAML). Here we find that 73% of 162 gene mutations recurrent in Black patients, including a hitherto unreported PHIP alteration detected in 7% of patients, were found in one white patient or not detected. Black patients with myelodysplasia-related AML were younger …

Determining The N-Glycan And Collagen/Extracellular Matrix Protein Compositions In A Novel Outcome Cohort Of Prostate Cancer Tissue Microarrays Using Maldi-Msi, Jordan P Hartig, Joseph E Ippolito, Et Al.

2020-Current year OA Pubs

Using matrix-assisted laser desorption/ionization mass spectrometry imaging techniques on a unique cohort of prostate cancer tissues, we highlighted several molecular characteristics of matrix that have potential to act as early predictors of prostate cancer metastasis.

Diclofenac Sensitizes Multi-Drug Resistant Acinetobacter Baumannii To Colistin, Fabiana Bisaro, Clay D. Jackson-Litteken, Jenna C. Mcguffey, Anna J. Hooppaw, Sophie Bodrog, Leila Jebeli, Manon Janet-Maitre, Juan C. Ortiz-Marquez, Tim Van Opijnen, Nichollas E. Scott, Gisela Di Venanzio, Mario F. Feldman

2020-Current year OA Pubs

Acinetobacter baumannii causes life-threatening infections that are becoming difficult to treat due to increasing rates of multi-drug resistance (MDR) among clinical isolates. This has led the World Health Organization and the CDC to categorize MDR A. baumannii as a top priority for the research and development of new antibiotics. Colistin is the last-resort antibiotic to treat carbapenem-resistant A. baumannii. Not surprisingly, reintroduction of colistin has resulted in the emergence of colistin-resistant strains. Diclofenac is a non-steroidal anti-inflammatory drug used to treat pain and inflammation associated with arthritis. In this work, we show that diclofenac sensitizes colistin-resistant A. baumannii clinical strains …

Association Between Glucagon-Like Peptide-1 Receptor Agonist Use And Progression Of Monoclonal Gammopathy Of Uncertain Significance To Multiple Myeloma Among Patients With Diabetes, Nikhil Grandhi, Lawrence Liu, Mei Wang, Theodore Thomas, Martin Schoen, Kristen Sanfilippo, Feng Gao, Graham A Colditz, Kenneth R Carson, Murali Janakiram, Su-Hsin Chang

2020-Current year OA Pubs

BACKGROUND: In patients with diabetes and monoclonal gammopathy of uncertain significance (MGUS), the impact of glucagon-like peptide-1 (GLP-1) receptor agonists on the natural history of MGUS is unknown. We aimed to assess the association of GLP-1 receptor agonist use in the progression of MGUS to multiple myeloma in patients with diabetes.

METHODS: This is a population-based cohort study of veterans diagnosed with MGUS from 2006 to 2021 with a prior diagnosis of diabetes. A validated natural language processing algorithm was used to confirm MGUS and progression to multiple myeloma. We performed 1:2 matching for individuals with and without GLP-1 receptor …

A Case Report Of An Unprovoked Neonatal Pulmonary Embolism: Management Strategies And Cardiopulmonary Complications, Aashana Dhruva Cowan, Ezinwanne Rosemary Emelue, George Spyropoulos, Mehul Thakkar, Jorge Di Paola, Andrew Glatz, Edon J Rabinowitz

2020-Current year OA Pubs

BACKGROUND: Neonatal pulmonary embolism is a rare occurrence, especially when idiopathic, instead occurring in patients with identifiable risk factors including severe dehydration, presence or history of a central venous line, or identifiable genetic causes. Given the rarity of paediatric and neonatal pulmonary emboli, few guidelines exist to support the clinician in both the initial resuscitation and ongoing management of the critically ill patient with pulmonary emboli.

CASE SUMMARY: We present a 5-day-old female with unprovoked massive pulmonary embolism and associated haemodynamic compromise. She presented with central cyanosis and weak respiratory effort with hypoxaemia, persistent tachycardia, and hypotension despite initial fluid …

Effectiveness Of Original Monovalent And Bivalent Covid-19 Vaccines Against Covid-19-Associated Hospitalization And Severe In-Hospital Outcomes Among Adults In The United States, September 2022-August 2023, Jennifer Decuir, Jennie H Kwon, Et Al.

2020-Current year OA Pubs

BACKGROUND: Assessments of COVID-19 vaccine effectiveness are needed to monitor the protection provided by updated vaccines against severe COVID-19. We evaluated the effectiveness of original monovalent and bivalent (ancestral strain and Omicron BA.4/5) COVID-19 vaccination against COVID-19-associated hospitalization and severe in-hospital outcomes.

METHODS: During September 8, 2022 to August 31, 2023, adults aged ≥ 18 years hospitalized with COVID-19-like illness were enrolled at 26 hospitals in 20 US states. Using a test-negative case-control design, we estimated vaccine effectiveness (VE) with multivariable logistic regression adjusted for age, sex, race/ethnicity, admission date, and geographic region.

RESULTS: Among 7028 patients, 2924 (41.6%) were …

Efficacy, Safety, And Quality Of Life 4 Years After Valoctocogene Roxaparvovec Gene Transfer For Severe Hemophilia A In The Phase 3 Gener8-1 Trial, Andrew D Leavitt, Elaine Majerus, Et Al.

2020-Current year OA Pubs

BACKGROUND: Valoctocogene roxaparvovec, an adeno-associated virus-mediated gene therapy for severe hemophilia A, enables endogenous factor (F)VIII expression and provides bleed protection.

OBJECTIVES: Determine valoctocogene roxaparvovec durability, efficacy, and safety 4 years after treatment.

METHODS: In the phase 3 GENEr8-1 trial, 134 adult male persons with severe hemophilia A without inhibitors and previously using FVIII prophylaxis received a 6 × 10

RESULTS: Median follow-up was 214.3 weeks; 2 participants discontinued since the previous data cutoff. Declines from baseline in mean treated annualized bleed rate (-82.6%;

CONCLUSION: Valoctocogene roxaparvovec provides persistent FVIII expression, hemostatic control, and health-related quality of life improvements with …

A Finite Element Model For Biomechanical Characterization Of Ex Vivo Peripheral Nerve Dysfunction During Stretch, Nicholas C Vasas, Adam M Forrest, Nathaniel A Meyers, Michael B Christensen, Jenny L Pierce, Sidney M Kaufmann, Kimberly B Lanaghen, Randal C Paniello, Julie M Barkmeier-Kraemer, Jonathan P Vande Geest

2020-Current year OA Pubs

Peripheral nerve damage can cause debilitating symptoms ranging from numbness and pain to sensory loss and atrophy. To uncover the underlying mechanisms of peripheral nerve injury, our research aims to develop a relationship between biomechanical peripheral nerve damage and function through finite element modeling. A noncontact, ex vivo electrophysiology chamber, capable of axially stretching explanted nerves while recording electrical signals, was used to investigate peripheral nerve injury. Successive stretch trials were run on eight sciatic nerves (four females and four males) excised from Sprague-Dawley rats. Nerves were stretched until 50% compound action potential (CAP) amplitude reduction was obtained. A constitutive …

Impact Of Self-Reported Race On Villalta Scale Postthrombotic Syndrome Scores And Correlation With Venous Disease-Specific Quality Of Life: An Exploratory Analysis Of The Acute Venous Thrombosis: Thrombus Removal With Adjunctive Catheter-Directed Thrombolysis Trial, James Shih, Chu-Shu Gu, Suresh Vedantham, John Kaufman, Susan R Kahn

2020-Current year OA Pubs

BACKGROUND: The Villalta Scale (VS) to diagnose postthrombotic syndrome (PTS) consists of 5 patient-reported leg symptoms and 6 clinician-rated leg signs. It is unknown how the scale performs across racial groups.

OBJECTIVES: Our study explored if there were differences in VS scores, particularly clinician-rated signs components, according to self-reported race.

METHODS: Exploratory analysis of the ATTRACT trial, a randomized controlled trial conducted at 56 US sites that investigated pharmacomechanical catheter-directed thrombolysis to prevent PTS after proximal deep vein thrombosis (DVT). At the 6-month visit after randomization, we compared self-reported Black (n = 123) and White (n = 541) participants for …

Evaluation Of Combat Harmonization For Reducing Across-Tracer Differences In Regional Amyloid Pet Analyses, Braden Yang, Tom Earnest, Sayantan Kumar, Deydeep Kothapalli, Tammie Benzinger, Brian Gordon, Aristeidis Sotiras

2020-Current year OA Pubs

Differences in amyloid positron emission tomography (PET) radiotracer pharmacokinetics and binding properties lead to discrepancies in amyloid-β uptake estimates. Harmonization of tracer-specific biases is crucial for optimal performance of downstream tasks. Here, we investigated the efficacy of ComBat, a data-driven harmonization model, for reducing tracer-specific biases in regional amyloid PET measurements from [