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Β2 And Β3a Regulatory Subunits Can Coassemble In The Same Bk Channels, Yu Zhou, Vivian Gonzalez-Perez, Xiao-Ming Xia, Gopal S Kallure, Sandipan Chowdhury, Christopher J Lingle

2020-Current year OA Pubs

Ca2+- and voltage-activated BK-type K+ channels are influenced profoundly by associated regulatory subunits, including β subunits (Kcnmb1-4; β1-β4). Although overlap in expression of different BK β subunits occurs in native tissues, whether they can coassemble in the same channel complex is not known. We coexpress β2 and β3a subunits together with BK α and, through a combination of macroscopic and single-channel recordings, along with quantitative pull-down of tagged subunits, test whether coassembly can occur. We evaluate two models: (1) random mixing in which β2 and β3a subunits coassemble in the same channels, and (2) segregation in which β2 and β3a …

White Matter Hyperintensity Burden And Decline In Driving Performance Among Older Adults, Madhur Parihar, Yasheng Chen, Byron Xu, Semere Bekena, Ramkrishna K Singh, Yiqi Zhu, Jean-Francois Trani, Jin-Moo Lee, David B Carr, Chia-Ling Phuah, Ganesh M Babulal, Driving Real-World In-Vehicle Evaluation System (Drives) Project

2020-Current year OA Pubs

IMPORTANCE: White matter hyperintensity (WMH) burden is associated with cognitive decline, but its association with driving performance among older adults and the associations of modifiable risk factors remain unclear.

OBJECTIVE: To evaluate the association of total and regional WMH burden with longitudinal naturalistic driving performance in cognitively normal older adults and evaluate moderating associations of cognitive decline and antihypertensive therapy.

DESIGN, SETTING, AND PARTICIPANTS: This prospective longitudinal cohort study enrolled community-dwelling older adults (≥65 years) in the Driving Real-World In-Vehicle Evaluation System Project. Baseline 3-T brain magnetic resonance imaging (MRI) scans and data from continuous in-vehicle driving monitoring were collected …

Prospective Audit And Feedback By Antibiotic Stewardship Teams To Reduce Antibiotic Overuse At Hospital Discharge: A Stepped-Wedge Cluster-Randomized Clinical Trial, Daniel J Livorsi, Michael Joshua Hendrix, Erin Rachmiel, Jahnavi Bongu, Alice Bewley, Kevin Hsueh, Et Al.

2020-Current year OA Pubs

IMPORTANCE: Antibiotics prescribed at hospital discharge are frequently unnecessary or suboptimal. Strategies to improve prescribing are not well defined.

OBJECTIVE: To evaluate whether a discharge-focused prospective audit and feedback process decreases antibiotic overuse at hospital discharge.

DESIGN, SETTING, AND PARTICIPANTS: This stepped-wedge cluster-randomized clinical trial was conducted across participating units at 10 hospitals with antibiotic stewardship (AS) teams and supporting staff from December 5, 2022, to November 17, 2023. After a 24-week baseline period, 1 hospital crossed into the intervention arm every 2 weeks.

INTERVENTION: The intervention consisted of disseminating institutional guidelines for oral antibiotic step-down to frontline prescribers and …

Cumulative Lifespan Stress, Inflammation, And Racial Disparities In Mortality Between Black And White Adults, Isaiah D Spears, Aaron J Gorelik, Sara A Norton, Michael J Boudreaux, Megan W Wolk, Jayne Siudzinski, Sarah E Paul, Mary A Cox, Cynthia E Rogers, Thomas F Oltmanns, Patrick L Hill, Ryan Bogdan

2020-Current year OA Pubs

IMPORTANCE: In the US, Black individuals experience higher mortality risk than White individuals. Greater stress exposure and its biological sequelae are theorized to drive this heightened risk.

OBJECTIVE: To evaluate whether greater cumulative lifespan stress exposure and elevated inflammation are associated with increased mortality risk among Black compared with White US individuals.

DESIGN, SETTING, AND PARTICIPANTS: This longitudinal cohort study (St Louis Personality and Aging Network) recruited participants from 2007 to 2011 from the St Louis, Missouri, metropolitan area. Participants were required to have a mailing address to permit longitudinal follow-up and sixth grade reading level to facilitate understanding of …

Impaired Complement Regulation Drives Chronic Lung Allograft Dysfunction After Lung Transplantation, Hrishikesh S. Kulkarni, Laneshia K. Tague, Fuyi Liao, Zhiyi Liu, Lorena Garnica, Nishanth R. Shankar, Xiaobo Wu, Dequan Zhou, Yan Tao, Victoria E. Davis, Cory T. Bernardt, Derek E. Byers, Chad A. Witt, Daniel Kreisel, John P. Atkinson, Andrew E. Gelman, Et Al.

2020-Current year OA Pubs

A greater understanding of chronic lung allograft dysfunction (CLAD) pathobiology, the primary cause of death after lung transplantation (LTx), is needed to improve outcomes. The complement system links innate to adaptive immune responses and is activated early after lung transplantation to form C3 convertase, a critical enzyme that cleaves the central complement component C3. We hypothesized that LTx recipients with a genetic predisposition to enhanced complement activation have worse CLAD-free survival mediated through increased adaptive alloimmunity. We interrogated a known functional C3 polymorphism (C3 R102G) that increases complement activation through impaired C3 convertase inactivation in 2 independent LTx recipient cohorts. …

Relationship Among Sleep Disturbance, Stress, And Suicidal Ideation In Clinical High Risk For Psychosis, Heather M Wastler, Daniel Mamah, Et Al.

2020-Current year OA Pubs

BACKGROUND AND HYPOTHESIS: Sleep disturbance is a well-established risk factor for suicide, though few studies to date have examined whether sleep disturbance contributes to suicide risk among individuals at clinical high risk for psychosis (CHR). The current study addressed this gap in the literature. We hypothesized that sleep disturbance would have a unique relationship with suicidal ideation/attempts when accounting for other variables in the model. We also hypothesized that the interaction between sleep disturbance/attenuated positive symptoms and sleep disturbance/stress would be related to suicidal ideation/attempts in CHR.

STUDY DESIGN: The current study used data generated by the Accelerating Medicines Partnership® …

Mutations In Hsp40 Co-Chaperone Change The Canonical Interdomain Interactions Stimulating Lgmdd1 Myopathy, Ankan K Bhadra, Geetika Aggarwal, Anshuman Jaysingh, Daniel Chen, Jil Daw, Conrad C Weihl, Heather L True

2020-Current year OA Pubs

Limb-girdle muscular dystrophy D1 (LGMDD1) is a rare, dominantly inherited neuromuscular protein-misfolding chaperonopathy caused by mutations in the Hsp40 co-chaperone DNAJB6, primarily in the glycine-phenylalanine (GF) or J-domains. Currently, no treatments are available, and a challenge in understanding the disease is identifying a specific client protein for DNAJB6 in skeletal muscle. DNAJB6 has homology to the yeast DNAJ family member, Sis1. Our previous research indicated that LGMDD1 GF domain mutants in Sis1 exhibit substrate-specific effects, influenced by Hsp70 activity. Herein, we employed functional assays along with advanced molecular simulation studies to understand the regulatory interdomain interactions in disease-causing mutants of …

Excellent Outcomes In Feasibility Study Of Radiation-Free Conditioning And Transplant In Pediatric Severe Aplastic Anemia, Mithra Lakshmi Narasimhan, Irem Eldem, Jeffrey J Bednarski, Ginny L Schulz, Robert J Hayashi, Shalini Shenoy

2020-Current year OA Pubs

Severe aplastic anemia (SAA) is treated with a hematopoietic cell transplant (HCT) in the presence of an HLA-matched sibling donor (MSD) with disease-free survival (DFS) of >90%. In the absence of an MSD, immunosuppressive therapy (IST) can induce remission but concerns for relapsed/refractory disease and clonal hematopoiesis persist. IST failure is an indication for HCT. Modern HCT approaches target barriers such as graft rejection (GR), graft-versus-host disease (GVHD), and transplant-related toxicities. Traditionally, total body irradiation (TBI) inclusive HCT conditioning helps decrease GR, but the use of TBI in children increases concerns for late effects such as malignancies. To describe outcomes …

Mouse Alport Podocytes Are Susceptible To Aav9 Transduction In Vivo, Meei-Hua Lin, Kohei Omachi, Joshua F Begin, Jennifer L Richardson, Jeffrey H Miner

2020-Current year OA Pubs

INTRODUCTION: Alport syndrome features a defective glomerular basement membrane (GBM) due to variants in COL4A3, COL4A4, and COL4A5. The most severe forms, which lack the GBM's collagen α3α4α5(IV) network, progress from hematuria in early childhood to proteinuria, chronic kidney disease, and kidney failure by the age of ∼30. As a monogenic disease without specific treatments, and with podocytes being the only glomerular cells that synthesize collagen α3α4α5(IV), the ability to efficiently deliver genes to Alport podocytes could open up new possibilities for treatment.

METHODS: As a proof-of-concept study, we investigated whether podocytes in X-linked Alport mice were susceptible to transduction …

Cgrp Expression And Signaling Sensitization In A Mouse Model Of Chronic Oxaliplatin-Induced Peripheral Neuropathy, Junwei Du, Leland C Sudlow, Margaret H Johnson, Kanishk Satish, Abraham Villagomez, Hongzhen Hu, Mikhail Y Berezin

2020-Current year OA Pubs

Chemotherapy-induced peripheral neuropathy (CIPN) is a frequent and dose-limiting side effect of oxaliplatin treatment, yet its molecular mechanisms remain incompletely understood. Calcitonin gene-related peptide alpha (CGRPα, encoded by

Participatory Systems Modeling In Implementation Research: Exploring Benefits, Facilitators, And Future Needs, Natalie Riva Smith, Jennifer L Cruz, Jessica Gannon, Stephanie Mazzucca-Ragan

2020-Current year OA Pubs

BACKGROUND: Implementation science increasingly uses participatory systems modeling (PSM) approaches to handle the complexity inherent to implementation science issues. To support the process of integrating PSM with implementation science, we aimed to understand and explicate the benefits, facilitators, and future needs of applying PSM to implementation research.

METHODS: We conducted semi-structured qualitative interviews with 23 researchers (n = 18) and practitioners (n = 5). We purposively sampled participants and identified additional participants through recommendations. Interviews were inductively analyzed. Key concepts were identified via iterative description, comparison, and conceptualization.

RESULTS: Engagement with people in the system was typically focused in earlier …

Mapping Functional Connectivity In The Pigeon Brain With Wide-Field Optical Imaging, Kathryn C Chenard, Annie R Bice, Seana H Bice, Joseph P Culver, Paula Gerliz, Xavier Helluy, Onur Güntürkün, Jason W Trobaugh, Mehdi Behroozi, Carlos A Botero

2020-Current year OA Pubs

SIGNIFICANCE: Adapting optical imaging technology to avian models can overcome many limitations imposed by functional magnetic resonance imaging (fMRI), which currently restricts the number of species used to study functional connectivity. Developing advanced technology to expand the diversity of species that can be effectively imaged is crucial for addressing significant questions that are currently unreachable, such as understanding the evolution of cognition from a comparative perspective.

AIM: We assessed the potential of optical imaging technology to measure functional connectivity in birds, utilizing pigeons as an avian model. We evaluated whether we could partition the dorsal surface of the pigeon brain …

The Impact Of Fixation Method And Surgical Approach On Outcomes Following Hip Hemiarthroplasty For Femoral Neck Fracture, Brian D Rust, Mitchel R Obey, Jenna-Leigh Wilson, Christopher M Mcandrew, Marschall B Berkes

2020-Current year OA Pubs

INTRODUCTION: Hip hemiarthroplasty is commonly performed for displaced femoral neck fractures in older adults, with implants placed either cemented or uncemented. While cemented fixation offers immediate stability, uncemented fixation reduces operative time and pulmonary complications. Large single-center analyses comparing these techniques remain limited, and this study aims to assess this.

METHODS: We conducted a retrospective case-control study of 634 adult patients undergoing hip hemiarthroplasty at a single Level 1 trauma center from 2019 to 2025. Patients were classified by cemented (n=403) or uncemented (n=231) fixation and further stratified by surgical approach (anterolateral vs posterior). Outcomes included length of stay, postoperative …

Sonobiopsy For Enrichment Of Circulating Micrornas In Glioma Patients, Jinyun Yuan, Yuanxiang Li, Chih-Yen Chien, Lu Xu, Andrew H Stark, Siaka Fadera, Zhaoning Gu, Yu Xuan Chin, Kevin Xu, Arash Nazeri, Umeshkumar Athiraman, Xiaowei Wang, Hong Chen, Eric C Leuthardt

2020-Current year OA Pubs

BACKGROUND: Sonobiopsy is a promising new technique that employs focused ultrasound (FUS) to noninvasively enrich brain tumor-derived biomarkers from spatially targeted brain location into the bloodstream. Building upon our recent first-in-human sonobiopsy trial demonstrating enrichment of circulating tumor DNA (ctDNA), here we investigated whether sonobiopsy can enhance the release and detection of tumor-derived microRNAs (miRNAs).

METHODS: Eleven patients with glioma underwent FUS sonication immediately prior to surgical resection. Peripheral blood samples were collected 5 min before and 5, 10, and 30 min after sonication. Plasma and brain tissue miRNA levels were quantified through small RNA sequencing and compared among different …

Concordance Of Fluorescence In Situ Hybridization, Whole-Exome Sequencing, And Chromosomal Microarray For Evaluating High-Risk Molecular Features In Meningiomas, Brenndan Crumley, Emilie Russler-Germain, Sonika Dahiya

2020-Current year OA Pubs

BACKGROUND: Meningiomas are the most common primary intracranial tumors, classified into three WHO grades based on histologic and/or molecular criteria. cIMPACT-NOW Update 8 underscores the increasing importance of molecular testing in grading and risk stratification, noting that morphologically WHO grade 1 tumors with concurrent 1p and 22q losses demonstrate clinical behavior comparable to WHO grade 2 meningiomas. This study aimed to assess the concordance of fluorescence in situ hybridization (FISH), chromosomal microarray analysis (CMA), and whole-exome sequencing (WES) in defining the molecular risk profile of meningiomas.

METHODS: A total of 113 meningiomas were analyzed by WHO grade to assess the …

Immortalization And Characterization Of Schwann Cell Lines Derived From Nf1-Associated Cutaneous Neurofibromas, Hua Li, Angela Hirbe, Et Al.

2020-Current year OA Pubs

Neurofibromatosis type 1 (NF1) is an autosomal dominant condition in which patients are heterozygous for a disruptive pathogenic variant in the NF1 gene. The most characteristic feature of the condition NF1 is the neurofibroma, a benign, multi-cellular tumor which initiates when a cell of the Schwann cell lineage gains a somatic pathogenic variant of the other NF1 allele. Neurofibromas developing at nerve termini in the skin are termed "cutaneous" neurofibromas (cNFs), while those developing within larger nerves are termed "plexiform." Most patients develop cNFs beginning in late childhood or early adulthood, continuing throughout life at variable rates. Some patients may …

Spatial Variation In Socio-Economic Vulnerability To Influenza-Like Infection For The Us Population, Shrabani S. Tripathy, Joseph V. Puthussery, Taveen S Kapoor, John R. Cirrito, Rajan K. Chakrabarty

2020-Current year OA Pubs

This study aims to quantify environmental health impacts and assess risk by understanding the disproportionate burden of infectious diseases, specifically Influenza-like Illness (ILI), across regions with varying socio-economic characteristics. We introduce a novel vulnerability-based approach to better understand the complex relationship between socio-economic factors and ILI burden. We develop a machine-learning-driven framework to assess and map state-level socio-economic vulnerability to ILI in the United States. A vulnerability index was created by integrating 39 diverse socio-economic and health indicators from the latest CENSUS. A Random Forest Regression model then weighed these indicators to quantify each state's vulnerability for the ILI values …

Characterization Of The Spatiotemporal Representations Of Visual, Semantic, And Memorability Features In The Human Brain, Yue Wang, Peter Brunner, Jon T. Willie, Runnan Cao, Shuo Wang

2020-Current year OA Pubs

Object recognition requires integrated processing that extends beyond the visual cortex, incorporating semantic and memory-related processes. However, it remains unclear how different attributes, such as visual, semantic, and memorability features, are encoded and interact during perception. Here, we recorded intracranial electroencephalography from 5,143 channels while participants viewed natural object images. We systematically characterized the spatiotemporal patterns of neural encoding for visual, semantic, and memorability attributes and showed that memorability was encoded in a distributed manner, which can be dissociated from visual and semantic coding. While the ventral temporal cortex (VTC) was engaged in encoding all three attributes, the representations were …

Evaluation Of Mycoplasma Genitalium Positivity And Co-Infection With Chlamydia Trachomatis And/Or Neisseria Gonorrhoeae At Various Care Sites Across The United States, Rebecca Lillis, Stacey House, Et Al.

2020-Current year OA Pubs

OBJECTIVES: We evaluated Mycoplasma genitalium (MG) positivity and co-infection with Chlamydia trachomatis (CT) and/or Neisseria gonorrhoeae (NG), based on results from a trial assessing clinical performance of the Cobas® Liat CT/NG/MG point-of-care test.

METHODS: A prospective, US, multicenter, noninterventional study assessed MG positivity in prospective urine samples (male) and clinician-collected vaginal swabs (female) from symptomatic/asymptomatic patients aged ≥14 years attending various clinical settings. Participants were designated positive or negative for MG, CT, and NG based on combined results from three US Food and Drug Administration-approved assays and one laboratory-developed test. MG co-infection with CT and/or NG was assessed.

RESULTS: Among …

An Integrated Analysis Of Three Medulloblastoma Clinical Trials Refines Risk-Stratification Approaches For Reducing Toxicity And Improving Survival, Kyle S Smith, Jeff M Michalski, Et Al.

2020-Current year OA Pubs

BACKGROUND: The identification of clinical and molecular heterogeneity in medulloblastoma has produced risk-stratified therapy, but establishing the most effective yet least toxic regimens has remained elusive owing to numerous treatment options. To improve risk-stratification, we performed an integrated analysis from three clinical trials.

METHODS: Medulloblastoma patients from ACNS0331/NCT00085735, ACNS0332/NCT00392327, and SJMB03/NCT00085202 were included if they had methylation profiling. Molecular groups [WNT, SHH, Group 3 (G3), and Group 4 (G4)], subgroups, and copy number variations were procured from methylation profiles and mutations from next-generation sequencing. Data was assembled into an interactive portal to capture patient characteristics. Cross-trial comparisons, univariable, and multivariable …

Influence Of Obesity And Insulin Resistance With Hepatic Steatosis On The Human Plasma Lipidome, Max C Petersen, Gordon I Smith, Aaron M Armando, Xiong Su, Oswald Quehenberger, Edward A Dennis, Samuel Klein

2020-Current year OA Pubs

Insulin resistance accompanied by hepatic steatosis is a common complication of obesity. In an effort to identify plasma lipids that could be biomarkers or causes of insulin resistance with steatosis in people with obesity, we evaluated the plasma lipidome in three distinct groups separated by adiposity, hepatic steatosis, and insulin sensitivity, assessed by using the hyperinsulinemic-euglycemic clamp procedure: i) insulin-sensitive lean (ISL, n = 13); ii) insulin-sensitive obese (ISO, n = 14); and iii) insulin-resistant obese with hepatic steatosis (IROS, n = 13). We evaluated 759 complex lipid species in 16 subclasses (including phospholipids, glycerolipids, sphingolipids, acylcarnitines, and cholesteryl esters) …

Identifying Disparities In Same-Day Surgery Cancellations: Impact Of Race And Socioeconomic Factors In A Pediatric Health System, Nicole M Santucci, Daniel Alligood, Amanda Maytin-Hevia, Danyi Wang, Kelly Chilson, Jesse Vrecenak, Andrew Yeh, Colin A Martin

2020-Current year OA Pubs

PURPOSE: Same-day surgery (SDS) cancellations have significant implications on patients and hospitals. This study aimed to identify demographic and socioeconomic factors that impact SDS cancellations across a single pediatric health system.

METHODS: A case-control retrospective review captured patients (age < 18) who underwent SDS procedures from July 2022 to August 2024. Patients were included if they underwent any procedure at three operative sites: a tertiary pediatric academic hospital (PAH) and two outpatient surgery centers (OSC). Patients whose SDS was cancelled (n = 2,034) were compared to those whose surgeries proceeded as scheduled (n = 25,573). Patient zip codes were matched to Child Opportunity Index (COI) 2.0 data.

RESULTS: The overall SDS cancellation rate was 7.37 %, with a significantly higher rate observed at the PAH compared to OSC (11.4 % vs 53 %, p < 0.001). Patients with cancelled cases were more likely to identify as Black and have the lowest quintile COI (p < 0.001). Cancelled in preop and no shows were two reasons with the most racial disparities. In a sub-analysis comparing cancelled cases between operating sites, PAH cancelled patients tended to be Black (23.8 % vs 11.7 %, p < 0.001) and have very low COI (20.1 % vs. 10.6 %, p < 0.001).

CONCLUSION: SDS cancellation rates are significantly higher amongst patients who identify as Black and reside in low opportunity neighborhoods. Disparities in cancellation rate are more significant in patients scheduled at the urban PAH compared …

Beyond Restless Sleep: A Cross-Sectional Study Of Obstructive Sleep Apnea Risk, Aging Biomarkers, And Chronic Low Back Pain, Khalid W Freij, Fiona Bat Agbor, Philemon Domoyeri, Kiari R Kinnie, Asia M Wiggins, Demario S Overstreet, Tammie L Quinn, Shivraj S Grewal, S Justin Thomas, Walid W Freij, Shameka L Cody, Michael A Owens, Robert E Sorge, Burel R Goodin, Edwin N Aroke

2020-Current year OA Pubs

This secondary data analysis aimed to determine the nature of the relationship between obstructive sleep apnea (OSA) risk, biological age acceleration, and nonspecific chronic low back pain (CLBP). In total, 199 adults aged 18-82 years who filled both STOPBANG and pain questionnaires subsetted for secondary analysis. Based on the STOPBANG questionnaire, 104 had a low OSA risk and 95 had an intermediate or high OSA risk. Dunedin Pace of Aging Computed from the Epigenome (DunedinPACE), Horvath's, Hannum's, PhenoAge, and GrimAge clocks were used to determine biological age and pace of biological aging. Individuals with low OSA risk reported increased DunedinPACE …

An Integrated View Of The Structure And Function Of The Human 4d Nucleome, Job Dekker, Ting Wang, Daofeng Li, Et Al.

2020-Current year OA Pubs

The dynamic three-dimensional (3D) organization of the human genome (the 4D nucleome) is linked to genome function. Here we describe efforts by the 4D Nucleome Project

Lost Before Forgetting: Objective Driving Metrics Track Navigation Deficits Tied To Preclinical Alzheimer's Disease, Yiqi Zhu, Ramkrishna K Singh, Semere Bekena, David C Brown, Chen Chen, Matthew Blake, Jean-François Trani, Ganesh M Babulal

2020-Current year OA Pubs

BACKGROUND AND OBJECTIVES: Navigation is a complex, multisensory process in which subtle changes may emerge before the onset of symptomatic Alzheimer's disease (AD). This study investigated whether navigation abilities were associated with amyloid and tau pathology in cognitively normal older adults.

RESEARCH DESIGN AND METHODS: Among 285 cognitively unimpaired older adults, navigation and objective driving behaviors were assessed using the self-reported Santa Barbara Sense of Direction Scale (SBSOD) and a datalogger, respectively. Amyloid and tau burden were quantified using PET-MRI 2 years post-initial driving data collection. Linear mixed-effects models were used to evaluate the associations between biomarker status and longitudinal …

Abnormalities In Sensorimotor Brain Function Are Related To Chronicity Of Low Back Pain, Jo Armour Smith, Rongwen Tain, Kelli G Sharp, Laura M Glynn, Linda R Van Dillen, Jesse V Jacobs, Steven C Cramer

2020-Current year OA Pubs

Maladaptive plasticity in the brain may contribute to chronic low back pain (LBP) and underlie the altered postural control of the lumbopelvic musculature that is evident in some individuals with LBP. We recently described an MRI-compatible leg-raise paradigm to measure brain activity associated with lumbopelvic postural control. The objective of this study was to compare brain function in young adults with and without a history of LBP and to determine relationships between brain function, pain, and postural control characteristics. We recruited 55 participants with a history of LBP, who were asymptomatic when studied, and 30 healthy controls. Postural control during …

Clinical Outcomes Following Mechanical Thrombectomy In Pulmonary Embolism Response Team-Consulted Patients: A Retrospective Analysis, Ryan Nolan, Maanasi Samant, Suresh Vedantham, Westley Ohman, Nathan Droz, Kristen Sanfilippo, Pavan Kavali

2020-Current year OA Pubs

PURPOSE: To determine if use of mechanical thrombectomy (MT) impacts survival and additional outcomes in patients with acute intermediate-high-risk and high-risk pulmonary embolism (PE) who were evaluated by a Pulmonary Embolism Response Team (PERT).

METHODS: This retrospective, single-center study included patients with intermediate-high-risk and high-risk PE who received PERT evaluation over 3.5 years and were treated with anticoagulation (AC) alone or MT + AC. The primary outcome was 30-day all-cause mortality, measured with inverse probability of treatment weighting. Exploratory outcomes included survival during the study period, PE-associated/caused mortality, hospital length of stay (LOS), supplemental oxygen at discharge, and MT-related metrics. …

Modeling Clinical Relevance And Risk In Yttrium-90 Radioembolization Of The Liver: Lung Shunt Fraction Variability According To Imaging Modality, Cancer Type, And Tumor Size, M Allan Thomas, Tharun Alamuri, Ryan C Lee, Dan Giardina, John Karageorgiou, Naganathan Mani, Daniel A Braga, Christopher D Malone

2020-Current year OA Pubs

PURPOSE: To test the hypothesis that lung shunt fraction (LSF) in yttrium-90 (

MATERIALS AND METHODS: This was a retrospective analysis of 354 consecutive cases from a 34-month period at a single institution. Cancer type (hepatocellular carcinoma [HCC] vs non-HCC) and maximum tumor size were tracked. LSF was computed from planar imaging (LSF

RESULTS: Median LSF was significantly different (all P < .001) among LSF

CONCLUSIONS: Despite significant variations with imaging modality and correction methods, consistent trends in LSF magnitude with cancer type and tumor size were still uncovered. The relative risk of observing clinically relevant LSF can be modeled for different liver tumor …

Psychological And Clinical Risk Factors For Substance Use In People With And Without Hiv, Joanna M Hobson, Shameka L Cody, Shannon R Gilstrap, Michael A Owens, Myles D Moody, Dyan M White-Gilliam, Stephen Justin Thomas, Emily J Bartley, Burel R Goodin

2020-Current year OA Pubs

BackgroundDespite growing concerns, limited research has demonstrated how psychological factors influence substance use in people with HIV (PWH). Therefore, we examined the association between heightened vigilance and substance use outcomes in people with (PWH) and without HIV (PWoH), while accounting for key risk factors.MethodsParticipants (n = 138) were recruited from an HIV clinic and the surrounding community, completing a urine drug screener (UDS) and questionnaires.ResultsPWH reported greater insomnia (

Nanoparticle Albumin-Bound Paclitaxel And Nivolumab For Pd-1 Inhibitor-Refractory Recurrent Or Metastatic Head And Neck Squamous-Cell Carcinoma, Douglas Adkins, Jessica C Ley, Christine Auberle, Brendan Knapp, Jesse Zaretsky, Jingxia Liu, Peter Oppelt

2020-Current year OA Pubs

INTRODUCTION: Standard therapy for PD-1 inhibitor-refractory recurrent or metastatic head and neck squamous-cell carcinoma (RM-HNSCC) has limited activity. Drugs bound to albumin selectively target cancer cells with upregulated macropinocytosis, a process driven by constitutively hyper-activated EGFR/RAS/PIK3CA signaling, which is common in HNSCC. Nanoparticle albumin-bound (nab)-paclitaxel is active in PD-1 inhibitor-naïve RM-HNSCC and alters immune cells to potentially prime tumor response and reverse resistance to PD-1 inhibitors.

METHODS: In a single-arm phase 2 trial, patients with PD-1 inhibitor-refractory RM-HNSCC received nab-paclitaxel and nivolumab given in 28-day cycles. The primary endpoint was objective response rate (ORR), using RECIST1.1. Key secondary endpoints were …