Digital Commons Network^™

Characteristics And Outcomes Of Patients With Hematologic Malignancies Hospitalized With Respiratory Viral Infections, Zulfiqar A Lokhandwala, Brenna Park-Egan, Ravneet Waraich, Colleen A Mcevoy, Andrew P Michelson, Alice F Bewley, Lynne Strasfeld, Rachel Cook, Brandon Hayes-Lattin, Catherine L Hough, Patrick G Lyons

2020-Current year OA Pubs

BACKGROUND: Respiratory viral infections in patients with hematologic malignancies or hematopoietic stem cell transplants (HCTs) are associated with increased morbidity and mortality. However, the hospital presentations and courses of these infections remain under-described.

METHODS: We performed a multicenter retrospective cohort study of hospitalized patients with hematologic malignancy or HCT at 2 comprehensive cancer centers between January 2019 and June 2023. We included all patients with acute viral respiratory infection (identified based on a constellation of test results and objective physiology), comparing clinical presentations, care processes, and patient outcomes across pathogens; the primary outcome was the composite of hospital death or …

Preparing For Long-Acting Technologies: A Multistate Analysis Of Prep Persistence And Hiv And Sti Lab Coverage Among Oral Prep Initiators In St. Louis, Missouri (2014-2021), Lindsey M Filiatreau, Rupa Patel, Kate Curoe, Ashley Underwood, Joseph Cherabie, Elvin H Geng, Aditi Ramakrishnan, Rachel Presti, Aaloke Mody

2020-Current year OA Pubs

BACKGROUND: Engagement in pre-exposure prophylaxis (PrEP) care and routine screening for HIV and sexually transmitted infections (STIs) is critical to realizing the full benefits of this HIV prevention strategy.

METHODS: We enrolled a cohort of individuals seeking PrEP services in two clinics in Missouri, an Ending the HIV Epidemic priority state, from June 2014 to November 2021. We used electronic health record and survey data to explore outcomes in the 2 years following linkage to care using multistate methods. We assessed transitions between eight mutually exclusive care states differentiated by receipt of a prescription, lab coverage status, and retention. We …

Intraoperative Neurophysiological Monitoring In Full-Endoscopic Cervical Endoscopic Ulbd, Miles Hudson, Sarah Esposito, Mark M Zaki, Simon M Glynn, Osama N Kashlan, John Ogunlade, Chandan Krishna, Joshua Bakhsheshian, Christoph P Hofstetter

2020-Current year OA Pubs

No abstract provided.

Epithelial-Mesenchymal Transition And Stress Adaptations Underlie Yttrium-90 Resistance In Liver Cancer Cell Lines, Alexander Zheleznyak, Dhanusha Duraiyan, Prasanth Thunuguntla, Jessica Camacho, Shuang Wu, Jingxia Liu, Jason D Weber, Daniel L J Thorek, Benjamin S Strnad, Ryan C Fields, Matthew A Ciorba, Christine Yoon, Valerie Blanc, Nicholas Davidson, Jessica Silva-Fisher, Christopher D Malone

2020-Current year OA Pubs

UNLABELLED: Molecular signatures predict prognosis in hepatocellular carcinoma, but their relevance to transarterial radioembolization (TARE) with yttrium-90 (90Y) is unknown. We aimed to identify baseline and treatment-induced pathways associated with response and nominate biomarkers. Ten transcriptomically diverse human liver cancer cell lines were exposed to escalating activities of glass 90Y microspheres for 10 days. Normalized AUC values quantified sensitivity. Whole-transcriptome RNA sequencing at baseline and after treatment was analyzed with elastic net regression and gene set enrichment. Findings were corroborated by qRT-qPCR and exploratory analysis of pretreatment tumor samples from patients undergoing TARE. Liver cancer cell line responses to 90Y …

The Cognitive-Affective Social Processing And Emotion Regulation (Casper) Model, M Catalina Camacho, Elina Deshpande, Michael T Perino

2020-Current year OA Pubs

Humans are intensely social creatures. It is therefore not surprising that many psychiatric disorder criteria include social dysfunctions; however, overlapping presentations and diverse, complex etiologies make treating social dysfunctions difficult. Here, we introduce the Cognitive Affective Social Processing and Emotion Regulation (CASPER) model. CASPER integrates research from social psychology, cognitive neuroscience, and developmental science to describe how real-world social processing unfolds and is associated with differing psychiatric social cognitive neurophenotypes. Briefly, social processing can be broken down into the following cognitive steps: identifying relevant social cues, attending to related cues, interpreting cues, and adjusting behavior appropriately. Each of these steps …

A Microenvironment-Driven Hla-Ii-Associated Insulin Neoantigen Elicits Persistent Memory T Cell Activation In Diabetes, Neetu Srivastava, Anthony N Vomund, Rongzhen Yu, Orion J Peterson, Yuqing Yang, David P Turicek, Omar Abousaway, Tiandao Li, Pamela Stone, Aisha Ansar, Rima Melhem, Bo Zhang, Chang Liu, Hao Hu, Chyi-Song Hsieh, Laura Campisi, Emil R Unanue, Ana Maria Arbelaez, Cheryl F Lichti, Xiaoxiao Wan, Et Al.

2020-Current year OA Pubs

The antigenic landscape of autoimmune diabetes reflects a failure to preserve self-tolerance, yet how novel neoantigens emerge in humans remains incompletely understood. Here we designed an immunopeptidomics-based approach to probe HLA-II-bound, islet-derived neoepitopes in patients with type 1 diabetes. We uncovered a Cys→Ser transformation, conserved between mice and humans, that reshapes autoreactivity to insulin at the single-residue level. This transformation, which we call C19S, arises from oxidative remodeling of insulin in stressed pancreatic islets and also occurs in cytokine-activated antigen-presenting cells, contributing to a feed-forward loop of neoepitope formation and presentation. Despite involving just one amino acid, C19S is recognized …

Frontline Aspiration Versus Stent Retriever Thrombectomy For M2 Occlusions: Insights From The Star Registry, Michael Gaub, Joshua Osbun, Et Al.

2020-Current year OA Pubs

BACKGROUND: Recent trials have furthered uncertainty regarding the endovascular benefit for medium vessel occlusions (MeVO). Stent retrievers (SR) were employed in the first attempt in most interventional arm participants. We sought to compare outcomes in acute MCA M2 occlusions between frontline aspiration and SR, and to delineate procedural and anatomical covariates associated with differential treatment effect.

METHODS: Retrospective analysis of a multicenter stroke thrombectomy cohort identified cases of MT for M2 occlusions. Unmatched and propensity score-matched (PSM) cohorts were generated comparing frontline aspiration to standalone and combined SR. The primary outcome was functional independence (mRS 0-2) at 90 days. Recanalization, …

Focused Ultrasound-Enhanced Nose-To-Brain Delivery Of A Therapeutic Antibody In A Large-Animal Model, Siaka Fadera, Cristian Antonio Wieczorek Villas Boas, Yimei Yue, Zhaoning Gu, Jinyun Yuan, Debolina De, Buck E Rogers, Arash Nazeri, Hong Chen

2020-Current year OA Pubs

No abstract provided.

A Survey-Based Assessment Of Treatment Preferences For Distal Radius Fractures In Participants Aged 65 Years And Older, Zayd Al Rawi, Elizabeth Graesser, Lindley B Wall

2020-Current year OA Pubs

PURPOSE: The management of distal radius fractures (DRF) in patients aged ≥65 years is debated because there is evidence that operative and nonsurgical treatment yield similar outcomes 1 year after injury. When more than one reasonable treatment option exists, shared decision-making between the patient and physician should be used. This study elicited preferences for the treatment of DRF using a survey of participants aged ≥65 years.

METHODS: A survey for participants ≥65 years was administered using Amazon Mechanical Turk. Participants were presented with a theoretical scenario in which they sustained a DRF, followed by two treatment options (surgery or casting) …

Phase I Trial Of Adp-A2afp Tcr T-Cell Therapy In Patients With Advanced Hepatocellular Or Gastric Hepatoid Carcinoma, Tim Meyer, Benjamin R Tan, Et Al.

2020-Current year OA Pubs

BACKGROUND & AIMS: Patients with advanced hepatocellular carcinoma (HCC) generally experience poor outcomes despite current therapies, necessitating the development of alternative treatments. ADP-A2AFP is an investigational autologous T-cell therapy with an affinity-enhanced T-cell receptor (TCR) targeting alpha-fetoprotein (AFP).

METHODS: We describe a phase I, open-label, first-in-human clinical trial of ADP-A2AFP (NCT03132792) in human leukocyte antigen-eligible participants with AFP-expressing HCC (or other tumor) not amenable to transplant/resection who progressed on, were intolerant to, or refused prior systemic therapy. Participants received lymphodepletion chemotherapy (cyclophosphamide 500 mg/m

RESULTS: Twenty-one participants, 20 with advanced HCC and one with gastric hepatoid carcinoma received ≥1 ADP-A2AFP …

Coordinated Regulation Of Capping Protein By Carmil And V-1/Myotrophin, John A Hammer, John A Cooper

2020-Current year OA Pubs

Capping Protein (CP) plays a central role in controlling actin filament dynamics in almost all eukaryotic cell types by virtue of its ability to block monomer addition and loss at the barbed end of the actin filament. Like other proteins that control actin assembly, CP is subject to regulation. Here we focus on two direct regulators of CP-CARMIL and V-1/Myotrophin. Specifically, we review recent biochemical, structural, imaging, and cell biological data that argue these two proteins cooperate to create a regulatory cycle for CP that controls its availability, activity, and site of action in the cell. Finally, we discuss unresolved …

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 …

Diverse Misfolding Mutant Digestive Enzymes Cause Chronic Pancreatitis Through Common Pathways, Steven J Wilhelm, Grace E Curry, Neel Matiwala, Jianguo Lin, Tran Quach, Mark E Lowe, Miklós Sahin-Tóth, Xunjun K Xiao

2020-Current year OA Pubs

BACKGROUND & AIMS: Increasing evidence suggests that protein misfolding and proteotoxicity is an important mechanism of chronic pancreatitis (CP) in patients with genetic variants. Two mouse models carrying misfolding digestive enzyme variants, CPA1 N256K and PNLIP T221M, recapitulate the human CP phenotype. We hypothesized that both models develop CP through similar disease mechanisms.

METHODS: We conducted a comprehensive analysis of mice aged 1 to 6 months using histology, immunohistochemistry, protein immunoblotting, quantitative polymerase chain reaction (qPCR), transmission electron microscopy (TEM), and RNA sequencing (RNA-seq) analysis to characterize pancreatic pathological changes.

RESULTS: Both homozygous models exhibited CP hallmarks, including progressive acinar …

A Deep Learning Model To Guide Personalized Mechanical Circulatory Support Use In Cardiogenic Shock Patients Undergoing Pci, Amit P Amin, Richard G Bach, Darren C Tsang, Weili S Zheng, Raed A Qarajeh, Emmanouil S Brilakis, Hemant Kulkarni

2020-Current year OA Pubs

BACKGROUND: Cardiogenic shock (CS) in patients undergoing percutaneous coronary intervention (PCI) involves rapidly changing clinical, hemodynamic, and metabolic factors that current models cannot effectively integrate.

OBJECTIVES: The purpose of this study was to develop and validate a deep learning (DL) model to guide personalized use of mechanical circulatory support (MCS) devices in CS patients undergoing PCI.

METHODS: The authors analyzed data from 1,408 CS patients treated with intra-aortic balloon pump (IABP) or microaxial flow-pump (mAFP) at multiple hospitals (2004-2019). Clinical, hemodynamic, and metabolic variables from admission to MCS placement were compiled into longitudinal vectors. Using Python 3.7 and TabNet in …

Genome-Wide Gene-Sleep Interaction Study Identifies Novel Lipid Loci In 732,564 Participants, Raymond Noordam, Karen Schwander, Lisa De Las Fuentes, Mary F Feitosa, Anh Do, C Charles Gu, Changwei Li, Michael A Province, Dabeeru C Rao, Et Al.

2020-Current year OA Pubs

BACKGROUND AND AIMS: Deviations from the population mean in sleep duration have been associated with increased risk for developing dyslipidemia and atherosclerotic cardiovascular disease, but the mechanism of effect is poorly characterized. We performed large-scale genome-wide gene-sleep interaction analyses of lipid levels to identify genetic variants underpinning the biomolecular pathways of sleep-associated lipid disturbances and to suggest possible druggable targets.

METHODS: We collected data from 55 cohorts with a combined sample size of 732,564 participants (87 % European ancestry) with data on lipid traits (high-density lipoprotein [HDL-c] and low-density lipoprotein [LDL-c] cholesterol and triglycerides [TG]). Short (STST) and long (LTST) …

Oculomics And Ai: The Eye As A Biomarker For Health Span, Joy Le Yi Wong, Rajendra S Apte, Et Al.

2020-Current year OA Pubs

As the world's population ages, the focus of healthcare is shifting from extending life span to promoting health span. There is an unmet need to identify sensitive and reliable markers of health span through more cost-effective and non-invasive methods, to enable early and effective intervention on modifiable aging factors. The eye offers a unique window into systemic health, providing direct visualization of the body's vascular and neural health. This review presents an overview of how various ocular structures can serve as biomarkers of health span-drawing on insights from ocular imaging, metabolomics, and proteomics, with evidence from basic science, animal models, …

Airway Management In Emergency Department Thoracotomy: A Narrative Review, Aaron J Lacy, Adam Liebendorfer, Sarah M Guess, Rami S Al-Aref, Anthony P Kronfli, Rachel E Armstrong, Amelia W Maiga, Alexander Bracey, Ryan N Barnicle

2020-Current year OA Pubs

INTRODUCTION: Emergency department thoracotomy (EDT) is a high-risk, life-saving intervention for patients in traumatic cardiac arrest. A critical component of EDT is airway management, typically performed by emergency physicians, yet formal guidance regarding optimal strategies remains limited. Airway management in this setting is uniquely complex due to concurrent anatomic injury, physiologic instability, and the procedural demands of thoracotomy.

DISCUSSION: Endotracheal intubation (ETI) during EDT presents multiple challenges. Anatomic difficulties may arise from facial or cervical trauma, restricted positioning, and the presence of cervical collars. Cognitive load is heightened by the chaotic, multidisciplinary environment, requiring strategies such as pre-briefing, checklists, and …

Identification Of Distinct Subtypes In Immune Tolerance After Hematopoietic Cell Transplantation Using The Prospective Able1.0 Pediatric Study Cohort, Bernard Ng, Shalini Shenoy, Et Al.

2020-Current year OA Pubs

The lack of immune tolerance after hematopoietic cell transplantation (HCT) can result in chronic graft-versus-host disease (cGvHD), which is the primary nonrelapse limitation of successful HCT. To date, immune tolerance has been considered a single biological entity, but we hypothesized that post-HCT immune tolerance could develop through multiple pathways. Using the ABLE network database, which comprises measurements of 75 cell populations, 10 cytokines and chemokines, lymphocyte population telomere length, KRECs and TRECs, and 132 metabolites from the largest pediatric cGvHD cohort (n = 241), we applied clustering analysis to patients with primary immune tolerance (PIT; no acute GvHD [aGvHD] or …

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 …

A Single-Cell Atlas Characterizes Dysregulation Of The Bone Marrow Immune Microenvironment Associated With Outcomes In Multiple Myeloma, William C Pilcher, Lijun Yao, Yizhe Song, Kazuhito Sato, Julia T Wang, Reyka G Jayasinghe, Jennifer A Foltz, Mark A Fiala, Chiang I-Ling, Julie Fortier, Michael Slade, Stephen T Oh, Michael P Rettig, John F Dipersio, Shaji Kumar, Ravi Vij, Li Ding, Et Al.

2020-Current year OA Pubs

Multiple myeloma (MM) remains incurable despite advances in treatment options. Although tumor subtypes and specific DNA abnormalities are linked to worse prognosis, the impact of immune dysfunction on disease emergence and/or treatment sensitivity remains unclear. We developed an Immune Atlas of MM by generating profiles of 1,397,272 single cells from the bone marrow (BM) of 337 newly diagnosed participants and characterized immune and hematopoietic cell populations. Cytogenetic risk-based analysis revealed heterogeneous associations with T cells of BM, with 17p13 deletion showing distinct enrichment of a type 1 interferon signature. The disease progression-based analysis revealed the presence of a proinflammatory immune …

A Catecholamine-Independent Pathway Controlling Adaptive Adipocyte Lipolysis, Xiao Zhang, Sreejith S Panicker, Jordan M Bollinger, Anurag Majumdar, Rami Kheireddine, Lila F Dabill, Clara Kim, Brian Kleiboeker, Fengrui Zhang, Kristann L Magee, Adam Kepecs, Gretchen A Meyer, Irfan J Lodhi, Erica L Scheller, Et Al.

2020-Current year OA Pubs

Several adipose depots, including constitutive bone marrow adipose tissue, resist conventional lipolytic cues. However, under starvation, wasting or cachexia, the body eventually catabolizes stable adipocytes through unknown mechanisms. Here we developed a mouse model of brain-evoked depletion of all fat, including stable constitutive bone marrow adipose tissue, independent of food intake, to study this phenomenon. Genetic, surgical and chemical approaches demonstrated that catabolism of stable adipocytes required adipose triglyceride lipase-dependent lipolysis but was independent of local nerves, the sympathetic nervous system and catecholamines. Instead, concurrent hypoglycaemia and hypoinsulinaemia activated a potent catabolic state by suppressing lipid storage and increasing catecholamine-independent …

Perceived Hiv Risk, Barriers, And Preferences For Hiv Testing In Structurally Vulnerable Communities In St. Louis: A Best-Worst Scaling Survey, Emmanuel K Tetteh, Noelle Le Tourneau, Gregory Gross, Mckenzie Swan, Tyrell Manning, Justin Cole, Katie Wolf, Lawrence Hudson-Lewis, Julia D López, Todd Combs, Virginia R Mckay

2020-Current year OA Pubs

BackgroundPersistent gaps in efforts to end the HIV epidemic in the United States highlight the need for community-specific, evidence-based HIV testing strategies. This study investigated barriers and preferences around HIV testing among underserved populations, including Black, queer, and young adults in the St. Louis, Missouri area.MethodsWe conducted a Best-Worst Scaling (BWS) survey with adults (16+ years) recruited at community events, collecting responses electronically and providing a $25 incentive. The survey assessed the relative importance of 13 potential barriers to HIV testing such as stigma, structural barriers, and perceived HIV risk, chosen based on literature review and community input. Mean preference …

Comparison Of Breast And Gastric Her2 Immunohistochemistry (Ihc) Scoring Criteria In The Assessment Of Endometrial Carcinoma, Rachel L Furuya, Whitney Grither, Matthew A Powell, Premal H Thaker, Et Al.

2020-Current year OA Pubs

BACKGROUND: Immunohistochemistry (IHC) testing is the primary method to determine HER2 status at many institutions, often with reflex to in situ hybridization (ISH). DNA- and RNA- based platforms are emerging for HER-2 assessment. While approved IHC algorithms exist for HER2 scoring in breast and gastric carcinomas, neither has been validated in endometrial cancer. This study seeks to compare them and evaluate patterns of DNA and RNA expression.

METHODS: 263 endometrioid endometrial adenocarcinoma (EEA), 275 serous endometrial carcinoma (SEC), and 214 uterine carcinosarcoma (UCS) specimens were randomly selected. Previously stained HER2 IHC slides underwent blinded review by two board-certified pathologists and …

Defining Radiological Healing In Perianal Fistulizing Crohn's Disease: A Topclass Global Expert Delphi Consensus, Easan Anand, Jalpa Devi, David H Ballard, Shivani Joshi, Phil Tozer, Ailsa Hart, Anna Antoniou, Parakkal Deepak, Jaap Stoker, Phillip Lung, Topclass Collaborative Authors

2020-Current year OA Pubs

BACKGROUND & AIMS: Perianal fistulising Crohn's disease (pfCD) affects one-fifth of patients with Crohn's disease (CD), significantly affecting their quality of life. Magnetic resonance imaging is the gold standard for evaluating fistula healing in pfCD, but variability in radiological definitions hampers meaningful clinical interpretation and consistent trial design. This study aimed to establish an international consensus on the definition of radiological healing in pfCD.

METHODS: The study was conducted in 2 phases. Phase 1 involved a systematic review to identify magnetic resonance imaging-based variables and indices used to define healing in pfCD, assessing methodological quality using the COnsensus-based Standards for …

Atomic Models Of The Toxoplasma Cell Invasion Machinery, Jianwei Zeng, Yong Fu, Pengge Qian, Wei Huang, Qingwei Niu, Wandy L Beatty, Alan Brown, L David Sibley, Rui Zhang

2020-Current year OA Pubs

Apicomplexan parasites, responsible for toxoplasmosis, cryptosporidiosis and malaria, invade host cells through a unique gliding motility mechanism powered by actomyosin motors and a dynamic organelle called the conoid. Here, using cryo-electron microscopy, we determined structures of four essential complexes of the Toxoplasma gondii conoid: the preconoidal P2 ring, tubulin-based conoid fibers, and the subpellicular and intraconoidal microtubules. Our analysis identified 40 distinct conoid proteins, several of which are essential for parasite lytic growth, as revealed through genetic disruption studies. Comparative analysis of the tubulin-containing complexes sheds light on their functional specialization by microtubule-associated proteins, while the structure of the preconoidal …

Mapping The Genetic Landscape Across 14 Psychiatric Disorders, Andrew D. Grotzinger, Alexander S. Hatoum, Emma C. Johnson, Et Al.

2020-Current year OA Pubs

No abstract provided.

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 …

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) …

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 …

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 …