Facilitating return of actionable genetic research results from a biobank repository: Participant uptake and utilization of digital interventions.

Research participants report interest in receiving genetic research results. How best to return results remains unclear. In this randomized pilot study, we sought to assess the feasibility of returning actionable research results through a two-step process including a patient-centered digital intervention as compared with a genetic counselor (GC) in the Penn Medicine biobank.

Radiomics Analysis for the Identification of Invasive Pulmonary Subsolid Nodules From Longitudinal Presurgical CT Scans.

Purpose: Effective identification of malignant part-solid lung nodules is crucial to eliminate risks due to therapeutic intervention or lack thereof. We aimed to develop delta radiomics and volumetric signatures, characterize changes in nodule properties over three presurgical time points, and assess the accuracy of nodule invasiveness identification when combined with immediate presurgical time point radiomics signature and clinical biomarkers.

Materials And Methods: Cohort included 156 part-solid lung nodules with immediate presurgical CT scans and a subset of 122 nodules with scans at 3 presurgical time points.

Initial and Long-Term Prescribing of Opioids and Non-steroidal Anti-inflammatory Drugs Following Total Hip and Knee Arthroplasty.

Introduction: Limited evidence exists on health system characteristics associated with initial and long-term prescribing of opioids and nonsteroidal anti-inflammatory drugs (NSAIDs) following total hip and knee arthroplasty (THA/TKA), and if these characteristics differ among individuals based on preoperative NSAID exposure. We identified orthopedic surgeon opioid prescribing practices, hospital characteristics, and regional factors associated with initial and long-term prescribing of opioids and NSAIDs among older adults receiving THA/TKA.

Materials And Methods: This observational study included opioid-naïve Medicare beneficiaries aged ≥65 years receiving elective THA/TKA between January 1, 2014 and July 4, 2017.

Therapeutic silencing in TREM2 cardiac macrophages suppresses atrial fibrillation.

Atrial fibrillation (AFib) and the risk of its lethal complications are propelled by fibrosis, which induces electrical heterogeneity and gives rise to reentry circuits. Atrial TREM2 macrophages secrete osteopontin (encoded by ), a matricellular signaling protein that engenders fibrosis and AFib. Here we show that silencing in TREM2 cardiac macrophages with an antibody-siRNA conjugate reduces atrial fibrosis and suppresses AFib in mice, thus offering a new immunotherapy for the most common arrhythmia.

Practical Considerations and Implementation of Sodium-Glucose Co-Transporter-2 Inhibitors in Chronic Kidney Disease: Who, When, and How? A Position Statement by Nephrologists.

Introduction: There remains an unmet need to reduce kidney and cardiovascular risk in patients with chronic kidney disease (CKD). This report is therefore intended to provide real-world clinical guidance to primary care providers on sodium-glucose co-transporter-2 (SGLT2) inhibitor use in patients with CKD, focusing on practical considerations. Initially developed as glucose-lowering drugs, SGLT2 inhibitors preserve kidney function and reduce risks of cardiovascular events and mortality.

LAG-3 and PD-1 synergize on CD8 T cells to drive T cell exhaustion and hinder autocrine IFN-γ-dependent anti-tumor immunity.

Overcoming immune-mediated resistance to PD-1 blockade remains a major clinical challenge. Enhanced efficacy has been demonstrated in melanoma patients with combined nivolumab (anti-PD-1) and relatlimab (anti-LAG-3) treatment, the first in its class to be FDA approved. However, how these two inhibitory receptors synergize to hinder anti-tumor immunity remains unknown.

Advances and ongoing challenges in eosinophilic gastrointestinal disorders presented at the CEGIR/TIGERs Symposium at the 2024 American Academy of Allergy, Asthma & Immunology meeting.

The Consortium of Eosinophilic Gastrointestinal disease Researchers (CEGIR) and The International Gastrointestinal Eosinophil Researchers (TIGERs) organized a daylong symposium at the 2024 annual meeting of the American Academy of Allergy, Asthma & Immunology. The symposium featured new discoveries in basic and translational research as well as debates on the mechanisms and management of eosinophilic gastrointestinal diseases. Updates on recent clinical trials and consensus guidelines were also presented.

Intracellular islatravir-triphosphate half-life supports extended dosing intervals.

Antiretroviral therapy has substantially reduced morbidity, mortality, and disease transmission in people living with HIV. Islatravir is a nucleoside reverse transcriptase translocation inhibitor that inhibits HIV-1 replication by multiple mechanisms of action, and it is in development for the treatment of HIV-1 infection. In preclinical and clinical studies, islatravir had a long half-life (t) of 3.

Quality of Care in the Last Two Years of Life for Children With Complex Chronic Conditions.

Context: Limited data exists about care received by children with complex chronic conditions (CCCs) in the final years of their disease and end-of-life (EOL).

Objective: To examine hospital performance on EOL quality measures and to describe healthcare services during the last two years of life for children with CCCs who died in-hospital.

Methods: Retrospective automated electronic health record review of children with ≥1 CCC ICD-10 diagnosis code, who died inpatient between October 2020 and March 2023 at a single quaternary U.

AP-1 Mediates Cellular Adaptation and Memory Formation During Therapy Resistance.

Cellular responses to environmental stimuli are typically thought to be governed by genetically encoded programs. We demonstrate that melanoma cells can form and maintain cellular memories during the acquisition of therapy resistance that exhibit characteristics of cellular learning and are dependent on the transcription factor AP-1. We show that cells exposed to a low dose of therapy adapt to become resistant to a high dose, demonstrating that resistance was not purely selective.

Quality of Life and Exercise Capacity in Early Stage and Subclinical Hypertrophic Cardiomyopathy: A Secondary Analysis of the VANISH Trial.

Background: The health-related quality of life (HRQOL) and cardiopulmonary exercise testing (CPET) performance of individuals with subclinical and early stage hypertrophic cardiomyopathy (HCM) have not been systematically studied. Improved understanding will inform the natural history of HCM and factors influencing well-being.

Methods: VANISH trial (Valsartan for Attenuating Disease Evolution in Early Sarcomeric HCM) participants with early stage sarcomeric HCM (primary analysis cohort) and subclinical HCM (sarcomere variant without left ventricular hypertrophy comprising the exploratory cohort) who completed baseline and year 2 HRQOL assessment via the pediatric quality of life inventory and CPET were studied.

Preoperative Radiographic Predictors of Subsequent Fusion After Lumbar Decompression Surgery.

Study Design: Retrospective cohort study.

Objective: The purpose of this study is to determine which demographic, surgical, and radiographic preoperative characteristics are most associated with the need for subsequent fusion after decompression lumbar spinal surgery.

Summary Of Background Data: There is a relatively high rate of the need for repeat decompression or fusion after an index decompression procedure for degenerative spine disease.

Exploring the interplay between addiction and time perception: A systematic review and meta-analysis.

Prior studies have investigated the immediate impacts of substances on temporal perception, the impact of temporal outlook, and the consequences of modified temporal perception on addictive behaviors. These inquiries have provided valuable perspectives on the intricate associations between addiction and time perception, enriching the groundwork for forthcoming research and therapeutic strategies. This comprehensive review aims to further explore intricate correlation among diverse addictive substances-namely alcohol, cannabis, nicotine, opioids-and non-substance addictions such as internet gaming, elucidating their influence on temporal perception.

Optimizing the post-CAR T monitoring period in recipients of axicabtagene ciloleucel, tisagenlecleucel, and lisocabtagene maraleucel.

CD19-directed chimeric antigen receptor T-cell (CAR T) therapies, including axicabtagene ciloleucel (axi-cel), tisagenlecleucel (tisa-cel), and lisocabtagene maraleucel (liso-cel), have transformed the treatment landscape for B-cell non-Hodgkin lymphoma, showcasing significant efficacy but also highlighting toxicity risks such as cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS). The US Food and Drug Administration has mandated patients remain close to the treatment center for 4 weeks as part of a Risk Evaluation and Mitigation Strategy to monitor and manage these toxicities, which, although cautious, may add to cost of care, be burdensome for patients and their families, and present challenges related to patient access and socioeconomic disparities. This retrospective study across 9 centers involving 475 patients infused with axi-cel, tisa-cel, and liso-cel from 2018 to 2023 aimed to assess CRS and ICANS onset and duration, as well as causes of nonrelapse mortality (NRM) in real-world CAR T recipients.

Spatial transcriptomics reveals influence of microenvironment on intrinsic fates in melanoma therapy resistance.

Resistance to cancer therapy is driven by both cell-intrinsic and microenvironmental factors. Previous work has revealed that multiple resistant cell fates emerge in melanoma following treatment with targeted therapy and that, , these resistant fates are determined by the transcriptional state of individual cells prior to exposure to treatment. What remains unclear is whether these resistant fates are shared across different genetic backgrounds and how, if at all, these resistant fates interact with the tumor microenvironment.

COVID-19 mRNA vaccination responses in individuals with sickle cell disease: an ASH RC Sickle Cell Research Network Study.

Children and adults with sickle cell disease (SCD) have increases in morbidity and mortality with COVID-19 infections. The American Society of Hematology Research Collaborative Sickle Cell Disease Research Network performed a prospective COVID-19 vaccine study to assess antibody responses and analyze whether messenger RNA (mRNA) vaccination precipitated any adverse effects unique to individuals with SCD. Forty-one participants received 2 doses of the Pfizer-BioNTech vaccine and provided baseline blood samples before vaccination and 2 months after the initial vaccination for analysis of immunoglobulin G (IgG) reactivity against the receptor binding domain (RBD) of the severe acute respiratory syndrome coronavirus 2 spike protein.

Age-Dependent Differences in Blood Levels of Glial Fibrillary Acidic Protein but Not Ubiquitin Carboxy-Terminal Hydrolase L1 in Children.

Objectives: Despite the growing evidence of the clinical utility of blood-brain biomarkers in adults with traumatic brain injury (TBI), less is known about the performance of these biomarkers in children. We characterize age-dependent differences in levels of ubiquitin carboxy-terminal hydrolase L1 (UCH-L1) and glial fibrillary acidic protein (GFAP) in children without TBI.

Methods: Plasma biobank specimens from children and adolescents aged 0-<19 years without TBI were obtained, and UCH-L1 and GFAP levels were quantified.

A Description and Safety Overview of Irreversible Electroporation for Prostate Tissue Ablation in Intermediate-Risk Prostate Cancer Patients: Preliminary Results from the PRESERVE Trial.

The PRESERVE study (NCT04972097) aims to evaluate the safety and effectiveness of the NanoKnife System to ablate prostate tissue in patients with intermediate-risk prostate cancer (PCa). The NanoKnife uses irreversible electroporation (IRE) to deliver high-voltage electrical pulses to change the permeability of cell membranes, leading to cell death. A total of 121 subjects with organ-confined PCa ≤ T2c, prostate-specific antigens (PSAs) ≤ 15 ng/mL, and a Gleason score of 3 + 4 or 4 + 3 underwent focal ablation of the index lesion.

A Neuroradiologist's Guide to Operationalizing the Response Assessment in Neuro-Oncology (RANO) Criteria Version 2.0 for Gliomas in Adults.

Radiographic assessment plays a crucial role in the management of patients with central nervous system (CNS) tumors, aiding in treatment planning and evaluation of therapeutic efficacy by quantifying response. Recently, an updated version of the Response Assessment in Neuro-Oncology (RANO) criteria (RANO 2.0) was developed to improve upon prior criteria and provide an updated, standardized framework for assessing treatment response in clinical trials for gliomas in adults.

Phase 1 Open-Label Study of Omigapil in Patients With LAMA2- or COL6-Related Dystrophy.

Background And Objectives: Omigapil is a small molecule which inhibits the GAPDH-Siah1-mediated apoptosis pathway. Apoptosis is a pathomechanism underlying the congenital muscular dystrophy subtypes LAMA2-related dystrophy (LAMA2-RD) and COL6-related dystrophy (COL6-RD). Studies of omigapil in the (dy/dy) LAMA2-RD mouse model demonstrated improved survival, and studies in the (dy/dy) LAMA2-RD mouse model and the (Col6a1) COL6-RD mouse model demonstrated decreased apoptosis.

Associations between brain network, puberty, and behaviors in boys with Klinefelter syndrome.

Background: Klinefelter syndrome (KS), also referred to as XXY syndrome, is a significant but inadequately studied risk factor for neuropsychiatric disability. Whether alterations in functional brain connectivity or pubertal delays are associated with aberrant cognitive-behavioral outcomes in individuals with KS is largely unknown. In this observational study, we investigated KS-related alterations in the resting-state brain network, testosterone level, and cognitive-behavioral impairment in adolescents with Klinefelter syndrome.