Innovative Insurance to Improve US Patient Access to Cell and Gene Therapy.

Unlabelled: Policy Points Cell and gene therapies (CGTs) offer treatment for rare and oftentimes deadly disease, but their prices are high, and payers may seek to limit spending. Total annual costs of covering all existing and expected CGTs for the entire US population 2023-2035 to amount to less than $20 per person and concentrate in commercial and state Medicaid plans. Reinsurance fees add to expected costs.

"They Make It So Hard on You": How Rurality Shapes Veterans' Health Experiences When Managing Gulf War Illness.

Background: Gulf War illness (GWI) is characterized by multiple, persistent symptoms (e.g., fatigue, musculoskeletal pain, concentration problems, and gastrointestinal disorders) across more than one body system that are severe enough to interfere with daily functioning.

Sudden Cardiac Arrest Associated with Hemodialysis: A Community-Based Study.

Background: Individuals with end-stage renal disease may be at increased risk of sudden cardiac arrest (SCA) associated with dialysis therapy. However, community-based studies with comprehensive adjudication of SCA are lacking.

Methods: We conducted a community-based study using a case-case study design in a US population of ≈1 million.

Outcome Measures to Evaluate Functional Recovery in Survivors of Respiratory Failure: A Scoping Review.

Background: Respiratory failure is a life-threatening condition affecting millions of individuals in the United States annually. Survivors experience persistent functional impairments, decreased quality of life, and cognitive impairments. However, no established standard exists for measuring functional recovery among survivors of respiratory failure.

Massively parallel characterization of transcriptional regulatory elements.

The human genome contains millions of candidate cis-regulatory elements (cCREs) with cell-type-specific activities that shape both health and many disease states. However, we lack a functional understanding of the sequence features that control the activity and cell-type-specific features of these cCREs. Here we used lentivirus-based massively parallel reporter assays (lentiMPRAs) to test the regulatory activity of more than 680,000 sequences, representing an extensive set of annotated cCREs among three cell types (HepG2, K562 and WTC11), and found that 41.

Addition of an NK1 receptor antagonist to standard antiemetic prophylaxis in patients with B-cell lymphoma receiving EPOCH.

Introduction: Data on the optimal management of patients with hematologic malignancies and chemotherapy-induced nausea and vomiting (CINV) are lacking, particularly for multiday chemotherapy regimens. We report our institutional experience in patients with B-cell lymphoma receiving multiday dose-adjusted R-EPOCH chemotherapy utilizing two CINV prophylaxis strategies.

Methods: We performed a retrospective, single-center, cohort study evaluating hospitalized patients with aggressive non-Hodgkin B-cell lymphoma receiving DA-R-EPOCH (April 2016 to October 2022).

Maternal derived antibodies and avian β-defensins expression patterns and their correlation in the yolk sac tissue of different chicken breeds (Gallus gallus).

The expression of maternal derived antibodies (MDAs) and avian β-defensins (AvBDs) in yolk sac tissue may be age-specific and influenced by breed, thereby immunological window difference in hatchlings. This study investigated the mRNA expression of MDAs and AvBDs in the yolk sac tissues of Beijing You and Hy-Line Gray chickens from the embryonic day (ED)7 to 3 days after hatch (DAH). Hy-Line showed a higher embryo bodyweight and a lower residual yolk weight at ED17 (P < 0.

A histochemical approach to activity-based copper sensing reveals cuproplasia-dependent vulnerabilities in cancer.

Copper is an essential nutrient for sustaining vital cellular processes spanning respiration, metabolism, and proliferation. However, loss of copper homeostasis, particularly misregulation of loosely bound copper ions which are defined as the labile copper pool, occurs in major diseases such as cancer, where tumor growth and metastasis have a heightened requirement for this metal. To help decipher the role of copper in the etiology of cancer, we report a histochemical activity-based sensing approach that enables systematic, high-throughput profiling of labile copper status across many cell lines in parallel.

Outcomes of mechanical thrombectomy for medium vessel occlusion in acute ischemic stroke patients with ASPECTS 4-5 vs. 6-7: a retrospective, multicenter, and multinational study.

Introduction: Mechanical thrombectomy (MT) efficacy in medium vessel occlusion (MeVO) stroke, particularly in patients with low Alberta Stroke Program Early Computed Tomography Score (ASPECTS), remains less explored.

Methods: This retrospective study analyzed data from 443 AIS patients treated with MT for MeVO and low ASPECTS (4-7) at 37 centers across North America, Asia, and Europe, from September 2017 to July 2021. Patients were categorized into ASPECTS of 4-5 and 6-7.

A Comparative Review of the Terms Epipharyngitis and Nasopharyngitis in Medical Literature.

This review explores the usage of the term "epipharyngitis" in medical literature, particularly in non-English-speaking contexts. The term, although rarely used in contemporary English-language medical literature, may lead to confusion due to its overlap with more commonly used terms like "nasopharyngitis." This review aims to trace the origins of the term, analyze its usage across different languages, and discuss the implications of term differences in clinical practice and medical education.

A unique case report on campylobacter rectus infection leading to acute motor axonal neuropathy in a pediatric patient.

A unique case report on campylobacter rectus infection leading to acute motor axonal neuropathy in a pediatric patient. Campylobacter rectus is an anaerobic bacterium found in the oral cavity. While it has been linked to periodontal disease, its association with acute motor axonal neuropathy (AMAN), a variant of Guillain-Barre Syndrome, remains unverified.

Validation of Clinical Dynamic Contrast-Enhanced Magnetic Resonance Imaging Perfusion Modeling and Neoadjuvant Chemotherapy Response Prediction in Breast Cancer Using FDG and Cu-DOTA-Trastuzumab Positron Emission Tomography Studies.

Purpose: Perfusion modeling presents significant opportunities for imaging biomarker development in breast cancer but has historically been held back by the need for data beyond the clinical standard of care (SoC) and uncertainty in the interpretability of results. We aimed to design a perfusion model applicable to breast cancer SoC dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) series with results stable to low temporal resolution imaging, comparable with published results using full-resolution DCE-MRI, and correlative with orthogonal imaging modalities indicative of biophysical markers.

Methods: Subsampled high-temporal-resolution DCE-MRI series were run through our perfusion model and resulting fits were compared for consistency.

Highly multiplexed imaging reveals prognostic immune and stromal spatial biomarkers in breast cancer.

Spatial profiling of tissues promises to elucidate tumor-microenvironment interactions and generate prognostic and predictive biomarkers. We analyzed single-cell, spatial data from three multiplex imaging technologies: cyclic immunofluorescence (CycIF) data we generated from 102 breast cancer patients with clinical follow-up, and publicly available imaging mass cytometry and multiplex ion-beam imaging datasets. Similar single-cell phenotyping results across imaging platforms enabled combined analysis of epithelial phenotypes to delineate prognostic subtypes among estrogen-receptor positive (ER+) patients.

The CD74 inhibitor DRhQ improves short-term memory and mitochondrial function in 5xFAD mouse model of Aβ accumulation.

Neuroinflammation and mitochondrial dysfunction are early events in Alzheimer's disease (AD) and contribute to neurodegeneration and cognitive impairment. Evidence suggests that the inflammatory axis mediated by macrophage migration inhibitory factor (MIF) binding to its receptor, CD74, plays an important role in many central nervous system (CNS) disorders such as AD. Our group has developed DRhQ, a novel CD74 binding construct which competitively inhibits MIF binding, blocks macrophage activation and migration into the CNS, enhances anti-inflammatory microglia cell numbers and reduces pro-inflammatory gene expression.

AxonFinder: Automated segmentation of tumor innervating neuronal fibers.

Neurosignaling is increasingly recognized as a critical factor in cancer progression, where neuronal innervation of primary tumors contributes to the disease's advancement. This study focuses on segmenting individual axons within the prostate tumor microenvironment, which have been challenging to detect and analyze due to their irregular morphologies. We present a novel deep learning-based approach for the automated segmentation of axons, AxonFinder, leveraging a U-Net model with a ResNet-101 encoder, based on a multiplexed imaging approach.

Predictive equation derived from 6,497 doubly labelled water measurements enables the detection of erroneous self-reported energy intake.

Nutritional epidemiology aims to link dietary exposures to chronic disease, but the instruments for evaluating dietary intake are inaccurate. One way to identify unreliable data and the sources of errors is to compare estimated intakes with the total energy expenditure (TEE). In this study, we used the International Atomic Energy Agency Doubly Labeled Water Database to derive a predictive equation for TEE using 6,497 measures of TEE in individuals aged 4 to 96 years.

Occult collision tumor of the gastroesophageal junction comprising adenocarcinomas with distinct molecular profiles.

Collision tumors, characterized by the coexistence of two unique neoplasms in close approximation, are rare and pose diagnostic challenges. This is particularly true when the unique neoplasms are of the same histologic type. Here we report such a case where comprehensive tumor profiling by next generation sequencing (NGS) as well as immunohistochemistry revealed two independent adenocarcinomas comprising what was initially diagnosed as a single adenocarcinoma of the gastroesophageal (GEJ) junction.

Senescent cell-derived extracellular vesicles inhibit cancer recurrence by coordinating immune surveillance.

Senescence is a non-proliferative, survival state that cancer cells can enter to escape therapy. In addition to soluble factors, senescence cells secrete extracellular vesicles (EVs), which are important mediators of intercellular communication. To explore the role of senescent cell-derived EVs (senEVs) in inflammatory responses to senescence, we developed an engraftment-based senescence model in wild-type mice and genetically blocked senEV release in vivo, without significantly affecting soluble mediators.

Medicaid and the Promise for Cure.

Importance: Cell and gene therapies are revolutionizing the treatment landscape for children and adults with rare diseases and can be life-changing for patients and their families. Successful implementation of these new therapies into clinical practice depends on their accessibility and affordability, particularly through publicly funded Medicaid agencies, which cover many children and adults with rare diseases.

Objective: To provide a framework to broadly assess cell and gene therapies, evaluate payment options, and ensure equitable access through the lens of publicly funded Medicaid programs.

Real-World Evaluation of i-gel Introduction on Intraoperative Airway-Related Safety Events: A Retrospective Cohort Study From a New England Hospital Network.

Background: Several health care networks have fully adopted second-generation supraglottic airway (SGA) i-gel. Real-world evidence of enhanced patient safety after such practice change is lacking. We hypothesized that the implementation of i-gel compared to the previous LMA®-Unique™ would be associated with a lower risk of airway-related safety events.

Age-associated differences in FIRES: Characterizing prodromal presentation and long-term outcomes via the web-based NORSE/FIRES Family Registry.

Febrile infection-related epilepsy syndrome (FIRES) is a rare clinical presentation of refractory status epilepticus following a febrile infection. This study analyzes data from the NORSE/FIRES Family Registry, an international web-based registry available in six languages with data entered by patients, families, and clinicians to explore clinical presentations, survivorship, and long-term outcomes in adult and pediatric FIRES patients. We characterize and examine differences in demographics, prodromal symptoms, seizure frequency, anti-seizure medications (ASMs), quality of life, cognition, mood, and anxiety in adults vs pediatric populations with FIRES.