ReNeu: A Pivotal, Phase IIb Trial of Mirdametinib in Adults and Children With Symptomatic Neurofibromatosis Type 1-Associated Plexiform Neurofibroma.

Purpose: Pharmacologic therapies for neurofibromatosis type 1-associated plexiform neurofibromas (NF1-PNs) are limited; currently, none are US Food and Drug Administration-approved for adults.

Methods: ReNeu is an open-label, multicenter, pivotal, phase IIb trial of mirdametinib in 58 adults (≥18 years of age) and 56 children (2 to 17 years of age) with NF1-PN causing significant morbidities. Patients received mirdametinib capsules or tablets for oral suspension (2 mg/m twice daily, maximum 4 mg twice daily), regardless of food intake, in 3 weeks on/1 week off 28-day cycles.

Perinephric Extramedullary Disease in Multiple Myeloma.

Extramedullary disease represents an aggressive form of multiple myeloma occurring outside the skeleton and is a poor prognostic indicator. Extramedullary disease most commonly involves the skin, muscle, pleura, lymph nodes, liver, and central nervous system. Infrequently, extramedullary disease can involve the kidneys or perirenal space.

The Pigmentation of Blue Light Is Mediated by Both Melanogenesis Activation and Autophagy Inhibition through OPN3-TRPV1.

Blue light, a high-energy radiation in the visible light spectrum, was recently reported to induce skin pigmentation. In this study, we investigated the involvement of TRPV1-mediated signaling along with OPN3 in blue light-induced melanogenesis as well as its signaling pathway. Operating downstream target of OPN3 in blue light-induced melanogenesis, blue light activated TRPV1 and upregulated its expression, resulting in calcium influx.

Impact of Atopic Status on Clinical Presentation and Treatment Response in Pediatric Patients With Eosinophilic Esophagitis.

Background: Nearly 80% of patients with eosinophilic esophagitis (EoE) have coexisting atopic disease, yet a subset do not. It is unclear if this lack of atopy impacts presentation or response to therapy.

Objectives: To characterize the presentation and response to therapy in atopic versus nonatopic pediatric patients with EoE.

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.

DNA structural features and variability of complete MHC locus sequences.

The major histocompatibility (MHC) locus, also known as the Human Leukocyte Antigen (HLA) genes, is located on the short arm of chromosome 6, and contains three regions (Class I, Class II and Class III). This 5 Mbp locus is one of the most variable regions of the human genome, yet it also encodes a set of highly conserved and important proteins related to immunological response. Genetic variations in this region are responsible for more diseases than in the entire rest of the human genome.

RANKL-mediated osteoclast formation is required for bone loss in a murine model of Staphylococcus aureus osteomyelitis.

Staphylococcus aureus osteomyelitis leads to extensive bone destruction. Osteoclasts are bone resorbing cells that are often increased in bone infected with S. aureus.

Myosin light chain phosphatase is a downstream target of Rho-kinase in endothelin-1-induced transactivation of the TGF-β receptor.

Background: Rho-kinase (ROCK) regulates actomyosin contraction, coronary vasospasm, and cytoskeleton dynamics. ROCK and of NADPH oxidase (NOX) play an essential role in cardiovascular disease and proteoglycan synthesis, which promotes atherosclerosis by trapping low density lipoprotein. ROCK is activated by endothelin-1 (ET1) and transactivates the transforming growth factor beta receptor (TGFβR1), intensifying Smad signaling and proteoglycan production.

Simulation in Nurse Anesthesia Educational Programs: A Report by the AANA Simulation Subcommittee.

Simulation is an integral part of the healthcare educational landscape and a key element in the future of graduate professional education. For the past three decades, simulation-based educational methodology has been gaining popularity in nurse anesthesia educational programs (NAEP). There is currently limited objective evidence documenting modalities used or educational outcomes addressed through simulation in NAEPs.

Langerhans cell histiocytosis: NACHO update on progress, chaos, and opportunity on the path to rational cures.

Langerhans cell histiocytosis (LCH) is a myeloid neoplastic disorder characterized by lesions with CD1a-positive/Langerin (CD207)-positive histiocytes and inflammatory infiltrate that can cause local tissue damage and systemic inflammation. Clinical presentations range from single lesions with minimal impact to life-threatening disseminated disease. Therapy for systemic LCH has been established through serial trials empirically testing different chemotherapy agents and durations of therapy.

Central nervous system embryonal tumors with EWSR1-PLAGL1 rearrangements reclassified as INI-1 deficient tumors at relapse.

Purpose: Central nervous system (CNS) embryonal tumors are a diverse group of malignant tumors typically affecting pediatric patients that recently have been better defined, and this paper describes evolution of a unique type of embryonal tumor at relapse.

Methods: Two pediatric patients with CNS embryonal tumors with EWSR1-PLAGL1 rearrangements treated at Arkansas Children's Hospital with histopathologic and molecular data are described.

Results: These two patients at diagnosis were classified as CNS embryonal tumors with EWSR1-PLAGL1 rearrangements based on histologic appearance and molecular data.

RAS-RAF-miR-296-3p signaling axis increases Rad18 expression to augment radioresistance in pancreatic and thyroid cancers.

Oncogenic RAS and RAF signaling has been implicated in contributing to radioresistance in pancreatic and thyroid cancers. In this study, we sought to better clarify molecular mechanisms contributing to this effect. We discovered that miRNA 296-3p (miR-296-3p) is significantly correlated with radiosensitivity in a panel of pancreatic cancer cells, and miR-296-3p is highly expressed in normal cells, but low in cancer cell lines.

Systemic and Neurosarcoidosis With Rare Involvement of the Extremities' Peripheral Nerves.

We present a case of sarcoidosis with a rare presentation of involvement of peripheral nerves of the lower limbs and subcutaneous nodules detected on 18 F-FDG PET/CT. The patient also had involvement of the spinal nerves and dura, histologically proven to be sarcoidosis. There were other manifestations of systemic sarcoidosis like metabolically active cervical and mediastinal lymphadenopathy.

Trends in Medicare Submitted Charges to Allowed Payment Ratios for Ophthalmology Services.

Purpose: Many physicians charge more than the Medicare insurance program pays. Current charge-to-payment ratios in ophthalmology and trends over the years are unknown. In this work, we examined physician charge-to-payment ratios in ophthalmology across procedures and consultations.

Percutaneous Patent Foramen Ovale Closure: Stroke and Beyond.

Over 750,000 individuals suffer from stroke annually in the United States, with 87% of these strokes being ischemic in nature. Roughly 40% of ischemic strokes occur in individuals 60 years of age or under. A quarter of all ischemic strokes have no identifiable cause despite extensive workup and are deemed cryptogenic in nature.

Refining the identity of mesenchymal cell types associated with murine periosteal and endosteal bone.

Single-cell RNA-seq has led to novel designations for mesenchymal cells associated with bone as well as multiple designations for what appear to be the same cell type. The main goals of this study were to increase the amount of single-cell RNA sequence data for osteoblasts and osteocytes, to compare cells from the periosteum to those inside bone, and to clarify the major categories of cell types associated with murine bone. We created an atlas of murine bone-associated cells by harmonizing published datasets with in-house data from cells targeted by Osx1-Cre and Dmp1-Cre driver strains.

Safety of primary nasotracheal intubation in the pediatric intensive care unit (PICU).

Background: Nasal tracheal intubation (TI) represents a minority of all TI in the pediatric intensive care unit (PICU). The risks and benefits of nasal TI are not well quantified. As such, safety and descriptive data regarding this practice are warranted.

Design and Impact of a Novel Rural Hospital Alliance.

Without rural hospitals, many patients may not have access to essential services, or even any health care. Rural hospitals provide a community hub for local access to primary care and emergency services, as well as a bridge to specialized care outside the community. The goal of this review was to demonstrate how the University of Arkansas for Medical Sciences supports and empowers rural hospitals through an alliance that provides cost savings through clinical networks, collaborative purchasing, and leveraged services; workforce recruitment and education; telemedicine and distance learning; community outreach; and access to best practices, resources, and tools for hospital transformation.

Maximizing Readmission Reduction in Colon Cancer Patients.

Introduction: Multiple studies have identified risk factors for readmission in colon cancer patients. We need to determine which risk factors, when modified, produce the greatest decrease in readmission for patients so that limited resources can be used most effectively by implementing targeted evidence-based performance improvements. We determined the potential impact of various modifiable risk factors on reducing 30-d readmission in colon cancer patients.