Pharmacokinetic Evaluation of Neutral Sphinghomyelinase2 (nSMase2) Inhibitor Prodrugs in Mice and Dogs.

: Extracellular vesicles (EVs) can carry pathological cargo, contributing to disease progression. The enzyme neutral sphingomyelinase 2 (nSMase2) plays a critical role in EV biogenesis, making it a promising therapeutic target. Our lab previously identified a potent and selective inhibitor of nSMase2, named DPTIP (IC = 30 nM).

Discovery of Orally Available Prodrugs of Itaconate and Derivatives.

Itaconate, an endogenous immunomodulator from the tricarboxylic acid (TCA) cycle, shows therapeutic effects in various disease models, but is highly polar with poor cellular permeability. We previously reported a novel, topical itaconate derivative, SCD-153, for the treatment of alopecia areata. Here, we present the discovery of orally available itaconate derivatives for systemic and skin disorders.

Assessment of decision-making with locally run and web-based large language models versus human board recommendations in otorhinolaryngology, head and neck surgery.

Introduction: Tumor boards are a cornerstone of modern cancer treatment. Given their advanced capabilities, the role of Large Language Models (LLMs) in generating tumor board decisions for otorhinolaryngology (ORL) head and neck surgery is gaining increasing attention. However, concerns over data protection and the use of confidential patient information in web-based LLMs have restricted their widespread adoption and hindered the exploration of their full potential.

Type 2 biomarkers in olfactory cleft mucus correlate with SNOT-22 in chronic rhinosinusitis independent of nasal polyp status.

Background: Quantitative mucus cytokine analysis to examine the sinonasal microenvironment may bridge the gap between patient-reported outcome measures (PROMs) and empirical measures of inflammation in patients with chronic rhinosinusitis (CRS).

Objective: Investigate the correlation between mucus cytokine levels and Sino-Nasal Outcome Test (SNOT-22) scores, including individual subdomains.

Methods: Patients with CRS were prospectively recruited between 2016 and 2021 into a multi-institutional observational study.

Optimization of the preparation of a spiny spore high-concentrated Aspergillus brasiliensis suspension.

This work aimed to improve some steps of the existing guidelines of the European Standards to obtain an Aspergillus brasiliensis ATCC 16404 spore suspension with >75% spiny spores without mycelia and a concentration of at least 1.5 × 108 CFU ml-1. Several manufacturers' combinations of "strain/medium" were assessed in terms of yield of spiny spores.

Small cell transformation in EGFR-mutated non-small cell lung cancer: DLL3 expression and efficacy of immune checkpoint inhibitors or tyrosine kinase inhibitors combined with chemotherapy.

Introduction: Small cell transformation (SCT) is a typical mechanism of adaptive resistance to third generation epidermal growth factor receptor inhibitors (EGFRi) which have become the standard of care for EGFR-driven non-small cell lung cancer (EGFR+ NSCLC). Little is known about the optimal management of SCT patients. This study aimed to compare outcomes under platinum/etoposide chemotherapy alone (chemo) or in combination with EGFR inhibitors (EGFRi+chemo) or immune checkpoint inhibitors (ICI+chemo).

Pathoanatomy and pathomechanics of pertrochanteric fractures - an MRI study.

Background And Study Aims: Magnetic resonance imaging (MRI) has been used for more than 20 years in the region of the proximal femur to diagnose occult, or incomplete, fractures of the femoral neck and the trochanteric segment. MRI has also potential to contribute to the understanding of the pathogenesis and pathoanatomy of trochanteric fractures.

Methods: The group including 13 patients was examined by MRI for a suspected, or incomplete, fracture of the trochanteric segment within 24 hours post-injury.

Predictors of Durable Remission After Successful Surgery for Cushing Disease: Results From the Multicenter RAPID Registry.

Background And Objective: Cushing disease (CD) affects mortality and quality of life along with limited long-term remission, underscoring the need to better identify recurrence risk. The identification of surgical or imaging predictors for CD remission after transsphenoidal surgery has yielded some inconsistent results and has been limited by single-center, single-surgeon, or meta-analyses studies. We sought to evaluate the multicenter Registry of Adenomas of the Pituitary and Related Disorders (RAPID) database of academic US pituitary centers to assess whether robust nonhormonal recurrence predictors could be elucidated.

The SWELL1 Channel Promotes Ischemic Brain Damage by Mediating Neuronal Swelling and Glutamate Toxicity.

Cytotoxic neuronal swelling and glutamate excitotoxicity are two hallmarks of ischemic stroke. However, the underlying molecular mechanisms are not well understood. Here, it is reported that SWELL1, the essential subunit of the volume-regulated anion channel (VRAC), plays a dual role in ischemic injury by promoting neuronal swelling and glutamate excitotoxicity.

Impact of sociodemographic status and sex on chronic rhinosinusitis and olfaction in people with cystic fibrosis.

Background: Sociodemographic status (SDS) including race/ethnicity and socioeconomic status as approximated by education, income, and insurance status impact pulmonary disease in people with cystic fibrosis (PwCF). The relationship between SDS and chronic rhinosinusitis (CRS) remains understudied.

Methods: In a prospective, multi-institutional study, adult PwCF completed the 22-Question SinoNasal Outcome Test (SNOT-22), Smell Identification Test (SIT), Questionnaire of Olfactory Disorder Negative Statements (QOD-NS), and Cystic Fibrosis Questionnaire-Revised (CFQ-R).

An eosinophil peroxidase activity assay predicts acute exacerbations in post-operative chronic rhinosinusitis.

EPX activity has been correlated with eCRS diagnosis and baseline disease severity. Herein, EPX activity is shown to correlate with post-operative antibiotic and steroid use in CRS. EPX activity has potential to act as a prognostic biomarker of CRS disease severity and control.

Chemokine CCL19 and Its Receptors CCR7 and CCRL1 in Chronic Rhinosinusitis.

Background: CCL19 has been shown to predict disease severity in COVID-19 and treatment response in rheumatoid arthritis. CCL19 can exert both pro- and anti-inflammatory effects and is elevated in chronic rhinosinusitis (CRS). However, its role in CRS remains unknown.

The Impact of Acute Peri-operative Particulate Matter Exposure on Endoscopic Sinus Surgery Outcomes: A Preliminary Multi-site Investigation.

Background: Environmental exposures have been postulated to play an important role in the pathophysiology of chronic rhinosinusitis (CRS). Particulate matter (PM) is one of the most widely studied ambient air pollutants, but its peri-operative impact on CRS is unknown.

Objective: To determine the effect of acute, peri-operative PM exposure on outcomes after endoscopic sinus surgery (ESS).

Quantification of Budesonide Retained in the Sinonasal Cavity After High-Volume Saline Irrigation in Post-Operative Chronic Rhinosinusitis.

Background: Budesonide high-volume saline irrigations (HVSIs) are routinely used to treat chronic rhinosinusitis (CRS) due to improved sinonasal delivery and efficacy compared to intranasal corticosteroid sprays. The off-label use of budesonide is assumed to be safe, with several studies suggesting the systemically absorbed dose of budesonide HVSI is low. However, the actual budesonide dose retained in the sinonasal cavity following HVSI is unknown.

Site-Specific Quality of Life Outcomes Following Anterior Skull Base Surgery: A Systematic Review and Meta-Analysis.

Background: There is a limited understanding of site-specific, quality of life (QOL) outcomes in anterior skull base surgery (ASBS). The objective of the present investigation was to characterize postoperative change in QOL outcomes for anterior skull base lesions following open and endoscopic surgery.

Methods: A comprehensive review of the literature was performed according to Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines using the PubMed, Scopus, Embase, and Cochrane databases for studies reporting pre- and postoperative, site-specific, QOL outcome measures in ASBS using validated questionnaires.

Enhancement of microbicidal efficacy of chemical disinfectants when combined with ultrasound technology.

Aims: This study investigated the antimicrobial efficacy of ultrasound technology (US) in combination with two different disinfectants (Disinfectant A and Disinfectant B), containing peracetic acid (PAA) and quaternary ammonium compounds (QACs), respectively, against two sporigenic pathogens, Aspergillus brasiliensis and Bacillus subtilis.

Methods And Results: The microbicidal activity of the coupled treatment was compared with the use of the disinfectants alone, and the efficacy of the disinfection strategies was evaluated by the log reduction of the population of the microorganism inoculated onto stainless-steel surface. The combination treatment resulted in a log reduction of 5.

Health care disparities and chronic rhinosinusitis: Does neighborhood disadvantage impact outcomes in sinonasal disease?

Objective: Socioeconomic status (SES) is linked to health outcomes but has not been well studied in patients with chronic rhinosinusitis (CRS). The area deprivation index (ADI) is a comprehensive measure of geographic SES that ranks neighborhood disadvantage. This investigation used ADI to understand the impact of neighborhood disadvantage on CRS treatment outcomes.

Patient perspectives on chronic rhinosinusitis in cystic fibrosis: Symptom prioritization in the era of highly effective modulator therapy.

Background: Chronic rhinosinusitis (CRS) is common in people with cystic fibrosis (PwCF). Rhinologic symptom prioritization and areas that influence CRS treatment choices, including pursuing endoscopic sinus surgery (ESS), remain understudied.

Methods: Adult PwCF + CRS were enrolled at eight centers into a prospective, observational study (2019-2023).