Severe eosinophilic chronic rhinosinusitis with nasal polyps (ECRSwNP) remains the most relapsed subtype of uncontrolled CRSwNP. CM310, a humanised anti-interleukin (IL)-4 receptor alpha monoclonal antibody, inhibits IL-4 and IL-13 signaling which underlying eosinophilic inflammation. This study aims to evaluate the efficacy and safety of CM310 in patients with severe ECRSwNP. A multicentre, randomised, double-blind, and placebo-controlled phase 2 clinical trial was conducted. 56 eligible adult patients with severe ECRSwNP were randomised 1:1 to receive subcutaneously either CM310 (300 mg) or placebo every 2 weeks under the background therapy of mometasone furoate nasal spray (MFNS) for 16 weeks, with 8 weeks of follow-up. Coprimary endpoints included the changes from baseline in nasal polyp score (NPS) and nasal congestion score (NCS) at week 16. Key secondary endpoints included sinus Lund-Mackay CT score, change in sinus volume occupied by disease, University of Pennsylvania Smell Identification Test score, 22-item Sino-nasal Outcome Test score, and total symptom score. Safety, pharmacodynamics, and changes in type 2 inflammation biomarkers were assessed. This study is registered with ClinicalTrials.gov, NCT04805398. Between April 6, 2021, and March 18, 2022, 27 patients respectively in both the CM310 and placebo groups completed the study. Findings suggested that CM310 improved the coprimary efficacy endpoints of decreasing nasal polyp size and alleviating nasal congestion compared with the placebo. Least squares (LS) mean differences (CM310 vs placebo) of change from baseline in NPS and NCS at week 16 were −2.1 (95% CI −2.9, −1.4; p < 0.0001) and −0.9 (95% CI −1.4, −0.5; p < 0.0001), respectively. Sinus CT scan revealed that Lund-Mackay CT score (LS mean difference [95% CI] −7.6, [−9.4, −5.8]; p < 0.0001) and sinus volume occupied by disease (LS mean difference [95% CI] −37%, [−47%, −28%]; p < 0.0001) were significantly improved with CM310 compared with placebo. In addition, CM310 significantly relieved the daily symptoms of patients with CRSwNP and improved their quality of life reflected by the improvements in the TSS (−2.6 [95% CI −3.5, −1.6]), UPSIT (10.4 [95% CI 6.8, 14.0]) and SNOT-22 score (−19.1 [95% CI −29.8, −8.5]). Compared with placebo, CM310 administration significantly reduced type 2-related biomarkers including the serum TARC and total IgE, and tissue eosinophils. The most common adverse events were upper respiratory tract infection, blood cholesterol increased, and tinnitus, but none were considered drug-related. These findings support CM310 as an effective additional treatment option to the standard of care in patients with severe ECRSwNP. KeyMed Biosciences (Chengdu) Limited.

Interaural time difference and interaural level difference signals are insufficient in patients with single-sided deafness (SSD). This insufficiency leads to an absence of sound localization abilities and a decrease in speech intelligibility in noisy environments. SSD occurring in children further affects their language learning and cognitive abilities and their academic performance because they lack spatial abilities and binaural hearing. The early stages of central auditory system development are critical for auditory function development and morphological refinement. SSD occurring in the critical period can cause significant lateralization in the bilateral auditory pathway. This may increase the risk that affected individuals cannot re-establish binaural benefits after rehabilitation of hearing loss in the post-sensitive period. For otorhinolaryngologists, there is the concern that children with congenital SSD cannot benefit from cochlear implantation. Only a few studies have investigated auditory rehabilitation in children with congenital SSD with cochlear implantation and their results were inconsistent. The present review aims to clarify the main problems and challenges of clinical rehabilitation of congenital SSD, particularly focusing on the effect of CI on sound localization ability in children with congenital SSD.

BACKGROUND:The aim of this study was to investigate the association between sex and speech-ABR in adults, and its relationship to sex hormone levels. MATERIAL AND METHODS:Speech-ABR were elicited with the consonant-vowel syllable (/da/) in a total of...

We investigated the mechanisms underlying the therapeutic effects of Yiqi Jiemin decoction (YJD), a traditional Chinese medicine (TCM), in the ovalbumin (OVA)-induced allergic rhinitis (AR) model in guinea pigs. YJD significantly decreased infiltration of mast cells and eosinophils into the nasal mucosa of AR model guinea pigs. YJD also increased expression of TGF-β in the nasal mucosa, restored the balance of Th1/Th2 immune cell responses, and decreased serum levels of various pro-inflammatory mediators, including histamine (HA), neuropeptide Y (NPY), acetylcholine (ACH), norepinephrine and immunoglobulin E (IgE). Metabolic analyses using liquid chromatography coupled with high-resolution mass spectrometry revealed that YJD improved cellular metabolism in AR model guinea pigs and increased serum levels of glycocholic acid while decreasing levels 1-palmitoyl lysophosphatidic acid. RNA-sequencing analysis identified BPIFB2 as a potential diagnostic biomarker and therapeutic target for AR. Functional enrichment analyses showed that YJD significantly inhibited cytokine secretion pathways in AR model guinea pigs. These findings demonstrate that YJD protects against OVA-induced AR in guinea pigs by suppressing inflammation in the nasal mucosa, restoring Th1/Th2 balance, and improving cellular metabolism.