TGFß mediates collagen production in human CRSsNP nasal mucosa-derived fibroblasts through Smad2/3-dependent pathway and CTGF induction and secretion.

Chronic rhinosinusitis without nasal polyp (CRSsNP) is characterized by tissue remodeling and fibrosis. Transforming growth factor-ß (TGF-ß) is considered a master switch in the induction of the profibrotic program which can induce fibroblasts to synthesize and contract extracellular matrix (ECM) proteins. A previous study has shown TGF-ß1 signaling and collagen overproduction in the CRSsNP, but the responsible cells and mechanism of action remain unclear. Therefore, this study was aimed to investigate the relationship between TGF-ß1 stimulation and collagen expression and to explore the role of connective tissue growth factor (CTGF) during the remodeling process using human CRSsNP nasal mucosa tissues and mucosa-derived fibroblasts as main materials. We found that TGF-ß1 and its isoforms could promote collagen protein expression. Concomitantly, TGF-ß1 caused CTGF expression and secretion. An addition of exogenous CTGF to fibroblasts also caused collagen expression. In accordance with these observations, TGF-ß1, CTGF, and collagen were highly expressed in the subepithelial stroma region of CRSsNP nasal mucosa, as determined by immunohistochemistry. The TGF-ß1-mediated collagen expression could be blocked by actinomycin D and SIS3, suggesting that the induction was through transcriptional regulation and Smad2/3-dependent pathway. Finally, we demonstrated that CTGF small interfering RNA knockdown led to a substantial decrease in TGF-ß1-mediated collagen expression. Collectively, our results provide first and further evidence that TGF-ß1 mediates collagen expression-production through a canonical Smad2/3-dependent pathway and CTGF induction and secretion in human nasal fibroblasts. Moreover, TGF-ß1, CTGF, and collagen are highly expressed in human CRSsNP nasal mucosa specimens, suggesting their roles in tissue remodeling during CRSsNP progression.

Peptidoglycan induces bradykinin receptor 1 expression through Toll-like receptor 2 and NF-κB signaling pathway in human nasal mucosa-derived fibroblasts of chronic rhinosinusitis patients.

Numerous studies have demonstrated that Gram-positive microbiomes play an important role in the pathogenesis and in the way of treatment of chronic rhinosinusitis (CRS). Kinins are inflammatory mediators and one of their receptors, namely bradykinin receptor 1 (BKR1 or B1R), is believed to be induced and involved in inflammation in pathophysiological conditions. In the present study, we investigated the effect of peptidoglycan (PGN), a major cell wall component of G(+) bacteria, on BKR expression and its signaling pathway in nasal fibroblasts from CRS without nasal polyp (CRSsNP). The PGN induced increases in B1R mRNA and protein production. The induction was abolished by the NF-κB and protein kinase A inhibitor. In parallel, the PGN treatment directly activated IκB/NF-κB signaling and CREB phosphorylation. Interestingly, a further analysis suggested no involvement of cAMP/PKA/CREB pathway in this induction. The B1R expression and IκB/NF-κB signaling pathway could be attenuated by Toll-like receptor-2 (TLR2) blocking/neutralizing Ab. In a functional assay, the addition of B1R selective agonist (Des-Arg10 -kallidin) to the fibroblasts after PGN stimulation led to an increase in CXCL8 release and p38 MAPK and ERK1/2 phosphorylation, which could be inhibited by the B1R antagonist. Taken together, our results revealed for the first time that PGN can increase B1R expression in human nasal mucosa-derived fibroblasts through TLR2 activation and NF-κB signaling pathway. This induction functionally leads to MAPKs activation and CXCL8 release upon B1R stimulation. Our results also suggest that a major component of G(+) bacteria can participate in B1R upregulation in nasal mucosa during CRSsNP progression.

The role of lateral pharyngoplasty in obstructive sleep apnea syndrome.

Recent studies have shown that lateral pharyngoplasty is an effective procedure to correct obstructive sleep apnea. The objective of the paper was to evaluate factors contributing to obstructive sleep apnea syndrome and identify the different severity categories of obstructive sleep apnea that could benefit from lateral pharyngoplasty. We included 60 patients undergoing uvulopalatopharyngoplasty with or without lateral pharyngoplasty from December 1, 2008 to May 31, 2012. Six who did not complete the post-operative survey were excluded. 54 participants were assigned alternatively to either uvulopalatopharyngoplasty alone (control group, n = 29) or to uvulopalatopharyngoplasty with lateral pharyngoplasty (intervention group, n = 25). The reduction of apnea-hypoxia index in the intervention group (49.3%) was higher than it was in the control group (30.4%), but the average value was not statistically significant (p = 0.088). Only patients with moderate obstructive sleep apnea in the intervention group achieved a significant reduction of apnea-hypoxia index (30.7 vs. 10.8%; p = 0.020). Factors such as body mass index, nadir/mean SpO2, snoring index, Epworth sleepiness scale and periodic limb movement index did not change significantly following lateral pharyngoplasty. To evaluate patients' upper airway anatomy, we employed cephalometry, and found that the retroglossal space played a critical role in severe obstructive sleep apnea. Our study showed that only patients in the moderate category can be benefited from adding lateral pharyngoplasty to uvulopalatopharyngoplasty; however, patients in the mild or severe category did not benefit from adding this procedure. This information is vital when considering surgery for patients with obstructive sleep apnea syndrome. Level of evidence Prospective cohort study, Level II.

Long-term rare giant sialolithiasis for 30 years: A case report and review of literature.

BACKGROUND: Sialolithiasis is one of the most common salivary gland disorders, most commonly affecting the submandibular gland. Submandibular sialolithiasis can be treated using non-invasive conservative measures and invasive treatments. Treatment selection was based on the ductal system anatomy and the size and location of the stones. This study aimed to review the updates on sialolithiasis treatment and compare the different management strategies of the variables. CASE SUMMARY: This report presents a case of a long-term, rare, and giant sialolithiasis within the submandibular gland parenchyma for 30 years in an older adult. Our patient presented with painless right submandibular swelling. Computed tomography revealed a calcified mass measuring 35 mm × 20 mm within the right submandibular gland. In this case, the infection and fibrosis of the affected gland and size of the stone did not provide us with other alternatives except for the excision of the involved gland. Thus, right submandibular sialoadenectomy was performed via the transcervical approach. After the surgery, the patient recovered without any complaints, side effects, or complications. CONCLUSION: Tailored management is important for preserving gland function, maintaining low risk, and reducing patient discomfort.

Endonasal Septoplasty Using a Septal Cartilaginous Batten Graft for Managing Caudal Septal Deviation.

Caudal nasal septal deviation is an important condition altering nasal obstruction and cosmetic appearance and many surgical techniques have been published on how to correct caudal septal deviation, as successful management of caudal septal deviation is challenging. The goal of our study was to explore the effect of endonasal septoplasty using a septal cartilaginous batten graft for managing caudal septal deviation. We tested 26 participants with caudal septal deviation who received endonasal septoplasty using a septal cartilaginous batten graft from 1 April 2019 to 29 June 2022, and followed up for at least 6 months. Nasal Obstruction Symptom Evaluation (NOSE) Scale and visual analog scale (VAS) were recorded at baseline, 1 month, and 6 months after surgery. Valid samples were analyzed by repeated measures ANOVA and paired sample t-test. Average participant age was 36.15 ± 11.02 years old. The preoperative, 1-month postoperative, and 6-month postoperative NOSE scale decreased significantly (75.38 ± 15.62, 13.85 ± 7.79, and 14.04 ± 9.90; p < 0.001), while preoperative, 1-month postoperative, and 6-month postoperative VAS (convex/concave side) also improved (7.50 ± 0.81/3.38 ± 0.94, 2.27 ± 0.53/1.54 ± 0.58, and 2.31 ± 0.55/1.58 ± 0.58; p < 0.001). Our results showed that endonasal septoplasty using a septal cartilaginous batten graft had good surgical outcomes without an open scar or severe complications.

CPAP Treatment Improves Pure Tone Audiometry Threshold in Sensorineural Hearing Loss Patients with Sleep-Disordered Breathing.

This article investigates the effects of continuous positive airway pressure (CPAP) on hearing impairment in sensorineural hearing loss (SNHL) patients with sleep-disordered breathing (SDB). This retrospective and observational study took place from September 2016 to February 2021, accumulating 77 subjects with SNHL and SDB (60.7 ± 11.1 years). Of which, 28 received CPAP treatment (63.0 ± 8.5 years). In our methodology, hearing thresholds at low, medium, high, and average frequencies are assessed by pure-tone audiometry at baseline (BL), three (3 m), six (6 m), and 12 (12 m) months. Our results show that the BL of at least three frequencies in all subjects is positively associated with old age, males, smoking, alcohol, coronary artery disease, hypertension, and apnea-hypopnea index [AHI] (all p < 0.05). Moreover, low, medium, and average frequencies are negatively correlated at CPAP-6 m (-5.60 ± 2.33, -5.82 ± 2.56, and -5.10 ± 2.26 dB; all p < 0.05) and CPAP-12 m (-7.97 ± 2.74, -8.15 ± 2.35, and -6.67 ± 2.37 dB; all p < 0.01) against corresponding measures of CPAP-BL. High, medium, and average frequencies positively correlated with age (p < 0.001 for high and average frequencies and <0.01 for medium frequencies). We conclude that in SNHL patients with SDB, hearing thresholds at low and medium frequencies improves under CPAP use after six months, which persists at least to the end of one year.

Increased incidence of age-related macular degeneration in sensorineural hearing loss: A population-based cohort study.

BACKGROUND: To evaluate the incidence of age-related macular degeneration (AMD) in patients diagnosed with sensorineural hearing loss (SNHL) via the application of the National Health Insurance Research Database in Taiwan. METHODOLOGY/PRINCIPAL FINDINGS: A retrospective cohort study was conducted. Patients with a diagnosis of SNHL was enrolled in the study group after exclusion and a propensity score matched group without SNHL was served as the control group with a 1:2 ratio. The main outcome was regarded as the emergence of AMD diagnostic codes. Cox proportional hazard regression was applied to analyze the incidence and adjusted hazard ratio (aHR) of AMD in the multivariate model. A total of 15,686 patients with SNHL were included in the study group while another 31,372 non-SNHL patients served as the control group. After a follow-up interval up to 16 years, there were 484 AMD events occurred in the study group and 660 AMD cases in those non-SNHL patients with a significantly higher aHR compared to the control group after adjusting for multiple potential risk factors (aHR: 1.399, 95% CI: 1.244-1.574). Other prominent risk factors for AMD included older age, ischemic heart disease, hyperlipidemia, Alzheimer's disease, liver disease and kidney disease. Besides, a higher cumulative probability of AMD was observed in the study group (log-rank P <0.0001). CONCLUSION: The patients with SNHL demonstrated a higher incidence of developing AMD.

The development of optic neuropathy after chronic rhinosinusitis: A population-based cohort study.

BACKGROUND: To evaluate the risk of developing optic neuropathy (ON) in patient with both non-surgery and surgery-indicated chronic rhinosinusitis (CRS) via the national health insurance research database in Taiwan. METHODOLOGY/PRINCIPAL FINDINGS: 44,176 Patients with a diagnostic code of CRS was selected, which included 6,678 received functional endoscopic sinus surgery (FESS) regarded as the surgery-indicated CRS. Each individual in the study group was matched to two non-CRS patients by age and gender. The outcome was set as the occurrence of ON according to the diagnostic codes occurred after the index date. Poisson regression was used to calculate the adjusted relative risk (aRR) and conditional Cox proportional model was used to estimate the adjusted hazard ratio (aHR). There were 131 and 144 events of ON occurred in the study group and the control group respectively during the follow-up period. The whole study group, whether received FESS or not, demonstrated both significant aRR and aHR compared to the control group after adjusting demographic data, prominent ocular diseases, and systemic co-morbidities. In addition, both the aRR and aHR were higher in CRS patient received FESS than those with CRS but without FESS management. CONCLUSION: The existence of CRS, especially the surgery-indicated CRS is a significant risk factor for the following ON using multivariable analysis.