MiRNA expression affects survival in patients with obstructive sleep apnea and metastatic colorectal cancer.

Introduction: The relationship between obstructive sleep apnea (OSA) and cancer has been recognized for some time now. However, little is known about the mechanisms by which sleep apnea promotes tumorigenesis and the impact of OSA on survival after cancer diagnosis. In the last few years, research has focused on the exploration of different biomarkers to understand the mechanisms underlying this relationship and miRNAs, non-coding single strands of about 22 nucleotides that post-transcriptionally regulate gene expression, have emerged as possible actors of this process.The aim of the study was to evaluate the impact of OSA on survival of metastatic colorectal cancer (mCRC) patients based on the expression of specific miRNAs. Methods: The expression of 6 miRNAs, respectively miR-21, miR-23b, miR-26a, miR-27b, miR-145 and miR-210, was analyzed by qRT-PCR in patients' sera. Response to first-line therapy, Kaplan-Meier curves of overall and progression-free survival were used to evaluate survival in mCRC patients with and without OSA stratified for the expression of miRNAs. Results: The expression of miR-21, miR-23b, miR-26a and miR-210 was significantly upregulated in mCRCs with OSA compared to no OSA. In mCRC patients with OSA and increasing expression of miR-21, miR-23b, miR-26a and miR-210 risk of progression after first-line therapy was higher and both overall and progression-free survival were significantly worst. Conversely, as miR-27b and miR-145 expression increased, the life expectancy of patients diagnosed with OSA and mCRC improved markedly. Conclusions: This study highlights the relevance of specific miRNAs on OSA in mCRCs and their significance as non-invasive biomarkers in predicting the prognosis in patients with mCRC and OSA.

Posterior fossa decompression in patients with Chiari malformation type 1: effect on sleep apnea and follow-up outcomes.

PURPOSE: Sleep apnea, posing significant health risks, is frequently associated with Chiari malformation (CM), characterized by cerebellar tonsil herniation through the foramen magnum. Central sleep apnea (CSA) in CM results from impaired brain-to-muscle signaling and requires treatment. Conversely, obstructive sleep apnea (OSA), arising from throat muscle relaxation, typically unrelated to CM, often coexists. This study evaluates the effectiveness of posterior fossa decompression (PFD) on sleep apnea. METHODS: A retrospective chart review was conducted of pediatric patients with CM-1 and sleep apnea who underwent PFD between April 1, 2004, and September 30, 2022. Data collected included demographics, clinical characteristics, adenotonsillectomy status, PFD details, and sleep study parameters like the apnea-hypopnea index and respiratory disturbance index. Statistical analysis assessed the surgery's impact on sleep apnea severity. RESULTS: The study included eleven patients, predominantly male (63.6%). All had OSA (100%), with 63.6% also having CSA. Preoperative sleep studies classified OSA severity as 36.4% mild, 18.2% moderate, and 45.5% severe, with no change post-surgery. CSA severity initially included seven mild cases, which became three mild, one moderate, and three resolved cases post-surgery. Among seven patients who had adenotonsillectomy before decompression, five showed no improvement in OSA severity post-surgery. CONCLUSION: This study elucidates the complex relationship between CM-1, sleep apnea, and PFD. The findings show the persistence of sleep apnea in some patients and highlight the need for continuous monitoring of these patients in order to optimize their care after surgery.

Impact of frenectomy on the oral exercise in patients with ankyloglossia and obstructive sleep apnea: double-blind randomized controlled clinical trials.

OBJECTIVE: This study compares the efficacy of oral exercise alone to oral exercise with frenectomy in improving obstructive sleep apnea (OSA) symptoms and quality of life (QOL) in patients with ankyloglossia. MATERIALS AND METHODS: A prospective, controlled, double-blind clinical study enrolled fifteen adults (20-60 years) newly diagnosed with mild to moderate OSA and ankyloglossia. Participants were randomly assigned to either oral exercise alone (control group; n = 8) or oral exercise with frenectomy (intervention group; n = 7). Outcomes were assessed after a 3-month therapy period using polysomnography, the Epworth Sleepiness Scale (ESS), tongue strength (measured in kPa), and QOL questionnaires. RESULTS: Both control (-2.88 ± 1.73; p = 0.02) and intervention (-4.00 ± 3.65; p = 0.03) groups showed a significant reduction in ESS scores, indicating both improved sleepiness. Although the apnea-hypopnea index (AHI) increased in both groups after treatment, these changes were not statistically significant (control 4.73 ± 15.55; p = 0.48, intervention 10.42 ± 14.66; p = 0.12). Tongue strength significantly increased in both groups: control group (p = 0.04) and intervention group (p = 0.03). Satisfaction rates with the overall treatment process were 100% in the control group and 57.1% in the intervention group. Furthermore, 75.0% and 57.1% of participants in the respective groups reported an improvement in QOL. CONCLUSION: Frenectomy improved tongue mobility and the ability to perform oral exercises in individuals with OSA and ankyloglossia. However, these exercises did not significantly improve OSA-related symptoms or QOL. CLINICAL RELEVANCE: While frenectomy enhances tongue mobility, thereby enabling better engagement in oral exercises. These exercises alone did not significantly improve OSA-related symptoms or QOL. This suggests that oral exercises focusing solely on tongue mobility may not be sufficient for managing OSA. TRIAL REGISTRATION: The Thai Clinical Trials Registry was TCTR20220429002.

Effect of inflammatory cytokines and plasma metabolome on OSA: a bidirectional two- sample Mendelian randomization study and mediation analysis.

Background: Obstructive sleep apnea (OSA) is a common sleep disorder. Inflammatory factors and plasma metabolites are important in assessing its progression. However, the causal relationship between them and OSA remains unclear, hampering early clinical diagnosis and treatment decisions. Methods: We conducted a large-scale study using data from the FinnGen database, with 43,901 cases and 366,484 controls for our discovery MR analysis. We employed 91 plasma proteins from 11 cohorts (totaling 14,824 participants of European descent) as instrumental variables (IVs). Additionally, we conducted a GWAS involving 13,818 cases and 463,035 controls to replicate the MR analysis. We primarily used the IVW method, supplemented by MR Egger, weighted median, simple mode, and weighted mode methods. Meta-analysis was used to synthesize MR findings, followed by tests for heterogeneity, pleiotropy, and sensitivity analysis (LOO). Reverse MR analysis was also performed to explore causal relationships. Results: The meta-analysis showed a correlation between elevated Eotaxin levels and an increased risk of OSA (OR=1.050, 95% CI: 1.008-1.096; p < 0.05). Furthermore, we found that the increased risk of OSA could be attributed to reduced levels of X-11849 and X-24978 (decreases of 7.1% and 8.4%, respectively). Sensitivity analysis results supported the reliability of these findings. Conclusions: In this study, we uncovered a novel biomarker and identified two previously unknown metabolites strongly linked to OSA. These findings underscore the potential significance of inflammatory factors and metabolites in the genetic underpinnings of OSA development and prognosis.

The long-term prognostic implications of free triiodothyronine to free thyroxine ratio in patients with obstructive sleep apnea and acute coronary syndrome.

Objective: Obstructive sleep apnea (OSA) and thyroid dysfunction frequently overlap clinically and are risk factors for cardiovascular disease. The free triiodothyronine to free thyroxine (FT3/FT4) ratio as a novel biomarker of cardiovascular disease prognosis, but the impact of the FT3/FT4 ratio on the prognosis of OSA in patients with acute coronary syndromes (ACS) remains uncertain. Methods: In this prospective cohort study, 2160 patients with ACS were recruited and underwent portable sleep monitoring at Beijing Anzhen Hospital from June 2015 to January 2020. OSA was diagnosed when apnea-hypopnea index of ≥15 events/h. Patients were further divided into tertiles according to FT3/FT4 ratio. All patients had scheduled follow-up visits at 1, 3, 6, 9 and 12 months after discharge, with subsequent outpatient visits or telephone follow-up visits every 6 months. The primary endpoint was major adverse cardiovascular and cerebrovascular events (MACCE), including cardiovascular death, myocardial infarction (MI), stroke, ischemia-driven revascularization, or hospitalization for unstable angina or heart failure. Results: Among 1,547 euthyroid patients enrolled (mean age, 56.0 ± 10.5 years), 812 patients (52.5%) had OSA. The FT3/FT4 ratio between OSA and non-OSA patients was not significantly different. During 2.8 (1.4, 3.5) years follow up, the risk of MACCE increased with the decreasing FT3/FT4 tertiles in patients with OSA (tertile3 as reference, tertile2: hazard ratio (HR) 1.26, 95% CI: 0.85-1.86, P = 0.255; tertile1: 1.60, 95% CI 1.11-2.32; P = 0.013). After adjustment for confounders, the lowest FT3/FT4 tertile was still independently associated with an increased risk of MACCE (adjusted HR 1.66, 95% CI 1.11-2.50, P = 0.015). Conclusion: Lower FT3/FT4 ratio associated with poor prognosis in patients with ACS and OSA.

The Role of Continuous Positive Airway Pressure in Acute Bilateral Vocal Cord Paresis or Paralysis Post-Thyroidectomy.

OBJECTIVES: Acute post-thyroidectomy bilateral vocal cord paresis or paralysis (BVCP) is often managed with observation, botulinum toxin injection or tracheostomy. However, only a few cases discuss obstructive sleep apnea (OSA) in the context of BVCP with limited exploration of home sleep test (HST) and continuous positive airway pressure (CPAP) as post-operative assessment and management tools. This study suggests CPAP as a less invasive approach while awaiting vocal cord recovery. METHODS: A retrospective chart review was conducted on 2 female patients who presented with dyspnea and sleep-disordered breathing (SDB) symptoms post-thyroidectomy. Both patients underwent laryngoscopy and HSTs, followed by CPAP prescription. RESULTS: Case 1 (body mass index [BMI]: 32.6 kg/m2) and Case 2 (BMI: 20.1 kg/m2), aged 66 and 77 respectively, presented with post-surgery dyspnea and SDB symptoms. Laryngoscopy revealed left vocal cord paresis and right vocal cord paralysis in both cases. Although tracheostomy could provide definitive treatment, both cases were deferred for non-invasive options, which led to HST, confirming moderate OSA (PAT-derived apnea-hypopnea index (pAHI): 18/hour and 27.1/hour) leading to CPAP recommendation. In Case 2, 5 weeks of CPAP use resulted in dramatic improvements in her sleep quality, with continued benefits at 3-month follow-up. CONCLUSION: These cases underscore the value of considering sleep studies and CPAP as adjunctive tools in acute post-thyroidectomy BVCP management while awaiting vocal motion recovery. This report also further supports that BVCP sufficiently narrows the glottic airway, predisposing patients to OSA.

Phenotypes of Velopharyngeal Tube Law in Obstructive Sleep Apnea.

OBJECTIVE: The biomechanics of upper airway collapse in obstructive sleep apnea (OSA) remains poorly understood. The goal of this study is to compare the area-pressure relationship (tube law) of the velopharynx at peak inspiration and peak expiration. STUDY DESIGN: Cross-sectional. SETTING: Academic tertiary medical center. METHODS: The velopharyngeal tube law was quantified in a convenience sample of 20 OSA patients via step reductions in nasal mask pressure during drug induced sleep endoscopy (DISE). The velopharyngeal airspace cross-sectional area was estimated from endoscopy while luminal pressure was recorded with a catheter. The tube law was quantified for nasal mask pressures from 14 to 0 cmH2O at peak inspiration and at peak expiration in all patients. The tube law was also quantified during the breathing cycle at a constant nasal mask pressure of 4 cmH2O in 3 patients representing different phenotypes. RESULTS: Velopharyngeal compliance (the slope of the tube law) was not statistically different in the peak inspiration versus peak expiration tube laws. Three phenotypes were observed, namely inspiratory collapse (phenotype 1), expiratory collapse (phenotype 2 = palatal prolapse), and a mostly stable airway during inspiration and expiration that collapsed as CPAP was reduced (phenotype 3). CONCLUSION: Velopharyngeal compliance is not significantly different at peak inspiration and peak expiration, which suggests that muscle tone is low when luminal pressure is above the closing pressure. Additional studies are needed to investigate how different phenotypes of velopharyngeal collapse may affect therapeutic outcomes.

Curcumin activates the Wnt/ß-catenin signaling pathway to alleviate hippocampal neurogenesis abnormalities caused by intermittent hypoxia: A study based on network pharmacology and experimental verification.

The purpose of this work was to investigate how curcumin (Cur) might enhance cognitive function and to gain a better understanding of the molecular mechanisms behind Cur's impacts on neurogenesis deficits brought on by intermittent hypoxia (IH). Using network pharmacology, we explored possible targets for Cur's obstructive sleep apnea (OSA) therapy. We established an IH model using C57BL/6 mice and c17.2 cells, and we assessed the influence of Cur on treatment outcomes as well as the effect of IH on cognitive function. Hippocampal damage and neurogenesis, as well as expression of core targets, were then examined. Network pharmacology analysis revealed that Cur has the potential for multi-target, multi-pathway therapy, with CTNNB1 and MYC as core target genes. The Morris water maze test showed that Cur (100 mg/kg, intragastrically) significantly improved cognitive dysfunction induced by IH. The hematoxylin and eosin (H&E) and Nissl staining indicated that Cur could alleviate damage to the hippocampus caused by IH. Immunohistochemistry, immunofluorescence, and western blotting results showed that Cur might promote neurogenesis and upregulate the expression of ß-catenin and c-myc. In vitro, Cur (0.5 µM) has a protective effect on IH-induced neural stem cells (NSCs) injury and apoptosis and can restore the Wnt/ß-catenin. Cur significantly increased the neurogenesis via the Wnt/ß-catenin pathway, providing the scientific groundwork for the development of new treatment strategies for neurological damage linked to OSA.

Correlations between clinical parameters and PSQ in children with suspected OSA.

The aim of this study was to measure tonsils and adenoid vegetations, investigate the modified Mallampati score, determine BMI according to body mass and corresponding percentile, and compare these data with the results of the Pediatric Sleep Questionnaire (PSQ). The subjects were children aged 2 to 18 who were indicated for adenotonsillectomy at the Clinic for Otorhinolaryngology and Head and Neck Surgery. A doctor specialist conducted the clinical examinations. According to the PSQ, 75 subjects were divided into two groups: those at high risk and those at low risk for developing obstructive sleep apnea (OSA). The PSQ results showed that 45 subjects (60 %) were at high risk for OSA, and these subjects had significantly lower weight and BMI. Although a higher number of subjects had grade 4 tonsils and grade 3 and 4 adenoids, this distribution was not statistically significant. There was no statistically significant difference in the distribution of the modified Mallampati score when compared with the PSQ results. Lower body mass and BMI were statistically significant risk factors for OSA, while the size of the tonsils and adenoids, as well as the modified Mallampati score, did not show any statistically significant difference in comparison with the PSQ results.