Obstructive sleep apnea in a mouse model is associated with tissue-specific transcriptomic changes in circadian rhythmicity and mean 24-hour gene expression.

Intermittent hypoxia (IH) is a major clinical feature of obstructive sleep apnea (OSA). The mechanisms that become dysregulated after periods of exposure to IH are unclear, particularly in the early stages of disease. The circadian clock governs a wide array of biological functions and is intimately associated with stabilization of hypoxia-inducible factors (HIFs) under hypoxic conditions. In patients, IH occurs during the sleep phase of the 24-hour sleep-wake cycle, potentially affecting their circadian rhythms. Alterations in the circadian clock have the potential to accelerate pathological processes, including other comorbid conditions that can be associated with chronic, untreated OSA. We hypothesized that changes in the circadian clock would manifest differently in those organs and systems known to be impacted by OSA. Using an IH model to represent OSA, we evaluated circadian rhythmicity and mean 24-hour expression of the transcriptome in 6 different mouse tissues, including the liver, lung, kidney, muscle, heart, and cerebellum, after a 7-day exposure to IH. We found that transcriptomic changes within cardiopulmonary tissues were more affected by IH than other tissues. Also, IH exposure resulted in an overall increase in core body temperature. Our findings demonstrate a relationship between early exposure to IH and changes in specific physiological outcomes. This study provides insight into the early pathophysiological mechanisms associated with IH.

TRIM24 Up-Regulates ORM2 to Alleviate Abnormal Lipid Metabolism, Inflammation, and Oxidative Stress in Mice with Obstructive Sleep Apnea Syndrome and Metabolic Dysfunction-Associated Steatotic Liver Disease.

Obstructive sleep apnea syndrome (OSAS) is associated with the development and progression of metabolic dysfunction-associated steatotic liver disease (MASLD). Tripartite motif containing 24 (TRIM24) deficiency causes hepatic lipid accumulation and hepatitis. However, the expression, function, and mechanism of TRIM24 in OSAS and MASLD remain unclear. Herein, an OSAS and MASLD mouse model was established by intermittent hypoxia (IH) and high-fat diet. IH- and 1% free fatty acid-induced mouse liver cells served as an in vitro model. TRIM24 and HIF1A were up-regulated under the IH condition. HIF1A enhanced the transcriptional activity of TRIM24. Overexpression of TRIM24 reduced hepatic lipid accumulation, decreased serum levels of total cholesterol, triglyceride, and low-density lipoprotein cholesterol, and increased serum levels of high-density lipoprotein cholesterol in OSAS and MASLD mice. Additionally, overexpression of TRIM24 alleviated inflammation and oxidative stress, and modulated aberrant lipid metabolism. Mechanically, TRIM24 up-regulated the expression of ORM2, a key regulator of hepatic lipogenesis, by binding to H3K27ac and recruiting retinoic acid receptor-α to ORM2 promoter. The cell rescue model was used to verify that ORM2 mediated the hepatoprotective effects of TRIM24. The current study reveals the important role of TRIM24 as an epigenetic coregulator of transcription in OSAS and MASLD, providing additional insights into understanding the pathogenesis and preventing the development of OSAS and MASLD.

Tet1-mediated 5hmC regulates hippocampal neuroinflammation via wnt signaling as a novel mechanism in obstructive sleep apnoea leads to cognitive deficit.

BACKGROUND: Obstructive sleep apnoea (OSA) is a sleep-disordered breathing characterized by intermittent hypoxia (IH) that may cause cognitive dysfunction. However, the impact of IH on molecular processes involved in cognitive function remains unclear. METHODS: C57BL / 6 J mice were exposed to either normoxia (control) or IH for 6 weeks. DNA hydroxymethylation was quantified by hydroxymethylated DNA immunoprecipitation (hMeDIP) sequencing. ten-eleven translocation 1 (Tet1) was knocked down by lentivirus. Specifically, cognitive function was assessed by behavioral experiments, pathological features were assessed by HE staining, the hippocampal DNA hydroxymethylation was examined by DNA dot blot and immunohistochemical staining, while the Wnt signaling pathway and its downstream effects were studied using qRT-PCR, immunofluorescence staining, and Luminex liquid suspension chip analysis. RESULTS: IH mice showed pathological changes and cognitive dysfunction in the hippocampus. Compared with the control group, IH mice exhibited global DNA hydroxylmethylation in the hippocampus, and the expression of three hydroxylmethylases increased significantly. The Wnt signaling pathway was activated, and the mRNA and 5hmC levels of Wnt3a, Ccnd2, and Prickle2 were significantly up-regulated. Further caused downstream neurogenesis abnormalities and neuroinflammatory activation, manifested as increased expression of IBA1 (a marker of microglia), GFAP (a marker of astrocytes), and DCX (a marker of immature neurons), as well as a range of inflammatory cytokines (e.g. TNFa, IL3, IL9, and IL17A). After Tet1 knocked down, the above indicators return to normal. CONCLUSION: Activation of Wnt signaling pathway by hippocampal Tet1 is associated with cognitive dysfunction induced by IH.

Assessment of cephalometric parameters and correlation with the severity of the obstructive sleep apnea syndrome.

BACKGROUND: In individuals diagnosed with obstructive sleep apnea syndrome (OSAS), variations in craniofacial structure have been inconsistently documented, showing differing degrees of alteration between obese and nonobese patients. In addition, sleep disturbance has also been shown to induce disequilibrium in this population of patients. This pilot observational study aimed to assess craniofacial values in obese and nonobese subpopulations of patients with OSAS and their correlation and association with the severity of OSAS. We also assessed whether OSAS patients are characterized by an impaired equilibrium in relation to and associated with the severity of OSAS. METHODS: We included all consecutive adult patients with OSAS. Through cephalometry, we assessed the upper (UPa-UPp) and lower (LPa-LPp) pharynx diameters, superior anterior facial height (Sor-ANS), anterior facial height (ANS-Me), anterior vertical dimension (Sor-Me), posterior facial height (S-Go) and craniovertebral angle (CVA). Furthermore, we analyzed postural equilibrium through a stabilometric examination. RESULTS: Forty consecutive OSAS patients (45% female with a mean age of 56 ± 8.2 years) were included. The subgroup of nonobese patients had a reduced UPa-UPp (p = 0.02). Cephalometric measurements were correlated with the severity of OSAS in nonobese patients, whereas only Sor-ANS was correlated with the severity of OSAS in the obese subpopulation. In the overall population, altered craniofacial values are associated with severe OSAS. Although there are differences in equilibrium between obese and nonobese OSAS patients, the stabilometric measurements were not correlated or associated with OSAS severity. CONCLUSION: Altered craniofacial values and compromised equilibrium in OSAS patients are linked to OSAS severity. Therefore, the management of OSAS should be tailored not only to weight management but also to craniofacial and postural rehabilitation to enhance patient outcomes.

Single-night continuous positive airway pressure treatment improves blood fluid properties in individuals recently diagnosed with obstructive sleep apnoea.

Obstructive sleep apnoea (OSA) is a prevalent disorder that causes repetitive, temporary collapses of the upper airways during sleep, resulting in intermittent hypoxaemia and sleep fragmentation. Given those with OSA also exhibit decreased blood fluidity, this clinical population is at heightened risk for cardiovascular disease (CVD) development. Continuous positive airway pressure (CPAP) remains a primary therapy in OSA, which improves sleep quality and limits sleep fragmentation. While CPAP effectively ameliorates nocturnal hypoxic events and associated arousals, it remains unclear whether CVD risk factors are positively impacted. The aim of the present study was thus to assess the effects of an acute CPAP therapy on sleep quality and the physical properties of blood that determine blood fluidity. Sixteen participants with suspected OSA were recruited into the current study. Participants attended the sleep laboratory for two visits: an initial diagnostic visit that included confirmation of OSA severity and comprehensive assessments of blood parameters, followed by a subsequent visit where participants were administered an individualised, acute CPAP therapy session and had their blood assessments repeated. Holistic appraisal of blood rheological properties included assessment of blood and plasma viscosity, red blood cell (RBC) aggregation, deformability, and osmotic gradient ektacytometry. Acute CPAP treatment significantly improved sleep quality parameters, which were associated with decreased nocturnal arousals and improved blood oxygen saturation. Whole blood viscosity was significantly decreased following acute CPAP treatment, which might be explained by the improved RBC aggregation during this visit. Although an acute increase in plasma viscosity was observed, it appears that the alterations in RBC properties that mediate cell-cell aggregation, and thus blood viscosity, overcame the increased plasma viscosity. While deformability of RBC was unaltered, CPAP therapy had mild effects on the osmotic tolerance of RBC. Collectively, novel observations demonstrate that a single CPAP treatment session acutely improved sleep quality, which was accompanied by improved rheological properties.

Machine learning approach for obstructive sleep apnea screening using brain diffusion tensor imaging.

Patients with obstructive sleep apnea (OSA) show autonomic, mood, cognitive, and breathing dysfunctions that are linked to increased morbidity and mortality, which can be improved with early screening and intervention. The gold standard and other available methods for OSA diagnosis are complex, require whole-night data, and have significant wait periods that potentially delay intervention. Our aim was to examine whether using faster and less complicated machine learning models, including support vector machine (SVM) and random forest (RF), with brain diffusion tensor imaging (DTI) data can classify OSA from healthy controls. We collected two DTI series from 59 patients with OSA [age: 50.2 ± 9.9 years; body mass index (BMI): 31.5 ± 5.6 kg/m2 ; apnea-hypopnea index (AHI): 34.1 ± 21.2 events/h 23 female] and 96 controls (age: 51.8 ± 9.7 years; BMI: 26.2 ± 4.1 kg/m2 ; 51 female) using a 3.0-T magnetic resonance imaging scanner. Using DTI data, mean diffusivity maps were calculated from each series, realigned and averaged, normalised to a common space, and used to conduct cross-validation for model training and selection and to predict OSA. The RF model showed 0.73 OSA and controls classification accuracy and 0.85 area under the curve (AUC) value on the receiver-operator curve. Cross-validation showed the RF model with comparable fitting over SVM for OSA and control data (SVM; accuracy, 0.77; AUC, 0.84). The RF ML model performs similar to SVM, indicating the comparable statistical fitness to DTI data. The findings indicate that RF model has similar AUC and accuracy over SVM, and either model can be used as a faster OSA screening tool for subjects having brain DTI data.

Characterisation of brain microstructural alterations in children with obstructive sleep apnea syndrome using diffusion kurtosis imaging.

Obstructive sleep apnea (OSA) is a common chronic sleep-related breathing disorder in children. Previous studies showed widespread alterations in white matter (WM) in children with OSA mainly by using diffusion tensor imaging (DTI), while diffusional kurtosis imaging (DKI) extended DTI and exhibited improved sensitivity in detecting developmental and pathological changes in neural tissues. Therefore, we conducted whole-brain DTI and DKI analyses and compared the differences in kurtosis and diffusion parameters within the skeleton between 41 children with OSA and 32 healthy children. Between-group differences were evaluated by tract-based spatial statistics (TBSS) analysis (p < 0.05, TFCE corrected), and partial correlations between DKI metrics and sleep parameters were assessed considering age and gender as covariates. Compared with the controls, children with OSA showed significantly decreased kurtosis fractional anisotropy (KFA) mainly in white matter regions with a complex fibre arrangement including the posterior corona radiate (PCR), superior longitudinal fasciculus (SLF), and inferior fronto-occipital fasciculus (IFOF), while decreased FA in white matter regions with a coherent fibre arrangement including the posterior limb of internal capsule (PLIC), anterior thalamic radiation (ATR), and corpus callosum (CC). Notably, the receiver operating characteristic (ROC) curve analysis demonstrated the KFA value in complex tissue regions significantly (p < 0.001) differentiated children with OSA from the controls. In addition, the KFA value in the left PCR, SLF, and IFOF showed significant partial correlations to the sleep parameters for children with OSA. Combining DKI derived kurtosis and diffusion parameters can provide complementary neuroimaging biomarkers for assessing white matter alterations, and reveal pathological changes and monitor disease progression in paediatric OSA.

Cognitive and Brain Gray Matter Changes in Children with Obstructive Sleep Apnea: A Voxel-Based Morphological Study.

BACKGROUND: To explore the neural difference between children with obstructive sleep apnea (OSA) and healthy controls, together with the relation between this difference and clinical severity indicator of children with OSA. METHODS: Twenty-seven children with OSA (7.6 ± 2.5 years, apnea hypopnea index [AHI]: 9.7 ± 5.3 events/h) and 30 healthy controls (7.8 ± 2.6 years, AHI: 1.7 ± 1.2 events/h) were recruited and matched with age, gender, and handedness. All children underwent 3.0 T magnetic resonance imaging of the brain and cognitive testing evaluating. Volumetric segmentation of cortical and subcortical structures and voxel-based morphometry were performed. Pearson's correlation analysis was performed between these features of gray matter volume (GMV) and obstructive apnea index (OAI) among children with OSA. RESULTS: In the comparison of children's Wechsler test scores of full-scale intelligence quotient and verbal intelligence quotient, the OSA group was significantly lower than the control group (p < 0.05). Compared with the control group, the GMV of many brain regions in the OSA group was significantly decreased (p < 0.05). In the correlation analysis of GMV and OAI in OSA group, right inferior frontal gyrus volume was significantly negatively correlated with OAI (r = - 0.49, p = 0.02). CONCLUSION: Children with OSA presented abnormal neural activities in some brain regions and impaired cognitive functions. This finding suggests an association between the OSA and decreased GMV in children.

Alterations of Limbic Structure Volumes in Patients with Obstructive Sleep Apnea.

OBJECTIVES: We investigated the change in limbic structure volumes and intrinsic limbic network in patients with obstructive sleep apnea (OSA) compared to healthy controls. METHODS: We enrolled 26 patients with OSA and 30 healthy controls. They underwent three-dimensional T1-weighted magnetic resonance imaging (MRI) on a 3 T MRI scanner. The limbic structures were analyzed volumetrically using the FreeSurfer program. We examined the intrinsic limbic network using the Brain Analysis with Graph Theory program and compared the groups' limbic structure volumes and intrinsic limbic network. RESULTS: There were significant differences in specific limbic structure volumes between the groups. The volumes in the right amygdala, right hippocampus, right hypothalamus, right nucleus accumbens, left amygdala, left basal forebrain, left hippocampus, left hypothalamus, and left nucleus accumbens in patients with OSA were lower than those in healthy controls (right amygdala, 0.102 vs. 0.113%, p = 0.004; right hippocampus, 0.253 vs. 0.281%, p = 0.002; right hypothalamus, 0.028 vs. 0.032%, p = 0.002; right nucleus accumbens, 0.021 vs. 0.024%, p = 0.019; left amygdala, 0.089 vs. 0.098%, p = 0.007; left basal forebrain, 0.020 vs. 0.022%, p = 0.027; left hippocampus, 0.245 vs. 0.265%, p = 0.021; left hypothalamus, 0.028 vs. 0.031%, p = 0.016; left nucleus accumbens, 0.023 vs. 0.027%, p = 0.002). However, there were no significant differences in network measures between the groups. CONCLUSION: We demonstrate that the volumes of several limbic structures in patients with OSA are significantly lower than those in healthy controls. However, there are no alterations to the intrinsic limbic network. These findings suggest that OSA is one of the risk factors for cognitive impairments.

Serum C-reactive protein level and sleep characteristics in obstructive sleep apnea syndrome comorbid with panic disorder: a preliminary study.

OBJECTIVE: Investigate the sleep characteristics of patients with obstructive sleep apnea syndrome (OSAS) comorbidity with panic disorder (PD), exploring its potential association with serum C-reactive protein (CRP) levels. PATIENTS AND METHODS: Fifty-four patients (25 OSAS patients with PD and 29 without PD) and 25 healthy controls (HCs) were included. The Self-rating anxiety scale (SAS), self-rating depression scale (SDS), and Pittsburgh sleep quality index (PSQI) were used to assess the mood and sleep quality of the subjects. All patients had circulating CRP levels and polysomnography was performed. RESULTS: OSAS with PD had higher SAS, SDS, PSQI than the OSAS without PD. Compared to OSAS without PD, OSAS with PD had higher percentage of non- rapid eye movement sleep 1 and 2 (N1 and N2%), sleep latency, and a lower percentage of rapid eye movement sleep (REM%). Respiratory-related microarousal index, AHI, and time below 90% oxygen saturation (T90) were low, and the lowest oxygen saturation (LO2) was high. Serum CRP levels in OSAS patients with PD were lower than that in OSAS patients without PD, but higher than that in HCs. In OSAS patients with PD, serum CRP levels were negatively correlated with wake time after sleep onset and SAS scores but positively correlated with sleep efficiency and N2%. Serum CRP levels were positively correlated with T90 and negatively correlated with LO2. CONCLUSION: OSAS patients with PD had worse sleep quality, less severe OSAS, and low serum CRP levels. Serum CRP levels in OSAS patients with PD were associated with poorer sleep quality and duration of hypoxia rather than AHI.

Molecular Mechanisms Responsible for Mesenchymal Stem Cell-Based Modulation of Obstructive Sleep Apnea.

Mesenchymal stem cells (MSCs) are adult stem cells that reside in almost all postnatal tissues where, due to the potent regenerative, pro-angiogenic and immunomodulatory properties, regulate tissue homeostasis. Obstructive sleep apnea (OSA) induces oxidative stress, inflammation and ischemia which recruit MSCs from their niches in inflamed and injured tissues. Through the activity of MSC-sourced anti-inflammatory and pro-angiogenic factors, MSCs reduce hypoxia, suppress inflammation, prevent fibrosis and enhance regeneration of damaged cells in OSA-injured tissues. The results obtained in large number of animal studies demonstrated therapeutic efficacy of MSCs in the attenuation of OSA-induced tissue injury and inflammation. Herewith, in this review article, we emphasized molecular mechanisms which are involved in MSC-based neo-vascularization and immunoregulation and we summarized current knowledge about MSC-dependent modulation of OSA-related pathologies.

Molecular Pathology, Oxidative Stress, and Biomarkers in Obstructive Sleep Apnea.

Obstructive sleep apnea syndrome (OSAS) is characterized by intermittent hypoxia (IH) during sleep due to recurrent upper airway obstruction. The derived oxidative stress (OS) leads to complications that do not only concern the sleep-wake rhythm but also systemic dysfunctions. The aim of this narrative literature review is to investigate molecular alterations, diagnostic markers, and potential medical therapies for OSAS. We analyzed the literature and synthesized the evidence collected. IH increases oxygen free radicals (ROS) and reduces antioxidant capacities. OS and metabolic alterations lead OSAS patients to undergo endothelial dysfunction, osteoporosis, systemic inflammation, increased cardiovascular risk, pulmonary remodeling, and neurological alterations. We treated molecular alterations known to date as useful for understanding the pathogenetic mechanisms and for their potential application as diagnostic markers. The most promising pharmacological therapies are those based on N-acetylcysteine (NAC), Vitamin C, Leptin, Dronabinol, or Atomoxetine + Oxybutynin, but all require further experimentation. CPAP remains the approved therapy capable of reversing most of the known molecular alterations; future drugs may be useful in treating the remaining dysfunctions.

Evaluation of the clinical efficacy of nasal surgery in the treatment of obstructive sleep apnoea.

STUDY OBJECTIVES: The aim of the study was to evaluate the clinical efficacy of nasal surgery in the treatment of obstructive sleep apnoea (OSA) by comparing the improvement of subjective symptoms and objective metrics before surgery and after 6 months of surgery. METHODS: Patients with the main complaint of nasal congestion combined with habitual snoring who were hospitalized and treated were selected. Patients underwent subjective symptom tests and objective indicator monitoring both before surgery and 6 months after surgery. Comparisons between groups were performed using the independent samples t-test. RESULTS: Subjective scale evaluations demonstrated that nasal congestion, daytime sleepiness, snoring, nose-related symptoms, and sleep symptoms in patients with simple snoring or with OSA were improved after nasal surgery. Additionally, vitality was improved in all groups except for the patients with simple snoring and emotional consequence was improved in patients with simple snoring and mild OSA. Objective evaluations indicated the apnoea-hypopnoea index (AHI), the thickness of the soft palate, and the maximum cross-sectional area of the sagittal plane of the soft palate decreased after surgery in patients with mild OSA. The lowest blood oxygen concentration (LSaO2) and anteroposterior diameter of the soft palate increased after surgery in patients with mild OSA. The arousal index also significantly decreased in patients with mild and moderate OSA. The nasal cavity volumes (NCVs) and the nasal minimal cross-sectional areas (NMCAs) of all groups showed significant differences after surgery. CONCLUSIONS: Nasal surgery can effectively improve nose and sleep symptoms in patients with simple snoring or with OSA. It can significantly reduce the nasal resistance and increase the ventilation volume. STATEMENT OF SIGNIFICANCE: Obstructive sleep apnoea (OSA) is becoming a global health problem. OSA is associated with several coexisting conditions, reduced health-related quality of life, and impaired work productivity. This study performed nasal surgery on OSA patients with the main complaint of nasal congestion combined with snoring and patients with simple snoring to compare the improvement of subjective symptoms and objective metrics before and after surgery. We found that: (1) symptoms such as nasal congestion, daytime sleepiness or snoring were improved after nasal surgery; (2) the apnoea-hypopnoea index (AHI) and arousal index decreased after surgery in patients with OSA; (3) the nasal and oropharyngeal cavity volumes increased after surgery. These findings suggest that patients with OSA or with simple snoring could benefit from nasal surgery.

Advances in Molecular Pathology of Obstructive Sleep Apnea.

Obstructive sleep apnea (OSA) is a common syndrome that features a complex etiology and set of mechanisms. Here we summarized the molecular pathogenesis of OSA, especially the prospective mechanism of upper? airway dilator fatigue and the current breakthroughs. Additionally, we also introduced the molecular mechanism of OSA in terms of related studies on the main signaling pathways and epigenetics alterations, such as microRNA, long non-coding RNA, and DNA methylation. We also reviewed small molecular compounds, which are potential targets for gene regulations in the future, that are involved in the regulation of OSA. This review will be beneficial to point the way for OSA research within the next decade.

[Cephalometric CBCT analysis of the upper airways]. / Tsefalometricheskii analiz prosveta verkhnikh dykhatel'nykh putei s pomoshch'yu konusno-luchevoi komp'yuternoi tomografii.

The purpose of this literature review is to optimize the use of cephalometric diagnostic methods for assessing the condition of the upper respiratory tract. The article examines the areas of the upper respiratory tract associated with obstructive sleep apnea syndrome (OSA). Cephalometric analysis can be a useful tool for screening this pathology. However, it should be noted that there is still no clear understanding of the results of cephalometric changes in OSA, and therefore further research is necessary.

Tim-3 is a potential regulator that inhibits monocyte inflammation in response to intermittent hypoxia in children with obstructive sleep apnea syndrome.

The mechanism of the characteristic intermittent hypoxia (IH) of obstructive sleep apnea syndrome (OSAS) on monocyte remain unclear. Our study found that OSAS children had a significantly upregulated expression in circulating proinflammatory cytokines IL-6 and IL-12, and endothelial injury markers VEGF and ICAM1. Association analysis revealed that the plasma TNFα, IL-1ß, IL-6, IL-10 and IL-12 concentration were negatively associated with the minimal SpO2, a negative index for disease severity. OSAS monocytes presented an inflammatory phenotype with higher mRNA levels of inflammatory cytokines. Importantly, we noted a significant decrease in T-cell immunoglobulin and mucin domain (Tim)-3 expression in OSAS monocytes with the increase of the plasma proinflammatory cytokines. In vitro assay demonstrated that IH induced THP-1 cell overactivation via NF-κB dependent pathway was inhibited by the Tim-3 signal. Our results indicated that activation of monocyte inflammatory responses is closely related to OSAS-induced IH, and negatively mediated by a Tim-3 signaling pathway.

Proangiogenic factor midkine is increased in melanoma patients with sleep apnea and induces tumor cell proliferation.

Midkine (MDK) might mediate the proangiogenic effect of intermittent hypoxia (IH) in patients with obstructive sleep apnea (OSA) and cutaneous melanoma (CM). We compare circulating MDK in CM patients with and without OSA, and their relationship with tumor aggressiveness, while exploring in vitro effects of soluble MDK on human lymphatic endothelial (HLEC) and melanoma cell proliferation. In 360 CM patients, sleep studies and MDK serum level measurements were performed. The effect of MDK on cell proliferation was assessed using HLEC and melanoma cell lines with patient sera under both normoxia and IH. MDK levels were higher in severe OSA compared to mild OSA or non-OSA patients, whereas no differences in VEGF levels emerged. In OSA patients, MDK levels correlated with nocturnal hypoxemia and CM mitotic rate. In vitro, MDK promotes HLEC proliferation under IH conditions. Moreover, cultures of the human melanoma cell line C81-61 with sera from patients with the highest MDK levels promoted tumor cell proliferation, which was attenuated after the addition of MDK antibody. These responses were enhanced by IH exposures. In conclusion, in CM patients, OSA severity is associated with higher MDK levels, which, appear to enhance both the lymphangiogenesis as the intrinsic aggressiveness of CM tumor cells.

Sleep-disordered breathing and its management in children with rare skeletal dysplasias.

Sleep-disordered breathing (SDB) is common in patients with skeletal dysplasias. The aim of our study was to analyze SDB and respiratory management in children with rare skeletal dysplasias. We performed a retrospective analysis of patients with spondyloepiphyseal dysplasia congenita (SEDC), metatropic dysplasia (MD), spondyloepimetaphyseal dysplasia (SEMD), acrodysostosis (ADO), geleophysic dysplasia (GD), acromicric dysplasia (AD), and spondylocostal dysplasia (SCD) between April 2014 and October 2020. Polygraphic data, clinical management, and patients' outcome were analyzed. Thirty-one patients were included (8 SEDC, 3 MD, 4 SEMD, 1 ADO, 4 GD, 3 AD, and 8 SCD). Sixteen patients had obstructive sleep apnea (OSA): 11 patients (2 with SEDC, 1 with SEMD, 1 with ADO, 1 with GD, 2 with AD, and 4 with SCD) had mild OSA, 2 (1 SEMD and 1 GD) had moderate OSA, and 3 (1 SEDC, 1 MD, 1 SEMD) had severe OSA. Adenotonsillectomy was performed in one patient with SCD and mild OSA, and at a later age in two other patients with ADO and AD. The two patients with moderate OSA were treated with noninvasive ventilation (NIV) because of nocturnal hypoxemia. The three patients with severe OSA were treated with adenotonsillectomy (1 SEDC), adeno-turbinectomy and continuous positive airway pressure (CPAP; 1 MD), and with NIV (1 SEMD) because of nocturnal hypoventilation. OSA and/or alveolar hypoventilation is common in patients with skeletal dysplasias, underlining the importance of systematic screening for SDB. CPAP and NIV are effective treatments for OSA and nocturnal hypoventilation/hypoxemia.

Cushing Syndrome is Associated with Increased Stage N2 Sleep and Decreased SWS Partially Reversible After Treatment.

The aim of the present study was to evaluate the sleep parameters of patients with Cushing syndrome (CS) at the time of diagnosis and 12-months after treatment. Thirty four newly diagnosed patients with endogenous CS (17 with ACTH-secreting pituitary adenoma, 17 with adrenal CS) and 23 controls with similar age were included in the study. Two polysomnography (PSG) recordings were performed; one at the time of diagnosis and the other 12 months after resolution of hypercortisolemia. Control group had only baseline PSG. Based on the PSG findings, stage N2 sleep was found to be prolonged, stage N3 and REM sleep were shortened in patients with CS. Average heart rate and mean Apnea Hypopnea Index (AHI) score were higher in patients with CS than the control subjects. Sixteen (47.1%) patients with CS and 4 (17.4%) controls had obstructive sleep apnea (OSA; AHI ≥5). There were no significant differences in sleep parameters of patients according to the etiology of CS (adrenal vs. pituitary) patients. Following 12-months of treatment, a significant decrease in stage N2 sleep and a significant increase in stage N3 sleep were detected, but there was no change in terms of AHI. In conclusion, Cushing syndrome has disturbing effects on sleep structure and these effects are at least partially reversible after treatment. However, the increased risk of OSA was not reversed a year after treatment indicating the importance of early diagnosis and treatment of CS.

Interhemispheric sleep depth coherence predicts driving safety in sleep apnea.

Obstructive sleep apnea is associated with increased risk of car crashes; however, conventional measures of sleep apnea severity do not clearly identify those individuals who are at greatest risk. Here we tested whether, among individuals with sleep apnea, those with reduced interhemispheric sleep depth coherence, measured by correlation between right and left hemisphere odds ratio product, are at greater risk. The sample was derived from the Sleep Heart Health Study, a prospective observational cohort study, and included 1,378 adults with sleep apnea. The occurrence of a car crash was ascertained by a questionnaire administered 2 years after the sleep study, which asked about the occurrence of crashes during the year prior to questionnaire administration. We computed the sleep depth coherence from electroencephalograms recorded during baseline sleep studies and after 5 years. The weighted kappa coefficient and Bangdiwala's B were 0.34 and 0.59, respectively, indicating a fair to moderate stability over a 5-year interval. Multivariate logistic regression, adjusted for age, sex, race, body mass index and miles driven per year, was used to assess the risk of a car crash. Compared to the lowest quartile of sleep depth coherence (<0.86), individuals in the highest quartile (>0.93) had a 62% (95% confidence interval, 22%-81%) lower risk of an accident. Further adjustments for usual sleep duration and sleepiness did not meaningfully alter these findings. Higher interhemispheric sleep depth coherence is associated with significantly lower risk of motor vehicle crashes in individuals with sleep apnea. This suggests that high interhemispheric sleep depth coherence may be a marker of resistance to sleep apnea-related adverse neurocognitive outcomes.