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Obstructive sleep apnea is associated with an increased risk of acute ischemic cerebrovascular accidents in adults. However, this association has not been well established in the pediatric population. We report a case of acute right internal capsule lacunar infarct manifesting as left-sided hemiplegia in an adolescent with severe obesity. Severe untreated obstructive sleep apnea was identified during the hospital stay. Positive airway pressure therapy, weight loss, and tonsillectomy eventually normalized sleep-disordered breathing. The patient recovered completely without any residual neurological deficits with multidisciplinary care. Lacunar infarcts due to hypertension-related cerebral vasculopathy are a well-known cause of stroke in adults. Untreated obstructive sleep apnea may cause hypertension and potentially predispose even the pediatric population to develop lacunar infarcts. Polysomnography needs to be considered as a part of the diagnostic algorithm in pediatric patients with stroke. CITATION: Chen B, Gorantla S, Shah V. Acute lacunar infarct in an obese adolescent with obstructive sleep apnea. J Clin Sleep Med. 2021;17(8):1743–1747.

STUDY OBJECTIVES: Because existing data investigating obstructive sleep apnea (OSA) and insulin resistance (IR) are inconsistent, we examine OSA and IR in a pediatric obesity clinic. METHODS: Children (2–18 years) in the obesity clinic (2013–2017) undergoing polysomnography (PSG), anthropometric measurements, and fasting laboratory tests were included. Linear regression assessed OSA defined by the obstructive apnea-hypopnea index (oAHI) with the homeostatic model assessment of insulin resistance (HOMA-IR). Secondary aims assessed oxygen desaturation index (ODI) and age interactions with HOMA-IR. Logistic regression models and receiver operating characteristic analysis were performed to investigate optimal oAHI and ODI cutoffs relative to HOMA-IR ≥ 3. RESULTS: Eighty children were included (mean age, 11.4 ± 4.0 years; 56% female; 46% Caucasian; median body mass index [BMI], 34.6 kg/m(2) [interquartile ratio, 29.9–40.1], median BMI z-score, 2.5 [interquartile ratio, 2.3–2.8); 46% with oAHI ≥ 5 events/h. HOMA-IR was higher in the OSA group (oAHI ≥ 5 events/h): 5 vs 3.8 (P = .034). After adjustment for sex, race, and BMI z-score, oAHI ≥ 5 events/h retained significance with HOMA-IR (P = .041). HOMA-IR increased in older children (age ≥ 12 years) when adjusting for waist circumference z-score and waist-height ratio (statistical interaction, P = .020 and .034, respectively). Receiver operating characteristic showed optimal cut points of oAHI and ODI for predicting significant IR 4.9 (area under the curve, 0.70; 95% confidence interval, 0.57–0.83; sensitivity, 0.76; specificity, 0.66) and 4.6 (area under the curve, 0.68; 95% confidence interval, 0.55–0.80; sensitivity, 0.70; specificity, 0.67), respectively. CONCLUSIONS: In a clinic-based pediatric cohort with obesity, OSA is associated with increased IR even after adjusting for confounders including obesity defined by the BMI z-score. Age ≥ 12 years was associated with AHI relative to IR after adjustment for waist circumference z-score and waist-height ratio. Significant IR could be discriminated by oAHI ≥ 4.9 with moderate sensitivity/specificity. Future studies are needed to verify these findings. CITATION: Siriwat R, Wang L, Shah V, Mehra R, Ibrahim S. Obstructive sleep apnea and insulin resistance in children with obesity. J Clin Sleep Med. 2020;16(7):1081–1090.

CONTEXT: Polycystic ovary syndrome (PCOS) is a common endocrine disorder and is associated with metabolic syndrome (MS). Development of MS in PCOS is likely multifactorial and may relate to poor sleep. OBJECTIVE: The objective of this research is to investigate differences in objective markers of sleep in adolescents with obesity and PCOS with and without MS. We also aimed to examine the relationships between markers of sleep with MS markers. DESIGN: A cross-sectional study was conducted. PARTICIPANTS: Participants included adolescents with PCOS and obesity with MS (N = 30) or without MS (N = 36). OUTCOME MEASURES: Hormone and metabolic measurements, abdominal magnetic resonance imaging for hepatic fat fraction, actigraphy to estimate sleep, and overnight polysomnography (PSG). RESULTS: Adolescents with obesity and PCOS who also had MS had significantly worse sleep-disordered breathing including higher apnea-hypopnea index (AHI, P = .02) and arousal index (P = .01) compared to those without MS. Actigraphy showed no differences in habitual patterns of sleep behaviors including duration, timing, or efficiency between groups. However, a greater number of poor sleep health behaviors was associated with greater number of MS components (P = .04). Higher AHI correlated with higher triglycerides (TG) (r = 0.49, P = .02), and poorer sleep efficiency correlated with higher percentage of liver fat (r = –0.40, P = .01), waist circumference (r = –0.46, P

Importance Hypoglossal nerve stimulation (HNS) and positive airway pressure (PAP) have been shown to improve patient-reported outcomes (PROs) in obstructive sleep apnea (OSA). However, to our knowledge, there are no data that compare change in PROs between HNS and PAP or that indicate whether HNS improves comorbid insomnia or depression in the long term. Objectives To determine whether HNS is associated with improvements in patient-reported sleepiness, insomnia, and depression in the long term and to compare the respective associations of HNS and PAP with improved PROs. Design, setting, and participants This retrospective cohort study used data from patients treated at the Cleveland Clinic for OSA. Participants received either HNS (referred sample) from November 1, 2015, to September 31, 2018, or PAP (previous cohort) from January 1, 2010, to December 31, 2014, for OSA. Patients were matched 3:1 for PAP:HNS based on age, body mass index (BMI; calculated as weight in kilograms divided by height in meters squared), sex, and apnea hypopnea index (AHI). Data were collected at baseline and at prespecified follow-up points. Data were analyzed from March 26, 2020, to September 9, 2021. Exposures Treatment with HNS vs PAP. Main outcomes and measures Data collected included AHI and Epworth Sleepiness Scale (ESS), Functional Outcomes of Sleep Questionnaire (FOSQ), Insomnia Severity Index (ISI), and Patient Health Questionnaire-9 (PHQ-9; depression) scores. Results Among 85 patients receiving HNS (mean [SD] age, 62.8 [9.5] years; 59 men [69.4%]; 77 White patients [90.6%]; mean [SD] BMI, 28.8 [3.1]), compared with 217 matched patients receiving PAP (mean [SD] age, 62.1 [9.9] years; 157 men [72.4%]; 173 White patients [81.2%]; mean [SD] BMI, 29.5 [3.1]) included in the analysis, significant improvements were seen in PHQ-9 scores for HNS vs PAP (least square means, -4.06 [95% CI, -5.34 to -2.79] vs -2.58 [95% CI, -3.35 to -1.82]; mean difference, -1.48 [95% CI, -2.78 to -0.19]) with comparable improvements in ESS, FOSQ, and ISI scores. Clinically meaningful differences were observed in 42 of 65 HNS group patients (64.6%) vs 118 PAP group patients (54.5%) for ESS scores, 29 of 49 HNS group patients (59.2%) vs 67 of 217 PAP group patients (30.9%) for FOSQ scores, 14 of 48 HNS group patients (29.2%) vs 53 of 217 PAP group patients (24.4%) for PHQ-9 scores, and 23 of 49 HNS group patients (46.9%) vs 79 of 217 PAP group patients (36.4%) for ISI scores. At the 1-year post-HNS assessment, meaningful improvements were seen in 17 of 28 patients (60.7%) for ESS scores, 11 of 20 patients (55.0%) for FOSQ scores, 7 of 23 patients (30.4%) for PHQ-9 scores, and 11 of 25 patients (44.0%) for ISI scores. Conclusions and relevance In this cohort study of patients with OSA, sustained improvements in PROs were observed 1 year after HNS and were comparable to those for PAP at 3 months. These findings suggest that HNS is a viable treatment for improving insomnia and depression in patients with OSA.

Introduction There is lack of clarity of sleep disordered breathing (SDB)--including the role of nocturnal hypoxia and confounding influence of obesity--on the clinical course of human coronavirus disease 2019 (COVID-19). We postulate that SDB portends increased risk of adverse COVID-19 clinical outcomes even after accounting for confounding factors. Methods A retrospective cohort analysis of COVID-19 and sleep laboratory observational registries March-November 2020 within the Cleveland Clinic health system was performed. Ordinal logistic regression assessed the association of SDB indices and World Health Organization (WHO)-7 COVID-19 clinical outcome (hospitalization, use of supplemental oxygen, non-invasive ventilation, mechanical ventilation/ECMO and death) in an unadjusted model and adjusted for age, sex, race, body mass index(BMI,kg/m2),diabetes mellitus, hypertension, coronary artery disease, heart failure, asthma, chronic obstructive pulmonary disease (COPD), cancer and smoking using SAS software. Results Of 19,449 (32%) patients positive for SARS-CoV-2,2,290 (6%) had an available sleep study. The analytic sample included 1788 of which 1,484(64%) had an apnea hypopnea index (AHI, 3–4% hypopnea oxygen desaturation)≥5. The median duration from sleep study to COVID test was 5.8 years (IQR:3.3–9.0). Age was 56.5±14.4 years,50.4% female,28% African American with BMI=35.9±8.9kg/m2. Nine percent of patients were hospitalized,10% with supplemental oxygen,6% used non-invasive ventilation,2% required ECMO or mechanical ventilation and 2% died. For every AHI increase of 5, the odds of a higher WHO-7 level increased 2% (OR=1.02,95%CI1.01-1.04,p=0.005),but the association was mitigated in the adjusted model (OR=1.00,95%CI:0.98,1.02,p=0.80). Per 5% increase in time spent with SaO2 Conclusion Even after adjustment for obesity, underlying cardiopulmonary disease and smoking, sleep-related hypoxemia was a potential key pathophysiologic mechanism associated with increased morbidity and mortality in COVID-19. Elucidation of sleep-related hypoxemia as a risk stratification measure, particularly given the silent hypoxia inherent to early COVID-19, is critical for future investigation, as is the role of sleep-related hypoxia reversal as a target to improve COVID-19 outcomes. Support (if any) Cleveland Clinic Neurologic Institute Resource Development Award

Introduction Obstructive sleep apnea(OSA) is highly prevalent and under-diagnosed in the overweight/obese pediatric population largely due to limitations of existing pediatric OSA screening instruments including lack of efficiency and practical implementation and lack of careful consideration of physical examination(PE) findings with high predictive value for OSA. We sought to identify PE finding(s) predictive of pediatric OSA in overweight/obese patients to inform development of an OSA screening tool. Methods Overweight/obese patients presenting to the Cleveland Clinic weight-management clinic between 2013-2018 with polysomnogram (PSG) data were included. The association of PE predictors: age, sex, race (white, black, other), neck (NC), waist circumference (WC), tonsil size (TS), height, systolic and diastolic blood pressure (BP) percentiles) in relation to OSA defined by apnea-hypopnea index (AHI)≥5,i.e. clinically significant pediatric OSA, were assessed using univariate and multivariate logistic regression models (OR,95%CI). Results Retrospective analysis of 180 overweight/obese patients (BMI percentile>85th for age and sex) and age 12.5±3.7 years were included. The multivariate model showed that only WC was significantly associated (1.03, 1.00 - 1.07, p=0.038) with OSA defined as AHI≥5. A statistically significant interaction of age and sex was observed such that the likelihood of OSA increased in males with older age and conversely decreased in females with older age. (1.26,1.04 -1.52, p=0.038) The reduced multivariate model, which included age, sex, WC, and age*sex interaction term, correctly discriminated AHI Conclusion In this large clinic-based overweight/obese pediatric sample, males, older age and WC were significant predictors of OSA and TS was not. A significant interaction of age and sex was observed supporting increased OSA with increasing age in males. Data generated supports value of PE findings of age, sex and WC to incorporate in development of an OSA screening tool for overweight/obese children. Support

Introduction The relationship of OSA and human coronavirus (COVID-19) in the pediatric population is unknown. We postulate that OSA is associated with SARS-CoV-2 positivity and with adverse COVID-19 outcomes in children. Methods A retrospective review of 120 consecutive patients ( Results Cases (n=36) were 11.8±4.4 years, 61% male, 27.8% black and 88.9% with OSA, while 85.7% of controls (n=84) had OSA. OSA was not associated with increased SARS-CoV-2 positivity: OR=1.33(0.40, 4.45,p=0.64). No significant difference between cases and controls for mean AHI 3.7(1.5,6.0) vs 3.5(1.5,7.1),p=0.91,SpO2 nadir 88.6±5.4 vs 89.1±4.4,p=0.58,%time SpO2 Conclusion In this first report of which we are aware focused on COVID-19 in pediatric OSA, we use a case control design leveraging COVID-19 and sleep laboratory registries. Albeit not statistically significant, pediatric patients with OSA had a higher percentage of worse clinical outcomes. Larger network studies are needed to clarify whether poorer COVID-19 outcomes may be attributable to OSA or modulated via high risk health conditions. Support (if any)

The incidence of hepatocellular carcinoma (HCC) has increased significantly in United States over the last few decades in parallel with the epidemic of nonalcoholic fatty liver disease (NAFLD). Limited data suggests that HCC could arise in steatotic liver without the presence of cirrhosis. The present study was conducted to characterize patients with NAFLD presenting with HCC in non-cirrhotic liver (NCL) compared to the NAFLD- HCC patients in association with cirrhotic liver (CL).A retrospective analysis of all patients diagnosed with HCC and NAFLD diagnosis seen at our institution between 2003 and 2012 was done. The patients were characterized based on demographic and clinical variables as well as histological and tumor features. Comparisons between the NCL and CL groups were done using analysis of variance (ANOVA) or the non-parametric Kruskal-Wallis tests and Pearson's chi-square tests or Fisher's Exact tests as appropriate. P value of0.05 was considered statistically significant.Thirty-six patients with NAFLD and HCC in NCL (HCC-NCL group) were identified and compared to 47 patients with NAFLD-HCC and Liver Cirrhosis (HCC-LC group). Liver fibrosis was not present in 55.9 % of patients in the HCC-NCL group (F0), stage 1 was present in 17.6 %, stage 2 in 8.8 % and stage 3 in 17.6 %. Lobular inflammation was present in 63.6 % of non-cirrhotic patients. Patients in the HCC-NCL were older (67.5 ± 12.3 vs. 62.7 ± 8.1 years), and less likely to be obese (52 % vs. 83 %) or have type 2 diabetes (38 % vs. 83 %), with p value0.05 for all. More importantly, compared with the HCC-CL group, those in the HCC-NCL group were more likely to present with a single nodule (80.6 % vs. 52.2 %), larger nodule size (5 cm) (77.8 % vs. 10.6 %), and receive hepatic resection as the modality of HCC treatment (66.7 % vs. 17 %); and were less likely to receive loco-regional therapy (22.3 % vs. 61.7 %) or orthotopic liver transplantation (OLT) (0 % vs. 72.3 %), with p value0.001 for all. Furthermore, 86 % of patients without cirrhosis had HCC recurrence compared to only 14 % in patients with cirrhosis (p0.001). Unadjusted analysis indicates that non-cirrhotics had worse survival with mortality rate of 47 % vs. 28 % in CL group (p = 0.03); however this difference in survival between two groups was not significant after adjusting for age or OLT (p0.05).Patients with HCC in the absence of liver cirrhosis are more likely to present at an older age with larger tumor and have higher rates of tumor recurrence. Studies to assess the cost-effectiveness of HCC surveillance in this group should be conducted.

Background: The incidence of hepatocellular carcinoma (HCC) has increased significantly in United States over the last few decades in parallel with the epidemic of nonalcoholic fatty liver disease (NAFLD). Limited data suggest that HCC could arise in steatotic livers without the presence of cirrhosis. The aim of the current study was to characterize patients with NAFLD presenting with HCC in non-cirrhotic liver (NCL) compared to those with HCC in association with liver cirrhosis (LC). Methods: A retrospective analysis was performed on all patients with HCC and NAFLD diagnosis seen at our institution between 2003 and 2012. We characterized the patients with respect to demographic, clinical, histological and tumor features. Comparisons between the NCL and LC groups were done using t-test, Mann Whitney U test, and Chi square test as appropriate. P value 5 cm) (77.8% vs. 23 %), and receive hepatic resection as the modality for HCC treatment (66.7% vs. 17%); and were less likely to receive loco-regional therapy (16.7% vs. 51.1%) or liver transplant (0% vs. 72.3%), p value < 0.001 for all. Furthermore, 62% of patients without cirrhosis had HCC recurrence compared to only 12.5% in patients with cirrhosis (p < 0.001) and had worse survival with mortality rate of 41.7% at last follow up for the HCC-NCL group compared to 27.7% in the cirrhotic group (p = 0.008). Conclusion: Patients with HCC in the absence of liver cirrhosis are more likely to present at an older age with larger tumor and have higher rates of tumor recurrence. Studies to assess the cost-effectiveness of HCC surveillance in this group should be conducted.