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Analysis of upper airway obstruction by sleep videofluoroscopy in obstructive sleep apnea: a large population-based study.

OBJECTIVES/HYPOTHESIS: To analyze the pattern of the upper airway obstruction in a large cohort of obstructive sleep apnea (OSA) patients using sleep videofluoroscopy (SVF).

STUDY DESIGN: Retrospective analysis.

METHODS: This study included 922 OSA patients who underwent both polysomnography and SVF. Their mean age, apnea-hypopnea index, and body mass index were 46.8 years, 34.2 per hour, and 26.2 kg/m2, respectively. Sleep was induced by intravenous injection of midazolam, and the obstruction pattern was determined on SVF when oxygen saturation dropped by more than 4% in pulse oxymetry.

RESULTS: The anatomic structure and airway level, which were most commonly involved in obstruction, were the soft palate (77.9%) and the oropharynx (88.1%), respectively. The soft palate alone was the most common obstructed structure in mild OSA (43.2%), and the combination of the soft palate and the tongue base was more frequent in severe OSA (45.2%). The tongue base or the hypopharynx was progressively more involved in moderate/severe OSA cases (P<.001, respectively), and a multiplicity of obstruction pattern also increased according to OSA severity (P<.001). However, 32.4% of the patients with mild OSA also had multiple obstructive anatomic structures.

CONCLUSIONS: Even if multiplicity of obstruction pattern was most commonly associated with severe OSA, almost one third of mild OSA patients also showed multiple anatomic structures and levels of obstruction. Therefore, a precise evaluation for multiplicity of obstruction patterns should precede the decision of a treatment plan, regardless of disease severity.

CPAP for the metabolic syndrome in patients with obstructive sleep apnea.

Obstructive sleep apnea is associated with an increased prevalence of the metabolic syndrome and its components. It is unclear whether treatment of obstructive sleep apnea syndrome with continuous positive airway pressure (CPAP) would modify these outcomes.

METHODS: In our double-blind, placebo-controlled trial, we randomly assigned patients with obstructive sleep apnea syndrome to undergo 3 months of therapeutic CPAP followed by 3 months of sham CPAP, or vice versa, with a washout period of 1 month in between. Before and after each intervention, we obtained measurements of anthropometric variables, blood pressure, fasting blood glucose levels, insulin resistance (with the use of homeostasis model assessment), fasting blood lipid profile, glycated hemoglobin levels, carotid intima-media thickness, and visceral fat. The metabolic syndrome was defined according to National Cholesterol Education Program Adult Treatment Panel III criteria, with Asian cutoff values for abdominal obesity.

RESULTS: A total of 86 patients completed the study, 75 (87%) of whom had the metabolic syndrome. CPAP treatment (vs. sham CPAP) was associated with significant mean decreases in systolic blood pressure (3.9 mm Hg; 95% confidence interval [CI], 1.4 to 6.4; P=0.001), diastolic blood pressure (2.5 mm Hg; 95% CI, 0.9 to 4.1; P<0.001), serum total cholesterol (13.3 mg per deciliter; 95% CI, 5.3 to 21.3; P=0.005), non-high-density lipoprotein cholesterol (13.3 mg per deciliter; 95% CI, 4.8 to 21.8; P=0.009), low-density lipoprotein cholesterol (9.6 mg per deciliter; 95% CI, 2.5 to 16.7; P=0.008), triglycerides (18.7 mg per deciliter; 95% CI, 4.3 to 41.6; P=0.02), and glycated hemoglobin (0.2%; 95% CI, 0.1 to 0.4; P=0.003). The frequency of the metabolic syndrome was reduced after CPAP therapy (reversal found in 11 of 86 patients [13%] undergoing CPAP therapy vs. 1 of 86 [1%] undergoing sham CPAP). Accelerated hypertension developed 1 patient receiving CPAP therapy first, intolerance to CPAP developed in 2 others, and another patient declined to continue sham CPAP.

CONCLUSIONS: In patients with moderate-to-severe obstructive sleep apnea syndrome, 3 months of CPAP therapy lowers blood pressure and partially reverses metabolic abnormalities. (Funded by Pfizer; ClinicalTrials.gov number, NCT00694616.).

Disorders of glucose metabolism and insulin resistance in patients with obstructive sleep apnoea syndrome.

Insulin resistance (IR) and disorders of glucose metabolism (DGM) are risk factors for cardiovascular diseases. There are different reasons for development of DGM in patients with obstructive sleep apnoea syndrome (OSAS) and this association is controversial. We investigated the frequency of DGM and IR in patients with OSAS and determining factors for these disorders.

METHOD: One hundred and twelve untreated patients with OSAS and 19 non-apnoeic snoring subjects upon polysomnography were included in this study. Oral glucose tolerance test (OGTT) was performed in all subjects who had fasting blood glucose < 125 mg/dl. IR method was analysed using homeostasis assessment model (HOMA-IR). Diabetes mellitus (DM), impaired glucose tolerance (IGT) and impaired fasting glucose (IFG) were defined according to values of OGTT. DGM was defined as having one of the diagnoses of DM, IGT or IFG. Subjective sleepiness of all subjects was assessed with Epworth Sleepiness Scale (ESS). Excessive daytime sleepiness (EDS) was described as ESS score ≥ 10.

RESULTS: Fasting glucose and the rate of DGM in patients with OSAS were higher than in non-apnoeic snoring subjects. DGM were shown in % 15.7 of non-apnoeic snoring subjects, 29.6% of mild sleep apnoea, 50% of moderate sleep apnoea and 61.8% of severe sleep apnoea. The rate of DGM in patients with moderate and severe OSAS was higher than in non-apnoeic snoring subjects and in patients with severe OSAS higher than in patients with mild OSAS. DGM are associated with body mass index (BMI), severity of OSAS, arousal index and EDS. In addition, IR is associated with apnoea hypopnoea index, BMI, arousal index and ESS score.

CONCLUSION: Obstructive sleep apnoea syndrome is associated with high frequency of DGM. In addition, the progression of disease from simple snoring and mild OSAS to severe OSAS increases the rate of DGM. Thus, DGM especially in patients with severe OSAS should be examined in regular periods.

Quantitative classification based on CT histogram analysis of non-small cell lung cancer: Correlation with histopathological characteristics and recurrence-free survival.

Quantification of the CT appearance of non-small cell lung cancer (NSCLC) is of interest in a number of clinical and investigational applications. The purpose of this work is to present a quantitative five-category (α, β, γ, δ, and ɛ) classification method based on CT histogram analysis of NSCLC and to determine the prognostic value of this quantitative classification.

Methods: Institutional review board approval and informed consent were obtained at the National Cancer Center Hospital. A total of 454 patients with NSCLC (maximum lesion size of 3 cm) were enrolled. Each lesion was measured using multidetector CT at the same tube voltage, reconstruction interval, beam collimation, and reconstructed slice thickness. Two observers segmented NSCLC nodules from the CT images by using a semi-automated three-dimensional technique. The two observers classified NSCLCs into one of five categories from the visual assessment of CT histograms obtained from each nodule segmentation result.re Interobserver variability in the classification was computed with Cohen's κ statistic. Any disagreements were resolved by consensus between the two observers to define the gold standard of the classification. Using a classification and regression tree (CART), the authors obtained a decision tree for a quantitative five-category classification. To assess the impact of the nodule segmentation on the classification, the variability in classifications obtained by two decision trees for the nodule segmentation results was also calculated with the Cohen's κ statistic. The authors calculated the association of recurrence with prognostic factors including classification, sex, age, tumor diameter, smoking status, disease stage, histological type, lymphatic permeation, and vascular invasion using both univariate and multivariate Cox regression analyses.

Results: The κ values for interobserver agreement of the classification using two nodule segmentation results were 0.921 (P < 0.001) and 0.903 (P < 0.001), respectively. The κ values for the variability in the classification task using two decision trees were 0.981 (P < 0.001) and 0.981 (P < 0.001), respectively. All the NSCLCs were classified into one of five categories (type α, n = 8; type β, n = 38; type γ, n = 103; type δ, n = 112; type ɛ, n = 193) by using a decision tree. Using a multivariate Cox regression analysis, the classification (hazard ratio 5.64; P = 0.008) and disease stage (hazard ratio 8.33; P < 0.001) were identified as being associated with an increased recurrence risk.

Conclusions: The quantitative five-category classifier presented here has the potential to provide an objective classification of NSCLC nodules that is strongly correlated with prognostic factors.

FDG-PET as a pharmacodynamic biomarker for early assessment of treatment response to linifanib (ABT-869) in a non-small cell lung cancer xenograft model.

Linifanib (ABT-869) is a multitargeted receptor tyrosine kinase inhibitor. This work aims to evaluate F-fluorodeoxyglucose-positron emission tomography (FDG-PET) as a pharmacodynamic (PD) biomarker for linifanib treatment utilizing the Calu-6 model of human non-small cell lung (NSCLC) cancer in SCID-beige mice.

Animals received either vehicle or 12.5 mg/kg linifanib orally twice a day for the duration of the study. Imaging was performed at -1, 1, 3, and 7 days after beginning treatment (n = 12-14 per group). Linifanib inhibited tumor growth and suppressed tumor metabolic activity. Changes in tumor FDG uptake were observed as early as 1 day after beginning linifanib treatment and were sustained for the duration of the study.

This study confirms that linifanib is efficacious in this xenograft model of human NSCLC and confirms FDG-PET is a potential PD biomarker strategy for linifanib therapy.

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