Josko Bozic

Improvement of Cognitive and Psychomotor Performance in Patients with Mild to Moderate Obstructive Sleep Apnea Treated With Mandibular Advancement Device: A Prospective 1-Year Study.

STUDY OBJECTIVES This study aimed to provide the evidence on effect of mandibular advancement device (MAD) therapy on long-term cognitive and psychomotor performance, excessive daytime sleepiness, and quality of life in patients with mild to moderate obstructive sleep apnea (OSA). METHODS A total of 15 patients with mild to moderate OSA were treated with MAD therapy and they were followed up after 3 mo and 1 y of therapy. The patients were tested on three different tests of cognitive and psychomotor performance using the computer-based system Complex Reactionmeter Drenovac (CRD-series) at baseline and at the time of follow-up, and the 36-Item Short Form Health Survey (SF-36) questionnaire and Epworth Sleepiness Scale were used to assess their quality of life and excessive daytime sleepiness, respectively. RESULTS The mean apnea-hypopnea index (AHI) decreased significantly from 22.9 ± 5.9 events/h at baseline, to 9.7 ± 4.5 events/h after 1 y of MAD therapy (p < 0.001). There was significant improvement on all three CRD-series tests used after 1 y of MAD therapy, considering total test solving time (TTST) and minimal single task solving time (MinT), whereas total number of errors committed during the tests (TE) remained unchanged. Self-reported measures, excessive daytime sleepiness, and three domains of quality of life, social functioning, general health perception, and health change following MAD therapy showed significant improvements after 1 y of MAD therapy. CONCLUSIONS This study demonstrates significant improvements in cognitive and psychomotor performance, particularly in the domain of perceptive abilities, convergent thinking (constructing and solving simple mathematical tasks) and psychomotor reaction times, excessive daytime sleepiness, and quality of life in patients with mild to moderate OSA following MAD therapy.

The Missing Link - Likely Pathogenetic Role of GM3 and Other Gangliosides in the Development of Diabetic Nephropathy

Despite scientific advances, diabetic nephropathy remains both a therapeutical challenge, and one of the major diabetic complications. Chemical structure of gangliosides, the most complex of glycosphingolipids, is characterised by one or more sialic acids and carbohydrate groups linked to a ceramide structure. Their potential pathogenetic role in a number of disorders linked to diabetes mellitus has recently been conjectured, due to evidence of their negative modulation of the insulin-mediated signaling and general effects on key cell functions like proliferation, differentiation, apoptosis, cellular signaling and adhesion. Elevated levels of advanced glycation products (AGE) usually found in diabetic conditions seem to be responsible for increased concentration of a-series gangliosides in tissues, most notably GM3. GM3 was shown to compromise the renal pericyte and mesangial cell regeneration via the inactivation of VEGF receptor and the receptor-associated Akt signaling pathway. Likewise, the lipid raft theory opened a new research area for GM3 influence, since in the glycosynapse model glycosphingolipids have a key cell-to-cell communication unit with modulating capabilities on signaling receptors. The goal of this review is to provide insight into currently available theories on proposed mechanisms that mark the GM3 as a pathophysiological mediator in the development of diabetic nephropathy.

Ganglioside GM3 content in skeletal muscles is increased in type 2 but decreased in type 1 diabetes rat models: implications of glycosphingolipid metabolism in pathophysiology of diabetes

Ganglioside GM3 is found in the plasma membrane, where its accumulation attenuates insulin receptor signaling. Considering the role of skeletal muscles in insulin‐stimulated glucose uptake, the aim of the present study was to determine the expression of GM3 and its precursors in skeletal muscles of rat models of type 1 and type 2 diabetes mellitus (T1DM and T2DM, respectively).

Health-related quality of life in type 2 diabetes mellitus patients with different risk for obstructive sleep apnea

Purpose Our study primarily aimed to investigate health-related quality of life (HRQoL) in type 2 diabetes mellitus (T2DM) patients with different risk for obstructive sleep apnea (OSA). Patients and methods This cross-sectional, questionnaire-based study included 466 adult patients with T2DM on regular visit to Center for Diabetes of University Hospital of Split from April to September 2017. All subjects underwent detailed anamnestical evaluation and physical examination with anthropometric measurements. Additionally, all subjects completed STOP (Snoring, Tiredness, Observed apnea, and high blood Pressure) questionnaire to assess risk for OSA, Epworth Sleepiness Scale to assess daytime sleepiness, and Medical Outcomes Study Short Form-36 (SF-36) instrument to evaluate HRQoL. Results Most subjects (N=312, 67.0%) represented high-risk OSA group based on STOP questionnaire (STOP score ≥2). Statistically significantly lower HRQoL scores in all SF-36 dimensions were found in T2DM patients with high risk for OSA compared to low-risk group (P<0.001). STOP score showed statistically significant negative correlation with all SF-36 dimensions (P<0.001). In multiple linear regression analysis, STOP score was confirmed as statistically significant independent predictor for all SF-36 components, adjusted for body mass index, age, glycated hemoglobin, and T2DM duration (P<0.001). Conclusion Our study found that high proportion of patients with T2DM are at high risk for OSA. Furthermore, we showed that group of T2DM patients with high risk for OSA has lower HRQoL in all SF-36 dimensions compared to low-risk patients.

Adropin and Inflammation Biomarker Levels in Male Patients With Obstructive Sleep Apnea: A Link With Glucose Metabolism and Sleep Parameters

STUDY OBJECTIVES The main objectives of the study were to determine plasma adropin, systemic inflammation biomarker levels, and glucose metabolism parameters in patients with moderate and severe obstructive sleep apnea (OSA) compared to healthy controls. METHODS In this study, we included 50 male patients with OSA (25 moderate and 25 severe) and 25 age- and sex-matched control subjects. All subjects underwent fasting sampling of peripheral blood for laboratory analyses. RESULTS Adropin plasma levels were significantly lower in the severe OSA group in comparison with the moderate and control groups (4.50 ± 1.45 versus 6.55 ± 1.68 versus 8.15 ± 1.79 ng/mL, P < .001). Plasma biomarkers of systemic inflammation were significantly increased in patients with moderate OSA (interleukin [IL]-6 and tumor necrosis factor alpha [TNF-α]) and severe OSA (IL-6, TNF-α, high-sensitivity C-reactive protein) when compared with controls (P < .001). Adropin levels showed a significant negative correlation with IL-6 (r = -.419, P < .001), TNF-α (r = -.540, P < .001), fasting glucose (r = -.331, P = .004), hemoglobin A1c (r = -.438, P < .001), homeostatic model assessment insulin resistance index (r = -.213, P = .046), and polysomnographic parameters including apnea-hypopnea index (r = -.615, P < .001) and oxygen desaturation index (r = -.573, P < .001). A multivariate regression analysis showed that plasma adropin remained as a significant negative predictor of severe OSA status, when adjusted for age and body mass index and computed along with other inflammatory biomarkers in the regression model (odds ratio 0.069, 95% confidence interval 0.009-0.517, P = .009). CONCLUSIONS Plasma adropin concentrations significantly correlate with indices of disease severity in patients with OSA, suggesting that adropin potentially plays an important role in the complex pathophysiology of the disease.

The midrange left ventricular ejection fraction (LVEF) is associated with higher all-cause mortality during the 1-year follow-up compared to preserved LVEF among real-world patients with acute heart failure: a single-center propensity score-matched analysis

The objectives of the study were to characterize and compare different acute heart failure (AHF) subgroups according to left-ventricular ejection fraction (LVEF) in terms of all-cause mortality and HF-related readmissions during the 1-year follow-up (FU). Three hundred and fifty-six AHF patients admitted to Cardiology ward and/or CCU were retrospectively included in the study and analyzed during the 1-year FU. Patients were stratified according to LVEF as those with preserved (HFpEF), midrange (HFmrEF) and reduced LVEF (HFrEF). During the FU period, 148 (43.3%) patients died, and 116 HF-related readmission events were recorded. HFmrEF group had significantly higher standardized all-cause mortality rate, unadjusted for age, compared to HFpEF group and significantly lower than HFrEF group (41 vs. 18 and 41 vs. 62.5 events per 100 patient-years; χ2 = 41.08, p < 0.001 and χ2 = 16.62, p < 0.001, respectively). A propensity score-matched analysis in which all HF groups were matched for age and other covariates confirmed that HFmrEF group had significantly higher all-cause mortality rate than HFpEF group (χ2 = 15.66, p < 0.001) while no significant differences in readmission rates were observed across all groups (p = NS). The hazard risk for a composite endpoint of death and readmission was highest in HFrEF group (HR 6.53, 95% CI 3.53–12.08, p < 0.001), followed by HFmrEF group (HR 3.30, 95% CI 1.86–5.87, p < 0.001) when compared to HFpEF group set as a reference. Among AHF patients, the HFmrEF phenotype was associated with significantly higher all-cause mortality compared to HFpEF, during the 1-year FU. This finding might implicate more stringent clinical approach towards this patient group.