Depression with obstructive sleep apnea lead to high cardiovascular disease morbidity/all-cause mortality: Findings from the SHHS cohort.

The aim of this study is to explore the association between depression and obstructive sleep apnea, and cardiovascular disease morbidity/all-cause mortality using Sleep Heart Health Study data. This post hoc analysis of a prospective study used patient data from the Sleep Heart Health Study conducted between 1995 and 1998. The association between depression and obstructive sleep apnea, and cardiovascular disease morbidity/all-cause mortality was explored using multivariable Cox proportional hazard models. A total of 4918 participants, 656 (13.3%) with obstructive sleep apnea (obstructive sleep apnea group), 1614 (32.8%) with depression (depression group), 482 (9.8%) with depression and obstructive sleep apnea (depression and obstructive sleep apnea group), and 2166 (44%) with neither obstructive sleep apnea nor depression (health group), were included. The incidence of cardiovascular disease was 24.5%, 31.0%, 31.6% and 41.7% for healthy, depression, obstructive sleep apnea, and depression and obstructive sleep apnea groups, respectively. The risk of cardiovascular disease in depression and obstructive sleep apnea participants was increased compared with that in healthy participants, which was consistent across various definitions of obstructive sleep apnea (hazard ratio [95% confidence interval]: 1.24 [1.06-1.47]; 1.25 [1.05-1.49]; 1.28 [1.06-1.54]; 1.55 [1.22-1.96] for apnea-hypopnea index ≥ 10 per hr, 15 per hr, 20 per hr, 30 per hr, respectively). The risk of all-cause mortality was increased in the depression and obstructive sleep apnea participants (hazard ratio: 1.46; 95% confidence interval: 1.07-1.99) compared with that in healthy participants when the definition of obstructive sleep apnea was apnea-hypopnea index ≥ 30. Participants with depression and obstructive sleep apnea might be at a greater risk of cardiovascular disease, and those with higher apnea-hypopnea index might be at a greater risk of all-cause mortality.

The Change Trend of Cause of Death in Patients With Stage I Non-Small Cell Lung Cancer After Surgery in US: A Long-Term Follow-Up Study Based on SEER Database.

There are few studies on the cause of death in patients with stage I non-small cell lung cancer after surgery. Our aim is to study the trend of cause of death and risk factors affecting prognosis in the patients. We retrospectively reviewed patients in Surveillance, Epidemiology and End results database from 2004 to 2015. The change trend between cause of death and follow-up time was studied by calculating the proportion of cause of death at different periods and analyzing the cumulative risk. COX risk regression model was performed by univariate and multivariate analyses for survival analysis. Finally, 23,652 patients were enrolled. In the whole cohort, lung cancer accounted for 18.68% of deaths, followed by other causes (9.57%), heart disease (5.12%) and COPD (3.89%). With the increasing of follow-up time, the cumulative incidence of lung cancer was always the highest, but the growth rate in the late follow-up period was slower than that caused by heart disease and COPD. The proportion of death due to lung cancer decreased from 53.1%-73.1% in 0-30 months after follow-up to 7.8%-41.4% in 90 months after follow-up, while the proportion of deaths due to heart disease and COPD increased. Age was an independent risk factor for lung cancer-, heart disease- and COPD-specific survival, while lobectomy resection was a protective factor, even in patients older than 70 years old. In conclusion, during the follow-up period, lung cancer was still the main cause of death, but the proportion of patients died of heart disease and COPD increased gradually, especially in elderly. Furthermore, age was an important independent factor affecting prognosis, particularly for heart disease- and COPD-related mortality. The application of wedge resection in elderly patients needs further exploration.

[Association between inflammation and cognitive function and effects of continuous positive airway pressure treatment in obstructive sleep apnea hypopnea syndrome].

OBJECTIVE: To explore the association between serum inflammation levels and cognitive function in patients with obstructive sleep apnea-hypopnea syndromes (OSAHS) and evaluate the effects of continuous positive airway pressure treatment (CPAP) on serum inflammation levels and cognitive function. METHODS: A total of 139 eligible patients were monitored by overnight polysomnography (PSG) at Sleep Center, Second Affiliated Hospital, Soochow University from June 2011 to April 2013. Based on the results of apnea-hypopnea index (AHI), they were divided into 4 groups of primary snoring (n = 18), mild OSAHS(n = 23), moderate OSAHS (n = 29) and severe OSAHS (n = 69). The questionnaires of Montreal Cognitive Assessment (MoCA), Mini-Mental State Examination (MMSE) and Epworth Sleepiness Scale (ESS) were administered to assess cognitive function and daytime sleepiness. The serum levels of high-sensitivity C-reactive protein (Hs-CRP), leptin and tumor necrosis factor alpha (TNF-α) were detected to evaluate systemic inflammation. The questionnaire scores, serum levels of Hs-CRP, leptin and TNF-α and PSG parameters were compared among 4 groups. Thirty-three patients in severe OSAHS group (treatment group) with good adherence were evaluated at baseline and after long-time CPAP treatment. RESULTS: Compared to primary snoring group, the serum Hs-CRP ((1.77 ± 1.19) vs (0.92 ± 0.82) mg/L), leptin ((15.21 ± 13.26) vs (6.35 ± 4.51) mmol/L) and TNF-α ((21.04 ± 7.78) vs (10.30 ± 5.23) pmol/L) levels increased significantly in severe OSAHS group (P < 0.05). After adjusting for body mass index (BMI), age and education years, MoCA scores showed negative correlations with serum TNF-α, AHI, oxygen reduction index (ODI) and TS90% (r = -0.266, -0.236, -0.201, -0.18 respectively, all P < 0.05) and positive correlations with minimum oxygen saturation (LSaO(2)) (r = 0.224, P < 0.05). The evaluations of MoCA subdomains further revealed selective reductions in visual space, executive function, attention and delayed memory function. The treatment group with good adherence to > 6-month continuous positive airway pressure (CPAP) treatment and after CPAP treatment, the serum levels of Hs-CRP, TNF-α and leptin improved markedly ((1.20 ± 0.88) vs (2.03 ± 1.58) mg/L, (14.12 ± 4.34) vs (22.74 ± 6.72) pmol/L and (7.37 ± 5.30) vs (13.69 ± 7.17) mmol/L respectively). The scores of MoCA and ESS also improved (27.79 ± 1.69 vs 24.76 ± 2.57, 4.33 ± 3.14 vs 12.61 ± 5.80 respectively) (all P < 0.01). The score of all MoCA subdomains improved after treatment. CONCLUSIONS: Cognitive dysfunction and inflammatory reaction are common in OSAHS patients. MoCA scores are correlated significantly with serum level of TNF-α and nocturnal intermittent hypoxia. Systemic inflammation may play an important role in cognitive dysfunction of OSAHS patients. And long-time CPAP treatment can improve systemic inflammatory response and cognitive impairment.

[Correlation between cognitive function and hippocampal atrophy and cerebral white matter lesions in patients with obstructive sleep apnea hypopnea syndrome].

OBJECTIVE: To explore the relationship between cognitive impairment and the changes of hippocampal structure and cerebral white matter on brain magnetic resonance imaging (MRI) in subjects with obstructive sleep apnea hypopnea (OSAHS). METHODS: A total of 81 snoring patients were monitored by overnight polysomnography (PSG) at Sleep Center, Second Affiliated Hospital, Soochow University from March 2012 to August 2013. Based on the results of apnea-hypopnea index (AHI), they were divided into mild (n = 23), moderate (n = 18), severe OSAHS (n = 23) and primary snoring (n = 17) groups. Periventricular hyperintensity (PVH) related to the severity of cerebral white matter lesions and hippocampal atrophy on brain MRI were evaluated according to the Fukudas method and Scheltens standard. The sequences of regular and perpendicular to bilateral hippocampal fluid attenuated inversion recovery (FIAIR) were used. Montreal cognitive assessment (MoCA) and mini-mental state examination (MMSE) were performed to evaluate the changes of cognitive function in all subjects. RESULTS: The cognitive function scores, especially MoCA, progressively decreased and the scores of hippocampal atrophy and PVH increased as the severity of OSAHS aggravated among these groups. Compared to primary snoring group, MoCA and MMSE scores decreased (24.5 ± 2.7 vs 28.0 ± 1.9, P = 0.000; 27.5 ± 1.4 vs 28.7 ± 1.3, P = 0.013) and hippocampal atrophy and PVH scores increased (2.4 ± 1.2 vs 1.5 ± 1.2, P = 0.007; 3.6 ± 1.0 vs 1.6 ± 1.5, P = 0.000) in the severe OSAHS group. The evaluations of MoCA subdomains further revealed selective reduction in visual space, execution function and delayed memory. PVH scores and hippocampal atrophy scores were negatively correlated with MoCA scores (r = -0.30, P = 0.010; r = -0.30, P = 0.006). Multiple linear regression analysis indicated that the degrees of AHI and hippocampal atrophy were the major risk factors for MoCA scores (standardized regression coefficient: -0.386, -0.247; P = 0.000, 0.020). The scores of hippocampal atrophy and PVH were positively correlated with AHI, oxygen reduction index (ODI) and respiratory related arousal index (RI) and negatively with minimum oxygen saturation (LSaO2) and average oxygen saturation (MSaO2) (P < 0.05). CONCLUSIONS: The changes of MRI in hippocampus and cerebral white matter are closely related with cognitive dysfunction. And it may become an objective indicator of assessing cognitive function in OSAHS patients.

[Association between obesity and cognition impairment in patients with moderate-to-severe obstructive sleep apnea-hypopnea syndrome].

OBJECTIVE: To explore the association between obesity and cognition impairment in patients with moderate-to-severe obstructive sleep apnea-hypopnea syndrome (OSAHS). METHODS: A total of 425 eligible patients with moderate-to-severe OSAHS were screened for this retrospective study at Sleep Center, Second Affiliated Hospital, Soochow University from January 2008 to January 2013. Based on body mass index (BMI), they were categorized into normal weight (18.5 ≤ BMI<24, n = 67), mild overweight (24 ≤ BMI<26, n = 100), severe overweight (26 ≤ BMI<28, n = 134) and obese (BMI ≥ 28, n = 124) groups. They were examined by overnight polysomnography (PSG). And cognitive functions were assessed by the Montreal Cognitive Assessment (MoCA) questionnaires. MoCA scores, clinical and polysomnographic variables were compared between the groups. And the correlations between MoCA scores and clinical and PSG parameters were further evaluated by stepwise multivariate regression. Two-way analysis of variance (two-way ANOVA) was performed to examine the effects of obesity and OSAHS on MoCA score. RESULTS: The scores of MoCA progressively decreased across the spectrum from mild overweight to obese groups. The highest BMI group (obese group) had the lowest MoCA score (25.45 ± 2.35 vs 26.26 ± 2.01, 26.29 ± 2.60, 26.05 ± 2.51, P = 0.030, 0.010, 0.048). The evaluations of MoCA subdomains further revealed selective reductions. Compare to normal weight group, the score of visuospatial and executive function, memory/delayed recall significant decreased in obese and severe overweight groups (visuospatial and executive function: 4.48 ± 0.63 vs 4.07 ± 0.94, 4.13 ± 1.04, P = 0.022, 0.048; memory/delayed recall: 3.54 ± 0.90 vs 2.77 ± 1.20, 2.87 ± 1.30, P = 0.001, 0.004). Stepwise multivariate regression analysis demonstrated that MoCA scores were correlated significantly with apnea-hypopnea index (AHI), BMI, age and years of education. Two-way ANOVA revealed that both obesity and OSAHS had independent effects on MoCA score (P = 0.004). The interactions between the effect of obesity and OSAHS on cognitive score were insignificant. It indicated that the effect of BMI on cognitive function did not change with AHI. CONCLUSIONS: In OSAHS patients, obesity aggravates cognitive impairment independently of AHI. And obesity is one of the most important influencing factors of cognitive function.

Prognostic value of visceral pleural invasion in the stage pT1-2N2M0 non-small cell lung cancer: A study based on the SEER registry.

BACKGROUND: Visceral pleural invasion (VPI) is considered an adverse prognostic factor in non-small cell lung cancer (NSCLC). However, the prognostic roles of VPI in Ⅲ/N2 NSCLC remain controversial. Therefore, this study aims to evaluate the prognostic value of VPI in patients with postoperative stage pT1-2N2M0 NSCLC. METHODS: Using the Surveillance, Epidemiology, and End Results (SEER) database, we screened for patients with stage T1-2N2M0 NSCLC who received surgery from 2010 to 2015. To reduce baseline differences between Non-VPI group and VPI group, two-to-one propensity score matching (PSM) was performed. Cox proportional hazards regression was used to identify factors associated with survival. Overall survival (OS) was between the Non-VPI group and the VPI+ group by the Kaplan-Meier analysis. RESULTS: We identified 1374 postoperative NSCLC patients with stage pT1-2N2M0. The majority of cases (N = 1047, 76.8%) are Non-VPI patients. The factors associated with VPI+ group included white race (P < 0.0001), and adenocarcinoma (P < 0.0001). When analyzed in the total study population, VPI status remained a significant independent predictor of worse OS compared with the Non-VPI group (HR, 1.343; 95% CI, 1.083-1.665 [P=0.007]). Besides, in a subgroup analysis by VPI status, the results showed that patients without treatment exhibited a higher risk level in the Non-VPI group (P<0.0001). However, we did not find statistically significant differences among treatments in the VPI+ group (P=0.199). Mean survival time was 49.5 months (95% CI: 45.7-53.3 months) for chemotherapy alone in the Non-VPI group, compared with 41.2 months (95% CI: 35.8-46.6 months) in VPI+ groups. In both the VPI group and the non-VPI group, there is no statistical difference between adjuvant chemotherapy combined with PORT and chemotherapy alone. CONCLUSION: This study emphasizes that the presence of VPI is a poor prognostic factor, even in patients with Ⅲ/N2 NSCLC. As the study shows, chemotherapy significantly improved overall survival of patients with postoperative stage pT1-2N2M0 NSCLC, especially for Non-VPI patients. However, the significance of PORT is still worth further exploration.

Effects of adjuvant chemotherapy on survival of patients with stage IB non-small cell lung cancer with visceral pleural invasion.

BACKGROUND: Adjuvant chemotherapy could improve the prognosis of stage II-III non-small cell lung cancer (NSCLC). However, its influences on stage IB were controversial. The purpose of this study was to investigate whether patients with stage IB NSCLC could benefit from adjuvant chemotherapy. METHODS: Stage IB NSCLC in 2010-2015 was selected from the surveillance, epidemiology, and end result database. Chi square test was used to compare the clinical characteristics of patients with different adjuvant chemotherapy status. Kaplan-Meier survival curves were plotted by the log-rank test. Cox proportional hazard regression was used to perform multivariate analysis on overall survival (OS), and the life table method was employed to calculate 1-, 3-, and 5-year survival rates. RESULTS: A total of 2915 patients were included in this study, and the number of patients with visceral pleural invasion (VPI) was 1096 (37.6%), of which 145 (13.2%) received adjuvant chemotherapy. There was no statistical difference in OS among the total population with or without chemotherapy (p = 0.295), nor in patients with VPI (p = 0.216). In patients with VPI, the 1-, 3-, 5-year survival curves of patients who are receiving adjuvant chemotherapy showed an upward trend compared with patients who did not. Additionally, female, high differentiated, adenocarcinoma, and tumor size ≤ 3 cm were also independent prognostic factors for improving the prognosis of patients with VPI. CONCLUSION: In our study, stage IB NSCLC did not benefit from adjuvant chemotherapy, even in patients with VPI. However, the significance of adjuvant chemotherapy in patients with VPI is still worth further exploration.

Increased CX3CL1 mRNA expression level is a positive prognostic factor in patients with lung adenocarcinoma.

Chemokines are a family of small cytokines, which are signalling proteins secreted by cells. The principal role of chemokines is to serve as chemoattractants to guide the migration of their target cells. Chemokine C-X3-C motif ligand 1 (CX3CL1) is a protein-coding gene of fractalkine, which serves as a ligand for chemokine C-X3-C motif receptor 1 (CX3CR1) and integrins. However, the roles of CX3CL1 in different pathological types of lung cancer remain poorly understood. The present study aimed to investigate the potential clinical and biological function of CX3CL1 mRNA expression in patients with lung cancer. In the present study, lung cancer data obtained from the Gene Expression Omnibus database and The Cancer Genome Atlas were downloaded and analysed, and the results demonstrated that an increased CX3CL1 mRNA expression in tumour tissues from lung adenocarcinoma (LUAD) was associated with improved overall survival. However, no significant association was identified between CX3CL1 expression and the prognosis of lung squamous cell carcinoma (LUSC). Furthermore, the genes whose expression levels were correlated with CX3CL1 expression were subjected to enrichment analysis, and the results for the LUAD data demonstrated that the most significant biological processes included 'positive regulation of cell adhesion', 'leukocyte cell-cell adhesion', 'leukocyte migration' and 'T cell activation', whereas, the important highly ranked pathways included 'cell adhesion molecules (CAMs)', 'leukocyte transendothelial migration' and 'natural killer cell-mediated cytotoxicity'. However, in the patients with LUSC, the genes that were highly correlated with CX3CL1 were not enriched for any biological processes or signalling pathways. Based on the data of the present study, it was hypothesised that CX3CL1 may serve as a prognostic marker for LUAD.

CIH-induced neurocognitive impairments are associated with hippocampal Ca(2+) overload, apoptosis, and dephosphorylation of ERK1/2 and CREB that are mediated by overactivation of NMDARs.

Chronic intermittent hypoxia (CIH) is commonly seen in patients with obstructive sleep apnea, and has been hypothesized to underlie the neurocognitive dysfunction in these patients. However, its cellular and molecular mechanisms remain to be defined. The present study aimed to investigate, in a mouse CIH model, the role of NMDA receptor (NMDAR) activation in mediating the CIH-induced neurocognitive impairments, caspase expression and dysregulated Ca(2+) signaling pathways in hippocampus. Male ICR mice (n=45) were exposed to CIH (8h/day) or room air (control) for 4 weeks. After 4-week treatment, neurobehavioral assessments were performed by Morris water maze test, hippocampal [Ca(2+)]i was evaluated by flow cytometry; and protein expressions of caspase-3, caspase-9, PARP, p-ERK1/2 and p-CREB in hippocampus were measured by Western blotting. Our results showed that, compared to control animals, 4-week exposure to CIH produced significant spatial learning and memory impairments in CIH mice. Increased caspase expression in hippocampus was observed in CIH mice associated with significant elevation of [Ca(2+)]i and dephosphorylation of ERK and CREB expression. When the NMDAR antagonist memantine was administered by intraperitoneal injection prior to daily exposure to CIH, at a sub-therapeutic dose of 5mg/kg/day not shown to impact the neurobehavioral performance in control animals, the neurocognitive impairments as well as the neurobiochemical changes were abolished or normalized in the CIH mice. Our study suggests that overactivation of NMDARs and the Ca(2+) overload-dependent ERK/CREB dysregulation is one of the important mechanisms in mediating the CIH-induced neurocognitive impairments.