Vacuum bell therapy for pectus excavatum: a retrospective study.

BACKGROUND: Pectus excavatum, the most common chest wall deformity, is frequently treated with Nuss procedure. Here we will describe non-invasive procedure and analyze the variables associated vacuum bell therapy for patients with pectus excavatum. METHODS: Retrospective case-control study in a single center between July 2018 and February 2022, including patients with pectus excavatum treated with vacuum bell. Follow-up was continued to September 2022. The Haller index and Correction index was calculated before and after treatment to analysis the effectiveness of vacuum bell therapy. RESULTS: There were 98 patients enrolled in the treatment group, with 72 available for analysis, and the follow-up period ranged from 1.1 to 4.4 years (mean 3.3 years). When analyzing with the Haller Index, 18 patients (25.0%) showed excellent correction, 13 patients (18.1%) achieved good correction, and 4 patients (5.6%) had fair correction. The remaining patients had a poor outcome. Characteristics predicting a non-poor prognosis included initial age ≤ 11 years (OR = 3.94, p = 0.013) and patients with use over 24 consecutive months (OR = 3.95, p = 0.013). A total of 9 patients (12.5%) achieved a CI reduction below 10. Patients who started vacuum bell therapy at age > 11 had significantly less change compared to those who started at age ≤ 11 (P < 0.05). Complications included chest pain (5.6%), swollen skin (6.9%), chest tightness (1.4%) and erythema (15.3%). CONCLUSIONS: A certain percentage of patients with pectus excavatum can achieve excellent correction when treated with pectus excavatum therapy. Variables predicting better outcome including initial age ≤ 11 years both in HI and CI and vacuum bell use over 24 consecutive months in HI. In summary, pectus excavatum is an emerging non-invasive therapy for pectus excavatum and will be widely performed in a certain group of patients.

Unraveling the associations and causalities between glucose metabolism and multiple sleep traits.

Purpose: The aim of our study is to estimate the associations and causalities of glucose metabolism traits of fasting blood glucose (FBG), fasting insulin (FINS), glycosylated hemoglobin (HbA1c), and 2-h glucose post-challenge (2hGlu) with sleep traits consisting of excessive daytime sleepiness (EDS), insomnia, and sleep duration. Methods: We employed standard quantitative analysis procedures to assess the associations between sleep traits and glucose metabolism. Moreover, we acquired published genome-wide association studies (GWAS) summary statistics for these traits and conducted Mendelian randomization (MR) analyses to estimate their causal directions and effects. Inverse variance weighting (IVW) was employed as the primary approach, followed by sensitivity analyses. Results: A total of 116 studies with over 840,000 participants were included in the quantitative analysis. Our results revealed that participants with abnormal glucose metabolism had higher risks for EDS (OR [95% CI] = 1.37 [1.10,1.69]), insomnia (OR [95% CI] = 1.65 [1.24,2.20]), and both short and long sleep duration (OR [95% CI] = 1.35 [1.12,1.63]; OR [95% CI] = 1.38 [1.13,1.67] respectively). In addition, individuals with these sleep traits exhibited alterations in several glycemic traits compared with non-affected controls. In MR analysis, the primary analysis demonstrated causal effects of 2hGlu on risks of EDS (OR [95% CI] = 1.022 [1.002,1.042]) and insomnia (OR [95% CI] = 1.020[1.001,1.039]). Furthermore, FINS was associated with short sleep duration (OR [95% CI] = 1.043 [1.018,1.068]), which reversely presented a causal influence on HbA1c (ß [95% CI] = 0.131 [0.022,0.239]). These results were confirmed by sensitivity analysis. Conclusion: Our results suggested mutual risk and causal associations between the sleep traits and glycemic traits, shedding new light on clinical strategies for preventing sleep disorders and regulating glucose metabolism. Future studies targeting these associations may hold a promising prospect for public health.

The causal associations of altered inflammatory proteins with sleep duration, insomnia and daytime sleepiness.

STUDY OBJECTIVES: Growing evidence linked inflammation with sleep. This study aimed to evaluate the associations and causal effects of sleep traits including insomnia, excessive daytime sleepiness (EDS), and sleep duration (short: <7 h; normal: 7-9 h; long: ≥9 h), with levels of C-reactive protein (CRP), tumor necrosis factor-alpha (TNF-α), and interleukins. METHODS: Standard procedures of quantitative analysis were applied to estimate the expression differences for each protein in compared groups. Then, a two-sample Mendelian randomization (MR) analysis was performed to explore their causal relationships with published genome-wide association study summary statistics. The inverse-variance weighted was used as the primary method, followed by several complementary approaches as sensitivity analyses. RESULTS: A total of 44 publications with 51 879 participants were included in the quantitative analysis. Our results showed that the levels of CRP, interleukin-1ß (IL-1ß), IL-6, and TNF-α were higher from 0.36 to 0.58 (after standardization) in insomnia compared with controls, while there was no significant difference between participants with EDS and controls. Besides, there was a U/J-shaped expression of CRP and IL-6 with sleep durations. In MR analysis, the primary results demonstrated the causal effects of CRP on sleep duration (estimate: 0.017; 95% confidence intervals [CI], [0.003, 0.031]) and short sleep duration (estimate: -0.006; 95% CI, [-0.011, -0.001]). Also, IL-6 was found to be associated with long sleep duration (estimate: 0.006; 95% CI, [0.000, 0.013]). These results were consistent in sensitivity analyses. CONCLUSIONS: There are high inflammatory profiles in insomnia and extremes of sleep duration. Meanwhile, elevated CRP and IL-6 have causal effects on longer sleep duration. Further studies can focus on related upstream and downstream mechanisms.

Associations between cardiometabolic phenotypes and levels of TNF-α, CRP, and interleukins in obstructive sleep apnea.

PURPOSE: Obstructive sleep apnea (OSA) shows a chronic inflammatory state which is often accompanied by cardiometabolic phenotypes. The aim of this study was to investigate whether or not there were differences of inflammatory proteins levels in patients with OSA with and without a certain phenotype so as to explore the associations between inflammation and additional OSA phenotypes. METHODS: The literature was systematically screened and available data were collected on levels of tumor necrosis factor-α (TNF-α), C-reactive protein (CRP), and several interleukins (ILs) in patients with OSA with and without a certain phenotype. Overall effect size of standard mean difference (SMD) was used to compare the expression of differences between the two groups. Data analysis was conducted by Review Manager 5.3, and the threshold of p value was set as < 0.05. RESULTS: A total of 31 articles were included, covering five traits of obesity, hypertension (HBP), metabolic syndrome (MS), heart disease, and sex. There were elevated levels of TNF-α (SMD = 0.63, p = 0.03), CRP (SMD = 0.64, p = 0.0001), and IL-6 (SMD = 0.83, p = 0.008) levels in OSA with obesity. Also, OSA with HBP showed significant increases of TNF-α (SMD = 0.36, p = 0.02), CRP (SMD = 0.98, p = 0.01), and IL-6 (SMD = 0.76, p < 0.0001) levels. A higher CRP level was also observed in OSA with MS (SMD = 0.31, p = 0.004) and female sex (SMD = 0.21, p = 0.002). There were no statistical differences for IL-1ß (p = 0.22) and CRP (p = 0.14) levels of OSA with obesity and heart disease respectively compared with OSA without corresponding phenotype. TNF-α (p = 0.66) and IL-6 (p = 0.49) levels also lacked statistically significant differences between female and male patients with OSA. CONCLUSIONS: Our results revealed that inflammatory proteins TNF-α, CRP, and IL-6 levels were higher in obese and hypertensive patients with OSA and CRP levels were higher in OSA with metabolic syndrome, highlighting a link between inflammation and cardiometabolic complications in patients with OSA.

Causal analysis between altered levels of interleukins and obstructive sleep apnea.

Background: Inflammation proteins including interleukins (ILs) have been reported to be related to obstructive sleep apnea (OSA). The aims of this study were to estimate the levels for several key interleukins in OSA and the causal effects between them. Method: Weighted mean difference (WMD) was used to compare the expression differences of interleukins between OSA and control, and the changed levels during OSA treatments in the meta-analysis section. A two-sample Mendelian randomization (MR) was used to estimate the causal directions and effect sizes between OSA risks and interleukins. The inverse-variance weighting (IVW) was used as the primary method followed by several other MR methods including MR Egger, Weighted median, and MR-Robust Adjusted Profile Score as sensitivity analysis. Results: Nine different interleukins-IL-1ß, IL-2, IL-4, IL-6, IL-8, IL-12, IL-17, IL-18, and IL-23-were elevated in OSA compared with control to varying degrees, ranging from 0.82 to 100.14 pg/ml, and one interleukin, IL-10, was decreased by 0.77 pg/ml. Increased IL-1ß, IL-6, and IL-8 rather than IL-10 can be reduced in OSA by effective treatments. Further, the MR analysis of the IVW method showed that there was no significant evidence to support the causal relationships between OSA and the nine interleukins-IL-1ß, IL-2, IL-4, IL-5, IL-6, IL-8, IL-10, IL-17, and IL-18. Among them, the causal effect of OSA on IL-5 was almost significant [estimate: 0.267 (-0.030, 0.564), p = 0.078]. These results were consistent in the sensitivity analysis. Conclusions: Although IL-1ß, IL-2, IL-4, IL-6, IL-8, IL-12, IL-17, IL-18, and IL-23 were increasing and IL-10 was reducing in OSA, no significant causal relationships were observed between them by MR analysis. Further research is needed to test the causality of OSA risk on elevated IL-5 level.

Elevated fasting insulin results in snoring: A view emerged from causal evaluation of glycemic traits and snoring.

BACKGROUND: Snoring and impaired glucose metabolism are common clinical manifestations and associated. The purpose of our study is to estimate the causal associations between snoring and glycemic traits. METHODS: We compared the weighted mean differences (WMD) for fasting insulin (FINS), glycosylated haemoglobin (HbA1c), fasting blood glucose (FBG) and 2 h-glucose post-challenge (2hGlu) levels between snorers and non-snorers by meta-analysis. Then, we obtained summary statistics from published GWAS of snoring and glycemic traits to perform bidirectional two-sample MR. Inverse variance weighting (IVW) method was applied as major estimate while MR Egger, Weighted median and MR-Robust Adjusted Profile Score (RAPS) played a subsidiary role. RESULTS: Snoring participants had higher FBG (WMD = 0.14 mmol/L, 95%CI = [0.10,0.19]), HbA1c (WMD = 0.10%, 95%CI = [0.07,0.13]), FINS (WMD = 0.92µIU/mL, 95%CI = [0.59,1.26]) and 2hGlu (WMD = 0.30 mmol/L, 95%CI = [0.06,0.55]) levels than non-snorers. Further, elevated FINS levels shown robust causal effect on snoring (IVW: OR = 1.07, 95%CI = [1.02,1.12], p = 2.2 × 10-3 ), which was consistent by complementary methods of MR Egger (OR = 1.14, 95%CI = [1.01-1.30], p = 4.72 × 10-2 ), Weighted median (OR = 1.11, 95%CI = [1.07,1.15], p = 1.53 × 10-7 ) and MR RAPS (OR = 1.07, 95% CI = [1.05,1.10], p = 2.81 × 10-9 ). Such causal situation was stable after identifying and removing the outliers in sensitivity analysis. However, there was no causality of snoring on increasing FINS levels. Additionally, there were no causal associations between snoring and other three traits of FBG, HbA1c and 2hGlu levels from either direction. CONCLUSIONS: Snorers are subjected to higher FBG, HbA1c, FINS and 2hGlu levels, and elevated FINS levels further provides robust causality on snoring, suggesting that behind common snoring may lie hyperinsulinemia or insulin resistance.

The causal relationships between obstructive sleep apnea and elevated CRP and TNF-α protein levels.

BACKGROUND: Obstructive sleep apnea (OSA) and inflammation are closely related. This study aimed to evaluate the associations and causal effect between C-reactive protein (CRP) and tumour necrosis factor-alpha (TNF-α) levels andOSA. METHODS: Pooled analysis was conducted to compare the expression differences of CRP and TNF-α between OSA patients with different severity and controls, and between continuous positive airway pressure (CPAP) and non-CPAP interventions for OSA patients. Using published GWAS summary statistics, we conducted a bidirectional two-sample Mendelian Randomization (MR) to estimate the causal relationships between CRP and TNF-α levels and OSA risk. Effect estimates were evaluated using inverse-variance weighted (IVW) as primary method, and several other MR methods as sensitivity analysis. RESULTS: Both TNF-α (WMD [95%CI] = 5.86 [4.80-6.93] pg/ml, p < .00001) and CRP (WMD [95%CI] = 2.66 [2.15-3.17] mg/L, p < .00001), showed a significant increase in OSA patients compared with controls and this increasing trend was associated with OSA severity. Besides, compared to blank control (non-CPAP), CPAP treatment can reduce high TNF-α (WMD [95%CI]= -4.44 [-4.81, -4.07]pg/ml, p < .00001) and CRP (WMD [95%CI]= -0.91 [-1.65, -0.17] mg/l, p = .02) in OSA. Moreover, the primary MR analysis by IVW showed that OSA was the genetically predicted cause of elevated CRP (estimate: 0.095; 95% CI, [0.010-0.179]; p = .029) using six SNPs as the instrument variable, which were repeated by weighted median (estimate: 0.053; 95% CI, [0.007, 0.100]; p =.024) and MR RAPS (estimate: 0.109; 95% CI, [0.079, 0.140]; p = 1.98x10-12). Besides, the causal effect from elevated CRP on increased OSA risk was almost significant by IVW (OR:1.053; 95% CI, [1.000, 1.111]; p = .053). However, there were no causal associations between TNF-α and OSA from both directions. CONCLUSIONS: Increased CRP and TNF-α were associated with OSA severity and sensible to CPAP treatment. Also, OSA had a suggestive causal effect on elevated CRP.

Variants of candidate genes associated with the risk of obstructive sleep apnea.

BACKGROUND: The researches on the associations between different candidate genes and obstructive sleep apnea (OSA) are inconsistent. Here, we performed a comprehensive qualitative and quantitative analysis to estimate the contribution of variants from candidate genes to the risk of OSA. METHODS: Qualitative analysis was conducted to find the relationships for all included genes. Then, quantitative analysis of both allele models and genotype models was applied to evaluate the risk variants for OSA. Furthermore, a similar analysis was performed in different ethnic groups. RESULTS: We included 152 publications containing 75 genes for qualitative analysis. Among them, we included 93 articles containing 28 variants from 16 genes for quantitative analysis. Through allele models, we found 10 risk variants for OSA (rs1801133 of MTHFR, ɛ4 of ApoE, -1438G/A of 5-HT2A, -308G/A of TNF-α, Pro1019Pro of LEPR, rs1130864 and rs2794521 of CRP, D/I of ACE, LPR and VNTR of 5-HTT) with the ORs of 1.21-2.07 in global population. We found that the variant of ɛ2 of ApoE could uniquely decrease the risk of OSA in the East Asian subgroup, while the other 6 variants, including ɛ4 in ApoE, -308G/A in TNF-α, Pro1019Pro in LEPR, D/I in ACE, LPR and VNTR in 5-HTT, could increase the risk of OSA. As for the European subpopulation, we only found that -308G/A in TNF-α could increase the risk for OSA. CONCLUSIONS: Eleven variants from the candidate genes are associated with the risk of OSA, which also show ethnicity differences in East Asian and European subgroups.