Impact of preoperative [18F]FDG PET/CT vs. contrast-enhanced CT in the staging and survival of patients with clinical stage I and II non-small cell lung cancer: a 10-year follow-up study.

OBJECTIVES: To elucidate the impact of [18F]FDG positron emission tomography/computed tomography (PET/CT) vs. CT workup on staging and prognostic evaluation of clinical stage (c) I-II NSCLC. METHODS: We retrospectively identified 659 cI-II NSCLC who underwent CT (267 patients) or preoperative CT followed by PET/CT (392 patients), followed by curative-intended complete resection in our hospital from January 2008 to December 2013. Differences were assessed between preoperative and postoperative stage. Five-year disease-free survival (DFS) and overall survival (OS) rates were calculated using the Kaplan-Meier approach and compared with log-rank test. Impact of preoperative PET/CT on survival was assessed by Cox regression analysis. RESULTS: The study included 659 patients [mean age, 59.5 years ± 10.8 (standard deviation); 379 men]. The PET/CT group was superior over CT group in DFS [12.6 vs. 6.9 years, HR 0.67 (95% CI 0.53-0.84), p < 0.001] and OS [13.9 vs. 10.5 years, HR 0.64 (95% CI 0.50-0.81), p < 0.001]. In CT group, more patients thought to have cN0 migrated to pN1/2 disease as compared with PET/CT group [26.4% (66/250) vs. 19.2% (67/349), p < 0.001], resulting in more stage cI cases being upstaged to pII-IV [24.7% (49/198) vs. 16.1% (47/292), p = 0.02], yet this was not found in cII NSCLC [27.5% (19/69) vs. 27.0% (27/100), p = 0.94]. Cox regression analysis identified preoperative PET/CT as an independent prognostic factor of OS and DFS (p = 0.002, HR = 0.69, 95% CI 0.54-0.88; p = 0.004, HR = 0.72, 95% CI 0.58-0.90). CONCLUSION: Addition of preoperative [18F]FDG PET/CT was associated with superior DFS and OS in resectable cI-II NSCLC, which may result from accurate staging and stage-appropriate therapy.

The changes of AHI after long-term CPAP in patients with comorbid OSA and cardiovascular disease.

PURPOSE: To evaluate the effect of long-term continuous positive airway pressure (CPAP) treatment on disease severity of obstructive sleep apnea (OSA). METHODS: We analyzed results from the Sleep Apnea and Cardiovascular Events (SAVE) study involving participants recruited at the Guangdong Provincial People's Hospital, China. Participants were aged 45-75 years with a history of cardiac or cerebrovascular disease. OSA was confirmed by home sleep apnea testing (HSAT). Participants were randomized to receive CPAP plus standard cardiovascular care (CPAP group) or standard care alone (UC group) and followed for several years. At the study conclusion, surviving participants were invited to repeat HSAT. Changes in OSA indicators were compared by independent samples t-tests and subgroup analysis was implied among groups stratified by OSA severity. RESULTS: One hundred two adults were recruited (51 per group) and followed for 48.0 ± 14.5 months. Daily CPAP usage in the CPAP group was 4.1 ± 1.9 h. AHI decreased from baseline to end-of-study in both CPAP and UC groups (- 5.0 (- 12.5,2.0), P = 0.000; - 4.0 (- 12.5,1.5), P = 0.007, respectively), with no between-group difference (P = 0.453). An improvement in nadir SpO2 showed from baseline to end-of-study in the CPAP but not UC group (2.3% ± 6.1%, P = 0.011 and - 0.7% ± 7.6%, P = 0.511, respectively; between-group difference P = 0.032). Subgroup analysis shows that CPAP could improve AHI in patients with moderate OSA (- 8.0 (- 11.8, - 2.8) in CPAP group, - 2.0 (- 0.8,6.0) in UC group, P = 0.022) and improve nadir SpO2 in patients with severe OSA (5.0 (- 0.8, - 0.8,7.0) in CPAP group, 0.0 (- 8.5,2.5) in UC group, P = 0.032). CONCLUSION: Long-term CPAP use did not result in clinically significant changes in AHI or ODI overall but showed variable effects stratified by OSA severity. CLINICAL TRIAL REGISTRATION: Registry: Clinical Trials.gov, title: Continuous Positive Airway Pressure Treatment of Obstructive Sleep Apnea to Prevent Cardiovascular Disease (SAVE), URL: www. CLINICALTRIALS: gov , identifier: NCT00738179.

Comparative study of a wearable intelligent sleep monitor and polysomnography monitor for the diagnosis of obstructive sleep apnea.

PURPOSE: Due to the lack of an objective population-based screening tool for obstructive sleep apnea (OSA), a large number of patients with potential OSA have not been identified in the general population. Our study compared an objective wearable sleep monitoring device with polysomnography (PSG) to provide a reference for OSA screening in a large population. METHODS: Using a self-control method, patients admitted to our sleep center from July 2020 to March 2021 were selected for overnight PSG and wearable intelligent sleep monitor (WISM) at the same time. The sensitivity and specificity of the device for the diagnosis of OSA were evaluated. RESULTS: A total of 196 participants (mean age: 45.1 ± 12.3 years [18-80 years]; 168 men [86%]) completed both PSG and WISM monitoring. Using an apnea-hypopnea index (AHI) ≥ 5 events/h as the diagnostic criterion, the sensitivity, specificity, kappa value, and area under the receiver operating characteristic curve of the WISM for OSA diagnosis were 93%, 77%, 0.6, and 0.95, respectively. Using an AHI ≥ 15 events/h as the diagnostic criterion for moderate-to-severe OSA, these values were 92%, 89%, 0.8, and 0.95, respectively. The mean difference in the AHI between PSG and the artificial intelligence oxygen desaturation index from the WISM was 6.8 events/h (95% confidence interval: - 13.1 to 26.7). CONCLUSION: Compared with the PSG, WISM exhibits good sensitivity and specificity for the diagnosis of OSA. This small, simple, and easy-to-use device is more suitable for OSA screening in a large population because of its single-step application procedure.

Left ventricular remodeling and systolic function changes in patients with obstructive sleep apnea: a comprehensive contrast-enhanced cardiac magnetic resonance study.

Background: A comprehensive assessment of left ventricular (LV) remodeling and systolic function using contrast-enhanced cardiac magnetic resonance (CMR) imaging in patients with obstructive sleep apnea (OSA) has not yet been reported. This retrospective case-control study aimed to explore and assess the myocardial structure, function, and tissue characteristic changes of LV remodeling in patients with OSA using the CMR method. Methods: Fifty-one selected participants 32 OSA and 19 non-OSA underwent overnight polysomnography and CMR examination using T1 mapping and feature tracking techniques. Twenty age- and sex-matched healthy controls were also enrolled for comparison between the groups. Results: Patients were grouped by apnea-hypopnea index (AHI): AHI <5 events/h as non-OSA group (n=19, 40.7±8.0 years), 5-30 events/h as mild-moderate OSA (n=13, 47.8±9.4 years), and >30 events/h as severe OSA (n=19, 39.0±10.0 years). The OSA group had a higher LV mass index (LVMI) to height2.7 than the non-OSA and healthy control groups (21.0±3.8 vs. 16.4±3.1 and 16.3±3.2 mL/m2.7, P<0.001). Compared with healthy controls, OSA patients had lower global circumferential strain values, although the LV ejection fraction was preserved. Late gadolinium enhancement was not detected in all participants, whereas the extracellular volume fraction was lower in patients with OSA than in the non-OSA and healthy control groups (24.4%±1.9% vs. 26.2%±2.5%, P=0.006 and 24.4%±1.9% vs. 26.5%±2.3%, P=0.004, respectively). The indexed cellular volume (iCV) of the myocardium was significantly higher in subjects with mild-to-moderate and severe OSA than in those without OSA (14.2±2.3 and 15.8±3.1 vs. 11.6±2.4 mL/m2.7, P<0.05). On multivariate linear regression analysis of patients with two different models, OSA severity remained significantly associated with increased LVMI (ß=0.348, P=0.004 and ß=0.233, P=0.048, respectively) and iCV (ß=0.337, P=0.004 and ß=0.231, P=0.047, respectively) after adjusting for clinical risk factors. Conclusions: LVMI is elevated in OSA with a normal LV ejection fraction, mainly with cellular hypertrophy. Cellular hypertrophy without focal fibrosis in OSA may be our main finding.

The interaction among OSA, CPAP, and medications in patients with comorbid OSA and cardiovascular/cerebrovascular disease: a randomized controlled trial.

BACKGROUND: Most patients with comorbid sleep apnea (OSA), cardiovascular (CV) disease, and/or cerebrovascular (CeV) disease simultaneously take medications. Whether OSA and continuous positive airway pressure (CPAP) interact with CV/CeV medications remains unknown. This study aimed to determine the interaction among OSA, CPAP, and CV/CeV medications; the effects of medications on major adverse cardiac and cerebrovascular events, and survival in patients with comorbid OSA and CV/CeV. METHODS: This was a post hoc analysis of the data from one center of the Sleep Apnea Cardiovascular Endpoints Study. Participants (aged 45-75 years) with comorbid OSA and CV/CeV were randomized to receive usual care with or without CPAP from December 2008 to November 2013. The primary endpoint was death and the secondary endpoint was a composite of death, myocardial infarction, stroke, hospitalization for unstable angina, heart failure, and transient ischemic attack. RESULTS: In total, 131 patients were analyzed. Sixty-three were in the CPAP group and 68 were in the usual care group, 41 had good adherence to CPAP (65.1%), and the median follow-up time was 43.0 (35.0, 54.0) months. In Cox regression analysis, ACE inhibitors and nitrates were independent factors for decreased survival in patients with comorbid OSA and CV/CeV (chi-square = 22.932, P = 0.003; ACE inhibitors: OR 7.241, P = 0.048, 95% CI 1.016-51.628; nitrates: OR 18.012, P = 0.011, 95% CI 1.923-168.750). ACE inhibitors increased mortality and secondary endpoints in the CPAP group (chi-square = 4.134, P = 0.042) but not in patients with good CPAP adherence. Clopidogrel and nitrates decreased survival in usual care group (clopidogrel: chi-square = 5.312, P = 0.021; nitrates: chi-square = 6.417, P = 0.011), but not in CPAP group. CONCLUSIONS: OSA may predispose patients with CV/CeV and CV/CeV medications to a negative effect. CPAP treatment may neutralize the negative effects of OSA by relieving chronic intermittent hypoxia. Trial registration ClinicalTrials.gov (NCT00738179, first registration date: 20/08/2008).

Cardiac imageology changes in patients with mild obstructive sleep apnea without cardiovascular disease.

PURPOSE: This study aims to assess changes in cardiac imageology of patients with mild obstructive sleep apnea (OSA) without cardiovascular disease. METHODS: All enrolled participants underwent polysomnography (PSG). Some participants underwent transthoracic echocardiography, speckle tracking echocardiography, and cardiac-enhanced magnetic resonance imaging (MRI) if they were willing. They were divided into three groups according to PSG results: non-OSA, mild OSA, and moderate-to-severe OSA. Imageology parameters were compared, and the relationship between OSA severity and imageology indices was analyzed by correlation analysis and multiple linear regression. RESULTS: Of the 352 enrolled participants, 274 participants with OSA had an apnea-hypopnea index (AHI) of ≥ 5 (86 mild OSA and 188 moderate-to-severe OSA cases), and 78 participants with non-OSA had an AHI of < 5. Transthoracic echocardiography showed that E/A and E'/A' values were lower in the mild OSA group than in the non-OSA group (1.12 ± 0.37 vs 1.27 ± 0.45 and 0.83 ± 0.33 vs 0.99 ± 0.42, respectively, p < 0.05). The aorta and ascending aorta widths were smaller in the mild OSA group than in the moderate-and-severe OSA groups (27.36 ± 2.87 mm vs 28.87 ± 2.95 mm and 30.27 ± 3.79 mm vs 31.63 ± 3.74 mm, respectively, p < 0.05). A regression analysis showed that cardiac function changes in patients with OSA may be related to age, obesity, and OSA severity. CONCLUSION: Patients with mild OSA without cardiovascular disease displayed changes in cardiac structure and function on transthoracic echocardiography.

The predictive value of Holter monitoring in the risk of obstructive sleep apnea.

BACKGROUND: Patients with obstructive sleep apnea (OSA) often present with cardiovascular symptoms. Holter monitors were reported to predict sleep apnea, though were rarely used in everyday clinical practice. In this study, by comparing Holter monitoring to polysomnography (PSG), we try to find out an operable way for clinicians to use Holter to predict OSA risk. METHODS: Patients (n=63) suspected of OSA underwent Holter monitoring with concurrent PSG at a sleep center. Respiration and heart rate variability (HRV) indices were calculated from the Holter and compared with PSG indices. RESULTS: The sensitivity of the Holter-derived respiratory waveform for OSA was 90.0%, and the specificity was 82.6%. The time domain indices including standard deviation of all NN intervals during 24 hours, mean of standard deviation of the averages of NN intervals in all 5-minute segments, square root of the mean squared differences of successive NN intervals, percentage of beat-to-beat NN interval differences that were more than 50 milliseconds, and the frequency domain index of high frequency decreased in participants with OSA and correlated with the PSG derived indices including apnea-hypopnea index (AHI), oxygen reduction index (ODI) and nadir SaO2. Logistic regression showed that standard deviation of all NN intervals during 24 hours and gender could predict the risk of OSA (P<0.001), with a sensitivity for diagnosing moderate to severe OSA of 87.5% and could accurately distinguish the risk of OSA in 77.8% of patients. Males with standard deviation of all NN intervals during 24 hours ≤177 ms or females with standard deviation of all NN intervals during 24 hours ≤80.9 ms were considered to be at high risk for OSA. CONCLUSIONS: Commercial and common parameters from Holter monitoring could predict the risk of OSA with high sensitivity. Therefore, the risk of OSA may be assessed using the Holter examination to improve the diagnosis and treatment rate of OSA.

A 'new lease of life': FnCpf1 possesses DNA cleavage activity for genome editing in human cells.

Cpf1 nucleases were recently reported to be highly specific and programmable nucleases with efficiencies comparable to those of SpCas9. AsCpf1 and LbCpf1 require a single crRNA and recognize a 5'-TTTN-3' protospacer adjacent motif (PAM) at the 5' end of the protospacer for genome editing. For widespread application in precision site-specific human genome editing, the range of sequences that AsCpf1 and LbCpf1 can recognize is limited due to the size of this PAM. To address this limitation, we sought to identify a novel Cpf1 nuclease with simpler PAM requirements. Specifically, here we sought to test and engineer FnCpf1, one reported Cpf1 nuclease (FnCpf1) only requires 5'-TTN-3' as a PAM but does not exhibit detectable levels of nuclease-induced indels at certain locus in human cells. Surprisingly, we found that FnCpf1 possesses DNA cleavage activity in human cells at multiple loci. We also comprehensively and quantitatively examined various FnCpf1 parameters in human cells, including spacer sequence, direct repeat sequence and the PAM sequence. Our study identifies FnCpf1 as a new member of the Cpf1 family for human genome editing with distinctive characteristics, which shows promise as a genome editing tool with the potential for both research and therapeutic applications.