Comprehensive circulating microRNA profile as a supersensitive biomarker for early-stage lung cancer screening.

PURPOSE:  Less-invasive early diagnosis of lung cancer is essential for improving patient survival rates. The purpose of this study is to demonstrate that serum comprehensive miRNA profile is high sensitive biomarker to early-stage lung cancer in direct comparison to the conventional blood biomarker using next-generation sequencing (NGS) technology combined with automated machine learning (AutoML). METHODS: We first evaluated the reproducibility of our measurement system using Pearson's correlation coefficients between samples derived from a single pooled RNA sample. To generate comprehensive miRNA profile, we performed NGS analysis of miRNAs in 262 serum samples. Among the discovery set (57 patients with lung cancer and 57 healthy controls), 1123 miRNA-based diagnostic models for lung cancer detection were constructed and screened using AutoML technology. The diagnostic faculty of the best performance model was evaluated by inspecting the validation samples (74 patients with lung cancer and 74 healthy controls). RESULTS: The Pearson's correlation coefficients between samples derived from the pooled RNA sample ≥ 0.98. In the validation analysis, the best model showed a high AUC score (0.98) and a high sensitivity for early stage lung cancer (85.7%, n = 28). Furthermore, in comparison to carcinoembryonic antigen (CEA), a conventional blood biomarker for adenocarcinoma, the miRNA-based model showed higher sensitivity for early-stage lung adenocarcinoma (CEA, 27.8%, n = 18; miRNA-based model, 77.8%, n = 18). CONCLUSION: The miRNA-based diagnostic model showed a high sensitivity for lung cancer, including early-stage disease. Our study provides the experimental evidence that serum comprehensive miRNA profile can be a highly sensitive blood biomarker for early-stage lung cancer.

Clinical evaluation of FAPlus/FNPlus bottles compared with the combination of SA/SN and FA/FN bottles in the BacT/Alert blood culture system.

Background : The comparison of the performance of FAPlus/FNPlus bottles and combination of SA/SN and FA/FN bottles is not yet reported. Methods : We used human blood samples to investigate microorganism detection rates and the time to positivity (TTP) in a before-vs.-after study (a combination of SA/SN and FA/FN bottles from September 2012 to August 2013 vs. FAPlus/FNPlus bottles from September 2013 to August 2014). Results : The microorganism detection rate was significantly higher in the later period than in the earlier period (11.2% vs. 9.6%, P < 0.001), particularly for Enterococcus and Streptococcus species, nonfermentative Gram-negative bacilli, and Helicobacter cinaedi. TTP for pathogens was longer when FAPlus/FNPlus bottles were used than when a combination of SA/SN and FA/FN bottles was used (14.9 vs. 13.3 h, P = 0.014), particularly, in the case of Gram-negative bacilli including Escherichia coli. Conclusion : The microorganism detection rate was improved with the use of FAPlus/FNPlus bottles compared with the combination of SA/SN and FA/FN bottles ; however, FAPlus/FNPlus bottles seemed to be inferior to SA/SN and FA/FN bottles in terms of TTP. J. Med. Invest. 67 : 90-94, February, 2020.

Endomyocardial radial strain rate imaging during dobutamine stress echocardiography for the evaluation of contractile reserve in patients with dilated cardiomyopathy.

PURPOSE: Myocardial contractile reserve is associated with clinical prognosis in patients with dilated cardiomyopathy (DCM). We assessed myocardial contractile reserve using tissue Doppler strain rate imaging with dobutamine stress echocardiography in DCM patients. METHODS: Simultaneous echocardiography and left ventricular (LV) catheterization during dobutamine stress were performed in 20 patients with DCM, and echocardiography was performed in 31 control subjects. Dobutamine was infused at a starting dose of 5 µg/kg/min for 5 minutes and then at 10 µg/kg/min. Peak endomyocardial radial strain (ɛ) and systolic strain rate (SRsys ) measured with echocardiography and the maximum first derivative of LV pressure (LV dP/dtmax ) derived from catheterization were used as indices of contractility. Their percentage change from baseline to the dose of 10 µg/kg/min was calculated. RESULTS: The ɛ and SRsys were significantly smaller in DCM patients than in controls. The LV dP/dtmax , ɛ, and SRsys were significantly higher at the dose of 10 µg/kg/min than at baseline. The percentage change in SRsys was significantly correlated with the percentage change in LV dP/dtmax . CONCLUSIONS: Strain rate imaging during dobutamine stress in DCM might prove noninvasively informative for the evaluation of myocardial contractile reserve and provide insight into LV systolic dysfunction. © 2016 Wiley Periodicals, Inc. J Clin Ultrasound 44:555-560, 2016.

The Effect of Habitual Physical Training on Left Ventricular Function During Exercise Assessed by Three-Dimensional Echocardiography.

BACKGROUND: Stroke volume (SV) in trained athletes continuously increases with progressive exercise intensity. We studied whether physical training affected left ventricle (LV) function response to exercise using 3D echocardiography and tissue Doppler imaging (TDI). METHODS: Eleven male university athletes and 12 male university nonathletes were enrolled in this study. After baseline data were collected, subjects performed a symptom-limited supine bicycle ergometer exercise test. Initial workload was 25 Watts (W) and increased 25 W every 3 minutes. At rest and every exercise stage, LV end-systolic and diastolic volume index (LVEDVI and LVESVI), SV index (SVI), cardiac index (CI), LV ejection fraction (LVEF), and early lateral mitral flow velocity (Ea) were evaluated. Heart rate (HR), and systolic and diastolic blood pressure (SBP and DBP) were continuously recorded. RESULTS: Nonathletes showed a slow increase in CI, and SVI reached a plateau value at a HR of 90 beats per minute (bpm). In contrast, CI and SVI increased progressively and continuously in athletes. Both CI and SVI were significantly higher in athletes than in nonathletes at HRs of 100, 110, and 120 bpm. LVEDVI kept increasing in athletes while it plateaued in nonathletes. In contrast, LVESV decreased continuously during exercise in both groups. There was no significant difference in LVEF, Ea, SBP, or DBP at rest and during exercise between the two groups. CONCLUSION: LV responses to exercise in athletes were different from those of in nonathletes; thus, habitual physical training may play an important role in the increase in both SVI and CI in young individuals.

Clinical value of procalcitonin for patients with suspected bloodstream infection.

OBJECTIVES: Procalcitonin (PCT) might be a useful marker to exclude bacteremia or to predict the severity of bacteremia and its outcome. However, most previous studies of PCT were limited to particular patient populations. In addition, reports about PCT levels in patients with renal dysfunction have been conflicting. We investigated the predictive value of PCT in an unselected population with suspected bloodstream infections and also assessed the relationship between PCT and renal function. METHODS: We retrospectively analyzed medical records of 1,331 patients (age ≥1 8 years) with suspected bloodstream infections who had concurrent biochemical data and blood culture results. RESULTS: The PCT level was significantly elevated in patients with positive blood cultures, and it showed a significant relation with survival in patients with bacteremia. The optimal cutoff value of PCT for predicting a positive blood culture showed an increase as the estimated glomerular filtration rate declined. CONCLUSION: PCT can be a useful marker to exclude bacteremia and also to predict severe bacteremia, but renal function should be taken into account.

Effects of aged garlic extract on left ventricular diastolic function and fibrosis in a rat hypertension model.

Daily consumption of garlic is known to lower the risk of hypertension and ischemic heart disease. In this study, we examined whether aged garlic extract (AGE) prevents hypertension and the progression of compensated left ventricular (LV) hypertrophy in Dahl salt-sensitive (DS) rats. DS rats were randomly divided into three groups: those fed an 8% NaCl diet until 18 weeks of age (8% NaCl group), those additionally treated with AGE (8% NaCl + AGE group), and control rats maintained on a diet containing 0.3% NaCl until 18 weeks of age (0.3% NaCl group). AGE was administered orally by gastric gavage once a day until 18 weeks of age. LV mass was significantly higher in the 8% NaCl + AGE group than in the 0.3% NaCl group at 18 weeks of age, but significantly lower in the 8% NaCl + AGE group than in the 8% NaCl group. No significant differences were observed in systolic blood pressure (SBP) between the 8% NaCl and 8% NaCl + AGE groups at 12 and 18 weeks of age. LV end-diastolic pressure and pressure half-time at 12 and 18 weeks of age were significantly lower in the 8% NaCl + AGE group compared with the 8% NaCl group. AGE significantly reduced LV interstitial fibrosis at 12 and 18 weeks of age. Chronic AGE intake attenuated LV diastolic dysfunction and fibrosis without significantly decreasing SBP in hypertensive DS rats.

Monitoring sleep-wake rhythm with actigraphy in patients on continuous positive airway pressure therapy.

BACKGROUND: Continuous positive airway pressure (CPAP) therapy has been shown to be effective in alleviating the underlying obstruction as well as reducing patients' excessive sleepiness and improving their functioning and health-related quality of life. However, residual excessive sleepiness is observed in some patients even though CPAP therapy eliminates sleep apnea and desaturation. OBJECTIVES: The aim of this study was to determine the prognostic effect of actigraphic sleep-wake rhythm evaluation in the management of patients with obstructive sleep apnea syndrome (OSAS) treated with CPAP. METHODS: Eighteen patients with OSAS diagnosed by standard polysomnography (PSG; 48.1 ± 12.5 years) were enrolled in this study. The sleep-wake parameters were determined by actigraphy before and after 1 month of CPAP treatment, and results were compared with PSG data. In addition, data obtained before CPAP were compared with those measured after 1 month of CPAP treatment. RESULTS: The total sleep time (TST) and sleep efficiency using PSG were significantly correlated with those using actigraphy. Bland-Altman plots of TST and sleep efficiency confirmed good agreement between PSG and actigraphy data. Sleep efficiency significantly improved following CPAP compared to baseline, and sleep fragmentation and sleep fragmentation >5 min determined by actigraphy were significantly lower during CPAP therapy than at baseline. Movement was significantly lower on CPAP therapy than at baseline. CONCLUSIONS: Actigraphy provides a valuable sleep-wake rhythm assessment in outpatients with OSAS where PSG is difficult to perform.

Insufficient sleep impairs driving performance and cognitive function.

Cumulative sleep deprivation may increase the risk of psychiatric disorders, other disorders, and accidents. We examined the effect of insufficient sleep on cognitive function, driving performance, and cerebral blood flow in 19 healthy adults (mean age 29.2 years). All participants were in bed for 8h (sufficient sleep), and for <4h (insufficient sleep). The oxyhaemoglobin (oxyHb) level by a word fluency task was measured with a near-infrared spectroscopy recorder on the morning following sufficient and insufficient sleep periods. Wisconsin card sorting test, continuous performance test, N-back test, and driving performance were evaluated on the same days. The peak oxyHb level was significantly lower, in the left and right frontal lobes after insufficient sleep than after sufficient sleep (left: 0.25+/-0.13 vs. 0.74+/-0.33 mmol, P<0.001; right: 0.25+/-0.09 vs. 0.69+/-0.44 mmol, P<0.01). The percentage of correct responses on CPT after insufficient sleep was significantly lower than that after sufficient sleep (96.1+/-4.5 vs. 86.6+/-9.8%, P<0.05). The brake reaction time in a harsh-braking test was significantly longer after insufficient sleep than after sufficient sleep (546.2+/-23.0 vs. 478.0+/-51.2 ms, P<0.05). Whereas there were no significant correlations between decrease in oxyHb and the changes of cognitive function or driving performance between insufficient sleep and sufficient sleep. One night of insufficient sleep affects daytime cognitive function and driving performance and this was accompanied by the changes of cortical oxygenation response.

Endomyocardial radial strain imaging and left ventricular relaxation abnormalities in patients with hypertrophic cardiomyopathy or hypertensive left ventricular hypertrophy.

BACKGROUND: Asymmetrical septal hypertrophy and impaired left ventricular (LV) diastolic function are common echocardiographic features of hypertrophic cardiomyopathy (HCM). However, it is difficult to differentiate nonobstructive HCM from hypertensive LV hypertrophy (H-LVH). METHODS AND RESULTS: Standard echocardiography and tissue Doppler imaging were performed in 14 patients with HCM, 16 patients with H-LVH, and 21 control subjects. Endomyocardial radial strain, systolic strain rate (SR), and the early diastolic SR at the posterior and septal segments of the LV short axis were calculated. Endomyocardial peak strain (epsilon) and the absolute value of peak early diastolic SR at the posterior segment were significantly smaller in patients with HCM than in those with H-LVH, whereas the thickness of the LV posterior wall did not differ between these 2 groups. Multivariate analysis of discrimination, including the ratio of interventricular septal thickness and posterior wall thickness (IVST/PWT), epsilon, and SR parameters, between HCM and H-LVH patients revealed that epsilon at the LV posterior segment was the highest discriminant parameter (discriminant coefficient: -14.6, P=0.012). The epsilon at the posterior segment significantly correlated with early diastolic mitral annular velocity. CONCLUSIONS: Endomyocardial radial strain imaging may prove informative for discriminating between HCM and H-LVH.