Dipotassium glycyrrhizate prevents oral dysbiosis caused by Porphyromonas gingivalis in an in vitro saliva-derived polymicrobial biofilm model.

OBJECTIVES: Oral microbiome dysbiosis prevention is important to avoid the onset and progression of periodontal disease. Dipotassium glycyrrhizate (GK2) is a licorice root extract with anti-inflammatory effects, and its associated mechanisms have been well-reported. However, their effects on the oral microbiome have not been investigated. This study aimed to elucidate the effects of GK2 on the oral microbiome using an in vitro polymicrobial biofilm model. METHODS: An in vitro saliva-derived polymicrobial biofilm model was used to evaluate the effects of GK2 on the oral microbiome. One-week anaerobic culture was performed, in which GK2 was added to the medium. Subsequently, microbiome analysis was performed based on the V1-V2 region of the 16S rRNA gene, and pathogenicity indices were assessed. We investigated the effects of GK2 on various bacterial monocultures by evaluating its inhibitory effects on cell growth, based on culture turbidity. RESULTS: GK2 treatment altered the microbiome structure and decreased the relative abundance of periodontal pathogenic bacteria, including Porphyromonas. Moreover, GK2 treatment reduced the DPP4 activity -a pathogenicity index of periodontal disease. Specifically, GK2 exhibited selective antibacterial activity against periodontal pathogenic bacteria. CONCLUSIONS: These findings suggest that GK2 has a selective antibacterial effect against periodontal pathogenic bacteria; thus, preventing oral microbiome dysbiosis. Therefore, GK2 is expected to contribute to periodontal disease prevention by modulating the oral microbiome toward a state with low inflammatory potential, thereby utilizing its anti-inflammatory properties on the host.

18F-sodium fluoride positron emission tomography following coronary computed tomography angiography in predicting long-term coronary events: a 5-year follow-up study.

PURPOSE: The predictive value of 18F-sodium fluoride (18F-NaF) positron emission tomography (PET) in combination with coronary computed tomography (CT) angiography (CCTA) for future coronary events has attracted interest. We evaluated the potential of 18F-NaF PET/CT following CCTA to predict major coronary events (MACE) during a 5-year follow-up period. METHODS: Forty patients with coronary atherosclerotic lesions detected on CCTA underwent 18F-NaF PET/CT examination. Each lesion was evaluated for luminal stenosis and high-risk plaque (HRP) with < 30 Hounsfield units and a > 1.1 remodeling index on CCTA. Focal 18F-NaF uptake in each lesion was quantified using the maximum tissue-to-background ratio (TBRmax), and the maximum TBRmax per patient (M-TBRmax) was determined. We followed MACE (cardiac death, acute coronary syndrome, and/or coronary revascularization > 6 months after 18F-NaF PET/CT) for 5 years. RESULTS: In total, 142 coronary lesions were analyzed. Eleven patients experienced any MACE. Patients with MACE showed a higher M-TBRmax than those without (1.40 ± .19 vs. 1.18 ± .18, P = .0011), and the optimal M-TBRmax cutoff to predict MACE was 1.29. Patients with M-TBRmax of ≥ 1.29 had a higher risk of MACE than those with lower values (P = .012, log-rank test), whereas patients with obstructive stenosis and those with HRP did not. Multivariate Cox proportional analysis adjusted for age, sex, coronary risk factors, and CCTA findings showed that M-TBRmax of ≥ 1.29 remained an independent predictor of 5-year MACE (hazard ratio, 5.4; 95% confidence interval, 1.1-25.4; P = .034). CONCLUSION: 18F-NaF PET/CT following CCTA provides useful strategies to predict 5-year MACE.

The reliability and utility of on-site CT-derived fractional flow reserve (FFR) based on fluid structure interactions: comparison with FFRCT based on computational fluid dynamics, invasive FFR, and resting full-cycle ratio.

Fractional flow reserve (FFR) derived off-site by coronary computed tomography angiography (CCTA) (FFRCT) is obtained by applying the principles of computational fluid dynamics. This study aimed to validate the overall reliability of on-site CCTA-derived FFR based on fluid structure interactions (CT-FFR) and assess its clinical utility compared with FFRCT, invasive FFR, and resting full-cycle ratio (RFR). We calculated the CT-FFR for 924 coronary vessels in 308 patients who underwent CCTA for clinically suspected coronary artery disease. Of these patients, 35 patients with at least one obstructive stenosis (> 50%) detected on CCTA underwent both CT-FFR and FFRCT for further investigation. Furthermore, 24 and 20 patients underwent invasive FFR and RFR in addition to CT-FFR, respectively. The inter-observer correlation (r) of CT-FFR was 0.93 (95% confidence interval [CI] 0.85-0.97, P < 0.0001) with a mean absolute difference of - 0.0042 (limits of agreement - 0.073, 0.064); 97.3% of coronary arteries without obstructive lesions on CCTA had negative results for ischemia on CT-FFR (> 0.80). The correlation coefficient between CT-FFR and FFRCT for 105 coronary vessels was 0.87 (95% CI 0.82-0.91, P < 0.0001) with a mean absolute difference of - 0.012 (limits of agreement - 0.12, 0.10). CT-FFR correlated well with both invasive FFR (r = 0.66, 95% CI 0.36-0.84, P = 0.0003) and RFR (r = 0.78, 95% CI 0.51-0.91, P < 0.0001). These data suggest that CT-FFR can potentially substitute for FFRCT and correlates closely with invasive FFR and RFR with high reproducibility. Our findings should be proven by further clinical investigation in a larger cohort.

A longitudinal pilot study to assess temporal changes in coronary arterial 18F-sodium fluoride uptake.

PURPOSE: How coronary arterial 18F-sodium fluoride (18F-NaF) uptake on positron emission tomography changes over the long term and what clinical factors impact the changes remain unclear. We sought to investigate the topics in this study. METHODS: We retrospectively studied 15 patients with ≥1 coronary atherosclerotic lesion/s detected on cardiac computed tomography who underwent baseline and follow-up (interval of >3 years) 18F-NaF positron emission tomography/computed tomography scans. Focal 18F-NaF uptake in each lesion was quantified using maximum tissue-to-background ratio (TBRmax). The temporal change in TBRmax was assessed using a ratio of follow-up to baseline TBRmax (R-TBRmax). RESULTS: A total of 51 lesions were analyzed. Mean R-TBRmax was 0.96 ± 0.21. CT-based lesion features (location, obstructive stenosis, plaque types, features of high-risk plaque) did not correlate with an increase in R-TBRmax. In multivariate analysis, baseline TBRmax significantly correlated with higher follow-up TBRmax (ß = 0.57, P < 0.0001), and the presence of diabetes mellitus significantly correlated with both higher follow-up TBRmax (ß = 0.34, P = 0.001) and elevated R-TBRmax (ß = 0.40, P = 0.003). CONCLUSION: Higher coronary arterial 18F-NaF uptake is likely to remain continuously high. Diabetes mellitus affects the long-term increase in coronary arterial 18F-NaF uptake.

Native Myocardial T1 Value in Predicting 1-Year Outcomes in Patients with Nonischemic Dilated Cardiomyopathy Experiencing Recent Heart Failure.

The evidence for the clinical implications, especially the short-term utility, of native myocardial T1 value (T1native) on cardiac magnetic resonance (CMR) in nonischemic dilated cardiomyopathy (NIDCM) is scant. We investigated the potential of T1native to assess left ventricular (LV) myocardial characteristics and predict 1-year outcomes in patient with NIDCM experiencing recent heart failure (HF).Forty-five patients with NIDCM and HF symptoms within 3 months underwent CMR with cine, non-contrast T1 mapping, and late gadolinium enhancement (LGE). T1native per patient was defined as an averaged T1 value of 5 short-axis slices of base-to-apex LV myocardium. The appearance of LGE was visually examined. T1native correlated with the LV end-diastolic dimension normalized to height (LVEDD) (r = 0.38, P = 0.0103), ejection fraction (r = -0.39, P = 0.009), and serum N-terminal pro-brain natriuretic peptide levels (r = 0.48, P = 0.001), whereas the presence and segmental extent of LGE correlated only with LVEDD. In the 1-year follow-up cohort, the optimal cutoffs of T1native for predicting LV reverse remodeling (LVRR) and combined cardiac events (cardiac death, ventricular tachycardia/fibrillation, heart failure hospitalization) were 1366 ms and 1377 ms, respectively. In multivariate analysis, T1native < 1366 ms and T1native > 1377 ms remained significant predictors of LVRR (odds ratio, 11.3) and cardiac events (hazard ratio, 15.3), respectively, whereas the presence and segmental extent of LGE did not.T1native in patients with NIDCM experiencing recent HF may offer a promising strategy for assessing LV myocardial characteristics and predicting 1-year LVRR and cardiac events.

Arthroscopic Distal Clavicle Resection for an Acromioclavicular Ganglion Cyst with Cuff Tear Arthropathy: A Case Report.

CASE: A 77-year-old man with an acromioclavicular joint ganglion cyst with cuff tear arthropathy had a large mass in the left shoulder. Arthroscopic distal clavicle resection successfully relieved his symptoms without loss of shoulder function by enlargement of the bypass between the cyst and subacromial space through the acromioclavicular joint. CONCLUSION: Arthroscopic distal clavicle resection can remove a 1-way check valve in a minimally invasive manner. This case indicated that arthroscopic distal clavicle resection could be a useful treatment option for patients with acromioclavicular joint ganglion cysts with functional but irreparable rotator cuff tears.

Relationship between interleukin-1ß gene expression in epicardial adipose tissue and coronary atherosclerosis based on computed tomographic analysis.

BACKGROUND: Anti-inflammatory therapy targeting interleukin (IL)-1ß reduced cardiovascular events in a randomized trial. We evaluated the relationship between IL-1ß mRNA expression in epicardial adipose tissue (EAT) and clinically-assessed coronary atherosclerosis on computed tomography (CT). METHODS: We studied 45 patients before cardiac surgery (coronary artery bypass grafting [CABG], n â€‹= â€‹18; non-CABG, n â€‹= â€‹27). EAT volume, the coronary calcium score (CCS), and the presence of non- and/or partially-calcified coronary plaques (NCPs) and high-risk coronary plaques (HRPs; minimum CT density <30 Hounsfield units and vascular remodeling index >1.1) on CT angiography were assessed. EAT samples were obtained during cardiac surgery. IL-1ß mRNA expression in EAT was measured using quantitative real-time PCR and normalized to that of ß-actin in each patient. RESULTS: There was no difference in IL-1ß mRNA levels between patients who were scheduled for CABG and non-CABG surgery or among subgroups based on the CCS. However, patients with NCPs (median [interquartile range], 4.1[2.0-11.6]E-4 versus 1.8[0.6-4.5]E-4, p â€‹= â€‹0.024) and HRP (7.6[3.0-20.4]E-4 versus 1.9[0.7-4.3]E-4, p â€‹= â€‹0.0023) had higher IL-1ß mRNA levels than those without these plaques. On multivariate analysis adjusted for age, sex, coronary risk factors, statin therapy, CCS, and EAT volume, the presence of HRPs was significantly correlated with elevated IL-1ß mRNA levels in EAT (ߠ​= â€‹0.39, p â€‹= â€‹0.047). CONCLUSION: Our data suggest a contribution of EAT to coronary atherosclerosis through molecular behavior, such as IL-1ß gene expression, which may be a new therapeutic target.

Relationship between coronary arterial 18F-sodium fluoride uptake and epicardial adipose tissue analyzed using computed tomography.

PURPOSE: 18F-Sodium fluoride (18F-NaF) positron emission tomography (PET) has the potential to detect high-risk coronary plaques. Epicardial adipose tissue (EAT) reportedly correlates with coronary atherosclerosis progression. We evaluated the relationship between coronary arterial 18F-NaF uptake and EAT findings using computed tomography (CT). METHODS: We studied 40 patients with ≥ 1 coronary plaque detected on cardiac CT who underwent 18F-NaF PET/CT. EAT volume was measured using CT and indexed to body surface area in each patient. Each plaque was evaluated for CT-based luminal stenosis and high-risk features. The mean EAT density surrounding each plaque was calculated as perilesional EAT density (PLED) using non-contrast CT images. Focal 18F-NaF uptake in each plaque was quantified using the maximum tissue-to-background ratio (TBRmax). RESULTS: EAT volume index was similar between patients with TBRmax ≥ 1.28 (previously reported optimal cutoff to predict coronary events) and those with lower TBRmax, but patients with TBRmax ≥ 1.28 showed higher maximum PLED per patient (- 86 ± 12 Hounsfield units (HU) versus - 98 ± 11 HU, P = 0.0044). In the lesion-based analysis (n = 92), PLED was positively correlated with TBRmax, and the optimal PLED cutoff to identify TBRmax ≥ 1.28 was - 97 HU. On multivariate analysis adjusted for lesion location, obstructive stenosis, and high-risk plaque on CT, PLED ≥ - 97 HU remained a significant predictor of TBRmax ≥ 1.28. CONCLUSIONS: Increased PLED was associated with significant coronary arterial 18F-NaF uptake. Step-by-step analyses of EAT density on CT and coronary arterial 18F-NaF uptake on PET may offer novel strategies for risk prediction in coronary artery disease.

Partial left superior pulmonary vein potential elimination by an inferior ganglionated plexus ablation.

Ganglionated plexus (GP) plays an important role in the initiation and maintenance of atrial fibrillation (AF). The GP ablation has been found to be effective for AF treatment. In this case, we reported an AF case in which the pulmonary vein (PV) potentials of the anterior region of the left superior PV were eliminated by an inferior right GP ablation.

Atrial electrical abnormality in patients with Brugada syndrome assessed by signal-averaged electrocardiography.

BACKGROUND: Ventricular fibrillation and atrial fibrillation are well-known arrhythmias in patients with Brugada syndrome. This study evaluated the characteristics of the atrial arrhythmogenic substrate using the signal-averaged electrogram (SAECG) in patients with Brugada syndrome. METHODS: SAECGs were performed during normal sinus rhythm in 23 normal volunteers (control group), 21 patients with paroxysmal atrial fibrillation (PAF; PAF group), and 21 with Brugada syndrome (Brugada group). RESULTS: The filtered P wave duration (fPd) in the control, Brugada, and PAF groups was 113.9±12.9ms, 125.3±15.0ms, and 137.1±16.3ms, respectively. The fPd in the PAF group was significantly longer compared to that in the control and Brugada groups (p<0.05). The fPd in the Brugada group was significantly longer than that in the control group (p<0.05) and significantly shorter than that in the PAF group (p<0.05). CONCLUSION: Patients with Brugada syndrome had abnormal P waves on the SAECG. The abnormal P waves on the SAECG in Brugada syndrome patients may have intermediate characteristics between control and PAF patients.

A Comparison between the Instantaneous Wave-free Ratio and Resting Distal Coronary Artery Pressure/Aortic Pressure and the Fractional Flow Reserve: The Diagnostic Accuracy Can Be Improved by the Use of both Indices.

Objectives The fractional flow reserve (FFR) is an index of the severity of coronary stenosis that has been clinically validated in several studies. The instantaneous wave-free ratio (iFR) and the resting distal coronary artery pressure/aortic pressure (Pd/Pa) are nonhyperemic pressure-derived indices of the severity of stenosis. This study sought to examine the diagnostic accuracy of the iFR and resting Pd/Pa with respect to hyperemic FFR. Methods Following an intracoronary injection of papaverine, the iFR, resting Pd/Pa, and FFR were continuously measured in 123 lesions in 103 patients with stable coronary disease. Results The iFR and resting Pd/Pa values were strongly correlated with the FFR (R=0.794, p<0.001, R=0.832, p<0.0001, respectively). A receiver operator curve (ROC) analysis revealed that the optimal iFR cut-off value for predicting an FFR of <0.80 was 0.89 (AUC 0.901, sensitivity 84.1%, specificity 80.0%, positive predictive value 69.8%, negative predictive value 90.0%, diagnostic accuracy 81.3%), while the optimal resting Pd/Pa cut-off value was 0.92 (AUC 0.925, sensitivity 90.9%, specificity 78.5%, positive predictive value 70.2%, negative predictive value 93.9%, diagnostic accuracy 82.9%). The lesions with an iFR value of ≤0.89 and a Pd/Pa value of ≤0.92 were defined as double-positive lesions, while the lesions with an iFR value of >0.89 and a Pd/Pa value of >0.92 were defined as double-negative lesions. In these 109 lesions, the sensitivity, specificity, positive predictive value, negative predictive value, and diagnostic accuracy were 92.3%, 82.9%, 75.0%, 95.1%, and 86.2%, respectively. Conclusion This analysis demonstrated that the iFR and resting Pd/Pa were strongly correlated with the FFR and that the diagnostic accuracy of the iFR was similar to that of the resting Pd/Pa. The diagnostic accuracy can be improved with the use of both the iFR and the resting Pd/Pa.

Contrast-induced Hyperemia as an Alternative to Drug-induced Hyperemia in the Evaluation of the Fractional Flow Reserve in Coronary Lesions.

Objective Measuring the fractional flow reserve (FFR) requires the induction of coronary hyperemia, usually with adenosine, adenosine triphosphate (ATP), or papaverine. However, adenosine can induce rhythmic complications, and intracoronary boluses of papaverine that prolong the QT interval can cause ventricular tachycardia. Injection of contrast media, which is routinely performed to validate the FFR guidewire placement, also induces hyperemia and may be an alternative method of measuring the FFR. We evaluated the diagnostic accuracy of the FFR after contrast hyperemia (FFRcont) compared to FFR evaluated after intracoronary papaverine (FFRpp). Methods This study included 109 lesions in 93 patients (mean age 70.4±8.7 years) with stable coronary disease. The FFR was measured as follows: 1) baseline pressure value; 2) FFRcont after intracoronary contrast injection (iopamidol, 8 mL for left coronary artery [LCA] or 6 mL for right coronary artery [RCA]); 3) FFRpp after intracoronary injection of papaverine (12 mg for LCA or 8 mg for RCA). Results FFRcont values were strongly correlated with FFRpp (R=0.940, p<0.0001; FFRpp = FFRcont ×1.007-0.032). The best cut-off point in the receiver operator curve analysis for predicting a FFRpp <0.80 was 0.82 (area under the curve =0.980; sensitivity 95.1%, specificity 91.2%, positive predictive value 86.7%, negative predictive value 96.9%). Conclusion FFRcont is highly accurate for predicting FFRpp. An FFRcont threshold value of 0.82 provides excellent sensitivity and a negative predictive value. FFRcont is an alternative method of inducing hyperemia.

The Difference between the optical coherence tomography (OCT) findings of newly progressed coronary lesions in symptomatic and asymptomatic patients.

BACKGROUND: Generally, newly progressed coronary lesions (NPCLs) are considered to be composed of lipid-rich plaques. In case of vulnerable plaque rupture, they may quickly become culprit lesions responsible for acute coronary syndromes. METHODS: Between September 2011 and September 2015, 2034 patients underwent scheduled follow-up coronary angiography (CAG) after percutaneous coronary intervention (PCI) in Tsuchiya General Hospital. Patients with NPCLs found by CAG during the follow-up period were evaluated by optical coherence tomography (OCT). NPCLs were defined as the lesions with less than 50% diameter stenosis, which progressed to more than 75% diameter stenosis within 3years after the previous CAG. Patients with restenosis after PCI were excluded. We compared OCT findings of NPCLs between symptomatic and asymptomatic patients. RESULTS: The follow-up CAG showed NPCLs in 64 patients (3.2%). OCT revealed fibrous plaque in 42 patients (65.6%) and thin-cap fibroatheroma in one patient. Thirteen patients had chest symptoms for one month before CAG and the remaining 51 patients were asymptomatic. The prevalence of fibrous plaque and intimal disruption or plaque rupture were not significantly different between symptomatic and asymptomatic patients (61.5% vs. 66.7%, p=0.752 and 30.8% vs. 11.8%, p=0.213, respectively). However, thrombi were more frequently observed in symptomatic patients (61.5% vs. 13.7%, p<0.001). CONCLUSIONS: The majority of NPCLs found in asymptomatic patients at follow-up CAG were not vulnerable; however, those found in symptomatic patients might be vulnerable. In clinical practice, NPCLs found in asymptomatic patients should be evaluated for functional severity of stenosis in order to determine the need for coronary revascularization.

Comparison of everolimus- and paclitaxel-eluting stents in dialysis patients.

BACKGROUND: We previously reported that the incidence of 1-year major adverse cardiac events (MACE) in patients treated with paclitaxel-eluting stents (PES) was lower than that in the sirolimus-eluting stents in dialysis patients. However, it remains unclear whether there are differences in clinical outcomes between everolimus-eluting stents (EES) and PES. METHODS: Between February 2010 and September 2013, 102 maintenance dialysis patients with 135 lesions treated with EES were compared to 107 maintenance dialysis patients with 147 lesions treated with PES. One-year clinical outcomes were investigated. RESULTS: Diabetes mellitus was present in 64.7% in the EES group and 71.0% in the PES group (p = 0.33). Heavy calcification was in 27.4% vs. 34.0% (p = 0.23). Rotational atherectomy was undergone in 11.1% vs. 23.1% (p < 0.01). Total stented length was not significantly different (23.5 ± 14.6 mm vs. 24.4 ± 13.2 mm, p = 0.60). One patient in the EES group was lost to follow up. At 12 months, MACE occurred in 13.2% in the EES group and 17.4% in the PES group (p = 0.25). Target lesion revascularization (TLR) was observed in 9.5% vs. 10.4% respectively (p = 0.77). Mortality was 11.8% vs. 13.1% (p = 0.35). Cardiac death was 5.0% vs. 7.7% (p = 0.09). Definite stent thrombosis was observed in 2.0% vs. 0% (p = 0.14). Subgroup analysis in patients with diabetes mellitus revealed no significant differences in MACE (12.7% vs. 14.9%, p = 0.36), TLR (8.3% vs. 7.4%, p = 0.42), mortality (13.7% vs. 13.2%, p = 0.28), and cardiac death (6.3% vs. 8.0%, p = 0.15) between the two groups. CONCLUSIONS: One-year clinical outcomes following EES and PES implantations are similar in dialysis patients.