Time-series transcriptome analysis of peripheral blood mononuclear cells obtained from individuals who received the SARS-CoV-2 mRNA vaccine.

Messenger ribonucleic acid (mRNA) vaccination against coronavirus disease 2019 (COVID-19) is an effective prevention strategy, despite a limited understanding of the molecular mechanisms underlying the host immune system and individual heterogeneity of the variable effects of mRNA vaccination. We assessed the time-series changes in the comprehensive gene expression profiles of 200 vaccinated healthcare workers by performing bulk transcriptome and bioinformatics analyses, including dimensionality reduction utilizing the uniform manifold approximation and projection (UMAP) technique. For these analyses, blood samples, including peripheral blood mononuclear cells (PBMCs), were collected from 214 vaccine recipients before vaccination (T1) and on Days 22 (T2, after second dose), 90, 180 (T3, before a booster dose), and 360 (T4, after a booster dose) after receiving the first dose of BNT162b2 vaccine (UMIN000043851). UMAP successfully visualized the main cluster of gene expression at each time point in PBMC samples (T1-T4). Through differentially expressed gene (DEG) analysis, we identified genes that showed fluctuating expression levels and gradual increases in expression levels from T1 to T4, as well as genes with increased expression levels at T4 alone. We also succeeded in dividing these cases into five types based on the changes in gene expression levels. High-throughput and temporal bulk RNA-based transcriptome analysis is a useful approach for inclusive, diverse, and cost-effective large-scale clinical studies.

Heterogeneity assessment of vaccine-induced effects using point-of-care surrogate neutralization test for severe acute respiratory syndrome coronavirus 2.

INTRODUCTION: Coronavirus disease (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has become a global pandemic even after vaccination. We aimed to identify immunological heterogeneity over time in vaccinated healthcare workers using neutralization antibodies and neutralizing activity tests. METHODS: Serum samples were collected from 214 healthcare workers before vaccination (pre) and on days 22, 90, and 180 after receiving the first dose of BNT162b2 vaccine (day 0). Neutralization antibody (NAb, SARS-CoV-2 S-RBD IgM/IgG) titers and two kinds of surrogate virus neutralization tests (sVNTs) were analyzed (UMIN000043851). RESULTS: The NAb (SARS-CoV-2 S-RBD IgG) titer peaked on day 90 after vaccination (30,808.0 µg/ml ± 35,211; p < 0.0001) and declined on day 180 (11,678.0 µg/ml ± 33,770.0; p < 0.0001). The neutralizing activity also peaked on day 90 and declined with larger individual differences than those of IgG titer on day 180 (88.9% ± 15.0%, 64.8% ± 23.7%, p < 0.0001). We also found that the results of POCT-sVNT (immunochromatography) were highly correlated with those of conventional sVNT (ELISA). CONCLUSIONS: Neutralizing activity is the gold standard for vaccine efficacy evaluation. Our results using conventional sVNT showed large individual differences in neutralizing activity reduction on day 180 (64.8% ± 23.7%), suggesting an association with the difference in vaccine efficacy. POCT-sVNT is rapid and user-friendly; it might be used for triage in homes, isolation facilities, and event venues without restrictions on the medical testing environment.

Association between acute myocardial infarction-to-cardiac rupture time and in-hospital mortality risk: a retrospective analysis of multicenter registry data from the Cardiovascular Research Consortium-8 Universities (CIRC-8U).

Despite the known association of cardiac rupture with acute myocardial infarction (AMI), it is still unclear whether the clinical characteristics are associated with the risk of in-hospital mortality in patients with AMI complicated by cardiac rupture. The purpose of this study was to investigate the association between the time of cardiac rupture occurrence and the risk of in-hospital mortality after AMI. We conducted a retrospective analysis of multicenter registry data from eight medical universities in Eastern Japan. From 10,278 consecutive patients with AMI, we included 183 patients who had cardiac rupture after AMI, and examined the incidence of in-hospital deaths during a median follow-up of 26 days. Patients were stratified into three groups according to the AMI-to-cardiac rupture time, namely the > 24-h group (n = 111), 24-48-h group (n = 20), and < 48-h group (n = 52). Cox proportional hazards regression analysis was used to estimate the hazard ratio (HR) and the confidence interval (CI) for in-hospital mortality. Around 87 (48%) patients experienced in-hospital death and 126 (67%) underwent a cardiac surgery. Multivariable Cox regression analysis revealed a non-linear association across the three groups for mortality (HR [CI]; < 24 h: 1.0, reference; 24-48 h: 0.73 [0.27-1.86]; > 48 h: 2.25 [1.22-4.15]) after adjustments for age, sex, Killip classification, percutaneous coronary intervention, blood pressure, creatinine, peak creatine kinase myocardial band fraction, left ventricular ejection fraction, and type of rupture. Cardiac surgery was independently associated with a reduction in the HR of mortality (HR [CI]: 0.27 [0.12-0.61]) and attenuated the association between the three AMI-to-cardiac rupture time categories and mortality (statistically non-significant) in the Cox model. These data suggest that the AMI-to-cardiac rupture time contributes significantly to the risk of in-hospital mortality; however, rapid diagnosis and prompt surgical interventions are crucial for improving outcomes in patients with cardiac rupture after AMI.

A multicenter study on the clinical characteristics and risk factors of in-hospital mortality in patients with mechanical complications following acute myocardial infarction.

Mechanical complications (MCs) following acute myocardial infarction (AMI), such as ventricular septal rupture (VSR), free-wall rupture (FWR), and papillary muscle rupture (PMR), are fatal. However, the risk factors of in-hospital mortality among patients with MCs have not been previously reported in Japan. The purpose of this study was to evaluate the prognostic factors of in-hospital mortality in these patients. The study cohort consisted of 233 consecutive patients with MCs from the registry of 10 facilities in the Cardiovascular Research Consortium-8 Universities (CIRC-8U) in East Japan between 1997 and 2014 (2.3% of 10,278 AMI patients). The authors conducted a retrospective observational study to analyse the correlation between the subtypes of MCs with in-hospital mortality, clinical data, and medical treatment. We observed a decreasing incidence of MC (1997-2004: 3.7%, 2005-2010: 2.1%, 2011-2014: 1.9%, p < 0.001). In-hospital mortality among patients with MCs was 46%. Thirty-three percent of patients with MCs were not able to undergo surgical repair due to advanced age or severe cardiogenic shock. In-hospital mortality among patients who had undergone surgical repair was 29% (VSR: 21%, FWR: 33%, PMR: 60%). In patients with MCs, hazard ratio for in-hospital mortality according to multivariate analysis of without surgical repair was 5.63 (95% CI 3.54-8.95). In patients with surgical repair, the hazard ratios of blow-out-type FWR (5.53, 95% confidence interval (CI) 2.22-13.76), those with renal dysfunction (3.11, 95% CI 1.37-7.05), and those receiving venoarterial extracorporeal membrane oxygenation (VA-ECMO) (3.79, 95% CI 1.81-7.96) were significantly high. Although primary percutaneous coronary intervention (PCI) is associated with decreased incidence of MCs, high in-hospital mortality persisted in patients with MCs that also presented with renal dysfunction and in those requiring VA-ECMO. Early detection and surgical repair of MCs are essential.

Survey of the current status of subclinical coronavirus disease 2019 (COVID-19).

OBJECTIVES: We investigated relationships between subclinical COVID-19 (coronavirus disease 2019) and background factors. METHODS: We determined SARS-CoV-2 antibody (IgG) prevalence in 1603 patients, doctors, and nurses in 65 medical institutions in Kanagawa Prefecture, Japan and investigated their background factors. Antibodies (IgG) against SARS-CoV-2 were analyzed by Immunochromatographic test. RESULTS: The 39 subjects (2.4%) were found to be IgG antibody-positive: 29 in the patient group (2.9%), 10 in the doctor/nurse group (2.0%), and 0 in the control group. After adjustment for age, sex, and the antibody prevalence in the control group, antibody prevalence was 2.7% in the patient group and 2.1% in the doctor/nurse group. There was no significant difference between the antibody-positive subjects and the antibody-negative subjects in any background factors investigated including overseas travel, contact with overseas travelers, presence/absence of infected individuals in the living area, use of trains 5 times a week or more, BCG vaccination, and use of ACE inhibitor and ARB. CONCLUSIONS: Antibody prevalence in the present survey at medical institution is higher than that in Tokyo and in Osaka measured by the government suggesting that subclinical infections are occurring more frequently than expected. No background factor that influenced antibody-positive status due to subclinical infection was identified.

Effects of sitagliptin on coronary atherosclerosis evaluated using integrated backscatter intravascular ultrasound in patients with type 2 diabetes: rationale and design of the TRUST study.

Patients with diabetes mellitus are at high risk for developing coronary artery disease (CAD), even if they are treated with statins. Several studies have shown the beneficial effects of dipeptidyl peptidase-4 (DPP-4) inhibitors on the cardiovascular system in an animal model. However, recent clinical trials using DPP-4 inhibitors have shown that these inhibitors fail to reduce the occurrence of cardiovascular events. Therefore, this study will be performed to evaluate the effects of sitagliptin, a DPP-4 inhibitor, on coronary atherosclerosis in patients with type 2 diabetes. This study will be a prospective, open-label, randomized multicenter trial performed in 6 centers in Japan. Stable CAD patients with type 2 diabetes who have undergone successful percutaneous coronary intervention under integrated backscatter (IB)-intravascular ultrasound (IVUS) guidance will be studied. They will be randomly assigned to either the sitagliptin group or a control group. After 48 weeks' treatment, the IVUS examination will be repeated in the same coronary artery as at baseline. The primary end point will be the percentage change in plaque volume measured using grayscale IVUS from baseline to the 48-week follow-up. This study will be the first multicenter trial to evaluate the effects of a DPP-4 inhibitor on coronary atherosclerosis evaluated using IB-IVUS, and the findings will clarify the anti-atherogenic effects of sitagliptin.

Comparison of the effects of pitavastatin versus pravastatin on coronary artery plaque phenotype assessed by tissue characterization using serial virtual histology intravascular ultrasound.

Thin-cap fibroatheroma (TCFA) is the most common type of vulnerable plaque and is the precursor of plaque rupture. However, rupture of a TCFA is not the only mechanism underlying thrombus formation or acute coronary syndrome. Although statin therapy changes the composition of coronary artery plaques, the effects of statins, particularly different types of statins, on plaque phenotype have not been fully examined. This study compared the effects of pitavastatin versus pravastatin on coronary artery plaque phenotype assessed by virtual histology (VH) intravascular ultrasound (IVUS) in patients with angina pectoris (AP). Coronary atherosclerosis in nonculprit lesions was evaluated using VH-IVUS at baseline and 8 months after statin therapy; analyzable IVUS data were obtained from 83 patients with stable AP (39 patients treated with pitavastatin and 44 with pravastatin) and 36 patients with unstable AP (19 patients treated with pitavastatin and 17 with pravastatin). Pitavastatin had a strong effect on reducing pathologic intimal thickening (PIT), especially in patients with unstable AP, but had no impact on VH-TCFA or fibroatheroma (FA). By contrast, pravastatin had weak effects on reducing PIT, VH-TCFA, or FA. Increases in the number of calcified plaques were observed for both statins. In conclusion, pitavastatin and pravastatin changed coronary artery plaque phenotype as assessed by VH-IVUS in patients with AP. However, the effects of these statins on coronary artery plaque phenotype were different.

Successful Treatment of Refractory Electrical Storm With Landiolol After More Than 100 Electrical Defibrillations.

Electrical storm (ES) was observed in an 82-year-old man with recent myocardial infarction. Conventional therapy, including amiodarone, could not suppress the ES. After more than 100 electrical defibrillations, we were finally able to control the ES with the administration of landiolol. It is known that landiolol can inhibit ES. However, we hesitate to use landiolol in patients with low cardiac output. We would like to emphasize that careful use of landiolol should be considered in patients with refractory ES after myocardial infarction, although cardiac output is severely reduced.

Low serum docosahexaenoic acid is associated with progression of coronary atherosclerosis in statin-treated patients with diabetes mellitus: results of the treatment with statin on atheroma regression evaluated by intravascular ultrasound with virtual histology (TRUTH) study.

BACKGROUND: Diabetes mellitus (DM) accelerates plaque progression despite the use of statin therapy. The purpose of the present study was to evaluate the determinants of atheroma progression in statin-treated patients with DM. METHODS: Coronary atherosclerosis in nonculprit lesions in a vessel undergoing percutaneous coronary intervention (PCI) was evaluated using virtual histology intravascular ultrasound. The study included 50 patients with DM who had been taking statin therapy for 8 months at the time of PCI. RESULTS: Twenty-six patients (52%) showed atheroma progression (progressors) and the remaining 24 patients (48%) showed atheroma regression (regressors) after 8 months of follow-up. Fewer progressors than regressors received intensive lipid-lowering therapy with pitavastatin (31% vs. 50%, p = 0.17) and the frequency of insulin use was higher in progressors (31% vs. 13%, p = 0.18). However, neither of these differences reached statistical significance. Risk factor control at baseline and at the 8-month follow-up did not differ between the 2 groups except for serum levels of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). Univariate regression analysis showed that serum EPA (r = -0.317, p = 0.03) and DHA (r = -0.353, p = 0.02) negatively correlated with atheroma progression. Multivariate stepwise regression analysis showed that low serum DHA and pravastatin use were significant independent predictors for atheroma progression during statin therapy (DHA: ß = -0.414, type of statin: ß = -0.287, p = 0.001). CONCLUSIONS: Low serum DHA is associated with progression of coronary atherosclerosis in statin-treated patients with DM. TRIAL REGISTRATION: UMIN Clinical Trials Registry, UMIN ID: C000000311.

Impacts of age on coronary atherosclerosis and vascular response to statin therapy.

Age is a well-established risk factor for cardiovascular disease. Recent trials using intravascular ultrasound (IVUS) have shown that lipid-lowering therapy with statins halts the progression or induces the regression of coronary artery plaques. However, impacts of age on coronary atherosclerosis and vascular response to statin therapy have not been fully evaluated. The effects of 8-month statin therapy on coronary atherosclerosis were evaluated using virtual histology-IVUS. IVUS data were analyzed from 119 patients who were divided into two groups according to age: elderly patients (≥65 years, n = 72) and non-elderly patients (<65 years, n = 47). No patients were taking statins or other lipid-lowering therapies at baseline. At baseline, external elastic membrane (EEM) volume (17.27 vs. 14.95 mm(3)/mm, p = 0.02) and plaque volume (9.49 vs. 8.11 mm(3)/mm, p = 0.03) in the elderly patients were significantly greater than in the non-elderly patients. The EEM volume (-2.4 %, p = 0.007) and plaque volume (-3.1 %, p = 0.007) after 8-month of statin therapy had significantly decreased in the non-elderly patients but not in the elderly patients. A significant positive correlation was observed between age and percentage change in plaque volume (r = 0.265, p = 0.004). A multivariate regression analysis showed that age was a significant predictor of the percentage change in plaque volume during statin therapy (ß = 0.223, p = 0.02). Coronary atherosclerosis was more advanced and vascular responses to statin therapy were attenuated in the elderly patients compared to the non-elderly patients.

Lipoprotein(a) is associated with necrotic core progression of non-culprit coronary lesions in statin-treated patients with angina pectoris.

BACKGROUND: Statin therapy results in regression and stabilization of coronary artery plaques, and reduces the incidence of coronary artery disease. However, statin therapy does not effectively halt the accumulation of necrotic core in all patients. The purpose of the present study was to identify the predictors associated with necrotic core progression during statin therapy. METHODS: Coronary atherosclerosis in non-culprit lesions was evaluated using virtual histology intravascular ultrasound at baseline and 8 months after statin therapy. One hundred nineteen patients were divided into 2 groups based on necrotic core progression or regression during an 8-month follow-up period. RESULTS: Patients with necrotic core progression had higher serum lipoprotein(a) [Lp(a)] levels than patients with regression at baseline (16 mg/dL vs. 12 mg/dL, p = 0.02) and at the 8-month follow-up (17 mg/dL vs. 10 mg/dL, p = 0.006). Patients with necrotic core progression had a higher fibro-fatty plaque volume (1.28 mm³/mm vs. 0.73 mm³/mm, p = 0.002), and less necrotic core (0.56 mm³/mm vs. 1.04 mm³/mm, p < 0.0001) and dense calcium (0.35 mm³/mm vs. 0.56 mm³/mm, p = 0.006) plaque volumes at baseline than patients with regression. Multivariate logistic regression analysis showed that Lp(a) was a significant independent predictor associated with necrotic core progression during statin therapy (odds ratio [OR]: 3.514; 95% confidence interval [CI]: 1.338-9.228; p = 0.01). CONCLUSIONS: Serum Lp(a) is independently associated with necrotic core progression in statin-treated patients with angina pectoris.

Long-term outcome and risk factors associated with events in patients with atrial fibrillation treated with oral anticoagulants: The ASSAF-K registry.

BACKGROUND: Oral anticoagulant therapy for atrial fibrillation (AF) has changed dramatically. Direct oral anticoagulant (DOAC) therapy is administered by general practitioners and specialists. However, the beneficial long-term effects and safety of DOACs have not been well investigated in real-world clinical practice. METHODS: The ASSAF-K (a study of the safety and efficacy of OAC therapy in the treatment of AF in Kanagawa), a prospective, multi-center, observational study, was conducted to clarify patient characteristics, status of OAC treatment, long-term outcomes, and adverse events, including cerebrovascular disease, bleeding, and death. RESULTS: A total of 4014 patients were enrolled (hospital: 2500 cases; clinic: 1514 cases). The number of patients in the final dataset was 3367 (mean age, 72.6 ±â€¯10.0 years; males, 66.3 %). CHA2DS2-VASc and HAS-BLED scores were 3.0 ±â€¯1.6 and 2.2 ±â€¯1.0, respectively. The risk factors of the primary composite outcome (all-cause death, serious bleeding events, cerebral hemorrhage, and stroke) were higher age, lower body mass index, lower diastolic blood pressure, lower creatine clearance, history of heart failure, history of stroke, and medication of anti-platelet agents. The event-free rates of the primary composite outcome with DOACs, warfarin, and without OACs were 92.7 %, 88.0 %, and 87.4 %, respectively. The event rate of DOACs was significantly lower than that of warfarin [HR 0.63 (95 % CI 0.48-0.81)], and similar results were observed after adjustment for AF stroke risk score [HR 0.70 (95 % CI 0.54-0.90)]. Serious bleeding events tended to occur less frequently with DOACs compared with warfarin [unadjusted HR 0.53 (95 % CI 0.31-0.91), adjusted HR 0.61 (95 % CI 0.33-1.11)]. CONCLUSIONS: This multi-center registry demonstrated the long-term outcome in patients with AF treated with and without OACs and suggests that DOAC therapy is safe and beneficial in hospitals and clinics.

Statin treatment for coronary artery plaque composition based on intravascular ultrasound radiofrequency data analysis.

BACKGROUND: Systemic therapy with statin has been shown to lower the risk of coronary events; however, the in vivo effects of statin therapy on plaque volume and composition are less understood. METHODS: We conducted a prospective, open-labeled, randomized, multicenter study in 11 centers in Japan. A total of 164 patients were randomized to receive either 4 mg/d of pitavastatin (intensive lipid-lowering therapy) or 20 mg/d of pravastatin (moderate lipid-lowering therapy). Analyzable intravascular ultrasound data were obtained for 119 patients at baseline and at 8-month follow-up. The primary end point was the difference of volume changes in each of the 4 main plaque components (fibrosis, fibrofatty, calcium, and necrosis), assessed by virtual histology intravascular ultrasound, between the 2 groups. RESULTS: The mean low-density lipoprotein cholesterol level at follow-up was significantly lower in the pitavastatin than in the pravastatin group (74 vs 95 mg/dL, P < .0001). During the 8-month follow-up period, statin therapy reduced the absolute and relative amount of fibrofatty component (pitavastatin: from 1.09 to 0.81 mm(3)/mm, P = .001; pravastatin: from 1.05 to 0.83 mm(3)/mm, P = .0008) and increased in the amount of calcium (pitavastatin: from 0.42 to 0.55 mm(3)/mm, P < .0001; pravastatin: from 0.44 to 0.55 mm(3)/mm, P = .005), whereas volume changes in both plaque components were not statistically different between the 2 groups. CONCLUSIONS: Both pitavastatin and pravastatin altered coronary artery plaque composition by significantly decreasing the fibrofatty plaque component and increasing the calcified plaque component.

Dexmedetomidine and clonidine inhibit ventricular tachyarrhythmias in a rabbit model of acquired long QT syndrome.

BACKGROUND: Agents with α-2 adrenoreceptor (AR) agonistic action have reportedly suppressed tachyarrhythmias. METHODS AND RESULTS: We hypothesized that α-2 AR agonists would have an inhibitory effect on abnormal repolarization-related ventricular tachyarrhythmias (VTs). To test this hypothesis, the effects of 2 clinically available α-2 AR agonists (dexmedetomidine and clonidine) on the occurrence of VTs were assessed in a methoxamine-sensitized rabbit model of acquired long QT syndrome (Study 1: n=45). In control rabbits, administration of methoxamine and nifekalant almost invariably caused VTs (14/15). In contrast, incidence of VT significantly decreased during the treatment with dexmedetomidine (1µg·kg(-1)·min(-1): 5/12 [P<0.01 vs. control]) or with clonidine (33.3µg·kg(-1)·min(-1): 10/18 [P<0.01]). To verify that VTs in this animal model are triggered by early afterdepolarization (EAD), the monophasic action potential on the left ventricular surface was recorded in 28 open-chest rabbits (Study 2). EAD-like hump was less frequently detected during treatment with clonidine or dexmedetomidine (2/14) than in saline-treated rabbits (9/10, P<0.005). Presence of a hump was significantly related to the advent of VTs (P<0.05). CONCLUSIONS: Agents with α-2 AR agonistic action have an inhibitory effect on VTs in a rabbit model of long QT syndrome. Alpha-2 AR agonists, especially dexmedetomidine, may be a therapeutic choice for abnormal repolarization-related VTs that are resistant to conventional treatment.

Impact of diabetes mellitus on coronary atherosclerosis and plaque composition under statin therapy ­ subanalysis of the TRUTH study ­.

BACKGROUND: Patients with diabetes mellitus (DM) have a markedly increased incidence of adverse cardiovascular events, but the mechanisms have not been well-characterized. METHODS AND RESULTS: The TRUTH study evaluated the effects of 8-month statin therapy on coronary artery plaque composition using virtual histology intravascular ultrasound (IVUS). Analyzable IVUS data were obtained from 119 patients, including 50 DM patients. The pattern of arterial remodeling, extent of coronary atherosclerosis, and plaque composition were compared in subjects with and without DM. Significant decreases in atheroma volume (-2.3%, P=0.02) and external elastic membrane volume (-1.7%, P=0.02) were observed only in the non-DM group. Although statin therapy significantly decreased the fibro-fatty component in both groups, this component at follow-up was significantly greater in the DM group (0.99 mm(3)/mm vs. 0.70 mm(3)/mm, P=0.03). Multivariate regression analysis showed that the presence of DM was associated with greater atheroma volume (ß=0.203, P=0.02), particularly fibro-fatty plaque volume at follow-up (ß=0.215, P=0.01). CONCLUSIONS: DM attenuated the degree of regression of coronary atherosclerosis under statin therapy. A large amount of fibro-fatty plaque volume under statin therapy may affect the development of coronary events in patients with DM.

Impacts of estimated glomerular filtration rate on coronary atherosclerosis and plaque composition before and during statin therapy in patients with normal to mild renal dysfunction: subanalysis of the TRUTH study.

AIM: Renal dysfunction is an independent risk factor for cardiovascular events. However, little is known regarding the impacts of renal dysfunction on coronary atherosclerosis. METHODS: The effects of 8-month statin therapy on coronary atherosclerosis were evaluated in the TRUTH study using virtual histology intravascular ultrasound in 164 patients with angina pectoris. We analyzed correlations between the estimated glomerular filtration rate (eGFR) and coronary atherosclerosis before and during statin therapy. RESULTS: Baseline eGFR was 64.5 mL/min per 1.73 m(2) . Serum low-density lipoprotein cholesterol level decreased significantly from 132 to 85 mg/dL (-35%, P < 0.0001) after 8 months. Weak, but significant, negative correlations were observed between eGFR and external elastic membrane volume (r = -0.228, P = 0.01) and atheroma volume (r = -0.232, P = 0.01) at baseline. The eGFR was also negatively correlated with fibro-fatty volume (r = -0.254, P = 0.005) and fibrous volume (r = -0.241, P = 0.008) at baseline. Multivariate regression analyses showed that eGFR was a significant independent predictor associated with statin pre-treatment volume in fibro-fatty (ß = -0.23, P = 0.01) and fibrous (ß = -0.203, P = 0.02) components. Furthermore, eGFR was positively correlated with volume change in the fibro-fatty component during statin therapy (r = 0.215, P = 0.02). CONCLUSION: Decreased eGFR is associated with expanding remodelling and a greater atheroma volume, particularly the fibro-fatty and fibrous volume before statin therapy in patients with normal to mild renal dysfunction. Reduction of fibro-fatty volume during statin therapy gradually accelerated with decreasing renal function.

Study on Continuation of Antibody Prevalence Six Months after Detection of Subclinical Severe Acute Respiratory Syndrome Coronavirus 2 Infections.

Objective To examine the continuation of antibody prevalence and background factors in antibody-positive subjects after asymptomatic infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Methods A study was carried out to investigate the SARS-CoV-2 antibody (IgG) prevalence. SARS-CoV-2 antibodies (IgG) were measured and analyzed with immunochromatographic tests. Patients Among 1,603 subjects, comprising patients, physicians, and nurses at 65 medical institutes in Kanagawa, Japan, 39 antibody-positive subjects received follow-up for 6 months. Results Of the 33 subjects who consented to the follow-up (23 patients and 10 medical professionals), continued positivity of IgG antibodies was confirmed in 11 of 32 cases (34.4%) after 2 months, 8 of 33 (24.2%) after 4 months, and 8 of 33 (24.2%) after 6 months. A significant difference was found in the sleeping time, drinking habits, hypertension, and use of angiotensin-receptor blockers on comparing subject background characteristics among three groups: patients with antibody production that continued for six months after the first detection of positivity, patients in whom antibody production stopped at four months, and patients in whom antibody production stopped at two months. Conclusion The continuation rate of IgG antibody prevalence was 24.2% at 6 months after the first detection of antibody positivity in cases with asymptomatic coronavirus disease 2019 (COVID-19) infections. This percentage is low compared with the antibody continuation rate in patients who have recovered from symptomatic COVID-19 infection.

The Proportion of Long-term Response to Anti-N IgG Antibody after 12 Months for COVID-19 Subclinical Infections and a Longitudinal Survey for COVID-19 Subclinical Infections in 2021.

Objective To examine the continuation of antibody prevalence status after 12 months and background factors in antibody-positive subjects following asymptomatic infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Methods We initially determined the SARS-CoV-2 anti-nucleocapsid protein immunoglobulin G (anti-N IgG) antibody prevalence in 1,603 patients, doctors, and nurses at 65 medical institutions in Kanagawa Prefecture, Japan. We then obtained consent from 33 of the 39 subjects who tested positive and performed follow-up for 12 months. Results Follow-up for up to 12 months showed that a long-term response of the anti-N IgG antibody could be detected in 6 of the 33 participants (18.2%). The proportions with hypertension, using an angiotensin-receptor blocker, and without a drinking habit were higher among the participants with a long-term anti-N IgG antibody response for up to 12 months than among those without a long-term antibody response. Conclusions The proportion of individuals with subclinical COVID-19 who continuously had a positive result for the anti-N IgG antibody at 12 months was low.

Deep anesthesia suppresses ventricular tachyarrhythmias in rabbit model of the acquired long QT syndrome.

BACKGROUND: Anesthesia sometimes suppresses ventricular tachyarrhythmias (VT) resistant to conventional pharmacological treatment. METHODS AND RESULTS: To know (1) whether deep anesthesia inhibits abnormal repolarization-related VT and (2) if α2-adrenoreceptor (AR) agonistic action is associated with the antiarrhythmic effect of anesthetics, the incidence of VT in a rabbit model of acquired long QT syndrome using different anesthetic regimen was assessed. In Study 1 (n = 30), 15 rabbits were lightly anesthetized with ketamine (123 ± 46 mg/kg) and an α2-AR agonist, xylazine (9.4±3.0mg/kg), while combination of these anesthetics at high doses were used in the other 15 rabbits (343 ± 78 mg/kg and 38.9 ± 3.0 mg/kg). Administration of α1-AR stimulant, methoxamine and nifekalant (Ikr blocker) caused VT in all lightly anesthetized rabbits. In contrast, VT was observed only in 1 of the 15 deeply anesthetized rabbits (P < 0.01). In Study 2 (n = 15), 10 rabbits were anesthetized with high-dose ketamine and low-dose xylazine. In the other 5 rabbits, low-dose ketamine and high-dose xylazine were used. QTc interval in the latter was longer than that of the former (399 ± 56 ms vs. 494 ± 57 ms, P < 0.01). Although no VT appeared in high/low-rabbits, VT occurred in 3 out of 5 low/high-rabbits (P < 0.05). CONCLUSIONS: These results suggest that (1) deep anesthesia suppresses abnormal repolarization-related VT and (2) antiarrhythmic effect of anesthesia on this type of VT is not dependent on α2-AR agonistic action.

The T wave inversion score is useful for evaluating the time-course of acute pulmonary embolism.

BACKGROUND: The 12-lead electrocardiogram (ECG) has relatively poor specificity for identifying acute pulmonary embolism (APE). The aim of this study was to investigate ECG abnormalities according to 2 different criteria and their usefulness for assessing changes in APE. METHODS AND RESULTS: Fifty-two APE patients underwent ECG examinations in the acute and chronic phases. ECG abnormalities were assessed according to Stein's criteria (QRS complex abnormalities and T wave inversion in any lead except aV(L), III, aV(R), or V1) and Kosuge's criteria (T wave inversion in any lead except aV(R) or aV(L)). Many patients had electrocardiographic abnormalities in the acute phase, but no specific abnormalities were found. According to Kosuge's criteria, the frequency of T wave inversion was higher than that of abnormal QRS complexes and T wave inversion according to Stein's criteria (P < 0.01). In 20 cases with preclinical ECG records, the time-course of changes in the T wave inversion score (total numbers of T wave inversions per patient) was examined. The peak T wave inversion score was noted at 3 days after onset (P < 0.01). CONCLUSIONS: These results suggest that the T wave inversion score, calculated according to Kosuge's criteria, is useful for predicting the time-course of APE.