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Background: The relationship between liver fibrosis and left atrial (LA) remodeling in atrial fibrillation (AF) remains uncertain. We examined the associations between the fibrosis-4 (FIB4) index, an indicator of liver fibrosis, and both LA low-voltage areas (LVAs) on electroanatomic mapping and AF recurrence postablation., Methods: We recruited 343 patients who underwent radiofrequency catheter ablation (RFCA) or cryoballoon ablation (CBA) for AF. First, the association between the FIB4 index and LA LVAs (<0.5 mV) was evaluated in RFCA using electroanatomic mapping ( n  = 214). Next, the utility of a FIB4 index ≥1.3, recommended cut-off value of liver fibrosis, was verified to assess the risk for AF recurrence in CBA without additional LVA ablation ( n  = 129)., Results: Patients with a FIB4 index ≥1.3 had a higher prevalence of LA LVAs (>5 cm 2 ) compared to those without. Additionally, the quantitative size of LVAs showed a positive correlation with the FIB4 index ( R  = .642, p  < .001). In multivariate logistic models, a FIB4 index ≥1.3 was related to the presence of LVAs after adjusting for LA diameter, right atrial end-systolic area, and nonparoxysmal AF (odds ratio 2.508; p  = 0.039). In CBA, AF recurrence rate was 13.1% during 3-12 months postablation. In multivariate Cox models, a FIB4 index ≥1.3 was an important predictor of AF recurrence (hazard ratio 3.796; p  = .037), suggesting that LVAs might be associated with AF recurrence after CBA., Conclusion: The FIB4 index was a novel predictor of the existence of LA LVAs on electroanatomic mapping and AF recurrence after CBA., Competing Interests: S.Y. and T.I. work for the Department of Arrhythmia and Cardiac Pacing, which is funded by Abbott Medical Japan LLC, Biotronik Japan, Inc, and Nihon Kohden Corporation. These companies are unrelated to the study's content. None of the other authors disclose any conflicts of interest., (© 2024 The Authors. Journal of Arrhythmia published by John Wiley & Sons Australia, Ltd on behalf of Japanese Heart Rhythm Society.)

Background: Both increases in red cell distribution width (RDW) levels and autonomic dysfunction are considered to be correlated with worsening heart failure. However, the relation of RDW levels to autonomic function remains uncertain. We aimed to investigate the association of RDW levels in heart failure with autonomic function, evaluated by heart rate variability (HRV) and heart rate turbulence (HRT), and prognosis., Methods: We studied 222 hospitalized patients with stable heart failure before discharge, and Holter recordings (HRV and HRT) were performed. Additionally, RDW levels were measured, and high RDW was defined as over 14.5%. We then divided the patients into two groups based on RDW levels: high RDW group (>14.5%, n = 92) and low RDW group (≤14.5%, n = 130). The relation of RDW to autonomic function and prognosis was assessed., Results: In the high RDW group, severely impaired HRV and HRT were found compared to the low RDW group. In the linear regression analysis after the adjustment of multiple confounders, RDW levels were correlated with a low-frequency (LF) to high-frequency (HF) ratio and very low-frequency (VLF) power (LF to HF ratio, β = -0.146, P  = .027, and VLF power, β = -0.137, P  = .041, respectively). During the observation period (median 1400 days), cardiac events (re-hospitalization of heart failure, cardiac death or sudden death) were found in 73 (32.8%) patients. The Kaplan-Meier analysis demonstrated that the high RDW group had a higher rate of cardiac events compared to the low RDW group (45.6% vs 23.8%, log-rank P  < .001)., Conclusion: High RDW levels were correlated with autonomic dysfunction, resulting in poor clinical outcomes., Competing Interests: None.None. The ethical committee of Fukushima Medical University approved this study (approval number: 1656, approval date: 04/22/2013)., (© 2020 The Authors. Journal of Arrhythmia published by John Wiley & Sons Australia, Ltd on behalf of the Japanese Heart Rhythm Society.)

Background: The clinical significance of premature ventricular complexes (PVCs) in heart failure (HF) remains unclear. We aimed to clarify the associations of PVC burden with re-hospitalization and cardiac death in HF patients., Methods: We studied 435 HF patients (271 men, mean age 65 years). All patients were hospitalized for worsening HF. After optimal medications, echocardiography, 24 hours Holter monitoring and cardiopulmonary exercise testing were performed before discharge. The clinical characteristics and outcomes of the HF patients were investigated., Results: During a median follow-up period of 2.3 years, there were 125 (28.7%) cardiac events (re-hospitalization due to worsening HF, fatal arrhythmias, or cardiac death). The patients with cardiac events had higher PVC burden compared to those without (median 0.374%/d [interquartile range 0.013-1.510] vs median 0.026%/d [interquartile range 0.000-0.534], P  < .001). We examined cutoff value of PVC burden for predicting cardiac events. Receiver-operating characteristic analysis showed PVC burden (>0.145%/d) to be a predictive factor of cardiac events (area under the curve: 0.64). Kaplan-Meier analysis demonstrated that cardiac events were more frequent in patients with high-PVC burden (>0.145%/d, n = 194) compared to those with low-PVC burden (≤0.145%/d, n = 241). Furthermore, the high-PVC burden patients had left ventricular (LV) and atrial dilatation, reduced LV ejection fraction, and impaired exercise capacity, compared to the low-PVC burden patients. In Cox proportional hazards analysis, high-PVC burden was significantly associated with cardiac events with a hazard ratio of 2.028 (95% confidence interval: 1.418-2.901, P  < .001)., Conclusion: These results suggest that PVC burden is an important predictor of cardiac events in HF patients., Competing Interests: Authors declare no conflict of interests for this article., (© 2019 The Authors. Journal of Arrhythmia published by John Wiley & Sons Australia, Ltd on behalf of the Japanese Heart Rhythm Society.)

Background: Melatonin is a multifunctional indolamine and has a cardioprotective role in a variety of cardiovascular processes via antioxidant, anti-inflammatory, antihypertensive, antithrombotic, and antilipemic effects. It has been reported that lower levels of circulating melatonin are significantly associated with a higher risk of acute myocardial infarction (AMI) and later cardiac remodeling. However, levels of melatonin in patients with dilated cardiomyopathy (DCM) and associations between melatonin levels and cardiac function remain unclear., Methods and Results: We measured and compared plasma levels of melatonin in 61 control subjects, 81 AMI patients, and 77 DCM patients. Plasma levels of melatonin were progressively decreased from 71.9 pg/mL in the control group to 52.6 pg/mL in the DCM group and 21.9 pg/mL in the AMI group. Next, we examined associations of melatonin levels with parameters of laboratory data, echocardiography, and right-heart catheterization. In the DCM patients, circulating melatonin showed significant correlations with both high-sensitivity troponin T (R = -0.422, P < 0.001) and cardiac output (R = 0.431, P = 0.003), but not with B-type natriuretic peptide (BNP), left ventricular ejection fraction (LVEF), pulmonary artery wedge pressure, or pulmonary artery pressure., Conclusion: Patients with not only AMI but also DCM had lower circulating melatonin levels. Circulating melatonin levels appear to correlate with myocardial injury and cardiac output in DCM patients., (© 2019 The Authors Journal of Pineal Research Published by John Wiley & Sons Ltd.)

Background. Aortic valve calcification (AVC) is a common feature of aging and is related to coronary artery disease. Although abdominal visceral adipose tissue (VAT) plays fundamental roles in coronary artery disease, the relationship between abdominal VAT and AVC is not fully understood. Methods. We investigated 259 patients who underwent cardiac and abdominal computed tomography (CT). AVC was defined as calcified lesion on the aortic valve by CT. %abdominal VAT was calculated as abdominal VAT area/total adipose tissue area. Results. AVC was detected in 75 patients, and these patients showed higher %abdominal VAT (44% versus 38%, p < 0.05) compared to those without AVC. When the cutoff value of %abdominal VAT was set at 40.9%, the area under the curve to diagnose AVC was 0.626. Multivariable logistic regression analysis showed that age (OR 1.120, 95% CI 1.078-1.168, p < 0.01), diabetes (OR 2.587, 95% CI 1.323-5.130, p < 0.01), and %abdominal VAT (OR 1.032, 95% CI 1.003-1.065, p < 0.05) were independent risk factors for AVC. The net reclassification improvement value for detecting AVC was increased when %abdominal VAT was added to the model: 0.5093 (95% CI 0.2489-0.7697, p < 0.01). Conclusion. We determined that predominance of VAT is associated with AVC.

Accumulation of visceral adipose tissue is associated with a risk of coronary artery disease (CAD). The aim of this study was to examine whether different types of adipose tissue depot may play differential roles in the progression of CAD. Consecutive 174 patients who underwent both computed tomography (CT) and echocardiography were analyzed. Cardiac and abdominal CT scans were performed to measure epicardial and abdominal visceral adipose tissue (EAT and abdominal VAT, resp.). Out of 174 patients, 109 and 113 patients, respectively, presented coronary calcification (CC) and coronary atheromatous plaque (CP). The EAT and abdominal VAT areas were larger in patients with CP compared to those without it. Interestingly, the EAT area was larger in patients with CC compared to those without CC, whereas no difference was observed in the abdominal VAT area between patients with CC and those without. Multivariable logistic regression analysis revealed that the presence of echocardiographic EAT was an independent predictor of CP and CC, but the abdominal VAT area was not. These results suggest that EAT and abdominal VAT may play differential pathological roles in CAD. Given the importance of CC and CP, we should consider the precise assessment of CAD when echocardiographic EAT is detected.

Although the number of elderly patients requiring dialysis has increased, data regarding the prognosis of elderly patients undergoing hemodialysis are limited. In the present study, prognosis in Japanese hemodialysis patients aged ≥80 years was evaluated. From January 1988 to July 2013, 1144 consecutive patients with end-stage renal disease required renal replacement therapy at our institution; of these, 141 were aged ≥80 years. These patients' charts were retrospectively reviewed for relevant clinical variables and survival time. The life expectancies table from the National Vital Statistics database was used, and prognostic factors were assessed by multivariate analysis. In total, 107 deaths (76%) were recorded during the study period. The median survival time and estimated life-shortening period in the patients were 2.6 years and -5.3 years, respectively. Eastern Cooperative Oncology Group Performance Status and hemoglobin level were revealed as prognostic factors in the multivariate analysis. Estimates of prognosis and prognostic factors may provide useful information for physicians as well as elderly patients with end-stage kidney disease.

An experiment was conducted with 16 Japanese Black cows to determine the effects of different days on feed (89, 208, 271 and 341 days), inclusion levels of grain in concentrate (60% vs. 40%; dry matter (DM) basis) and roughage sources (hay vs. rice straw) on finishing performance. Additional four cows were slaughtered at 0 days on feed to obtain non-fed carcass data. Maximum carcass weights were observed in cows fed for 271 days; an increase in carcass weight of only 14 kg was shown from 208 days to 271 days. The marbling score increased (P < 0.05) with days on feed. The percentage of fat in the subprimal rib linearly increased (P < 0.05) with days on feed. The percentage of lean meat was higher (P < 0.05) for cows fed rice straw than for cows fed hay as a roughage source. Increasing the days on feed decreased (P < 0.05) the yellowness of the fat. The effects of the inclusion levels of grain in concentrate on the finishing performance of cows were lower than the other two factors. In conclusion, feeding improves carcass values, but feeding over 208 days is an inefficient system of production in cows., (© 2011 The Authors. Animal Science Journal © 2011 Japanese Society of Animal Science.)

Inflammation plays an important role in progression and rupture of atherosclerotic plaque. Dynamic contrast-enhanced MRI has been proposed as a tool to evaluate inflammation in vivo by measuring the transfer constant and partial plasma volume, which are influenced by inflammation. This study sought to demonstrate the ability of dynamic contrast-enhanced MRI to provide localized measurements of transfer constant and partial plasma volume within plaque regions of different compositions. In order to do that, a highly automatic procedure for localized measurement of dynamic contrast-enhanced MRI parameters was developed. In 47 subjects, the average transfer constant and partial plasma volume were highest in loose matrix and fibrous tissue and substantially lower in intraplaque hemorrhage, lipid rich/necrotic core, and calcification. In addition, except for hemorrhage and calcification, statistically significant differences of transfer constant and partial plasma volume were observed for any pair of these components. This suggests that transfer constant and partial plasma volume could be helpful to differentiate different plaque components and that dynamic contrast-enhanced MRI has the potential to assess inflammatory burden in specific regions.

Background and Purpose: A new class of heterotricyclic glutamate analogues recently was generated by incorporating structural elements of two excitotoxic marine compounds, kainic acid and neodysiherbaine A. Rather than acting as convulsants, several of these 'IKM' compounds markedly depressed CNS activity in mice. Here, we characterize the pharmacological profile of the series with a focus on the most potent of these molecules, IKM-159., Experimental Approach: The pharmacological activity and specificity of IKM compounds were characterized using whole-cell patch clamp recording from neurons and heterologous receptor expression systems, in combination with radioligand binding techniques., Key Results: The majority of the IKM compounds tested reduced excitatory synaptic transmission in neuronal cultures, and IKM-159 inhibited synaptic currents from CA1 pyramidal neurons in hippocampal slices. IKM-159 inhibited glutamate-evoked whole-cell currents from recombinant GluA2- and GluA4-containing alpha-amino-3-hydroxyl-5-methyl-4-isoxazole-propionate (AMPA) receptors most potently, whereas kainate and NMDA receptor currents were not reduced by IKM-159. Antagonism of steady-state currents was agonist concentration dependent, suggesting that its mechanism of action was competitive, although it paradoxically did not displace [(3)H]-AMPA from receptor binding sites. IKM-159 reduced spontaneous action potential firing in both cultured hippocampal neurons in control conditions and during hyperactive states in an in vitro model of status epilepticus., Conclusions and Implications: IKM-159 is an AMPA receptor-selective antagonist. IKM-159 and related nitrogen heterocycles represent structurally novel AMPA receptor antagonists with accessible synthetic pathways and potentially unique pharmacology, which could be of use in exploring the role of specific populations of receptors in neurophysiological and neuropathological processes.

Vasa vasorum in the adventitia of atherosclerotic arteries may play a role in plaque progression. In this investigation, a method for characterizing vasa vasorum in the carotid artery is proposed, in which the perfusion properties of the adventitia are probed via dynamic contrast-enhanced (DCE) MRI. A parametric "vasa vasorum image" is automatically generated that depicts the plasma volume (vp) and transfer constant (K trans). The average K trans within the adventitia is proposed as a quantitative measurement related to the extent of the vasa vasorum. In 25 subjects with lesions meeting the requirements for carotid endarterectomy (CEA) significantly higher adventitial K trans of 0.155 +/- 0.045 min(-1) was observed, compared to 0.122 +/- 0.029 min(-1) in the remaining 20 subjects with moderate disease (P < 0.01). In the 25 subjects with endarterectomy specimens, histological evaluation showed that adventitial K trans was significantly correlated with the amount of neovasculature (R = 0.41; P = 0.04) and macrophages (R = 0.49; P = 0.01) in the excised plaque. In the remaining 20 subjects without histology, elevated adventitial K trans was significantly correlated with the log of C-reactive protein (CRP) levels (R = 0.57; P = 0.01) and was elevated in active smokers compared to nonsmokers (0.141 +/- 0.036 vs. 0.111 +/- 0.017 min(-1); P = 0.02). Because these factors are all associated with higher risk of atherosclerotic complications, these results suggest that adventitial K(trans) may be a marker of risk as well., ((c) 2008 Wiley-Liss, Inc.)

Background: The aim of this study was to identify the independent histopathologic prognostic factors for patients with cervical carcinoma treated with radical hysterectomy including paraaortic lymphadenectomy., Methods: A total of 187 patients with stage IB to IIB cervical carcinomas treated with radical hysterectomy and systematic retroperitoneal lymphadenectomy were retrospectively analyzed. The median follow-up period was 83 months. Cox regression analysis was used to select independent prognostic factors., Results: Using multivariate Cox regression analysis, lymph node (LN) status (negative vs. metastasis to pelvic nodes except for common iliac nodes vs. common iliac/paraaortic node metastasis), histopathologic parametrial invasion, lymph-vascular space invasion (LVSI), and histology of pure adenocarcinoma were found to be independently related to patients' poor survival. For patients who had a tumor histologically confined to the uterus and have neither parametrial invasion nor lymph node metastasis, LVSI was the most important prognostic factor, and histologic type, depth of cervical stromal invasion, and tumor size were not related to survival. The survival of patients with a tumor extending to parametrium or pelvic lymph node(s) was adversely affected by histology of pure adenocarcinoma. When the tumor extended to common iliac or paraaortic nodes, patients' survival became quite poor irrespective of LVSI or histologic type of pure adenocarcinoma. Patients' prognosis could be stratified into low risk (patients with a tumor confined to the uterus not associated with LVSI: n = 80), intermediate risk (patients with a tumor confined to the uterus associated with positive LVSI, and patients with squamous/adenosquamous carcinoma associated with pelvic lymph node metastasis or parametrial invasion: n = 86), and high risk (patients with pure adenocarcinoma associated with pelvic lymph node metastasis or parametrial invasion, and patients with common iliac/paraaortic node metastasis: n = 21) with an estimated 5-year survival rate of 100 +/- 0 (mean +/- SE)%, 85.5 +/- 3.9%, and 25.1 +/- 9.7%, respectively., Conclusions: LN status, parametrial invasion, LVSI, and histology of pure adenocarcinoma are important histopathologic prognostic factors of cervical carcinoma treated with radical hysterectomy and systematic retroperitoneal lymphadenectomy. Prognosis for patients with cervical carcinoma may be stratified by combined analysis of these histopathologic prognostic factors. Postoperative therapy needs to be individualized according to these prognostic factors and validated for its efficacy using randomized clinical trials.

Background: We wanted to investigate the clinical usefulness of determining the pretreatment levels of multiple serum tumor markers in predicting lymph node status and the prognosis for patients with cervical carcinoma., Methods: The preoperative serum levels of squamous cell carcinoma antigen (SCC), cancer antigens CA125 and CA19-9 were assayed simultaneously in 103 patients with stages IB to IIB cervical SCC undergoing radical hysterectomy. The cut-off values of SCC, CA125, and CA19-9 in this study were 1.5 ng/ml, 35 U/ml, and 37 U/ml, respectively. The relation between preoperative tumor marker levels and histopathologic prognostic factors including lymph node metastasis and patient survival was studied., Results: Preoperative serum SCC, CA125, and CA19-9 levels were significantly related to the FIGO stage. In addition, serum SCC and CA125 levels were significantly related to tumor diameter, depth of cervical stromal invasion, lymph-vascular space invasion, and lymph node metastasis. We subsequently created a double-tumor-marker (DTM) index, which incorporated the number of positive markers of SCC and CA125. The DTM index was strongly related to the number of positive pelvic lymph nodes (p = 0.0002) and to the site of positive nodes (none vs. pelvic only vs. common iliac/paraaortic) (p = 0.0005). Probability of lymph node metastasis according to the DTM index = 0, 1, and 2 was 6/48 (12.5%), 14/45 (31.1%), and 8/10 (80.0%), respectively. The rate of common iliac/paraaortic node metastasis according to the DTM index = 0, 1, and 2 was 1/48 (2.1%), 2/45 (4.4%), and 3/10 (30.0%), respectively. By logistic regression analysis, it was shown that the DTM index and tumor diameter were independently related to lymph node metastasis. Using multivariate Cox regression analysis including singly determined serum SCC and CA125 levels, clinical stage (IB/IIA vs. IIB), tumor diameter ( 4 cm), parametrial invasion, lymph node metastasis, and the DTM index, the DTM index was found to be the most important prognostic factor (p = 0.0005). However, when the sites of positive nodes were included in the multivariate analysis, only the sites of positive nodes (p = 0.0008) and parametrial invasion (p = 0.041) showed independent prognostic significance., Conclusion: Combination assay of pretreatment serum SCC and CA125 levels seems to be useful in estimating lymph node status and the prognosis for patients with cervical SCC in a preoperative setting.

An enzyme-linked immunosorbent assay (ELISA) was developed for equine surfactant proteins SP-A and SP-D in bronchoalveolar lavage fluid (BALF). Anti-equine SP-A or SP-D monoclonal antibodies (mAb) were produced by hybridoma technology, purified by the antibody purification reagent, and analysed by Western blotting analysis. The immunoreaction (two-site sandwich ELISA) with a mAb, peroxidase-labelled mAb and BALF sample was carried out simultaneously and analytical recovery and precision were assayed. Six mAb for SP-A and four mAb for SP-D were successfully cloned in limiting dilution to monoclonality. These mAb were reacted with equine SP-A or SP-D on Western blotting analysis. For SP-A, a combination of solid-phase TA08 and horseradish peroxidase (HRP)-conjugated WA28 was found to be more sensitive than other combinations, gave a good dose response and was capable of measuring 0.78 to 100 ng of protein/ml. For SP-D, a combination of solid-phase TD13 and HRP-conjugated WD19 was found to be more sensitive than other combinations, had a good dose response and was capable of measuring 0.78 to 200 ng of protein/ml. The assay was used to determine the effect of 41 hours of road transport on the concentrations of SP-A and SP-D in the BALF of 30 horses. The concentrations of SP-A and SP-D decreased by 55 per cent and 36 per cent, respectively, decreases similar to the decrease in phosphatidylglycerol concentration previously reported by the authors.

Background: The incidence and distribution pattern of retroperitoneal lymph node metastasis in patients with cervical carcinoma should be investigated based on data from systematic pelvic lymph node (PLN) and paraaortic lymph node (PAN) dissection, so that a basis can be established for determining the site of selective lymph node dissection or sampling., Methods: A total of 208 patients with Stages IB, IIA, and IIB cervical carcinoma who underwent radical hysterectomy and systematic pelvic and PAN dissection were investigated for lymph node metastasis and histopathologic risk factors for lymph node metastasis., Results: Fifty-three patients (25.5%) had lymph node metastasis. The obturator lymph nodes were most frequently involved, with a rate of 18.8% (39/208). Forty-nine of 53 node-positive patients had lymph node metastasis in the obturator, internal iliac, or common iliac lymph nodes. Of 26 solitary lymph node metastases confined to one node group, 18 were in the obturator, 3 in the internal iliac, 3 in the parametrial, and 2 in the common iliac lymph nodes. A multiple logistic regression analysis revealed that deep cervical stromal invasion and lymph-vascular space invasion were related to PLN metastasis. It was also shown that metastasis to bilateral PLNs (excluding the common iliac lymph nodes) as well as metastasis to the common iliac lymph nodes were significantly related to PAN metastasis., Conclusions: The results of this study suggest that the obturator lymph nodes can be sentinel lymph nodes of cervical carcinoma. PAN metastasis appears to occur secondarily to wide-spread PLN metastasis. These results provide a basis for determining the site of selective lymph node dissection and for estimating the existence of PAN metastasis from the pattern of metastasis in PLN in patients with cervical carcinoma.

We have used serial microangiography and radioactive 133 Xe to study microvascular morphology and quantify blood flow in Walker 256 carcinomas implanted in rat tails during growth and immune rejection. No previous angiographic/quantitative studies during immune rejection are reported. Two tumor groups were identified. Group A grew rapidly, with a two- to six-fold increase in blood flow, and caused death in 10 days. Group B grew more slowly, and increased blood flow two to four times. At 6 to 8 days postimplant the B tumors diminished in size; blood flow decreased and extensive lymphocytic infiltration developed. By 21 days all evidence of the tumor had disappeared. The rejection appears to be cell-mediated, and the high incidence (65-70%) to be related to the number of tumor cells and/or presence of accumulated antigen in the innoculum. Microangiographic changes during immune rejection were specific, and included marked tortuosity of feeding vessels and a "ghostlike" fading out of tumor vessels, quite unlike the appearance of necrosis.