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Transthyretin amyloid cardiomyopathy (ATTR‐CM) is caused by the cardiac deposition of insoluble amyloid fibrils formed by misfolded transthyretin proteins and is associated with various cardiac symptoms, such as progressive heart failure, conduction disturbance, and arrhythmia. The implementation of 99mtechnetium (99mTc)‐labelled bone radiotracer scintigraphy for diagnosing ATTR‐CM has enabled accurate diagnosis of the disease with high sensitivity and specificity and positioned this diagnostic modality as an integral part of disease diagnostic algorithms. In 2020, 99mTc‐pyrophosphate scintigraphy received exceptional approval for Japanese national health insurance reimbursement as a diagnostic method of ATTR‐CM. Nevertheless, the utility of 99mTc‐labelled bone radiotracer scintigraphy and the importance of an early diagnosis of suspected ATTR‐CM using this technique have yet to be internalized as common practice by general cardiologists, and guidance on daily clinical scenarios to consider this technique for a diagnosis of suspected ATTR‐CM is warranted. In this review, we discuss the utility of 99mTc‐labelled bone radiotracer scintigraphy for the early diagnosis of ATTR‐CM based on published literature and the outcomes of an advisory board meeting. This review also discusses clinical scenarios that could support early diagnosis of suspected ATTR‐CM as well as common pitfalls, correct implementation, and future perspectives of 99mTc‐labelled bone radiotracer scintigraphy in daily clinical practice. The clinical scenarios to consider 99mTc‐labelled bone radiotracer scintigraphy in daily practice may include, but are not limited to, patients with a family history of the hereditary type of disease; elderly patients (aged ≥60 years) with unexplained cardiac findings (e.g. cardiac hypertrophy associated with abnormalities on an electrocardiogram, heart failure with preserved ejection fraction associated with unexplained left ventricular hypertrophy, and heart failure with reduced ejection fraction associated with atrial fibrillation and left ventricular hypertrophy); and patients with cardiac hypertrophy associated with diastolic dysfunction, right ventricular/interatrial septum/valve thickness, left ventricular sparkling, or apical sparing. Cardiac hypertrophy and persistent elevation in cardiac troponin in elderly patients are also suggestive of ATTR‐CM. 99mTc‐labelled bone radiotracer scintigraphy is also recommended in patients with characteristic cardiac magnetic resonance findings (e.g. diffuse subendocardial late gadolinium enhancement patterns, native T1 increase, and increase in extracellular volume) or patients with cardiac hypertrophy and bilateral carpal tunnel syndrome.

IgG4-related disease (IgG4-RD) is a systemic autoimmune disorder known to affect multiple organs. However, IgG4-RD rarely affects the myocardium. We herein report a case of left ventricular dysfunction due to cardiac involvement of IgG4-RD.

This report describes a successful transcatheter aortic valve replacement in an older patient with severe aortic stenosis, mitral paravalvular leak, and associated hemolytic anemia. Transcatheter aortic valve replacement is worth considering as a first-line procedure in this high-risk patient because of its beneficial impact on reducing shear forces at the mitral valve. (Level of Difficulty: Intermediate.), Graphical abstract

Background Patients with urolithiasis have a lower bone mineral density (BMD) than those without stones, suggesting a potential correlation between calcium stone formation and bone resorption disorders, including osteopenia and osteoporosis. Methods To investigate the influence of BMD on clinical outcomes in urolithiasis, we performed a single-center retrospective cohort study to analyze patients with urolithiasis who underwent both BMD examination and 24-h urine collection between 2006 and 2015. Data from the national cross-sectional surveillance of the Japanese Society on Urolithiasis Research in 2015 were utilized, and additional data related to urinary tract stones were obtained from medical records. The primary outcome was the development of stone-related symptoms and recurrences during follow-up. A total of 370 patients were included in this 10-year study period. Results Half of the patients had recurrent stones, and the two-thirds were symptomatic stone formers. While only 9% of patients had hypercalciuria, 27% and 55% had hyperoxaluria and hypocitraturia, respectively. There was a positive correlation between T-scores and urinary citrate excretion. Both univariate and multivariate analyses demonstrated that female sex was associated with recurrences (odds ratio = 0.44, p = 0.007), whereas a T-score p = 0.037; odds ratio = 0.45, p = 0.01; respectively). Conclusion These results revealed that low T-scores might cause symptoms in patients with urolithiasis, suggesting the importance of BMD examination for high-risk Japanese patients with urolithiasis having hypocitraturia.

Background The therapeutic strategy for giant cell myocarditis (GCM) remains controversial, so we reviewed the clinical status of Japanese patients with GCM.Methods and Results:We retrospectively reviewed 6 consecutive patients with GCM requiring percutaneous mechanical circulatory support (p-MCS), with 3 further requiring ventricular assist devices. One patient died during p-MCS. Cardiac function improved in the other 5 with immunosuppressive therapy, but only 3 patients treated with dual immunosuppressants, including cyclosporine (CyA), achieved >1-year survival. Conclusions The prognosis of patients with fulminant GCM is poor, but a treatment that combines MCS and early administration of CyA-based immunosuppressants will be useful.

The aortic regurgitation (AR) index, proposed as an objective indicator of postprocedural AR, decreases in proportion to AR severity, besides reportedly providing additional prognostic information. Meanwhile, left ventricular (LV) function has also been considered an essential prognostic factor. This study aimed to clarify whether LV function affected the AR index using cardiac catheterization data.A retrospective study was performed in patients whose LV function was evaluated using a micromanometer-tipped catheter. Patients with grade 2 or higher AR were excluded to explore non-AR factors affecting the AR index value. The AR index was calculated as a ratio of the gradient between the aortic diastolic blood pressure (DBP) and the LV end-diastolic pressure (EDP) to the aortic systolic blood pressure (SBP): AR Index = [ (DBP - LVEDP) / SBP] × 100.A total of 64 patients [age, 62 (interquartile range: 48-70) years; LV ejection fraction, 19% (16%-26%) ] were examined. AR index values ranged from 18.3 to 68.6. Despite having no AR, two patients displayed an AR index < 25, indicating significant AR. Multiple-regression analysis revealed that LV diastolic stiffness (β = -0.750, P < 0.001), LV max dP/dt (β = -0.296, P = 0.006), and heart rate (β = 0.284, P = 0.011) were independent determinants of the AR index value.Patients with impaired LV diastolic function and preserved systolic function had low AR index values. The additional prognostic information of the AR index may be related to LV diastolic function.

INTRODUCTION AND OBJECTIVE:Brown adipocytes consume energy and are known to improve metabolic syndrome. In previous studies using mice that brown adipocytes could prevent the formation of urinary s...

INTRODUCTION AND OBJECTIVE:Kidney stones are associated with metabolic syndrome (MetS). MetS has been shown to create a hypoxic environment in adipose tissue, resulting in inflammation. It has been...

ObjectiveAtrial functional mitral regurgitation (A-FMR) has been suggested as a new aetiology of functional MR (MR); however, its prognosis and prognostic predictors are not fully elucidated. Aim of this study was to investigate the prognosis and prognostic predictors of A-FMR in comparison with ventricular functional MR (V-FMR).MethodsThree hundred and seventy-eight consecutive patients with moderate-to-severe or severe functional MR were studied. Functional MR was classified into V-FMR (N=288) and A-FMR (N=90) depending on the alterations of left ventricle (LV) or left atrium (LA) along with clinical context and diagnosis of ischaemic heart disease or cardiomyopathy.ResultsDuring a median follow-up of 4.1 (2.0–6.7) years, all-cause mortality, cardiovascular mortality and heart failure (HF) hospitalisation occurred in 98 (26%), 81 (21%) and 177 (47%) patients, respectively, and rates of these events and the composite end point of all-cause mortality and HF hospitalisation were consistently higher in V-FMR than A-FMR (unadjusted HR 1.762 (95% CI 1.250 to 2.438), pConclusionsThe prognosis of V-FMR was significantly worse than that of A-FMR, and prognostic predictors were different between V-FMR and A-FMR. Our study suggests the importance of discriminating A-FMR and V-FMR, and that different treatment strategies may be considered for each aetiology.

According to recent studies, kidney stones are associated with metabolic syndrome. We focused on brown adipocytes and β3-stimulant-induced brown-like adipocytes to investigate how these adipocytes influence kidney stone disease. For the interscapular brown adipose tissue (iBAT) removal experiment, mice were subjected to either iBAT removal or sham operation (X-BAT group or sham group), and, after 3 wk, renal crystal deposition was induced by intra-abdominal injection of glyoxylate (GOX) for 6 days. For the β3-stimulant experiment, mice were administered intra-abdominal injections of the β3-stimulant (β3-group) or saline (control group) for 6 days. Thereafter, renal crystal deposition was induced by intra-abdominal injection of GOX for 6 days. iBAT removal decreased the expression of Sod1 and increased that of chemokine (C-C motif) ligand 2 ( Ccl2), EGF module-containing mucin-like receptor 1 ( Emr1), and tumor necrosis factor ( Tnf) in the kidneys. Renal crystal deposition was 2.06-fold higher in the X-BAT group than in the sham group. The β3-stimulant caused differentiation of white adipocytes into brown-like adipocytes. In the kidneys of the β3-group, the expression of Ccl2 and Emr1 decreased and that of Sod1 increased. Renal crystal deposition was 0.17-fold lower in the β3-group than in the control group. In summary, iBAT removal promoted kidney inflammation and renal crystal formation. β3-Stimulant-induced brown-like adipocytes reduced inflammation and improved antioxidant action in the kidneys, which suppressed renal crystal formation. This is the first report on the therapeutic role of brown and brown-like adipocytes for kidney stone formation.

Objectives To elucidate the difference in the lithogenesis of calcium oxalate and calcium phosphate stones. Methods Renal papillary tissues were obtained from 23 idiopathic calcium oxalate and seven calcium phosphate stone patients who had undergone endoscopic lithotripsy. Samples were individually collected from two different regions in each patient: the papillary mucosa containing Randall's plaque and mucosa not containing Randall's plaque. A microarray analysis was carried out on those tissues to compare their gene expression patterns. Furthermore, a causal pathway analysis comparing their differences was carried out. Results Cluster analysis showed that gene expression profiles of calcium phosphate stone patients markedly differed from those of calcium oxalate stone patients. Disease and function analysis showed that Randall's plaque-containing tissues of calcium phosphate stone-forming patients had significantly higher movement and migration of mononuclear leukocytes, and lower tendency toward infection and lymph node formation than Randall's plaque-containing tissues of calcium oxalate stone formers. Additional pathway analysis showed increased immune cell signaling in calcium phosphate formers, such as the helper T cell 1 and 2 pathways, which was confirmed by their messenger ribonucleic acid expression. Conclusions The present results show the upregulation of helper T-cell signaling pathways in Randall's plaque-containing papillae in calcium phosphate, but not in calcium oxalate stone formers. Thus, helper T-cell immune responses and the related inflammatory processes seem to lead to the formation of calcium phosphate stones on Randall's plaques.

Risk assessment for urinary stones has been mainly based on urinary biochemistry. We attempted to identify the risk factors for urinary stones by statistically analyzing urinary biochemical and inflammation-related factors. Male participants (age, 20–79 years) who visited Nagoya City University Hospital were divided into three groups: a control group (n = 48) with no history of stones and two stone groups with calcium oxalate stone experience (first-time group, n = 22; recurring group, n = 40). Using 25-µL spot urine samples, we determined the concentrations of 18 candidate urinary proteins, using multiplex analysis on a MagPix® system. In univariate logistic regression models classifying the control and first-time groups, interleukin (IL)-1a and IL-4 were independent factors, with significantly high areas under the receiver operating characteristic curve (1.00 and 0.87, respectively, P

To assess the impact of interactions between kidney stone formation and conventional risk factors on incident chronic kidney disease (CKD). A total of 11,402 subjects (men 30–69 years of age, Japanese) without CKD at baseline were observed over an average period of 4 years. Cox proportional hazards regression models were used to calculate hazard ratios (HRs) with 95% confidence intervals (CIs) to determine the association between incident CKD, kidney stone formation, and conventional risk factors (diabetes mellitus, hypertension, overweight/obesity, dyslipidemia, and hyperuricemia/gout). We also examined the interactions of renal stones and the conventional risk factors for CKD. In total, 2301 men (20.2%) developed incident CKD during the follow-up period. After multivariable adjustment, kidney stones were found to increase the risk of incident CKD (HR 1.16; 95% CI 1.03–1.32). Kidney stone formers with hypertension, dyslipidemia, or hyperuricemia/gout presented a greater risk for incident CKD than those who had either kidney stones or other risk factors. However, no significant interactions between kidney stones and other risk factors were found to increase CKD risk. On the other hand, a negative interactive effect between kidney stones and overweight/obesity was observed, leading to reversed risk of incident CKD in coexistence of both factors. Kidney stones were linked to a higher risk for the development of CKD. However, no positive interactive effects were identified between renal stones and conventional risk factors on the risk of incident CKD.

BackgroundsEarlier studies showed that in patients with heart failure (HF), circulating levels of B-type natriuretic peptide (BNP) at hospital discharge (BNPdis) are more predictive of prognosis than BNP levels on admission (BNPad). However, the mechanism underlying that difference has not been fully elucidated. We examined the association between confounding factors during hospitalisation and BNPdis in patients with HF.MethodsWe identified patients admitted to our hospital for HF (BNPad ≥100 pg/mL). Estimated left ventricular end-diastolic pressure (eLVEDP) was calculated using echocardiographic data. To identify the factors associated with the relation between BNPad and BNPdis, we performed a stepwise regression analysis of retrospective data. To validate that analysis, we performed a prospective study.ResultsThrough stepwise regression of the patient data (n=688, New York Heart Association 3–4, 88%), we found age, blood urea nitrogen and eLVEDP to be significantly (pdis. Through multivariate analysis after accounting for these factors, we created a formula for predicting BNP levels at discharge (predicted-BNPdis) from BNPad and other parameters measured at admission (pad was significantly improved (ppredicted-BNPdis and BNPdis (n=104, r=0.625, pConclusionThis study showed that statistically accounting for confounding factors affecting BNP levels improves the predictive power of BNP levels measured at the time of hospital admission, suggesting that these confounding factors are associated with lowering predictive power of BNP on admission.Trial registration numberUMIN 000034409, 00035428.

A 35-year-old woman was referred to our hospital for the management of acutely decompensated heart failure due to peripartum cardiomyopathy (PPCM). Generally, cardiac examinations are performed after the manifestation of heart failure in patients with PPCM. Thus, reports of serial cardiac examinations before the onset of PPCM are scarce. In this case, we were able to document the serial echocardiographic findings before the onset of life-threatening PPCM. We found that the left ventricular systolic function was preserved at 35 weeks of gestation but declined acutely after delivery at 38 weeks. Although speculative, these findings suggest that left ventricular dilation might precede the onset of PPCM.

Connective tissue disorders sometimes involve cardiovascular systems. This report describes the case of a middle-aged man with mitral regurgitation and heart failure. He had distinctive features of mucopolysaccharidosis type (MPS) III, but no gene mutations that were known to be associated with MPS. Meanwhile, he had a COL1A2 gene mutation that is associated with osteogenesis imperfecta (OI), and had some features that were compatible with OI. The patient might have had a rare connective tissue disorder with the characteristics of MPS III and OI, which was initially detected as a result of the cardiovascular manifestations.

Background/Aims: Previous results on the association between MTR gene A2756G polymorphism and PCa risk are inconclusive. Methods: We used odds ratios (ORs) with corresponding 95% confidence intervals (95% CIs) to evaluate the correlation between MTR A2756G polymorphism and risk of PCa in meta-analysis. Serum expression of MTR was detected by ELISA and in-silico tools were utilized to assess this variant. Results: Our study included 2,921 PCa patients and 3,095 control subjects. The results indicated that the MTR A2756G polymorphism is linked with an increased risk of PCa using three genetic models (G-allele vs. A-allele: OR = 1.16, 95%CI = 1.04 - 1.30; GA vs. AA: OR = 1.17, 95%CI = 1.02 - 1.33; GG+GA vs. AA: OR = 1.18, 95%CI = 1.04 - 1.34). Stratified analysis produced similar results. A significant association was also indicated in advanced PCa from the meta-analysis. Finally, our experiments showed evidence that serum MTR levels in PCa patients with AA genotypes were statistically higher than in those with GG/GA genotypes. Conclusions: Our present study suggests that the MTR A2756G polymorphism may contribute to the risk of developing PCa, particularly in Asian and hospital-based studies. Moreover, serum MTR might be utilized in diagnosis of PCa.

Background/Aims: MicroRNAs (miRNAs) are a class of small non-coding RNA molecules which play a significant role in transcriptional and translational regulation. Published data on the association between the miRNA SNPs and prostate cancer (PCa) risk are somewhat inconclusive. Methods: We performed a meta-analysis of all available studies including 2,227 patients and 2,331 control subjects to evaluate the impact of three common genetic variants of microRNAs in prostate cancer risk. Odds ratios (ORs) with 95% confidence intervals (CIs) were utilized to investigate the strength of the association. Results: For miR-499 polymorphism, a significant association was observed between the rs3746444 A>G polymorphism and PCa risk in heterozygote comparison and dominant genetic model, in particular in Asian population subgroup. For miR-146a polymorphism, the rs2910164 CC genotype was associated with decreased PCa risk in Asian population in homozygote comparison. In addition, rs2910164 CC genotype had a weekly higher percentage value in subgroup of Gleason score < 7. Similar results were also indicated in localized prostate cancer in subgroup analysis by tumor stage. For miR-196a2 polymorphism, no association was observed between this variant and PCa risk in the overall group. However, in stratified analysis by ethnicity, we found that rs11614913 T allele was a risk factor for Asian PCa patients. Conclusions: Polymorphisms of miR-196a2 rs11614913, miR-146a rs2910164, and miR-499 rs3746444 may contribute to the risk for developing prostate cancer in Asian descendants. Moreover, miR-146a rs2910164 polymorphism was related to PCa prognosis.

A 75-year old man with a history of inferior myocardial infarction was admitted with symptoms of progressive heart failure 3 months after undergoing transapical transcatheter aortic valve implantation (TAVI). Echocardiography revealed severe mitral regurgitation (MR) caused by posterior leaflet tethering, without traumatic injury of the mitral valve or chordae. The patient was successfully treated by percutaneous edge-to-edge mitral valve repair (MitraClip®). This case highlights the role of MitraClip® in high-risk patients suffering from MR, and suggests that apical contractile loss or adhesion caused by apical puncture and suturing in transapical TAVI may be one of the mechanisms of worsening MR.

// Li Zuo 1, * , Ke-Wei Ren 5, * , Yu Bai 1, * , Li-Feng Zhang 1, * , Jian-Gang Zou 1, * , Xi-Hu Qin 2 , Yuan-Yuan Mi 3 , Atsushi Okada 4 and Takahiro Yasui 4 1 Department of Urology, Changzhou No. 2 People’s Hospital Affiliated to Nanjing Medical University, Changzhou 213003, China 2 Department of General Surgery, Changzhou No. 2 People’s Hospital Affiliated to Nanjing Medical University, Changzhou 213003, China 3 Department of Urology, Third Affiliated Hospital of Nantong University, Wuxi 214041, China 4 Department of Nephrourology, Nagoya City University Graduate School of Medical Sciences, Aichi 4678601, Japan 5 Department of Orthopedics, The Affiliated Jiangyin Hospital of Southeast University Medical School, Jiangyin 214400, China * These authors have contributed equally to this work Correspondence to: Xi-Hu Qin, email: nj-likky@163.com Keywords: RNASEL, polymorphism, prostate cancer, meta-analysis Received: April 26, 2017 Accepted: August 07, 2017 Published: September 05, 2017 ABSTRACT The RNASEL gene (2’, 5’-oligoisoadenylate synthetase-dependent) encodes a ribonuclease that plays a significant role in the apoptotic and antiviral activities of interferons. Various studies have used polymorphisms in the RNASEL gene to evaluate prostate cancer risk but studies that show an association between RNASEL Arg462Gln (1385G>A, R462Q, rs486907) polymorphism and prostate cancer risk are somewhat inconclusive. To assess the impact of RNASEL Arg462Gln polymorphism on prostate cancer risk, we conducted a meta-analysis of all available studies including 11,522 patients and 10,976 control subjects. The overall results indicated no positive association between the variant and prostate cancer risk. However, in a subgroup analysis by ethnicity, obvious associations were observed in Hispanic Caucasians for allelic contrast (OR = 1.18, 95% CI = 1.00 - 1.39, P heterogeneity = 0.010), homozygote comparison (OR = 1.50, 95% CI = 1.02 – 2.20, P heterogeneity = 0.001), and the recessive genetic model (OR = 1.44, 95% CI = 1.01 - 2.05, P heterogeneity = 0.002) ; and in African descendants for homozygote comparison (OR = 2.59, 95% CI = 1.29 – 5.19, P heterogeneity = 0.194) and the recessive genetic model (OR = 2.61, 95% CI = 1.30 – 5.23, P heterogeneity = 0.195). In conclusion, the RNASEL Arg462Gln polymorphism may contribute to the risk of developing prostate cancer in African descendants and Hispanic Caucasians. Further larger and well-designed studies are warranted to evaluate this association in detail.

Although left ventricular (LV) systolic dysfunction in patients suffering from Takayasu arteritis (TA) has been reported, little is known regarding the development of heart failure in these patients. We report a novel finding of active TA and familial hypercholesterolaemia presenting with severe LV dysfunction through multimodality assessments of LV systolic dysfunction.

Both surgical myectomy and percutaneous transluminal septal myocardial ablation are effective treatments for drug-refractory symptomatic hypertrophic obstructive cardiomyopathy (HOCM). However, in some cases, it is not easy to elucidate the abnormal structure of left ventricular outflow obstruction to adopt these treatments. Here, we presented a young female patient with drug-refractory symptomatic HOCM. In this case, contrast-enhanced computed tomography enabled us to assess the suitability of percutaneous transluminal septal myocardial ablation. By creating three-dimensional printed models using computed tomography data, we could also visualize intracardiac structure and simulate the surgical procedure. A multimodality assessment strategy is useful for evaluating patients complicated with drug-refractory symptomatic HOCM.

Abnormal liver function test results are often observed in acute decompensated heart failure (ADHF). However, the prognostic value of bilirubin fractionation has not been elucidated. The prognostic value of direct bilirubin (DB), in comparison with total bilirubin (TB), was examined in 556 consecutive patients with ADHF. Patients with elevated DB showed mostly similar patient characteristics including signs of elevated right-sided pressure (frequent hepatomegaly, jugular venous distention, dilated inferior vena cava, and elevated gamma-glutamyltransferase) and decreased cardiac output (cold extremities, decreased pulse pressure, and lower blood pressure) and other parameters of heart failure (HF) severity (increased plasma renin activity, decreased sodium, total cholesterol, and ejection fraction) to elevated TB; however, only patients with elevated DB showed a significant difference in the frequency of HF history and alkaline phosphatase value. Kaplan-Meier analysis showed that patients with elevated DB had a significantly higher rate of the composite end point of all-cause mortality or HF readmission (p = 0.021) compared with those with normal DB, whereas patients with elevated TB did not show a statistically significant difference compared with those with normal TB (NS). A multivariate Cox hazards model showed that DB was an independent predictor of adverse events (adjusted hazard ratio 1.052, 95% confidence interval 1.001 to 1.099, p = 0.034), whereas TB was not (adjusted hazard ratio 1.017, 95% confidence interval 0.985 to 1.046, p = 0.27). Adding DB to existing prognostic variables resulted in higher C-statistics than adding TB (C-statistics: 0.670 to 0.675, 0.670 to 0.674, respectively). In conclusion, elevated DB in ADHF was an independent prognostic predictor that was superior to TB. DB may be useful for further risk stratification in ADHF.

To compare the longitudinal health-related quality of life (HRQoL) after surgical intervention with ureteroscopic lithotripsy (URSL) and shock wave lithotripsy (SWL) and to evaluate the factors affecting HRQoL in urolithiasis patients. A total of 262 patients who underwent lithotripsy (SWL, n = 61; URSL, n = 201) for upper urinary tract calculi treatment between June 2012 and January 2015 were evaluated. All patients were administered the Short-Form 36-item survey (SF-36) to assess HRQoL at four timepoints: before surgery, on the day of discharge, and 1 and 6 months after lithotripsy. Stone-free rates, complications, and analgesic requirements were evaluated to compare the effects of the two procedures on HRQoL. At the day of discharge, patients in the URSL group had significantly lower mean scores on five different subscales of the SF-36 questionnaire, namely, physical functioning, role-physical, social functioning, role-emotional, and mental health. The stone-free rate at 3 months after lithotripsy was significantly lower in the SWL group (72.1% vs. URSL, 93.0%; p

The prognostic value of nutritional status is poorly understood and evidence-based nutritional assessment indices are required in acute heart failure (AHF). We investigated the prognostic value of malnutrition assessed by the Controlling Nutritional Status (CONUT) score (range 0-12, higher=worse, consisting of serum albumin, cholesterol and lymphocytes) in AHF patients.The CONUT score was measured on admission in 635 consecutive AHF patients. The primary outcome was all-cause death.Median CONUT score was 3 (interquartile range 2 to 5). During the median follow-up of 324days, CONUT score was independently associated with death (HR 1.26, 95% CI 1.11-1.42, P0.001) after adjustment for confounders in a multivariate Cox model. The CONUT score demonstrated the best C-statistic for predicting death (0.71) among other common nutritional markers in HF. Furthermore, addition of the CONUT score to an established risk prediction model from the Organized Program to Initiate Lifesaving Treatment in Hospitalized Patients with Heart Failure study significantly increased the C-statistic from 0.75 to 0.77 (P=0.02). The net reclassification improvement afforded by CONUT score was 21% for all-cause death, 27% for survival and 49% overall (P0.001).Malnutrition assessed by the CONUT score on admission was an independent determinant of long-term death in AHF, and its prognostic value outweighed that of other nutritional indices. Moreover, addition of the score to the existing risk prediction model significantly increased the predictive ability for death, indicating beneficial clinical application of the CONUT score in AHF patients.

INTRODUCTION AND OBJECTIVE:Development of kidney stones has been linked to metabolic syndrome, which is characterized by insulin resistance (IR). In this prospective study, we followed the baseline...

The left ventricle is a less frequent location of cardiac myxomas overall. Meanwhile, cardiac myxomas related to Carney complex (CNC), which is a multiple neoplasia syndrome involving cardiac, endocrine, neural, and cutaneous tumours, more frequently occur in the left ventricle compared with sporadic cardiac myxomas. Herein, we report a case of a 20-year-old woman with CNC who underwent complete surgical excision of a large and mobile left ventricular myxoma. In our case, echocardiography performed 4 years earlier was normal. This case highlights the importance of annual follow-up by echocardiography in patients with CNC, because early diagnosis of cardiac myxomas might improve their prognosis. Besides, we should bear in mind the possibility of CNC if the patients have cardiac myxoma in a cardiac chamber other than the left atrium at a younger age.

Background Early detection for worsening renal function ( WRF ) is indispensable in patients with acute decompensated heart failure (HF). We tested the hypothesis that the difference in the circulating levels of each B‐type or brain natriuretic peptide ( BNP ) molecular form is associated with the occurrence of WRF . Methods and Results Circulating levels of pro BNP , the NT‐proBNP (N‐terminal pro BNP ), and total BNP (pro BNP +mature BNP ) were prospectively measured in patients with acute decompensated HF using specific and sensitive enzyme immunochemiluminescent assays. An estimated mature BNP (em BNP ) concentration was calculated by subtracting pro BNP levels from total BNP levels. WRF was defined as a >20% decrease in the estimated glomerular filtration rate during the hospitalization. One‐way repeated‐measures ANOVA was used to compare the changes of variables between the patients with and without WRF . In patients with acute decompensated HF (New York Heart Association class III – IV ; 96%) hospitalized for HF , NT ‐pro BNP levels did not differ during the hospitalization between patients with and without WRF (n=42 and 140, respectively). By contrast, em BNP levels were lower in patients with WRF than in those without WRF on day 3 after admission. NT ‐pro BNP /em BNP molar ratios were elevated on day 3 after admission in the patients with WRF , before estimated glomerular filtration rate declined, but were unchanged in patients without WRF . On day 3 after hospital admission, NT ‐pro BNP /em BNP ratios were strongly associated with percentage decreases in estimated glomerular filtration rate. Conclusions These findings suggest that elevation of NT ‐pro BNP /em BNP ratio precedes WRF in patients with acute HF and can be a potentially useful biomarker for risk stratification of cardiorenal syndrome.

AimsThere are significant differences in how atrial (A-type) and B-type natriuretic peptide (ANP and BNP) are secreted and metabolised, but there is little information available about the relative clinical significance of the two peptides. The aim of the present study was to investigate: (1) the association between the circulating level of each ANP molecular form and patient clinical background and (2) their prognostic power for patients with acute decompensated heart failure (ADHF).MethodsWe used specific chemiluminescence enzyme immunoassays to prospectively evaluate the levels of six bioactive molecular forms of ANP (pro-ANP, β-ANP and total ANP) and BNP (pro-BNP, N-terminal pro-BNP (NT-pro-BNP) and total BNP) in plasma samples collected from 173 patients with ADHF on their hospital admission.ResultsWe found that pro-ANP levels were strongly associated with left ventricular (LV) size and ejection fraction (pConclusionCirculating levels of pro-ANP are strongly associated with LV function and clinical outcomes of patients with ADHF. These findings suggest that during the acute phases of HF, pro-ANP has a prognostic power comparable with NT-pro-BNP independently of renal function.

INTRODUCTION AND OBJECTIVES:Kidney stone development has been linked to metabolic syndrome (MetS), which is characterized by insulin resistance. In a previous cross-sectional analysis, we reported ...

The diffusing capacity of the lung for carbon monoxide (DLCO) is indicative of the alveolar-capillary membrane function. A reduced DLCO is associated with poor prognosis in chronic heart failure (HF). However, the significance of DLCO as an independent prognostic predictor has not been established. Here, we aimed to determine the prognostic value of DLCO in patients with chronic HF.We enrolled 214 patients (139 females, mean age: 63 ± 16 years, left ventricular ejection fraction [LVEF]: 45 ± 21%) with stable chronic HF who underwent pulmonary function tests. Only never smokers were included in the analysis because smoking can decrease DLCO.During a median follow-up period of 2.1 years, 52 patients (24.3%) experienced cardiac events, including unplanned HF admissions, left ventricular assist device (LVAD) implantations, all-cause deaths, and cardiopulmonary arrests (CPAs). The median percent predicted DLCO (%DLCO) was 87.3%. In a Cox regression analysis, a %DLCO of ≤87.3% was independently associated with the cardiac events, even after adjusting for age, sex, systolic blood pressure (SBP), LVEF, anemia, brain natriuretic peptide, estimated glomerular filtration rate (eGFR), and prior HF admission (hazard ratio [HR]: 1.87, 95% confidence interval: 1.03-3.53, P = 0.030).A reduced DLCO is an independent predictor of poor prognosis in nonsmoking patients with chronic HF.

Background Delirium is a serious syndrome in critically ill patients. However, the prognostic impact of delirium and its determinants in acute heart failure (AHF) patients have not been fully elucidated. Methods We examined 611 AHF patients who were admitted to our institution. Delirium was diagnosed based on the Intensive Care Delirium Screening Checklist (ICDSC). Results Delirium developed in 139 patients (23%) during hospitalization. Patients with delirium had higher incidence of non-cardiovascular death (p=0.046) and worsening heart failure (p Conclusion In patients with AHF, the development of delirium was associated with poor clinical outcomes, suggesting the importance of early screening and careful monitoring of delirium in such patients.

Objectives To evaluate the effect of potassium-sodium citrate on the development of computed tomography-detected renal microcalculi into symptomatic stones in calcium stone-forming patients. Methods Patients (aged 20–80 years) with history of calcium component stones who visited Nagoya City Hospital, Nagoya, Aichi, Japan, between April 2009 and June 2014 were included. They were retrospectively divided into those who did not receive potassium-sodium citrate (non-citrate group, n = 157) and those who did (citrate group, n = 60). For patients in both groups, we evaluated blood and urine biochemistry and sediment, number of computed tomography-detected microcalculi, number of asymptomatic microcalculi disappearances, and pain events. Observations were made at study initiation and 12 months later. Results The citrate group showed a significantly increased urine pH (P < 0.001) and daily citrate excretion (P < 0.001) over the study period. The non-citrate group showed increased numbers of microcalculi at study completion (P = 0.002); over the same period, the number of microcalculi in the citrate group decreased significantly (P = 0.03). Additionally, multivariable analysis showed more asymptomatic microcalculi disappearances (odds ratio 2.84, 95% confidence interval 1.49–5.39) and fewer pain events (odds ratio 0.37, 95% confidence interval 0.16–0.72) in the citrate group than in the non-citrate group. A sex-adjusted analysis showed more asymptomatic microcalculi disappearances (odds ratio 3.96, 95% confidence interval 1.57–10.02) and fewer pain events (odds ratio 0.22, 95% confidence interval 0.07–0.70) in women than in men after citrate treatment. Conclusions Potassium-sodium citrate prevents the development of renal microcalculi into symptomatic stones in calcium stone-forming individuals.

Background: Epidemiological studies have assessed the association between kallikrein 3 (KLK3) polymorphisms and prostate cancer (PCa) susceptibility. However, published data on this association are somewhat inconclusive. Methods: Articles investigating the association between three KLK3 (rs1058205, rs2735839, and rs266882) variants and PCa susceptibility were searched from online databases, which included 35,838 patients and 36,369 control participants. Odds ratios (ORs) with 95% confidence intervals (CIs) were used to demonstrate the strength of the association. We also utilized ELISA to detect serum expression of KLK3. In addition, in silico tools were adopted to evaluate the relationship of KLK3 expression and PCa survival time. Results: The overall results indicated that polymorphism T>C of rs1058205 was associated with decreased risk of PCa (allele contrast: OR = 0.75, 95% CI = 0.64–0.88, Pheterogeneity < 0.001; homozygote comparison: OR = 0.58, 95% CI = 0.42–0.81, Pheterogeneity < 0.001), particularly in Caucasian population (allele contrast: OR = 0.77, 95% CI = 0.65–0.91, Pheterogeneity < 0.001; homozygote comparison: OR = 0.58, 95% CI = 0.41–0.82, Pheterogeneity < 0.001). No association was observed between the polymorphism A>G of rs2735839 and risk of PCa. In addition, no association was observed between polymorphism A>G of rs266882 and risk of PCa. Serum KLK3 levels in PCa patients carrying CC/CT genotypes were statistically lower than those carrying TT genotypes. Conclusion: This meta-analysis suggests that rs1058205 polymorphism of KLK3 is a risk factor for PCa development, polymorphism T>C of rs1058205 is associated with decreased susceptibility to PCa particularly in Caucasian population.

Exercise-induced pulmonary hypertension (EIPH) is associated with worse outcomes in patients with heart failure or valvular heart disease. However, little is known regarding the implications of EIPH in hypertrophic cardiomyopathy (HCM) patients. We retrospectively reviewed data of consecutive HCM patients who underwent clinically indicated exercise echocardiography using a semi-supine bicycle ergometer at our hospital. EIPH was defined as pulmonary artery systolic pressure ≥ 60 mmHg during exercise. The incidences of HCM-related mortality and HCM-related morbidity during follow-up period were evaluated. Of 42 patients (mean age 59 ± 21 years; 4 with resting obstruction, 19 with provoked obstruction, and 19 without obstruction), 16 (38%) developed EIPH. Patients with EIPH had significantly longer resting E wave deceleration time (271 ± 116 vs. 213 ± 66 ms; P = 0.04), higher resting pulmonary artery systolic pressure (35 ± 6 vs. 31 ± 5 mmHg; P = 0.04), and higher B-type natriuretic peptide level (283 [222, 465] vs. 142 [54, 423] pg/ml; P = 0.04) than those without EIPH. Kaplan–Meier curve analysis demonstrated that EIPH was significantly associated with HCM-related morbidity (log-rank; P = 0.01). In Cox regression analysis, EIPH was a significant predictor of HCM-related morbidity (hazard ratio: 5.98, 95% confidence interval 1.36–41.07; P = 0.02). In conclusion, EIPH was documented in about one-third of HCM patients. EIPH was a significant predictor of HCM-related morbidity in patients with HCM.

Pemetrexed is an antifolate agent that is regarded as an alternative second-line chemotherapy against advanced or metastatic urothelial carcinoma (UC). However, there is limited information on pemetrexed in a third-line setting. We report a case of metastatic UC treated with pemetrexed as third-line chemotherapy following gemcitabine and cisplatin (GC) and gemcitabine and docetaxel (GD) therapies. A 73-year-old man with a history of transurethral resection of bladder carcinoma presented with pollakiuria. CT revealed a mass in the left renal pelvis that had invaded into the parenchyma of the left kidney, as well as para-aortic and mediastinum lymph node enlargement. Urinary cytology of the lesion in the left renal pelvis revealed UC. Thus, the patient was diagnosed with left renal pelvic carcinoma (cT3N2M0). After having received 4 courses of GC therapy, another mediastinum lymph node was enlarged. He subsequently received 3 courses of GD therapy as second-line chemotherapy, which showed little efficacy against the metastatic lesions. The patient was administered 3 courses of pemetrexed as third-line chemotherapy; however, its effect on tumor reduction was not sufficient. Finally, metastasis to the liver was observed, and he died 21 months after initiation of chemotherapy. For pathological confirmation, needle biopsy of a metastatic lymph node performed after death revealed high-grade UC and a high positivity of programmed death ligand 1 (PD-L1) in the tumor, which suggested that he could have benefited from anti-PD-L1 antibody immunotherapy. This report describes the outcome of pemetrexed treatment and proposes another possible candidate as third-line chemotherapy against metastatic UC.

We previously established an experimental model of calcium oxalate crystal deposition in the mouse kidney using C57BL/6 mice. C57BL/6J (B6J) and C57BL/6N (B6N) are two core substrains of C57BL/6 mice. B6J and B6N substrains have approximately the same genomic sequence. However, in whole-genome analyses, substrains have slight genetic differences in some genes. In this study, we used these substrains as kidney crystal formation models and compared their genetic backgrounds to elucidate the pathogenic mechanisms of kidney stone formation. Eight-week-old male B6J and B6N mice (n = 15 in each group) were administered 80 mg/kg glyoxylate for 12 days, and the amount of kidney crystal depositions was compared. The expression levels of six genes (Snap29, Fgf14, Aplp2, Lims1, Naaladl2, and Nnt) were investigated by quantitative polymerase chain reaction, and the protein levels were evaluated by western blotting and immunohistochemistry. The amount of kidney crystal depositions was significantly higher in B6J mice than in B6N mice on days 6 and 12. The expression of nicotinamide nucleotide transhydrogenase (Nnt) gene was significantly lower in B6J mice than in B6N mice. The expression of Nnt protein was observed only in B6N mice, and preferential high expression was seen in renal tubular epithelial cells. The results of this study provide compelling evidence that differences in mouse substrains affect kidney crystal deposition and that the absence of Nnt protein could be involved in crystal formation in B6J mice.

Background High-sensitive cardiac troponin T (hsTnT) is a sensitive biomarker of myocardial damage and predictor of acute decompensated heart failure (ADHF). However, there is little information on changes over time in hsTnT level during ADHF management. The aim of this prospective study was to evaluate changes in hsTnT levels between admission and at discharge in patients with ADHF, and identify factors that determine such levels and their prognostic significance. Methods and results We evaluated 404 ADHF patients with abnormal hsTnT levels (≥0.0135 ng/ml) on admission. The median (interquartile ranges) hsTnT levels on admission, at discharge, and percent changes in hsTnT levels were 0.038 (0.026 to 0.065), 0.032 (0.021 to 0.049) ng/ml, and -12.0 (-39.8 to 7.4) % respectively. The numbers of patients with falling (hsTnT decrease > -15%), stable (hsTnT change between -15 and +15%) and rising (hsTnT increase > +15%) hsTnT level at discharge were 190, 146, and 68, respectively. The percent change in B-type natriuretic peptide (BNP) levels was greater in the falling group, compared to the stable (p

We established an experimental co-culture system for renal tubular cells and adipocytes to investigate kidney stone formation mechanisms under metabolic syndrome (MetS) conditions and examined the interaction between these cells morphologically and genetically. M-1s and 3T3-L1s were cultured individually (control, CON), with 24-h culture media from each cell type added to the other cell type (replacement, RP) in 2-layer co-culture dishes for 24 h (transwell, TW). M-1s were then exposed to calcium oxalate monohydrate (COM) crystals, and attached (14)C-labeled COM crystals were quantified. Expression of kidney stone- and adipocyte-related genes was analyzed. The radioactivity of adherent COM crystals significantly increased in TW and was relatively higher in RP compared to CON. M-1s demonstrated significant upregulation of adiponectin (Adipoq) in RP and secreted phosphoprotein 1 (Spp1) in TW compared to CON before COM crystal exposure, and significant downregulation of Spp1 in TW and upregulation of tumor necrosis factor (Tnf), interleukin 6 (Il-6), and chemokine (C-C motif) ligand 2 (Ccl2) compared to CON after COM crystal exposure. 3T3-L1s showed significant upregulation of Spp1, Adipoq, Tnf-α, and Ccl2 compared to CON. Enzyme-linked immunosorbent assays of co-culture medium revealed significantly increased TNF-α in TW. Our results highlight the potential for paracrine interactions between renal tubular cells and adipocytes and suggest that MetS conditions may lead to kidney stone formation.

To evaluate the efficacy of company-initiated training of urologists on shock wave lithotripsy (SWL) treatment results, we retrospectively assessed 602 patients who underwent SWL in Nagoya City University Hospital between January 2004 and June 2011 using Lithotripter S (Dornier MedTech, Japan). Training—provided by a training specialist of the company in June 2010—focused on the targeting of renal and proximal ureter stones with a combination of radiography and ultrasonography (US). The stretcher wedges were positioned in the semi-prone position or the semi-supine position for middle and distal ureter stones, respectively. Success rates between 519 pre-training treatments and 83 post-training treatments were compared. Patient age and stone location, burden, number, and composition did not significantly differ between pre- and post-training. Training improved the overall success rate from 66.3 to 87.2 % (P < 0.0001). The mean number of SWL treatments decreased from 1.8 ± 1.8 to 1.4 ± 1.3 (P = 0.01). The first SWL treatment success rate increased from 67.1 to 83.7 % (P = 0.002), and the need for multiple treatments decreased. The frequency of detection of renal and proximal ureter stones by both radiography and US increased from 10.5 % before training to 58.2 % after training (P < 0.0001). Significant factors for successful SWL were determined to be training and prone position for distal ureter stones by multivariate analysis and ultrasonic detection for renal and proximal ureter stones by univariate analysis. Skills in targeting stones using ultrasonography and selecting the proper therapeutic position are essential for improving the success rate of stone removal.

The objective of this study was to evaluate the efficacy of a gemcitabine and docetaxel (GD) combination as a second-line treatment for patients with metastatic urothelial carcinoma (UC) after failure of first-line treatment with platinum-based chemotherapy.From June 2006 to January 2012, 38 patients with metastatic UC previously treated with platinum-based chemotherapy received GD therapy. This consisted of gemcitabine 800 mg/m(2) and docetaxel 40 mg/m(2) on days 1 and 8 of each 21-day cycle as second-line chemotherapy. All the patients were evaluated for toxicity and assessed every cycle by imaging. We analyzed the efficacy of GD as second-line chemotherapy in the follow-up study.The median number of GD treatment cycles was 4 (range 2-9); the objective response rate was 47.4 %; and the median progression-free survival and median overall survival were 4.1 and 10.8 months, respectively. Univariate and multivariate analyses on the GD treated group showed that the existence of lung metastases was the only prognostic factor for tumor response. Grade 3 treatment-related toxicity included neutropenia (31.6 %) and thrombocytopenia (15.8 %), and only one patient with grade 4 toxicity had thrombocytopenia (2.6 %).The GD regimen as second-line chemotherapy was especially effective for lung metastatic UC and yielded favorable results in patients whose first-line platinum-based chemotherapy had failed. Given the safety and benefit profile seen in this study, a large prospective study is warranted to consider the potential utility of GD chemotherapy as a second-line for UC.

We investigated the association between kidney stones and coronary heart disease risk factors in Japanese men.This cross-sectional study included 13,418 Japanese men 30 to 69 years old who voluntarily underwent medical examination between April 1995 and March 2001. Participants were divided into controls, and past and current kidney stone formers based on ultrasound results and medical history. We evaluated conventional risk factors of coronary heart disease, including overweight/obesity, hypertension, diabetes mellitus, gout/hyperuricemia, dyslipidemia and chronic kidney disease. Associations between coronary heart disease risk factors and kidney stones were investigated.Of the 13,418 participants 404 current kidney stone formers (3.0%) had kidney stones on ultrasound and 1,231 past kidney stone formers (9.2%) had a history of kidney stones but no kidney stones on medical examination. Body mass index, systolic and diastolic blood pressure, and serum uric acid were significantly higher in past and current kidney stone formers than in controls. Logistic regression analysis indicated that the multivariate adjusted OR for overweight/obesity, hypertension, gout/hyperuricemia and chronic kidney disease significantly increased in the order corresponding to controls, and past and current kidney stone formers.Kidney stone formers, even past stone formers, are likely to have accumulated risk factors for coronary heart disease. They could be preferentially targeted for coronary heart disease prevention.