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We herein report an 80-year-old man showing a downsloping TP segment together with an increase in the height of the T wave in the precordial leads on a standard 12-lead electrocardiogram (ECG). Separately, an 87-year-old woman showed only a downsloping TP segment in the precordial leads on a standard 12-lead ECG. Neither patient reported chest pain or dyspnea when ECGs was obtained. This downsloping TP segment in the precordial leads on the standard 12-lead ECG is thought to be due to a cardiac impulse-tapping artifact. Differential diagnoses are also discussed.

In patients with wild-type transthyretin cardiac amyloidosis (ATTRwt-CA), the uptake of the tracer on technetium-99m-labeled pyrophosphate ( 99m Tc-PYP) scintigraphy, which indicates amyloid transthyretin (ATTR) per se, is often observed in skeletal muscles, such as the abdominal oblique and gluteal muscles. Among extracardiac biopsies for confirming ATTR deposition in ATTRwt-CA, a 99m Tc-PYP imaging-based computed tomography (CT)-guided core needle biopsy of the internal oblique muscle has relatively high sensitivity. In some patients, the 99m Tc-PYP uptake is more pronounced in the gluteal muscles than in oblique muscles. We herein report two cases of ATTRwt-CA in which a CT-guided biopsy of the gluteus medius muscle with 99m Tc-PYP uptake confirmed the presence of ATTR deposits.

Background: Technetium-99m-pyrophosphate ( 99m Tc-PYP) uptake in the internal oblique muscle (IOM), which is often observed in patients with wild-type transthyretin cardiac amyloidosis (ATTR-CA), indicates amyloid transthyretin (ATTR) deposition., Objective: This study aimed to assess the safety and efficacy of 99m Tc-PYP imaging-based computed tomography (CT)-guided core-needle biopsy of the IOM as a new extracardiac screening biopsy for confirming the presence of ATTR deposits., Methods: Patients with suspected ATTR-CA in whom myocardial tracer uptake was detected on chest- and abdomen-centered images of 99m Tc-PYP scintigraphy underwent CT-guided core-needle biopsy at the site with the highest tracer uptake in the IOM between September 2021 and November 2022., Results: All 18 consecutive patients (mean age, 86.3 years ± 6.5; 61.1% male) enrolled in the study showed 99m Tc-PYP uptake into the IOM. Adequate tissue samples were obtained from all patients except one without serious complications. Immunohistochemical analysis confirmed ATTR deposits in 16/18 (88.9%) patients. In the remaining two patients, ATTR deposits were observed via endomyocardial biopsy. All patients were diagnosed with wild-type ATTR-CA based on transthyretin gene sequence testing results., Conclusion: In wild-type ATTR-CA, 99m Tc-PYP imaging-based CT-guided core-needle biopsy of the IOM could be used as an extracardiac screening biopsy to confirm the presence of ATTR deposits.

Background: Dose reduction (DR) of adalimumab, etanercept and ustekinumab has proven to be (cost-)effective in psoriasis patients with low disease activity. Further implementation is needed to establish application of DR for eligible patients., Objectives: To evaluate the implementation of protocolized biologic DR in daily practice., Methods: A pilot implementation study was performed in 3 hospitals during 6 months. By combining education and protocol development, involved healthcare providers (HCPs) were directed toward the adoption of protocolized DR. DR of adalimumab, etanercept, and ustekinumab was achieved by stepwise injection interval prolongation. Implementation outcomes (fidelity, feasibility) were assessed. Factors for optimizing implementation were explored in interviews with HCPs. Uptake was measured in patients by chart review., Results: The implementation strategy was executed as planned. Implementation fidelity was less than 100% as not all provided tools were used across study sites. HCPs indicated the feasibility of implementing protocolized DR, although time investment was needed. Identified additional factors for successful implementation included support for patients, uptake of DR into guidelines, and supportive electronic health record systems. During the 6 months intervention period, 52 patients were eligible for DR of whom 26 (50%) started DR. The proposed DR protocol was followed in 22/26 patients (85%) on DR., Conclusion: Additional staff for support, extra time during consultations, education on DR for HCPs and patients, and effective tools such as a feasible protocol can lead to more patients on biologic DR.

Technetium-99m-labeled pyrophosphate imaging-based computed tomography-guided core-needle biopsy of the internal oblique muscle with tracer uptake is a safe and sensitive extracardiac screening biopsy. It can provide histopathological confirmation of the deposition of amyloid transthyretin in patients with wild-type transthyretin cardiac amyloidosis. This case report presents the case of a 73-year-old man receiving triple anti-thrombotic therapy for atrial flutter and coronary stenting who underwent this biopsy to confirm the diagnosis of transthyretin cardiac amyloidosis. The biopsy needle reached the internal oblique muscle via the external oblique muscle between the skin and the target. A type 1 intramuscular hematoma involving these muscles developed subsequently; however, manual compression hemostasis prevented further increase in size. Since this biopsy often targets elderly patients receiving anti-thrombotic therapy who are at high risk of bleeding owing to multimorbidity and polypharmacy, efforts should be made to reduce the frequency of complications, particularly bleeding, which can lead to the development of intramuscular hematoma., (© 2023 The Authors. Published by Elsevier Inc. on behalf of University of Washington.)

A synthesized 18-lead electrocardiograph is a specialized technology that mathematically computes the virtual electrocardiographic waveforms of the right chest leads (V3R, V4R, and V5R) and posterior leads (V7, V8, and V9) based on a standard 12-lead electrocardiograph input without additional lead placement or techniques. Synthesized 18-lead electrocardiography is a useful test for the identification of the culprit coronary arteries in patients with ST-segment elevation myocardial infarction of the right ventricular wall or the posterior/lateral left ventricular wall, which are often missed on standard 12-lead electrocardiography. However, few studies have examined the usefulness of this modality during exercise stress testing. We present a case of a 78-year-old man with a two-month history of typical angina. The synthesized 18-lead electrocardiogram obtained just after the Master two-step exercise test revealed ST-segment shifts in multiple leads, including synthesized V4R, V5R, and V7-9 leads, and U-wave changes in some leads, including the synthesized V9 lead. The diagnosis of the culprit coronary arteries causing exercise-induced myocardial ischemia is discussed with reference to coronary angiographic findings. This modality could potentially increase the sensitivity and specificity for the detection of coronary artery disease and accurately pinpoint the site of the lesion. If an electrocardiograph can display a synthesized 18-lead electrocardiogram, it should be used when evaluating the waveform due to myocardial ischemia., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2023, Takahashi et al.)

Background/aim: Mammalian target of rapamycin (mTOR) inhibitors represent the standard of care for metastatic renal cell carcinoma (RCC). However, treatment outcomes are relatively poor, suggesting a potential problem with tolerating mTOR inhibitors. The aim of this study was to establish everolimus-resistant sublines and to compare their molecular characteristics with those of their counterparts., Materials and Methods: Human-derived RCC, Caki-2, and 786-O cells were continuously exposed to everolimus at 1 μM, and the established resistant sublines were designated as Caki/EV and 786/EV, respectively. Cellular characteristics were compared between both cells., Results: Caki/EV and 786/EV cells showed a decrease in sensitivity to everolimus as well as other mTOR inhibitors. Expression of mTOR and its effectors exhibited no alteration in resistant sublines and their counterparts. However, phosphorylation of S6K, an index of mTOR activity, decreased in resistant sublines. PCR array analysis of mTOR signaling pathway-related factors indicated that the expression of INSR, TP53, and IGFBP3 increased in Caki/EV cells, whereas that of TELO2, HRAS, and SGK1 was up-regulated in 786/EV cells. The levels of DDIT4, DEPTOR, HIF1A, and PLD1 mRNAs decreased in both cell lines., Conclusion: The novel everolimus-resistant Caki/EV and 786/EV cells exhibited cross-resistance to other mTOR inhibitors and decreased mTOR activity. Furthermore, down-regulation of DDIT4, DEPTOR, HIF1A, and PLD1 may contribute to everolimus resistance., (Copyright © 2023 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

There have been numerous instances of lanthanide NIR emitting material where one or more types of ligands or metal ion-ligand complexes operate as antennas. The antenna's role in NIR emission has also been thoroughly investigated and validated. The emission properties of the different antennae are predicted to differ. Here we describe the structural and photophysical properties of two series of [Zn II -Ln III ] complexes, where a minor difference between the two series (ethoxy vs methoxy substitution) affected the photophysical properties, particularly the f-f transition, in an unprecedented manner. Both steady-state and time-resolved luminescence spectra were affected by this change. Detailed single-crystal X-ray diffraction (SCXRD) and X-ray photoelectron spectroscopy (XPS) studies of both complexes revealed the crucial structural differences in crystal packing, which astonishingly remains unaffected in solution.

Competing Interests: None declared.

Background/aim: Lenvatinib is a multiple-tyrosine kinase inhibitor used to treat hepatocellular carcinoma (HCC), and its systematic concentration varies according to liver function. The albumin-bilirubin (ALBI) grade is a novel indicator for predicting liver function in patients with hepatic disease. This study aimed to investigate the relationship between ALBI grade and HCC patients' lenvatinib treatment duration., Patients and Methods: This is a retrospective cohort study of patients with HCC and Child-Pugh A treated with lenvatinib between April 2018 and December 2019. The baseline liver function was determined using the ALBI grade. The primary outcome was discontinuation owing to adverse events. The risk factors for discontinuation owing to adverse effects were analyzed using logistic regression., Results: This investigation included 48 HCC patients. Patients with ALBI grade 2 had a significantly shorter time of discontinuation due to adverse events than those with grade 1 (p=0.036). However, the time of treatment failure did not differ between the groups. Multiple logistic regression analysis showed that ALBI grade 2 and non-use of antihypertensive drugs were independent factors for discontinuation due to adverse events [odds ratio (OR)=14.1, 95% confidence interval (CI)=1.46-135, p=0.022 and OR=5.48, 95% CI=1.13-23.9, p=0.024, respectively]., Conclusion: The ALBI grades may be useful in predicting adverse events caused by lenvatinib in patients with HCC and Child-Pugh A., (Copyright © 2023 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Purpose: 99mTc-pyrophosphate (99mTc-PYP) uptake in the skeletal muscles is minimal in patients with transthyretin cardiac amyloidosis (ATTR-CA) when assessed qualitatively and quantitatively. We previously demonstrated moderate- to high-grade 99mTc-PYP uptake in the subcutaneous abdominal fat of some patients with ATTR-CA and showed that this abnormal finding could reflect the regional amyloid burden of this tissue. We aimed to investigate the frequency of 99mTc-PYP uptake in skeletal trunk muscles of patients with ATTR-CA., Methods: Chest- and abdomen-centered 99mTc-PYP scintigraphy images were obtained 2 hours after IV injections of the tracer (20 mCi) in 36 patients with ATTR-CA. The frequency of 99mTc-PYP uptake in the following 11 skeletal trunk muscles was investigated: pectoralis major, deltoid, subscapularis, infraspinatus, trapezius, latissimus dorsi, erector spinae, psoas major, abdominal oblique, rectus abdominis, and the gluteus muscles., Results: Ten of the 11 muscles were involved in patients with the highest number of 99mTc-PYP uptake in the skeletal trunk muscles examined, whereas no muscle was involved in a patient with the least uptake. The muscle with the highest rate of 99mTc-PYP uptake, observed in 34 of 36 patients (94.4%), was the abdominal oblique. No tracer uptake was observed in the psoas major. The frequency of radiotracer uptake in the remaining examined muscles was between those of abdominal oblique and psoas major muscles., Conclusions: Radiotracer uptake was often detectable in some skeletal trunk muscles of ATTR-CA, although the muscles of patients examined and the skeletal trunk muscles of 1 patient showed heterogeneity in the uptake of 99mTc-PYP., Competing Interests: Conflicts of interest and sources of funding: none declared., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Radionuclide imaging using bone-avid tracers plays a critical role in diagnosing transthyretin cardiac amyloidosis (ATTR-CA), but technetium-99m-pyrophosphate (PYP) rarely allows the detection of extracardiac amyloid infiltration. We retrospectively investigated the frequency of PYP uptake in the subcutaneous abdominal fat of patients with ATTR-CA and its relevance to the results of fine-needle aspiration biopsy (FNAB) of this tissue., Methods: Chest-centered images of PYP scintigraphy were obtained 2 h after the intravenous injection of the tracer (20 mCi), and the frequency of PYP uptake in the subcutaneous abdominal fat was evaluated. Amyloid deposits of fat smears taken by subcutaneous abdominal fat FNAB were assessed by Congo red staining., Results: Twenty-four patients with ATTR-CA were included. Ten (41.7%) patients showed some PYP uptake in the subcutaneous abdominal fat (positive PYP group), and 14 patients did not (negative PYP group). Amyloid deposits were detected by subcutaneous abdominal fat FNAB in 7/10 patients (70.0%) of the positive PYP group versus 0/14 patients (0%) of the negative PYP group, and the difference was significant., Conclusions: In patients with ATTR-CA, abnormal PYP uptake in the subcutaneous abdominal fat could reflect the regional amyloid deposition confirmed by FNAB of this tissue., (© 2021. The Author(s) under exclusive licence to American Society of Nuclear Cardiology.)

Occupational therapists evaluate various aspects of a client's occupational performance. Among these, postural control is one of the fundamental skills that need assessment. Recently, several methods have been proposed to estimate postural control abilities using deep-learning-based approaches. Such techniques allow for the potential to provide automated, precise, fine-grained quantitative indices simply by evaluating videos of a client engaging in a postural control task. However, the clinical applicability of these assessment tools requires further investigation. In the current study, we compared three deep-learning-based pose estimators to assess their clinical applicability in terms of accuracy of pose estimations and processing speed. In addition, we verified which of the proposed quantitative indices for postural controls best reflected the clinical evaluations of occupational therapists. A framework using deep-learning techniques broadens the possibility of quantifying clients' postural control in a more fine-grained way compared with conventional coarse indices, which can lead to improved occupational therapy practice., Competing Interests: The authors declare that there is no conflict of interest regarding the publication of this article., (Copyright © 2022 Naoto Ienaga et al.)

Competing Interests: None.

Because many heavy metals, such as zinc, are used in plating plants, it is important for wastewater treatment technologies to comply with wastewater regulations. In zinc wastewater treatment, zinc is separated from wastewater via hydroxide precipitation. However, ammonia tends to enter the wastewater produced from the plating process and inhibits hydroxide precipitation, which causes difficulties in treating wastewater. In this study, we investigated the effect of ammonia stripping on plating wastewater to remove ammonia, which inhibits wastewater treatment. Based on the results of this study, it was observed that the effectiveness of ammonia removal depends on the pH and air flow rate. It was also found that the presence of zinc increased the ammonia removal effect in most cases. This increase was due to the transformation of some of the precipitated zinc hydroxide in the wastewater into zinc oxide, which afforded an ammonia adsorption effect. After the addition of ethylenediamine-N,N,N',N'-tetraacetic acid disodium salt dihydrate (EDTA・2Na), which is a complexing agent, the ammonia removal effect was slightly decreased. This result is attributed to the decrease in the amount of zinc oxide, which occurs due to the complex formation of EDTA with zinc precipitates in the wastewater. Furthermore, the addition of an excess amount of EDTA・2Na increased the concentration of free ammonia in the wastewater and increased the removal effect. Moreover, the effect of ammonia stripping was successfully applied to wastewater obtained from a zinc plating plant, and zinc wastewater treatment was improved with the removal of ammonia. These results indicate that ammonia stripping is effective in zinc wastewater treatment., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

An elderly Japanese woman developed acute decompensated heart failure caused by persistent atrial fibrillation (AF) and left ventricular systolic dysfunction. Approximately 6 days after starting intravenous administration of amiodarone (600 mg/day) for maintaining sinus rhythm after cardioversion of AF, electrocardiograms revealed a prolonged QT interval associated with torsade de pointes (TdP). The amiodarone-induced TdP disappeared after intravenous administration of landiolol plus magnesium and potassium, without discontinuation of amiodarone or overdrive cardiac pacing, although the prolonged QT interval persisted. To the best of our knowledge, this is the first report that landiolol could be effective for amiodarone-induced TdP., (© 2021 The Authors. Annals of Noninvasive Electrocardiology published by Wiley Periodicals LLC.)

Rationale: Recent studies have shown that QT interval prolongation is associated with disease severity and predicts mortality in systemic inflammatory diseases, particularly rheumatoid arthritis. Systemic pro-inflammatory cytokines released from synovial tissues in rheumatoid arthritis, such as interleukin (IL)-1β, IL-6, and tumor necrosis factor-α, could have direct effects on cardiac electrophysiology, particularly changes in the expression and function of potassium and calcium channels, resulting in QT interval prolongation on surface electrocardiogram (ECG) and an increased predisposition to develop lethal ventricular arrhythmias. However, reports on torsade de pointes (TdP) due to acquired long QT syndrome in patients with polymyalgia rheumatica (PMR) are limited., Patient Concerns: An 85-year-old Japanese woman with active PMR developed first syncope., Diagnosis: Frequent premature atrial contractions (PACs) with multiple patterns of aberrant conduction, QT interval prolongation, and morphological T-U wave variability followed by TdP were documented. PACs were the first beat of TdP., Interventions: Amiodarone, together with magnesium and potassium, was intravenously administered. However, TdP resulted in a ventricular arrhythmic storm, for which sedation with mechanical ventilatory support, temporary overdrive cardiac pacing, and intravenous landiolol administration in addition to multiple direct current shocks were effective., Outcomes: Approximately 2 years later, the patient was treated with amiodarone, propranolol, and prednisolone. She did not undergo implantable cardioverter-defibrillator implantation and was quite well, with no recurrence of ventricular tachyarrhythmia., Lessons: IL-6 hyperproduction in inflamed tissues has been widely confirmed in PMR. Frequent PACs with various patterns of aberrant conduction, QT interval prolongation, and morphological T-U wave variability followed by TdP, for which IL-6-mediated enhancement of L-type Ca2+ current and inhibition of the rapid component of the delayed rectifier K+ current are the most likely mechanisms, were documented in an elderly Japanese woman with PMR. ECG may be recorded once in patients with active PMR even when these patients do not complain of palpitation or syncope. If QT interval prolongation or arrhythmia, including even PACs, is observed, follow-up ECG may be warranted, particularly for patients with some risk factors for QT prolongation that could lead to TdP, such as advanced age, female sex, hypopotassemia, and polypharmacy., Competing Interests: The authors have no funding and conflicts of interest to disclose., (Copyright © 2021 the Author(s). Published by Wolters Kluwer Health, Inc.)

This report presents a rare case of acute decompensated heart failure with technetium-99m-pyrophosphate accumulation in extracardiac sites, such as chest and abdominal walls, in addition to intense myocardial uptake of the tracer. Subsequently, an abdominal fat pad fine-needle aspiration biopsy, which provided positive findings for transthyretin amyloidosis, was performed. ( Level of Difficulty: Advanced. )., Competing Interests: The authors have reported that they have no relationships relevant to the contents of this paper to disclose., (© 2021 The Authors.)

In a patient with variant angina of the proximal left anterior descending coronary artery, myocardial ischemia changed the QRS-ST-T configurations without J-waves into those resembling "lambda" waves at maximal ST-segment elevation, and couplets or triplets of supraventricular extrasystole (SVE) changed the ischemia-induced "lambda" waves into QRS-ST-T configurations resembling a "tombstone" morphology or "monophasic QRS-ST complex." At the resolution phase of coronary spasm, the QRS-ST-T configurations returned to those without J-waves and were changed by SVE into "lambda" waves. Interestingly, neither ischemia- nor SVE-induced "lambda" waves or SVE-induced "tombstone" morphology or "monophasic QRS-ST complex" were complicated by ventricular tachyarrhythmia.

This study aimed to leverage computer vision (CV) technology to develop a technique for quantifying postural control. A conventional quantitative index, occupational therapists' qualitative clinical evaluations, and CV-based quantitative indices using an image analysis algorithm were applied to evaluate the postural control of 34 typically developed preschoolers. The effectiveness of the CV-based indices was investigated relative to current methods to explore the clinical applicability of the proposed method. The capacity of the CV-based indices to reflect therapists' qualitative evaluations was confirmed. Furthermore, compared to the conventional quantitative index, the CV-based indices provided more detailed quantitative information with lower costs. CV-based evaluations enable therapists to quantify details of motor performance that are currently observed qualitatively. The development of such precise quantification methods will improve the science and practice of occupational therapy and allow therapists to perform to their full potential., Competing Interests: The authors declare that there are no conflicts of interest regarding the publication of this paper., (Copyright © 2020 Hiromichi Hagihara et al.)

Spontaneous coronary artery dissection (SCAD) is a relatively rare cause of acute coronary syndrome compared with atherosclerotic plaque rupture and predominantly occurs in young women. SCAD is associated with various conditions, such as emotional stress, pregnancy, hormonal therapy, collagen diseases, fibromuscular dysplasia, or vasospasm. Long-term cardiovascular events are common including the recurrence of SCAD. We report a case of SCAD with de novo recurrence at only 4 days after the first attack. < Learning objectives: Spontaneous coronary artery dissection (SCAD) is a relatively rare cause of acute coronary syndrome (ACS) compared with atherosclerotic plaque rupture, but if young to middle-aged women develop ACS, a high suspicion of SCAD is warranted. Recurrence of SCAD is common with 4- to 10-year follow-up. However, SCAD recurred early as in our case.>.

Aims: Retinoic acid receptor-related orphan nuclear receptor γt (RORγt) is a transcriptional factor responsible for IL-17-producing T-cell differentiation. Although it was demonstrated that RORγt plays essential roles in the onset of autoimmune myocarditis, pathophysiological significance of RORγt in cardiac remodeling after myocardial infarction (MI) remains to be fully elucidated., Methods and Results: MI was generated by ligating coronary artery. The expression of RORγt and IL-17A transcripts increased in murine hearts after MI. Additionally, immunohistochemical staining revealed that RORγt-expressing cells infiltrated in the border zone after MI. Flow cytometric analysis showed that RORγt-expressing cells were released from the spleen at day 1 after MI. Though RORγt-expressing cells in spleen expressed γδTCR or CD4, γδTCR+ cells were major population of RORγt-expressing cells that infiltrated into post-infarct myocardium. To address the biological functions of RORγt-expressing cells in infarcted hearts, we used mice with enhanced GFP gene heterozygously knocked-in at RORγt locus (RORγt+/- mice), which physiologically showed reduced expression of RORγt mRNA in thymus. Kaplan-Meier analysis showed that MI-induced mortality was higher in RORγt+/- mice than wild-type (WT) mice. Masson's trichrome staining demonstrated that cardiac injury was exacerbated in RORγt+/- mice 7 days after MI (Injured area: RORγt+/-; 42.1±6.5%, WT; 34.0±3.7%, circumference of injured myocardium: RORγt+/-; 61.8±4.8%, WT; 49.6±5.1%), accompanied by exacerbation of cardiac function (fractional shortening: RORγt+/-; 32.9±2.9%, WT; 38.3±3.6%). Moreover, immunohistochemical analyses revealed that capillary density in border zone was significantly reduced in RORγt+/- mice after MI, compared with WT mice, associated with the reduced expression of angiopoietin 2. Finally, the mRNA expression of RORγt, IL-17A, IL-17F and IL-23 receptor (IL-23R) mRNA and protein expression of IL-10 were decreased in RORγt+/- hearts., Conclusions: Heterozygous deletion of RORγt gene resulted in aggravated cardiac remodeling, accompanied by reduced capillary density, after MI, suggesting that RORγt-expressing cells contribute to tissue repair in infarcted myocardium.

Background: Regular physical activity (PA), including daily walking, reduces the risk of many chronic diseases, especially hypertension. Pedometer is a potential motivational aid for increasing PA. In the present study, we used a telemedicine system and analyzed the relationship between daily walking, calculated by pedometers, and blood pressure (BP)., Methods: BP was measured at home twice a day (morning and evening) using an oscillometric automatic device. Body weight (BW) and percent body fat (%BF) were measured after BP measurement. Daily walking steps (DWS) were calculated by a pedometer. These daily parameters were transmitted through the Internet to a central server computer and sent to the Medical Health Center., Results: Sixty-nine (N = 69) hypertensive patients were included in this study. The mean follow-up period was 378 days. Electronic data from a pedometer (DWS) were associated with reduced BW, body mass index, and %BF. Hypertensive patients were divided into two groups based on the DWS. In the high DWS group, morning systolic BP and diastolic BP and evening systolic BP were reduced after induction of the telemedicine system., Conclusion: A telemedicine system confirmed the usefulness of walking to control BP in hypertensive patients.

Familial lecithin:cholesterol acyltransferase (LCAT) deficiency is a rare inherited disorder that causes an extremely low high-density lipoprotein cholesterol concentration in serum. Recently, acquired LCAT deficiency caused by IgG antibodies to LCAT, without any LCAT gene mutation, was reported. Here we describe a case of acquired LCAT deficiency occurring in association with sarcoidosis. The patient was a Japanese female aged 70 years, had no mutation in the LCAT gene exon sequence, but had an LCAT inhibitor factor in her serum, detected using lipoprotein-deficient serum. She was diagnosed with acquired LCAT deficiency. Her abnormalities of serum lipoproteins improved spontaneously during three and a half years. Because they require different treatment strategies, distinction between familial lecithin:cholesterol acyltransferase deficiency (FLD) and acquired LCAT deficiency by gene sequencing is warranted, especially in cases without corneal clouding.

Interleukin (IL)-18 is a member of the IL-1 family of cytokines and was described originally as an interferon γ-inducing factor. Aldosterone plays a central role in the regulation of sodium and potassium homoeostasis by binding to the mineralocorticoid receptor and contributes to kidney and cardiovascular damage. Aldosterone has been reported to induce IL-18, resulting in cardiac fibrosis with induced IL-18-mediated osteopontin (OPN). We therefore hypothesized that aldosterone-induced renal fibrosis via OPN may be mediated by IL-18. To verify this hypothesis, we compared mice deficient in IL-18 and wild-type (WT) mice in a model of aldosterone/salt-induced hypertension. IL-18(-/-) and C57BL/6 WT mice were used for the uninephrectomized aldosterone/salt hypertensive model, whereas NRK-52E cells (rat kidney epithelial cells) were used in an in vitro model. In the present in vivo study, IL-18 protein expression was localized in medullary tubules in the WT mice, whereas in aldosterone-infused WT mice this expression was up-regulated markedly in the proximal tubules, especially in injured and dilated tubules. This renal damage caused by aldosterone was attenuated significantly by IL-18 knockout with down-regulation of OPN expression. In the present in vitro study, aldosterone directly induced IL-18 gene expression in renal tubular epithelial cells in a concentration- and time-dependent manner. These effects were inhibited completely by spironolactone. IL-18 may be a key mediator of aldosterone-induced renal fibrosis by inducing OPN, thereby exacerbating renal interstitial fibrosis. Inhibition of IL-18 may therefore provide a potential target for therapeutic intervention aimed at preventing the progression of renal injury., (© 2016 The Author(s). published by Portland Press Limited on behalf of the Biochemical Society.)

Hypercholesterolemia is a well-established risk factor for kidney injury, which can lead to chronic kidney disease (CKD). Osteopontin (OPN) has been implicated in the pathology of several renal conditions. This study was to evaluate the effects of OPN on hypercholesterolemia induced renal dysfunction. Eight-week-old male mice were divided into 4 groups: apolipoprotein E knockout (ApoE(-/-)) and ApoE/OPN knockout (ApoE(-/-)/OPN(-/-)) mice fed a normal diet (ND) or high cholesterol diet (HD). After 4 weeks, Periodic acid-Schiff (PAS) and oil red O staining revealed excessive lipid deposition in the glomeruli of ApoE(-/-)HD mice, however, significantly suppressed in ApoE(-/-)/OPN(-/-)HD mice. Lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1) expression was lower in the glomeruli of ApoE(-/-)/OPN(-/-)HD mice than ApoE(-/-)HD mice. In vitro study, primary mesangial cells were incubated with recombinant mouse OPN (rmOPN). RmOPN induced LOX-1 mRNA and protein expression in primary mesangial cells. Pre-treatment with an ERK inhibitor suppressed the LOX-1 gene expression induced by rmOPN. These results indicate that OPN contributes to kidney damage in hypercholesterolemia and suggest that inhibition of OPN may provide a potential therapeutic target for the prevention of hypercholesterolemia.

STAT3 is a cardioprotective molecule against acute myocardial injury; however, recent studies have suggested that chronic STAT3 activation in genetically modified mice was detrimental after myocardial infarction (MI). In the present study, we assessed the biological significance of STAT3 activity in subacute MI using tamoxifen (TM)-inducible cardiac-specific STAT3 knockout (STAT3 iCKO) mice. After coronary ligation, STAT3 was rapidly activated in hearts, and its activation was sustained to the subacute phase. To make clear the pathophysiological roles of STAT3 activation specifically in subacute MI, MI was generated in STAT3 iCKO mice followed by TM treatment for 14 consecutive days beginning from day 11 after MI, which ablated the STAT3 gene in the subacute phase. Intriguingly, mortality was increased by TM treatment in STAT3 iCKO mice, accompanied by an increased heart weight-to-body weight ratio. Masson's trichrome staining demonstrated that cardiac fibrosis was dramatically exacerbated in STAT3 iCKO mice 24 days after MI (fibrotic circumference: 58.3 ± 6.7% in iCKO mice and 40.8 ± 9.3% in control mice), concomitant with increased expressions of fibrosis-related gene transcripts, including matrix metalloproteinase 9, procollagen 1, and procollagen 3. Echocardiography clarified that cardiac function was deteriorated in STAT3 iCKO mice (fractional shortening: 20.6 ± 4.1% in iCKO mice and 29.1 ± 6.0% in control mice). Dihydroethidium fluorescence analysis revealed that superoxide production was increased in STAT3 iCKO mice. Moreover, immunohistochemical analyses revealed that capillary density was decreased in STAT3 iCKO mice. Finally, STAT3 deletion in subacute MI evoked severe cardiac hypertrophy in the border zone. In conclusion, the intrinsic activity of STAT3 in the myocardium confers the resistance to cardiac remodeling in subacute MI., (Copyright © 2015 the American Physiological Society.)

To examine the association between pulsatility index (PI) in the common carotid artery (CCA) as a marker of vascular resistance and cardiovascular risk factors, including serum homocysteine and inflammation, 67 hypertensive patients were enrolled. PI correlated with homocysteine and interleukin-6, monocyte count, gender, age and BMI, with monocyte count and age being independent determinants for PI. In turn, monocyte count correlated with homocysteine, tumor necrosis factor-alpha, and HDL-cholesterol, BMI, and gender, with HDL-cholesterol and homocysteine being independent determinants for monocyte count. These results indicated monocyte count determined by homocysteine is associated with arterial stiffness in hypertensive patients.

Hyperhomocystemia has been reported to be associated with cardiovascular disease, especially stroke. The resistive index (RI) estimated by carotid ultrasound is an established variable for estimating the risk of cerebral infarction. The aim of this study was to evaluate the relationship between homocysteine concentration and carotid RI, a marker of cerebral vascular resistance in essential hypertensive patients. We measured serum total homocysteine and carotid RI in 261 patients. Multiple linear regression analysis was used to determine the association of homocysteine with carotid RI and intima media thickness (IMT). Age, sex, BMI, systolic blood pressure (SBP), homocysteine, total cholesterol, high density lipoprotein-cholesterol (HDL-C), uric acid, CRP, HbA1c, estimated glomerular filtration rate, and use of antihypertensive agents were included as independent variables. Age, sex, use of antihypertensive agents, HDL-C and homocysteine levels were shown to be significant predictors of carotid RI, but not IMT. Multiple regression analysis in men older than 65 years showed homocysteine and SBP were associated significantly with carotid RI. In elderly male patients, homocysteine was the strongest predictor of carotid RI (B = 0.0068, CI = 0.0017-0.0120, P = 0.011) in the multivariate model. In conclusion, hyperhomocysteinemia is associated with carotid RI, a surrogate marker of cerebral vascular resistance, especially in elderly men.

Kimura's disease is a granulomatous disease of unknown origin that develops in the dermis, subcutaneous tissue and lymph nodes. Kimura's disease is frequently complicated by nephropathy, particularly membranous nephropathy (MN). It has recently been suggested that glomerular immunoglobulin (IgG)4 deposition may play a role in the pathogenesis of idiopathic MN. These IgG4 antibodies are thought to react with antigens, primarily the phospholipase A2 receptor (PLA2R) expressed on the podocyte cell membrane. We herein report a case of Kimura's disease with MN in which a renal biopsy specimen revealed positive staining for anti-IgG4 and anti-PLA2R antibodies.

Left ventricular hypertrophy (LVH) regression is an important issue in hypertensive patients. Patients with LVH who had received the angiotensin receptor blocker (ARB) treatment for 8 weeks and had not reached the target blood pressure level were enrolled in the study. Patients were assigned to either losartan (50 mg)/hydrochlorothiazide (HCTZ, 12.5 mg) group or ARB + CCB group (usual dose of ARB and calcium channel blocker, CCB). After 48 weeks, LV mass index was found to be reduced significantly in the losartan/HCTZ group but not in the ARB + CCB group. These results suggest that combination therapy of an ARB and diuretic has greater potential to cause regression compared with an ARB and CCB.

Background: We investigated an impact of the presence of chronic total coronary occlusion (CTO) in a non-infarct related coronary artery on microvascular reperfusion in patients with a first anterior ST-segment elevation myocardial infarction (STEMI) who underwent percutaneous coronary intervention (PCI)., Methods: In accordance with the presence or absence of CTO in a non-infarct related coronary artery, we analyzed Thrombolysis in Myocardial Infarction myocardial perfusion (TMP) grade on a scale of 0 to 3, with higher scores indicating better perfusion, and ST-segment resolution in sum of lead I, aVL, and V1 through V6 to evaluate microvascular reperfusion in a total of 140 consecutive patients with a first anterior STEMI., Results: We identified CTO in 15 patients (11% of total). The incidence of impaired microvascular reperfusion was greater in patients with CTO vs without CTO, defined as TMP grades 0 or 1 together with <30% ST-segment resolution (33% vs 6%, respectively; P=.0006) and the enzymatic infarct was larger (10304 ± 8060 IU/L vs 6804 ± 4959 IU/L; P=.009). Logistic regression analysis revealed that CTO is closely associated with incidental impaired microvascular reperfusion (odds ratio, 6.801; 95% confidence interval, 1.284-36.209; P=.024)., Conclusion: The presence of CTO in a non-infarct related coronary artery might confer a considerable disadvantage upon microvascular reperfusion and result in adverse clinical outcomes of PCI for a first anterior STEMI.

We assessed the clinical features of patients with myocardial rupture within 48 to 72 hours, defined as early myocardial rupture, after percutaneous coronary intervention (PCI) for ST-segment elevation acute myocardial infarction (STEMI). Six patients (4 men, 66 ± 13 years) with early myocardial rupture were identified from 1252 consecutive patients undergoing PCI for STEMI. We evaluated the degree of microvascular reperfusion using thrombolysis in myocardial infarction (TIMI) myocardial perfusion (TMP) grade and a resolution of sum of ST-segment elevation in a 12-lead electrocardiogram (ECG). Time from PCI to myocardial rupture was 11 ± 7 hours. All patients showed TMP grade 0 or 1 and an increase in sum of ST-segment elevation after PCI (1.9 ± 0.5 vs 2.5 ± 0.7 mV; P = .032), suggesting severely failed reperfusion at the level of microcirculation as the common feature to develop early myocardial rupture after PCI for STEMI.

Background/aims: Osteopontin (OPN) has been implicated in the pathology of several renal conditions. The aim of this study was to clarify the roles of OPN in diabetic nephropathy., Methods: Diabetes mellitus (DM) was induced in wild-type (WT) and OPN knockout (KO) mice by injecting streptozotocin. The mice were killed 20 weeks after induction of DM and their kidneys removed., Results: Renal mRNA expression of OPN was increased in WT-DM mice compared to WT-sham mice. Immunohistochemistry showed high levels of OPN expression in the proximal tubules of WT-DM mice. Kidney weight and urinary albumin excretion increased to similar levels in the WT-DM and KO-DM mice. Interstitial fibrosis was increased in WT-DM mice compared to KO-DM mice. However, there were no differences in the degree of mesangial expansion or glomerular hypertrophy between the two groups. F4/80-positive cells (macrophages) and FSP-1-positive cells (fibroblasts) showed significantly higher infiltration in WT-DM mice than in KO-DM mice. Renal mRNA expression of NADPH oxidase subunits and urinary 8-isoprostane excretion were also increased in WT-DM mice., Conclusions: These results indicated that OPN is a key molecule that induces interstitial fibrosis in the diabetic kidney, but does not induce glomerular sclerosis.

Urinary type IV collagen excretion (uT4C) in diabetic patients is higher than in normal subjects. In this study, we investigated the relationship between uT4C and renal hemodynamics in 42 patients with essential hypertension. The renal resistive index (RI) is calculated from blood flow velocities measured using pulsed-wave in interlobar arteries. There was a significant correlation between uT4C to creatinine ratio (uT4C/uCr) and age, hemoglobin A1c (HbA1c), and RI. A stepwise regression analysis showed that RI was independently associated with uT4C/uCr. These results indicated that uT4C may be a marker of renovascular stiffness due to glomerulosclerosis in patients with essential hypertension.

Osteopontin (OPN) has been implicated in the pathology of several renal conditions. Recently, we demonstrated in vitro that aldosterone has important roles in collagen synthesis by inducing OPN (Irita J, Okura T, Kurata M, Miyoshi K, Fukuoka T, Higaki J. Hypertension 51: 507-513, 2008). The aim of the present study was to clarify the roles of OPN in aldosterone-mediated renal fibrosis by infusing aldosterone into either wild-type (WT) or OPN knockout mice (OPN(-/-)). We used uninephrectomized mice treated with aldosterone and high salt to exacerbate renal fibrosis. After 4 wk of treatment with aldosterone, we showed similar increases in systolic blood pressure in both strains of mice. Urine albumin excretion was greater in aldosterone-infused WT mice than in aldosterone-infused OPN(-/-) mice. Immunohistochemical analysis showed high levels of OPN expression in aldosterone-infused WT mice. Interstitial fibrosis and inflammatory infiltrations were increased in aldosterone-infused WT mice compared with either vehicle-infused WT or aldosterone-infused OPN(-/-) mice. These changes were ameliorated markedly by eplerenone treatment in aldosterone-infused WT mice. Aldosterone-infused WT mice also had increased expression of NADPH oxidase subunits compared with aldosterone-infused OPN(-/-) mice. We observed a marked increase in oxidative stress markers in aldosterone-infused WT mice compared with aldosterone-infused OPN(-/-) mice. These results indicate that OPN is a promoter of aldosterone-induced inflammation, oxidative stress, and interstitial fibrosis in the kidney and suggest that inhibition of OPN may be a potential therapeutic target for prevention of renal injury.

A 70-year-old woman was admitted to our hospital because of sudden hearing loss. She was treated with intratympanic dexamethasone, but her hearing impairment progressed. After admission, she developed scleritis of her left eye. Laboratory findings included elevated white blood cell count and C-reactive protein level, microhematuria, and proteinuria. Serology was positive for myeloperoxidase antineutrophil cytoplasmic antibody (MPO-ANCA), but negative for proteinase 3 (PR3)-ANCA. Renal biopsy revealed a single glomerulus with extensive glomerular tuft necrosis, indicating necrotizing vasculitis. She was diagnosed with MPO-ANCA-associated polyangiitis. ANCA-related polyangiitis should be considered in the differential diagnosis of sudden deafness or scleritis.

Background: Serum cystatin C is not only a marker of renal function but also acts as an independent risk factor for cardiovascular damage, heart failure, and death. It is known that the initiation and progression of these cardiovascular events contributes to renal dysfunction and chronic inflammation. In this study, we investigated the relationship between cystatin C and proinflammatory cytokines., Methods: Eighty-eight patients with essential hypertension participated in the study, which involved measuring proinflammatory cytokines, tumor necrosis factor (TNF)-α, interleukin (IL)-6, and C reactive protein (CRP)., Results: Positive correlations were detected between cystatin C and estimated glomerular filtration rate (eGFR) (r = -0.503, p < 0.001), systolic blood pressure (r = -0.246, p = 0.034), and pulse pressure (r = -0.295, p = 0.010). In contrast, serum creatinine correlated only with eGFR (r = -0.755, p < 0.001) and eGFR correlated only with age (r = -0.339, p = 0.001) and not with the other clinical parameters, whereas cystatin C also correlated with log natural (ln) IL-6 (r = -0.247, p = 0.033) and ln TNF-α (r = -0.405, p < 0.001) but not with CRP (r = -0.188, p = 0.108). In contrast, plasma creatinine and eGFR did not correlate with any of these proinflammatory cytokines. Stepwise regression analysis showed that ln TNF-α, eGFR and pulse pressure were independent determinants of serum cystatin C concentration., Conclusion: This study showed that cystatin C is a marker of inflammation as well as renal function.

Aim: In patients with essential hypertension (EHT), the intrarenal resistance index (RI) has been shown to be related to the severity of target organ damage (TOD). Cystatin C is has been reported to be related to TOD in EHT. The aim of the present study was to clarify whether the RI predicts future renal function assessed by cystatin C levels in EHT., Methods: One-hundred and twelve patients participated. RI and cystatin C were measured at baseline, and 12 months later, cystatin C was measured again., Results: The patients were divided into 2 groups according to RI value: the low RI group (RI<0.7) and the high RI group (RI> or =0.7). After 12 months, cystatin C levels were significantly elevated in the high RI group, whereas the levels remained unchanged in the low RI group. Stepwise regression analysis using the baseline values of RI, age, pulse pressure, HbA1c, cystatin C, log-transformed (ln) C-reactive protein and ln urinary albumin/creatinine as covariates, showed baseline RI was the only independent determinant of the time-related changes in cystatin C levels., Conclusion: This finding suggests that the renal RI may be a marker of future renal dysfunction in EHT.

The development of vascular calcification is an active, highly regulated process with similarities to bone formation. Osteocalcin (OC), a vitamin K-dependent protein expressed by osteoblasts, contains 3 gamma-carboxyglutamic acid residues derived from the vitamin K-dependent posttranslational modification of glutamic acid residues. Circulating undercarboxylated OC (ucOC) is increased in vitamin K deficiency and serum ucOC is reported to be a clinical marker of vitamin K status. Vitamin K deficiency is associated with vascular calcification as well as osteoporosis. We evaluated the relationship between ucOC and carotid artery calcification in 92 patients with essential hypertension. Ultrasound of the common carotid artery was performed to identify vascular calcification and subjects were divided into 2 groups: a calcification (+) group and a calcification (-) group. Serum creatinine and ucOC levels were higher in the calcification (+) group than in the calcification (-) group and serum ucOC correlated with serum creatinine. To identify the independent determinant factor for carotid artery calcification, we applied both ucOC and estimated glomerular filtration rate as independent factors in logistic regression analysis. Serum ucOC was an independent determinant of carotid calcification, suggesting that circulating ucOC may be an important biomarker of carotid artery calcification., (Copyright 2010 S. Karger AG, Basel.)