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This study aimed to investigate the relationship between the restoration of coronary flow just before stent deployment and the final thrombolysis in myocardial infarction (TIMI) flow grade 3 in patients with ST-segment elevation myocardial infarction (STEMI) whose initial TIMI flow grade ≤ 1. In primary percutaneous coronary intervention (PCI), initial TMI flow grade ≤ 1 is closely associated with suboptimal final TIMI flow grade. We included 466 STEMI patients with initial TIMI flow grade ≤ 1 and divided into a restored flow group or an unrestored flow group according to the TIMI flow grade just before stent deployment. The primary endpoint was the achievement of final TIMI flow grade 3. We compared clinical characteristics between the two groups and performed a multivariate logistic analysis to investigate the association between the coronary flow restoration and the final TIMI flow grade. The prevalence of final TIMI flow grade 3 was significantly higher in the restored flow group than the unrestored flow group. The multivariate logistic regression analysis revealed that the restoration of coronary flow just before stent deployment was significantly associated with final TIMI flow grade 3 (OR 7.771, 95% CI 3.412-17.699, p < 0.001). The restoration of coronary flow just before stent deployment was significantly associated with the achievement of final TIMI flow grade 3 in STEMI patients with initial TIMI flow grade ≤ 1. Interventional cardiologist may pay more attention to the coronary flow restoration just before stent deployment when the initial TIMI flow grade is ≤ 1., Competing Interests: Declarations. Conflict of interest: Dr. Sakakura has received speaking honoraria from Abbott Vascular, Boston Scientific, Medtronic Cardiovascular, Terumo, OrbusNeich, Japan Lifeline, Kaneka, and NIPRO; he has served as a proctor for Rotablator for Boston Scientific, and he has served as a consultant for Abbott Vascular and Boston Scientific. Prof. Fujita has served as a consultant for Mehergen Group Holdings, Inc., (© 2025. The Author(s) under exclusive licence to Japanese Association of Cardiovascular Intervention and Therapeutics.)

The impact of clinical stage on the effectiveness of osimertinib for epidermal growth factor receptor (EGFR) mutation-positive non-small cell lung cancer (NSCLC) remains unexamined. We investigated osimertinib therapeutic efficacy variation between stage IVA or lower and stage IVB EGFR mutation-positive lung cancers, focusing on differences in pretreatment co-occurring genetic alterations in circulating tumor DNA. This was a secondary analysis of the ELUCIDATOR study, a multicenter prospective observational study in Japan that assessed the mechanisms underlying resistance to osimertinib as a first-line treatment for advanced NSCLC with EGFR mutations. We compared the progression-free survival (PFS), overall survival (OS), and pretreatment co-occurring genetic alterations detected in plasma between patients with stages IVA (n = 83) and IVB disease (n = 84). Multivariate analysis of PFS and OS revealed that stage IVB was associated with a poor prognosis (hazard ratio [HR]: 2.03, 95% confidence interval [CI]: 1.36-3.04, p < 0.001, HR: 2.35, 95% CI: 1.45-3.90, p < 0.001, respectively). Pre-osimertinib treatment, significantly more TP53- (52.4% vs. 27.7%, p = 0.002), EGFR amplification- (58.3% vs. 23.2%, p < 0.001), and MET amplification-positive cases (22.6% vs. 7.2%, p = 0.008) were found among stage IVB than among stage IVA or lower cases. Patients with EGFR-positive NSCLC in stage IVB exhibited significantly shorter PFS and OS than those in earlier stages when treated with first-line osimertinib. The prevalence of baseline TP53 mutations, EGFR amplification, and MET amplification in plasma were significantly higher in stage IVB cases, implicating them in the worse outcomes of this group., Competing Interests: Declarations. Ethical approval and consent to participate: This prospective observational study was registered on December 10, 2018, in the Japanese Register of Clinical Trials (JRCT; Clinical Trial Number: jRCTs031180051). Written informed consent was obtained from all patients before the study began, and the National Hospital Organization Review Board for Clinical Trials approved this protocol prior to the start of the study. Consent for publication: Not applicable. Competing interests: Taniguchi Y has received honoraria from Chugai Pharmaceutical, Ono Pharmaceutical, AstraZeneca, and MSD. Tamiya A received honoraria from Eli Lilly, Ono Pharmaceutical, Chugai Pharmaceutical, Boehringer Ingelheim, AstraZeneca, Bristol-Myers Squibb, Amgen, Taiho Pharmaceutical, Kyowa-Kirin, MSD, Takeda Pharmaceutical, Nihon-Kayaku, Novartis, Thermo Fischer, Amgen, Tsumura, Daiich-Sankyo, and Merck BioFarma, and research funding from Daiichi-Sankyo, Beigene, and AstraZeneca. Oki M has received Honoraria from AMCO, AstraZeneca, Canon Medical Systems, Chugai Pharmaceutical, Fujifilm Toyama Chemical, Kaneka Medix, Merit Medical Japan, Novartis Pharma, Olympus and Sanofi, and research funding from AbbVie, AstraZeneca, Chugai Pharmaceutical, Fujifilm Toyama Chemical, GlaxoSmithKline, Janssen Pharmaceutical, MSD, Ono Pharmaceutical, Parxel International, Pfizer, Sanofi. Mori M received honoraria from AstraZeneca, Boehringer Ingelheim, MSD, Eli Lilly, Novartis, Chugai Pharmaceutical, Taiho Pharmaceutical, Kyowa-kirin, Ono Pharmaceutical, Otsuka, Nihon-kayaku, Pfizer, Daiici-Sankyo, Takeda Pharmaceutical, and Shionogi and research funding from Chugai Pharmaceutical, Ono Pharmaceutical, MSD, and Delt-fly. Koh Y has received honoraria from Chugai Pharmaceutical, Guardant Health, Amgen, Takeda Pharmaceutical, and Tosoh Corporation and has received consulting or advisory roles from Tosoh Corporation and research funding from Boehringer Ingelheim, AstraZeneca, Chugai Pharmaceutical, Tosoh Corporation, Daiichi Sankyo, Zeon Corporation, Amgen, and Takeda Pharmaceutical. The other co-authors received no honoraria or research funding., (© 2025. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Primary percutaneous coronary intervention (PCI) is the cornerstone of treatment for ST-segment elevation myocardial infarction (STEMI). Previous studies suggest that direct transport by ambulance to a primary PCI facility is associated with better clinical outcomes in patients with STEMI. However, those studies included seriously ill patients for whom direct transport is the only option. We included 462 patients with STEMI who were supposed to select either direct transport by ambulance or indirect transport via primary care doctor, and compared the clinical outcomes between the direct transfer group (n = 172) and the indirect transfer group (n = 290). The primary endpoint was major adverse cardiovascular events (MACE), which was defined as the composite of all-cause death, non-fatal myocardial infarction, re-admission for heart failure, and target vessel revascularization. The median follow-up duration was 540 days (86-1266 days). Age was significantly higher in the indirect transfer group [72.0 (64-80) years] than in the direct transfer group [69.5 (58.3-77) years] (p = 0.013). Onset to balloon time was significantly shorter in the direct transport group (p < 0.001). The Kaplan-Meier curves revealed that MACE were similarly observed between the two groups (31.4% vs. 27.2%; p = 0.330). After adjusting for potential confounders, indirect transfer was not associated with MACE (adjusted hazard ratio: 0.740, 95% confidence interval: 0.485-1.128, p = 0.161). In conclusion, indirect transfer was not associated with poor clinical outcomes in patients with STEMI who were supposed to select either direct transport or indirect transport., Competing Interests: Declarations. Conflict of interest: None., (© 2024. The Author(s) under exclusive licence to Japanese Association of Cardiovascular Intervention and Therapeutics.)

Objective: To clarify the relationship between myelin water fraction (MWF) and R 1 ⋅R 2 * and to develop a method to calculate MWF directly from parameters derived from QPM, i.e., MWF converted from QPM (MWF QPM )., Materials and Methods: Subjects were 12 healthy volunteers. On a 3 T MR scanner, dataset was acquired using spoiled gradient-echo sequence for QPM. MWF and R 1 ⋅R 2 * maps were derived from the multi-gradient-echo (mGRE) dataset. Volume-of-interest (VOI) analysis using the JHU-white matter (WM) atlas was performed. All the data in the 48 WM regions measured VOI were plotted, and quadratic polynomial approximations of each region were derived from the relationship between R 1 ·R 2 * and the two-pool model-MWF. The R 1 ·R 2 * map was converted to MWF QPM map. MWF atlas template was generated using converted to MWF from R 1 ·R 2 * per WM region., Results: The mean MWF and R 1 ·R 2 * values for the 48 WM regions were 11.96 ± 6.63%, and 19.94 ± 4.59 s -2 , respectively. A non-linear relationship in 48 regions of the WM between MWF and R 1 ·R 2 * values was observed by quadratic polynomial approximation (R 2  ≥ 0.963, P < 0.0001)., Discussion: MWF QPM map improved image quality compared to the mGRE-MWF map. Myelin water atlas template derived from MWF QPM may be generated with combined multiple WM regions., (© 2024. The Author(s), under exclusive licence to European Society for Magnetic Resonance in Medicine and Biology (ESMRMB).)

Advances in chronic thromboembolic pulmonary hypertension (CTEPH) treatment have improved prognosis, shifting focus towards symptom management. This study aimed to identify factors influencing the World Health Organization functional class (WHO-FC) in CTEPH patients. The CTEPH AC registry is a prospective, multicenter database from 35 Japanese institutions, analyzing data from August 2018 to July 2023. We examined factors associated with achieving WHO-FC I and WHO-FC changes over time in 1,270 patients. Significant factors for WHO-FC I achievement included male sex (odds ratio: 1.86, p = 0.019), age (0.98, p = 0.007), pulmonary vasodilator use (0.51, p = 0.001), post-balloon pulmonary angioplasty (BPA) (1.93, p = 0.010), lower mean pulmonary arterial pressure (0.94, p = 0.004), and lower pulmonary vascular resistance (PVR) (0.78, p = 0.006). Multivariate analysis showed that WHO-FC improvement correlated with male sex, baseline PVR, and BPA during follow-up. WHO-FC deterioration was associated with cancer, history of pulmonary endarterectomy and/or BPA at registration, bleeding risks, and thyroid disease or hormone therapy. BPA implementation is closely linked to symptomatic improvement and achieving WHO-FC I, while symptom worsening is often associated with patient-specific, difficult-to-control conditions., Competing Interests: Declarations. Conflict of interest: Ikeda N. reports personal fees from Janssen Pharmaceutical, Bayer Yakuhin, Nippon Shinyaku, Daiichi Sankyo, and Bristol-Myers Squibb outside the submitted work. Hosokawa K. reports personal fees from Janssen Pharmaceutical, Bayer Yakuhin, Nippon Shinyaku, and Pfizer outside the submitted work. Taniguchi Y. reported grants from Janssen Pharmaceutical and Nippon Shinyaku and personal fees from Janssen Pharmaceutical and Nippon Shinyaku outside the submitted work. Inami T. reports personal fees from Janssen Pharmaceutical and Bayer Yakuhin outside the submitted work. Yamashita J. reports a grant from Abbott Vascular Japan and personal fees from Kaneka Medix, Boston Scientific Japan, Nihon Kohden, Philips Japan, Janssen Pharmaceutical, and Bayer Yakuhin outside the submitted work. Ogino H. reports consulting fees from Terumo, Japan Lifeline, and Century Medical, outside the submitted work. Tsujino I. reports personal fees from Janssen Pharmaceutical and Nippon Shinyaku and affiliation with the division supported by endowments from Nippon Shinyaku, Nippon Boehringer Ingelheim, Mochida Pharmaceutical, Kaneka, Takeyama, and the Medical System Network outside the submitted work. Yaoita N. reports personal fees from Bayer Yakuhin and Konica Minolta outside the submitted work. Shimokawahara H. reports a grant from Bayer Yakuhin and personal fees from Actelion Pharmaceuticals Japan, Bayer Yakuhin, and Nippon Shinyaku, outside the submitted work. Tanabe N. reports personal fees from Janssen Pharmaceutical, Bayer Yakuhin, and Nippon Shinyaku outside the submitted work. Kubota K. reports personal fees from Janssen Pharmaceutical and Nippon Shinyaku outside the submitted work. Ogihara Y. reports personal fees from Janssen Pharmaceutical, Bayer Yakuhin, and Nippon Shinyaku and grants from Bayer Yakuhin outside the submitted work. Kawakami T. reports personal fees from Kaneka Medix, Abbott Medical Japan., and ACIST Japan outside the submitted work. Tamura Y. reports grants from Bayer Yakuhin, Nippon Shinyaku, and Mochida Pharmaceutical and personal fees from Bayer Yakuhin, Nippon Shinyaku, Daiichi Sankyo, and Janssen Pharmaceutical outside the submitted work. Abe K. reports a grant from Konica Minolta and Daiichi Sankyo outside the submitted work. Masaki K., Funakoshi K., Adachi S., Hatano M, Shigeta A., Horimoto K., Dohi Y., and Tatsumi K. report no conflicts of interest., (© 2025. The Author(s) under exclusive licence to Japanese Association of Cardiovascular Intervention and Therapeutics.)

Bioresorbable scaffolds (BRS) were developed as an innovative solution to overcome the limitations of metallic stents. While polymeric BRS initially demonstrated comparable clinical outcomes to drug-eluting stent (DES) in clinical trials, subsequent large-scale studies revealed that patients implanted with polymeric BRS experienced higher rates of scaffold thrombosis (ScT) and target lesion failure compared to those with metallic stents. Resorbable magnesium scaffolds (RMS) have emerged as a promising alternative owing to magnesium's natural degradability and favorable mechanical properties. Learning from the mechanism of polymeric BRS failure and through continuous improvements, recent clinical trials have shown promising clinical performance for RMS technology. However, comparative studies between RMS and DES have continued to highlight the remaining challenges with RMS, particularly in regard to late lumen loss. Recent advancements in third-generation RMS show improvements in strut thickness and homogeneous degradation, which enhances sustained structural integrity throughout the degradation process. Based on encouraging results from a first-in-human trial of the latest version of RMS, a randomized controlled trial has been initiated to compare the outcomes between metallic stents and the latest RMS, with patient enrollment already underway. This review aims to explore the limitations of polymeric BRS and provide an overview of the current developments and future potential of magnesium-based BRS., (© 2024. The Author(s) under exclusive licence to Japanese Association of Cardiovascular Intervention and Therapeutics.)

Background: The objectives of this phase two study are to investigate the efficacy of two starting doses of 8.4 g and 16.8 g and evaluate the long-term safety of patiromer in Japanese patients with hyperkalemia., Methods: This study comprised three cohorts; non-dialysis patients with baseline serum potassium (sK) level of 5.1 to < 6.0 mmol/L (NDC1); 6.0 to < 6.5 mmol/L (NDC2); dialysis patients with baseline sK level of 5.5 to < 6.5 mmol/L (DC). The study design was one-week, randomized, double-blind, placebo-controlled, and open label extension for one year in NDC1, open label during the study in NDC2 and DC. Patients were randomly assigned to patiromer 8.4 g, 16.8 g or placebo in NDC1, 8.4 g or 16.8 g in NDC2 and DC. Dose was adjusted up to 25.2 g according to the titration algorism in open label period., Results: A total of 185 patients were randomized (NDC1:153, NDC2:10, and DC:22). The primary endpoint of the change in least squares mean sK levels at Week 1 in NDC1 was  - 0.55,  - 0.77 and  - 0.10 mmol/L for the 8.4 g, 16.8 g and placebo group (P < 0.001 for the patiromer group vs the placebo group). In all cohorts for each patiromer group, more than 80% of patients achieved normal sK at Week 5. There was no severe treatment-related adverse event., Conclusion: Treatment with patiromer was effective in lowering and maintaining target sK levels, also well tolerated for one year in Japanese patients with hyperkalemia., Competing Interests: Declarations. Conflict of interest: N Kashihara has received consulting fees from AstraZeneca, Gilead Sciences, Kyowa Kirin, and GlaxoSmithKline, and has received honoraria for lectures from Daiichi Sankyo, Takeda Pharmaceutical, Astellas Pharma, Otsuka Pharmaceutical, and Kyowa Kirin, and has received research grants from Mitsubishi Tanabe Pharma, Toray Industries, Baxter, Chugai Pharmaceutical, Kyowa Kirin, Bayer Yakuhin, Ono Pharmaceutical, Daiichi Sankyo, Nippon Boehringer Ingelheim, Astellas Pharma, and Takeda Pharmaceutical. Y Kumeda, Y Higashino, Y Maeda, Y Kaneko and H Kanai have no conflicts of interest to declare. Y Taniguchi, T Ishii and Y Tomioka are employees of Zeria Pharmaceuticals., (© 2024. The Author(s).)

Purpose: This study proposes a process for detecting slices with bone marrow edema (BME), a typical finding of axSpA, using MRI scans as the input. This process does not require manual input of ROIs and provides the results of the judgment of the presence or absence of BME on a slice and the location of edema as the rationale for the judgment., Methods: First, the signal intensity of the MRI scans of the sacroiliac joint was normalized to reduce the variation in signal values between scans. Next, slices containing synovial joints were extracted using a slice selection network. Finally, the BME slice detection network determines the presence or absence of the BME in each slice and outputs the location of the BME., Results: The proposed method was applied to 86 MRI scans collected from 15 hospitals in Japan. The results showed that the average absolute error of the slice selection process was 1.49 slices for the misalignment between the upper and lower slices of the synovial joint range. The accuracy, sensitivity, and specificity of the BME slice detection network were 0.905, 0.532, and 0.974, respectively., Conclusion: This paper proposes a process to detect the slice with BME and its location as the rationale of the judgment from an MRI scan and shows its effectiveness using 86 MRI scans. In the future, we plan to develop a process for detecting other findings such as bone erosion from MR scans, followed by the development of a diagnostic support system., (© 2024. CARS.)

The concept of lifetime management has not been discussed in the field of percutaneous coronary intervention (PCI), because the durability of drug-eluting stent (DES) is considered to be long enough for most patients. Furthermore, even if in-stent restenosis occurs, the treatment for in-stent restenosis is simple in most cases. On the other hand, the long-term clinical outcomes after DES implantation are worse in severely calcified coronary lesions than in non-calcified lesions. Moreover, the treatment for in-stent calcified restenosis or restenosis due to stent underexpansion is not simple. The concept of lifetime management of severely calcified lesions may be necessary like that of aortic stenosis. Recently, several algorithms have been published in PCI to severely calcified lesions, partly because of the emergence of IVL. These algorithms focus on the selection of cracking and debulking devices for the preparation of stenting. However, the optimal stent expansion does not guarantee the long-term patency, when the target lesion includes calcified nodules. Stent restenosis due to calcified nodules is difficult to manage. In this review article, we propose the algorithm for severely calcified lesions focused on the shape of calcification. We do not need to hesitate stenting when multiple cracks on circumferential calcification are observed by intravascular imaging devices. However, DCB may be an option as final device in some situations, when lifetime management of severely calcified lesions is considered., (© 2023. The Author(s) under exclusive licence to Japanese Association of Cardiovascular Intervention and Therapeutics.)

Serious complications including vessel perforation may occur during rotational atherectomy (RA) to left circumflex (LCX) ostial lesions. In fact, if perforation occurs around LCX ostium, bailout procedures including deployment of covered stents may cause fatal ischemia in the territory of left anterior descending artery, which results in broad anterior acute myocardial infarction and subsequent death. In this review article, we described tips and tricks for RA to LCX ostial lesions. First, we should cautiously decide the indication for RA to LCX ostial lesions, because there are several reasons to avoid RA to LCX ostial lesions. Before procedures, we should estimate the difficulty of RA to LCX ostial lesions, which is mainly determined by the combination of the bifurcation angle and the severity of stenosis. Thus, the combination of the large bifurcation angle and the tight stenosis makes RA to LCX ostial lesions most difficult. Appropriate position of guide catheter and RotaWire is a key to successful RA to LCX ostial lesions. Differential cutting is an essential concept for RA to LCX ostial lesions. However, since there is no guarantee that differential cutting always works, small burr (≤ 1.5 mm) would be a safe choice as initial burr for RA to LCX ostial lesions., (© 2023. The Author(s) under exclusive licence to Japanese Association of Cardiovascular Intervention and Therapeutics.)

Background: Amphiregulin (AREG) is a ligand of epidermal growth factor receptor (EGFR), which plays an important role in injury-induced kidney fibrosis. However, the clinical significance of serum soluble AREG in chronic kidney disease (CKD) is unclear. In this study, we elucidated the clinical significance of serum soluble AREG in CKD by analyzing the association of serum soluble AREG levels with renal function and other clinical parameters in patients with CKD., Methods: In total, 418 Japanese patients with CKD were enrolled, and serum samples were collected for the determination of soluble AREG and creatinine (Cr) levels, and other clinical parameters. Additionally, these parameters were evaluated after 2 and 3 years. Moreover, immunohistochemical assay was performed ate AREG expression in the kidney tissues of patients with CKD., Results: Soluble AREG levels were positively correlated with serum Cr (p < 0.0001). Notably, initial AREG levels were positively correlated with changes in renal function (ΔCr) after 2 (p < 0.0001) and 3 years (P = 0.048). Additionally, soluble AREG levels were significantly higher (p < 0.05) in patients with diabetic nephropathy or primary hypertension. Moreover, AREG was highly expressed in renal tubular cells in patients with advanced CKD, but only weakly expressed in patients with preserved renal function., Conclusion: Serum soluble AREG levels were significantly correlated with renal function, and changes in renal function after 2 and 3 years, indicating that serum soluble AREG levels might serve as a biomarker of renal function and renal prognosis in CKD., (© 2024. The Author(s), under exclusive licence to Japanese Society of Nephrology.)

Adult-onset still's disease is a rare condition that is generally treated by glucocorticoids. Importantly, due to the limited established treatments, glucocorticoid-refractory cases are particularly difficult to treat. Between December 2009 and August 2022, nine patients with adult-onset Still's disease were treated with tocilizumab (tocilizumab group). The therapeutic efficacy and safety of tocilizumab initiation in the acute phase were evaluated in cases of initial onset and recurrence. We also compared the efficacy of tocilizumab with that of methotrexate (methotrexate group, n = 13), which has been the drug of choice for adjunctive therapy. Tocilizumab demonstrated the expected efficacy in all four patients who received it at relapse and in three of the five patients who received it at the initial onset. However, two patients developed macrophage activation syndrome following treatment. A comparison of treatment effects between the methotrexate and tocilizumab groups revealed that the ferritin and C-reactive protein levels, severity score, and glucocorticoid doses decreased over time in both groups; nonetheless, the tocilizumab group experienced a more stable effect. Tocilizumab is undoubtedly a valuable treatment option for adult-onset Still's disease, especially when administered at relapse. This suggests that it shows both high safety and good efficacy. Nevertheless, a larger sample size is required to validate the efficacy and safety of tocilizumab compared with those of the existing alternatives. Key Points • We examined the significance of TCZ in terms of therapeutic efficacy, reduction in glucocorticoid usage, and safety in patients with AOSD. • We compared the therapeutic efficacy of TCZ with that of MTX, which is often used to treat glucocorticoid-resistant AOSD. • TCZ is undoubtedly a valuable treatment option for AOSD, especially when administered at relapse, suggesting both high safety and good efficacy., (© 2024. The Author(s).)

The situation around primary percutaneous coronary intervention (PCI) has dramatically changed since coronavirus disease 2019 (COVID-19) pandemic. The impact of COVID-19 pandemic on clinical outcomes as well as door-to-balloon time (DTBT), which is known as one of the indicators of early reperfusion, has not been fully investigated in patients with ST-elevation acute myocardial infarction (STEMI). The purpose of this study was to compare DTBT and in-hospital outcomes in patients with STEMI between before versus after COVID-19 pandemic. The primary interest was DTBT and the incidence of in-hospital outcomes including in-hospital death. We included 330 patients with STEMI who underwent primary PCI, and divided them into the pre COVID-19 group (n = 209) and the post COVID-19 group (n = 121). DTBT was significantly longer in the post COVID-19 group than in the pre COVID-19 group (p < 0.001), whereas the incidence of in-hospital death was comparable between the 2 groups (p = 0.238). In the multivariate logistic regression analysis, chest CT before primary PCI (OR 4.64, 95% CI 2.58-8.34, p < 0.001) was significantly associated with long DTBT, whereas chest CT before primary PCI (OR 0.76, 95% CI 0.29-1.97, p = 0.570) was not associated with in-hospital death after controlling confounding factors. In conclusion, although DTBT was significantly longer after COVID-19 pandemic than before COVID-19 pandemic, in-hospital outcomes were comparable between before versus after COVID-19 pandemic. This study suggests the validity of the screening tests including chest CT for COVID-19 in patients with STEMI who undergo primary PCI., (© 2022. The Author(s) under exclusive licence to Japanese Association of Cardiovascular Intervention and Therapeutics.)

Slow flow during primary percutaneous coronary intervention (PCI) is a common complication. Our group showed that the stent (or post-balloon) diameter-to-vessel diameter ratio was inversely associated with slow flow phenomenon. We advocated the utility of modest stent expansion strategy, which was defined as the stent (or post-balloon) diameter-to-culprit vessel diameter ratio < 0.71, for prevention of slow flow phenomenon. This study aimed to compare the long-term outcomes in patients with acute myocardial infarction (AMI) between the modest stent expansion strategy and the aggressive stent expansion strategy (the stent diameter-to-culprit vessel diameter ratio ≥ 0.71). We included 584 AMI patients, which were divided 177 patients in the modest stent expansion group and 146 patients in the aggressive stent expansion group. The primary endpoint was major adverse cardiac events (MACE), which was defined as a composite of cardiac death, ischemia driven target vessel revascularization, and stent thrombosis. The slow flow after stent deployment was more frequently observed in the aggressive stent expansion group (24.0%) than in the modest stent expansion group (4.0%) (P < 0.001). The Kaplan-Meier curves revealed that MACE was comparable between the two groups (P = 0.64). The multivariate COX hazard model showed the non-significant association between the modest stent expansion strategy and MACE (vs. aggressive stent expansion: hazard ratio 1.005, 95% confidence interval 0.619-3.242, P = 0.41). In conclusion, the modest stent expansion strategy was not associated with long-term MACE. Therefore, the modest stent expansion strategy may be a good choice for the culprit lesion of AMI., (© 2022. The Author(s) under exclusive licence to Japanese Association of Cardiovascular Intervention and Therapeutics.)

Purpose: The acquisition of osseointegration during implant therapy is slower and poorer in patients with diabetes compared with healthy persons. The serum concentration of adiponectin in patients with type II diabetes is lower than that of healthy persons via the suppression of AMP-activated protein kinase (AMPK). Therefore, we hypothesized that the AMPK activation enhances bone formation around implants, resulting in the improved acquisition of osseointegration. The purpose of this study was to evaluate the impact of AMPK activation on osteoblast differentiation and its mechanism of downstream signaling on titanium disc (Ti)., Methods: Confluent mouse pre-osteoblasts (MC3T3-E1) cells (1 × 10 5 cells/well) were cultured with BMP-2 for osteoblast differentiation, in the presence or absence AICAR, an AMPK activator. We examined the effects of AMPK activation on osteoblast differentiation and the underlying mechanism on a Ti using a CCK8 assay, a luciferase assay, quantitative RT-PCR, and western blotting., Results: Although the proliferation rate of osteoblasts was not different between a Ti and a tissue culture polystyrene dish, the addition of AICAR, AMPK activator slightly enhanced osteoblast proliferation on the Ti. AICAR enhanced the BMP-2-dependent transcriptional activity on the Ti, leading to upregulation in the expression of osteogenesis-associated molecules. AICAR simultaneously upregulated the expression of autophagy-associated molecules on the Ti, especially LC3-II. AdipoRon, an adiponectin receptor type1/type2 activator activated AMPK, and upregulated osteogenesis-associated molecules on Ti., Conclusions: AMPK activation enhances osteoblast differentiation on a Ti via autophagy, suggesting that it promotes the acquisition of osseointegration during implant therapy., (© 2024. The Author(s).)

Rotational atherectomy (RA) is technically more difficult in a diffuse calcified lesion than in a focal calcified lesion. We hypothesized that taking a halftime can be another option for RA to the diffuse calcified lesions. Halftime was defined as at least one long break during RA, in which an operator pulled out the Rotablator system from the guide catheter before crossing the lesion. This study aimed to compare the complications between RA with and without halftime. We included 177 diffuse long severely calcified lesions (lesion lengths ≥ 30 mm) that required RA, and divided those lesions into a halftime group (n = 29) and a no-halftime group (n = 148). The primary outcome was periprocedural myocardial infarction (MI). The reference diameter was smaller in the halftime group than in the no-halftime group [1.82 (1.70-2.06) mm versus 2.17 (1.89-2.59) mm, p = 0.002]. The total run time was longer in the halftime group than in the non-halftime group [133.0 (102.0-223.0) seconds versus 71.5 (42.0-108.0) seconds, p < 0.001]. Although creatinine kinase (CK) and CK-myocardial band (MB) was significantly higher in the halftime group than in the no-halftime group [CK: 156 (97-308) U/L versus 99 (59-216) U/L, p = 0.021; CK-MB: 15 (8-24) U/L versus 5 (3-15) U/L, p < 0.001], periprocedural MI was not observed in the halftime group. In conclusion, periprocedural MI was not observed in RA with halftime. This preliminary study suggests that halftime RA may be a safe option for diffuse severely calcified lesions., (© 2023. The Author(s).)

Percutaneous coronary intervention (PCI) is a standard strategy for non-ST-segment elevation myocardial infarction (NSTEMI) as well as for ST-segment elevation myocardial infarction (STEMI). The device cost for PCI may be more expensive in NSTEMI, because the culprit lesion morphology may be more complex in NSTEMI. This study aimed to compare the total device cost of PCI between STEMI and NSTEMI. We included 504 patients with acute myocardial infraction (AMI) who underwent PCI, and divided those into a STEMI group (n = 286) and a NSTEMI group (n = 218). We compared the total device cost, the number of used devices, and procedure cost between the 2 groups. The total device cost was significantly higher in the NSTEMI group [¥371,300 (¥320,700-503,350)] than in the STEMI group [¥341,200 (¥314,200-410,475)] (p = 0.001), whereas the procedure cost was significantly higher in the STEMI group [¥343,800 (¥243,800-343,800)] than in the NSTEMI group [¥220,000 (¥216,800-243,800)] (p < 0.001). Drug eluting stent (85.3% vs. 76.1%, p = 0.029) and aspiration catheter (16.8% vs. 2.3%, p < 0.001) were more frequently used in the STEMI group, whereas rotablator (0.7% vs. 8.3%, p < 0.001) were more frequently used in the NSTEMI group. The multivariate logistic regression analysis revealed that NSTEMI was significantly associated with the high device cost (odds ratio 1.899, 95% confidence interval 1.166-3.093, p = 0.01). In conclusion, the total device cost for PCI was significantly higher in the culprit lesions of NSTEMI than in those of STEMI, whereas the procedure cost was significantly higher in the culprit lesions of STEMI than in those of NSTEMI., (© 2021. Japanese Association of Cardiovascular Intervention and Therapeutics.)

Since slow flow can be a fatal complication in left main coronary artery (LMCA)-acute coronary syndrome (ACS) patients, it should be important to anticipate and prepare slow flow during primary PCI for LMCA-ACS. We hypothesized that intravascular ultrasound (IVUS) findings would be useful to predict slow flow for LMCA-ACS patients without cardiogenic shock (CS). The purpose of this study was to investigate clinical factors associated with slow flow in LMCA-ACS patients without CS. We included 60 LMCA-ACS patients without CS, and divided into the slow flow group (n = 18) and the non-slow flow group (n = 42). Slow flow was defined as either transient or persistent TIMI flow grade ≤ 2. The prevalence of ST-segment elevation myocardial infarction (STEMI) was significantly higher in the slow flow group (55.6%) than in the non-slow flow group (11.9%) (p = 0.002). In the IVUS analysis, remodeling index was significantly greater in the slow flow group (1.15 ± 0.17) than in the non-slow flow group (0.99 ± 0.11) (p = 0.001). The multivariate logistic regression analyses in the IVUS factors revealed that remodeling index was significantly associated with slow flow (0.1 increase: OR 2.238, 95% CI 1.144-4.379, p = 0.019). In conclusion, remodeling index was significantly associated with slow flow. Our results suggest that the remodeling index determined by IVUS would be useful to find high-risk features of slow flow in LMCA-ACS patients without CS., (© 2020. Japanese Association of Cardiovascular Intervention and Therapeutics.)

In most areas in Japan, patients with ST-elevation myocardial infarction (STEMI) would be transferred to the secondary hospitals or tertiary hospitals according to the judgement of emergency medical service (EMS) staff members. We hypothesized that in-hospital outcomes would be worse in STEMI patients judged as tertiary emergency than in those judged as secondary emergency, which may support the judgement of the current EMS systems. The purpose of this study was to compare in-hospital outcomes of STEMI between patients judged as secondary emergency and those judged as tertiary emergency. We included 238 STEMI patients who were transferred to our institution using EMS hotline, and divided those into the secondary emergency group (n = 106) and the tertiary emergency group (n = 132). The primary endpoint was in-hospital death. The prevalence of shock was significantly higher in the tertiary emergency group than in the secondary emergency group (32.6% vs. 10.4%, p < 0.001). The GRACE score was significantly higher in the tertiary emergency group than the secondary emergency group [146 (118-188) vs. 134 (101-155), p < 0.001]. The incidence of in-hospital death was significantly higher in the tertiary emergency group than in the secondary emergency group (8.0% vs. 2.1%, p = 0.014). The multivariate logistic regression analysis revealed that the tertiary emergency was significantly associated with in-hospital death (OR 3.52, 95% CI 1.24-10.02, p = 0.018) after controlling age and gender. In conclusion, the tertiary emergency was significantly associated with in-hospital death. Our results might validate the judgement of levels of emergency by local EMS staff members., (© 2020. Japanese Association of Cardiovascular Intervention and Therapeutics.)

The medical expenses for patients with acute myocardial infarction (AMI) has become enormous burden for global healthcare system. In AMI patients, total admission cost for patients with off-hours visit may be higher than those with on-hours visit, because of additional cost for emergent care during off-hours. This study aimed to compare total medical cost in AMI patients between on-hours visit versus off-hours visit. We retrospectively included 368 AMI patients who underwent PCI to the culprit lesion, and divided them into the on-hours group (n = 173) and the off-hours group (n = 195). We compared clinical characteristics, total admission cost, and clinical outcomes between the two groups. The prevalence of Killip class 3/4 was significantly greater in the off-hours group than in the on-hours group. Length of ICU and hospital stay were significantly longer in the off-hours group than in the on-hours group. Total admission cost was significantly higher in the off-hours group [¥1,570,400 (¥1,271,550-¥2,117,090)] than in the on-hours group [¥1,356,270 (¥1,100,990-¥1,957,225)] (P < 0.001). However, multivariate analysis revealed off-hours visit itself was not associated with high total admission cost after adjusting confounding factors. In conclusion, total admission cost was higher in AMI patients with off-hours visit than in those with on-hours visit. However, multivariate logistic regression analysis revealed that the off-hours visit itself was not associated with the highest total admission cost. Off-hours visit itself did not result in higher cost, but severer conditions in AMI patients with off-hours visit resulted in higher cost., (© 2022. The Author(s) under exclusive licence to Japanese Association of Cardiovascular Intervention and Therapeutics.)

Objectives: Ramucirumab (RAM) and docetaxel (DOC) are commonly used after first-line therapy for advanced non-small cell lung cancer (NSCLC). Therefore, we aimed to elucidate sequencing strategies of RAM and DOC following prior treatments, including immune checkpoint inhibitor (ICI), cytotoxic agent (CTx) alone, bevacizumab (BEV), and tyrosine kinase inhibitor (TKI)., Methods: We recruited patients with NSCLC who received RAM and DOC and compared the groups with and without prior ICI, CTx alone, BEV, and TKI, respectively. By tumor response to such treatments, the patients were further classified into "complete response (CR) + partial response (PR)," "stable disease," and "progressive disease" groups, respectively. We compared RAM and DOC efficacy among these groups., Results: In total, 237 patients were registered. In the group with prior ICI, the objective response rate and disease control rate were significantly higher than those without prior ICI (p = 0.012 and 0.028, respectively), and the median progression-free survival (PFS) was also significantly longer (p = 0.027). There were no significant differences in PFS between the groups with and without CTx alone, BEV, and TKI. Multivariate analysis revealed that prior ICI was an independent factor associated with better PFS. Furthermore, the prior ICI group with CR + PR significantly prolonged PFS compared to the group without prior ICI (p = 0.013)., Conclusion: RAM and DOC may be preferably administered after ICI, rather than after CTx alone, BEV, or TKI, and, furthermore, enhanced if the prior ICI has a favorable tumor response., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: It is unclear whether motor-cognitive dual tasks predict cognitive decline better than either motor or cognitive tasks alone., Aims: To examine the utility of the novel motor-cognitive dual-task test [Stepping Trail Making Test (S-TMT)], as a predictor of cognitive decline, and compare its predictive performance with single motor or cognitive tests., Methods: This 2-year population-based prospective study included 626 adults aged ≥ 70 years from Takashimadaira, Itabashi, Tokyo. The S-TMT measured the time taken to step on 16 numbers in order. Gait speed and TMT-A were assessed with standardized methods as single motor and cognitive tasks, respectively. A decline in the Mini-Mental State Examination score by ≥ 3 points over 2 years was defined as a significant cognitive decline., Results: Over 2 years, 97 (15.5%) experienced cognitive decline. After adjusting for confounders, binary logistic regression models showed no significant associations between gait speed, TMT-A time tertiles, and risk of cognitive decline, but participants in the longest tertile of S-TMT time were more likely to develop cognitive decline than those of the shortest tertile (odds ratio 2.14; 95% confidence interval 1.17-3.90). Only the addition of the S-TMT time to the covariates model significantly improved the reclassification indices for predicting cognitive decline (net reclassification improvement: 0.31, P < 0.01; integrated discrimination improvement: 0.01, P = 0.02)., Discussion and Conclusion: Only the S-TMT was significantly associated with cognitive decline and improved reclassification indices, indicating that it is more useful for predicting cognitive decline than individual gait speed or visual tracking tests alone.

This paper presents a counseling (ro)bot called Visual Counseling Agent (VICA) which focuses on remote mental healthcare. It is an agent system leveraging artificial intelligence (AI) to aid mentally distressed persons through speech conversation. The system terminals are connected to servers by the Internet exploiting Cloud-nativeness, so that anyone who has any type of terminal can use it from anywhere. Despite a promising voice communication interface, VICA shows limitations in conversation continuity on conventional 4G networks. Concretely, the use of the current 4G networks produces word dropping, delayed response, and the occasional connection failure. The objective of this paper is to mitigate these issues by leveraging a 5G/6G slice inclusive of mobile/multiple edge computing (MEC). First, we propose and partly implement the enhanced and advanced version of VICA. Servers of enhanced versions collaborate to increase speech recognition reliability. Although it significantly increases generated data volume, the advanced version enables a recognition of the facial expressions to greatly enhance counseling quality. Then, we propose a quality assurance mechanism using multiple levels of catalog, as well as 5G/6G slice inclusive of MEC, and conduct experiments to uncover issues related to the 4G. Results indicate that the number of speech recognition errors in Internet Cloud is more than twofold compared to edge computing, implying that quality assurance using 5G/6G in conjunction with VICA Counseling (ro)bot has higher efficiency., Competing Interests: Conflict of interestThere is no conflict of interest., (© The Author(s) 2022.)

Objectives As first line therapy, pembrolizumab provides longer progression free survival (PFS) and overall survival (OS) than platinum doublets in programmed death ligand 1 (PD-L1)-positive non-small cell lung cancer (NSCLC) with tumor propensity scores (TPS) ≥50%. However, clinical trials do not represent real-world patients. Materials and Methods This multicenter retrospective study conducted across 11 medical centers in Japan analyzed clinical data from patients receiving first-line pembrolizumab for NSCLC between February 1, 2017 and April 30, 2018. The efficacy, safety, and suitability of pembrolizumab monotherapy were evaluated. Results The median age of the 213 enrolled patients was 71 (range: 39-91) years. Among them, 176 (82.6%) were male, 20 (9.4%) were never smokers (median Brinkman index: 900), 172 (80.8%) had an ECOG PS of 0-1, 55 (25.8%) had squamous-cell carcinoma (SQ). PD-L1 TPS were 50-74%, 75-89%, and 90-100% in 97 (45.5%), 47 (22.1%), and 69 (32.4%) patients, respectively. Adverse events (AEs) of grades ≥3 were observed in 39 (18.3%) patients. Pneumonitis was the most common severe AE, occurring in 10 patients (4.7%) including 1 with grade 4 toxicity; no severe AE-related deaths occurred. The overall response rate, median PFS, and median OS was 51.2%, 8.3 months, and 17.8 months, respectively. On multivariate analysis, ECOG PS (0-1 vs. ≥2: HR: 1.69, 95.0% CI: 1.05-2.72; p = 0.03138), CRP/Alb (<0.3 vs. ≥0.3: HR: 1.92, 95.0% CI: 1.28-2.87; p = 0.00153), steroid usage (not usage vs. usage: HR: 2.94, 95.0% CI: 1.45-5.95; p = 0.00267), and PD-L1 TPS (50-89% vs. 90-100%: HR: 0.65, 95.0% CI: 0.43-1.00; p = 0.04984) were significantly and independently correlated with PFS of pembrolizumab. Conclusion The results confirm the efficacy and safety of pembrolizumab in real-world patients. Poor PS and steroid usage at the time of commencing pembrolizumab treatment indicate poor outcomes. First-line pembrolizumab particularly benefits patients with PD-L1 TPS ≥90% or low inflammatory states (CRP/ALB<0.3).

Objectives Vascular endothelial growth factor plays an important role in the pathogenesis of malignant pleural effusion (MPE). We previously showed the efficacy of bevacizumab (Bev) plus carboplatin (CBDCA)/paclitaxel (PTX) in the treatment of non-small lung cell cancer (NSCLC) with MPE. However, the toxicities were a little severe, and the efficacy was not satisfied sufficiently. Therefore, we conducted a phase II study for NSCLC with MPE to evaluate the efficacy and safety of Bev plus CBDCA/nab-PTX, which is a new combination therapy. Methods Chemotherapy-naive non-squamous (SQ) NSCLC patients with MPE participated in the study. A single aspiration (not allowing chest tube drainage) was allowed before chemotherapy. Patients received a maximum of six cycles of Bev (15 mg/kg, day1) plus CBDCA (AUC 6, day1)/nab-PTX (100 mg/m 2 , day1, 8) every 3 weeks followed by Bev (15 mg/kg, day1) plus nab-PTX (100 mg/m 2 , day1, 8) every 3 weeks without disease progression or unacceptable severe toxicities. The primary endpoint was objective response rate (ORR). Results The study enrollment was ceased because of suspension of the registration period (as scheduled) after 12 of 20 planned patients were treated successfully between March 2014 and February 2018. The ORR was 58.3 % (95 % CI, 27.7-84.8 %), and the disease control rate was 100 % (95 % CI, 73.5-100 %). Eight patients received maintenance therapy. Median progression-free and overall survival times were 14.4 and 26.9 months, respectively. Most patients experienced hematological toxicities, including ≥ grade 3 neutropenia and anemia; none experienced severe bleeding events and grade 5 toxicities. Conclusion The combination of Bev plus CBDCA/nab-PTX, a novel combination, might have efficacy with acceptable toxicities in chemotherapy-naïve non-SQ NSCLC patients with MPE.Trial Registration University Hospital Medical Information Network in Japan (UMIN) Clinical Trials Registry (No. UMIN000013329) registered on 4th March 2014., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC part of Springer Nature.)

Highly sensitive solid-phase colorimetry for nickel ion was demonstrated using an improved reflection colorimeter equipped with a coaxial optical-fiber cable. The nickel complex with α-furil dioxime was collected on a small-size membrane filter embedded in a disposable syringe filter unit. The leading edge of the optical-fiber cable was connected to the syringe filter unit via a Luer-lock fitting, and the color intensity of the sample on the filter was evaluated accurately. The detection limit was 0.8 ng in 2.5 mL of the complex solution (0.3 μg L -1 ). This improved configuration is applicable to highly sensitive on-site analysis without expensive instruments nor high laboratory skills.

Background: In 2011, the IgG4-related kidney disease (IgG4-RKD) working group of the Japanese Society of Nephrology proposed diagnostic criteria for IgG4-RKD. The aim of the present study was to validate those criteria and develop a revised version., Methods: Between April 2012 and May 2019, we retrospectively collected Japanese patients with kidney disease, for whom data on serum IgG4 values and/or immunohistological staining for IgG4 in renal biopsy samples were available. These patients were classified as IgG4-RKD or non-IgG4-RKD based on the diagnostic criteria for IgG4-RKD 2011, and the results were evaluated by expert opinion. Accordingly, we developed some revised versions of the criteria, and the version showing the best performance in the present cohort was proposed as the IgG4-RKD criteria for 2020., Results: Of 105 included patients, the expert panel diagnosed 55 as having true IgG4-RKD and 50 as mimickers. The diagnostic criteria for IgG4-RKD 2011 had a sensitivity of 72.7% and a specificity of 90.0% in this cohort. Of the 15 patients with true IgG4-RKD who were classified as non-IgG4-RKD, all lacked biopsy-proven extra-renal lesions, although many had clinical findings highly suggestive of IgG4-RD. The revised version to which "bilateral lacrimal, submandibular or parotid swelling, imaging findings compatible with type 1 autoimmune pancreatitis or retroperitoneal fibrosis" was added as an item pertaining to extra-renal organ(s) improved the sensitivity to 90.9% while the specificity remained at 90.0%., Conclusion: The revised version has considerably improved test performance after addition of the new extra-renal organ item (imaging and clinical findings).

Since intravascular imaging such as intravascular ultrasound (IVUS) can provide useful information for rotational atherectomy (RA), intravascular imaging should be attempted before RA. However, some calcified lesions do not allow imaging catheters to cross before RA. Although small burrs (1.25 mm or 1.5 mm) should be selected for such tight lesions, it is unknown whether a 1.25-mm burr or 1.5-mm burr is safer as the initial burr. The aim of this study was to compare the incidence of complications with a 1.25-mm versus a 1.5-mm burr as the initial burr for IVUS-uncrossable lesions. This was a retrospective, single-center study. A total of 109 IVUS-uncrossable lesions were included, and were divided into a 1.25-mm group (n =52) and a 1.5-mm group (n =57). The incidence of slow flow just after RA was not different between the 2 groups (1.25-mm group: 25%, 1.5-mm group: 31.6%, P =0.45). The incidence of peri-procedural MI with slow flow was not different and equally low in the 2 groups (1.25-mm group: 1.9%, 1.5-mm group: 3.5%, P =0.61). The use of the 1.5-mm burr as the initial burr was not significantly associated with slow flow after controlling for chronic renal failure on hemodialysis and reference diameter (vs. 1.25-mm: OR 2.34, 95% CI 0.89-6.19, P =0.09). In conclusion, the incidence of complications following RA was comparable between the 1.25-mm and the 1.5-mm burrs as the initial burr for IVUS-uncrossable lesions. The present study provides insights into the selection of an appropriate burr for IVUS-uncrossable lesions.

Remodeling in the right-sided heart plays an important role in the management of pulmonary hypertension (PH) patients. However, the effect of balloon pulmonary angioplasty (BPA) on right ventricular (RV) and right atrial (RA) morphology of patients with chronic thromboembolic pulmonary hypertension (CTEPH) remains uncertain. This study involved 45 CTEPH patients who underwent BPA with mean pulmonary artery pressure (mPAP) of 37.0 mmHg (all ≥ 25 mmHg). All patients underwent echocardiography and right-heart catheterization at baseline and 3 months after BPA. RV and RA remodeling was assessed as RV and the RA area, and RV systolic function was calculated by averaging peak speckle-tracking longitudinal strain of the RV free-wall (RV free-wall strain). Significant reverse remodeling in the right-sided heart was observed after BPA, resulting in improvement of mPAP and pulmonary vascular resistance (RV area: from 15.0 ± 5.3 to 9.6 ± 3.0 cm 2 , p < 0.0001; RA area: from 17.3 ± 6.6 to 13.4 ± 3.8 cm 2 , p = 0.0002; RV free-wall strain: from 15.9 ± 5.6 to 21.2 ± 4.9%, p < 0.0001). Furthermore, multiple regression analysis showed that the baseline RV area was an independent predictor of post-BPA normalization of RV systolic function defined as RV free-wall strain ≥ 20% (odds ratio = 1.16, p = 0.0305). Interestingly, significant RV reverse remodeling was also observed after additional BPA even in 18 CTEPH patients with residual pulmonary arterial stenosis, whose mPAP was normalized after BPA (RV area: from 11.5 ± 3.8 to 9.2 ± 3.8 cm 2 , p = 0.0045; RV free-wall strain: from 17.2 ± 4.8 to 22.8 ± 7.4%, p = 0.0216). Significant reverse remodeling in the right-sided heart, as well as hemodynamic improvement, was observed in CTEPH patients after BPA.

Background: No study has reported trajectories of kidney function in later life. This long-term prospective study attempted to classify trajectories of estimated glomerular filtration rate (eGFR) and identify factors associated with these trajectories., Methods: We collected data from annual geriatric health checkups conducted during 2002-2017 in Kusatsu Town, Gunma Prefecture, Japan. The participants were 1990 adults aged 65-90 years (mean [SD] age, 71.0 [5.7] years; 57.0% women), and the total number of observations was 9291. Data were analyzed with a group-based semiparametric mixture model and age-adjusted univariable cumulative logit models., Results: Trajectory of kidney function, as determined by eGFR, was classified as low, middle, and high (4.8%, 38.9%, and 56.3% of men, respectively, and 5.2%, 31.5%, and 63.3% of women). Among men and women in the low trajectory group, chronic kidney disease (CKD) stage worsened from stage G3a (51.8 ml/min/1.73 m 2 in men and 53.6 in women) at age 65 years to stage G4 (28.0 ml/min/1.73 m 2 in men and 28.5 in women) by age 85 years. A history of hypertension (men and women) and heart disease (men) were more likely in the low trajectory group than in the middle and high trajectory groups., Conclusions: About 5% of community-dwelling older adults had an eGFR < 30 later in life. Our findings suggest that those with stage G3a CKD at age 65 years should be managed intensively, to control risk factors for CKD progression.

Percutaneous coronary intervention has been developed for patients with coronary artery disease. Calcified lesions are recognized as an unsolved issue where many clinical devices have evolved and some disappeared. Understanding intracoronary imaging of the calcified lesions can help operators to make decisions during the procedure. There are several potential stories of progression of calcification, although a precise mechanism of progression of calcification remains unknown. In the process of a large calcification, it is histologically believed that lipid is replaced by calcification. This process can be observed by intracoronary imaging devices, i.e., intravascular ultrasound and optical coherence tomography. Calcified nodule is a unique type of calcifications. Among the calcified lesions, especially calcified nodule has serious clinical outcomes such as target lesion revascularization (TLR) with stent under-expansion. Additionally, in-stent calcified nodule is a distinctive type of restenosis pattern after stenting to calcified nodule, leading to malignant cycle of repeated TLR. Recently, calcified nodule is divided into two types based on the surface irregularity: (1) eruptive and (2) non-eruptive calcified nodule. Eruptive calcified nodule has higher rate of target vessel revascularization than non-eruptive calcified nodule despite greater stent expansion in eruptive calcified nodule. It is thought that there are differences of component such as the amount of fibrin and the size of calcific nodules between both, although it is common for both to include calcific nodules and fibrin. Histopathological understanding calcified nodule can be helpful to choose the treatment devices during the procedure in the area where there is no correct answer., Competing Interests: Declarations. Conflict of interest: Dr. Jinnouchi has received speaking honoraria from Abbott Vascular, Boston Scientific, Terumo and NIPRO. Prof. Sakakura has received speaking honoraria from Abbott Vascular, Boston Scientific, Medtronic Cardiovascular, Terumo, OrbusNeich, Japan Lifeline, Kaneka, and NIPRO; he has served as a proctor for Rotablator for Boston Scientific, and he has served as a consultant for Abbott Vascular and Boston Scientific. Prof. Fujita has served as a consultant for Mehergen Group Holdings, Inc., (© 2025. The Author(s) under exclusive licence to Japanese Association of Cardiovascular Intervention and Therapeutics.)

Balloon pulmonary angioplasty (BPA) is an innovative treatment for chronic thromboembolic pulmonary hypertension (CTEPH). We retrospectively examined the clinical outcomes and complications of BPA at Yokohama City University Hospital (YCUH) between 2012 and 2018. In 2012, we began to conduct BPA sessions in 46 patients with inoperable CTEPH; 34 completed the BPA scheme and the follow-up plan. A longitudinal sub-analysis was performed with cohorts 1 and 2 receiving BPA before and after April 2015. Significant improvements in the mean pulmonary arterial pressure, pulmonary vascular resistance, and other parameters were detected after BPA. The total rate of thoracic complications was 25%. Specifically, the increase in SaO 2 and home oxygen therapy discontinuation rate, and oral riociguat discontinuation rate was significantly higher in cohort 2 (+ 7.7, 75, and 59%) compared to cohort 1 (+ 3.1, 27, and 10%) (P < 0.05). Moreover, the need for non-invasive positive pressure ventilation was significantly lower: 0% (cohort 2) vs. 7% (cohort 1) (P < 0.05). The BPA sessions conducted at the YCUH resulted in significant improvements in patients with CTEPH. This study demonstrates a clear learning curve regarding the effectiveness of BPA both in normalizing SaO 2 and facilitating the cessation of home oxygen therapy, as well as in reducing the incidence of severe complications., Competing Interests: Declarations. Conflict of interest: The authors declare that there are no conflicts of interest. Ethics approval and consent to participate: This study was approved by the Ethics Committee of YCUH (approval number: F230500041) and adhered to the ethical guidelines of the 1975 Declaration of Helsinki. Research information and consent forms were provided to patients in an opt-out format after the investigation because of the retrospective nature of this study. Consent to publish: Not applicable., (© 2024. The Author(s).)

Fibrillin microfibrils are ubiquitous elements of extracellular matrix assemblies that play crucial roles in regulating the bioavailability of growth factors of the transforming growth factor beta superfamily. Recently, several "a disintegrin and metalloproteinase with thrombospondin motifs" (ADAMTS) proteins were shown to regulate fibrillin microfibril function. Among them, ADAMTS17 is the causative gene of Weill-Marchesani syndrome (WMS) and Weill-Marchesani-like syndrome, of which common symptoms are ectopia lentis and short stature. ADAMTS17 has also been linked to height variation in humans; however, the molecular mechanisms whereby ADAMTS17 regulates skeletal growth remain unknown. Here, we generated Adamts17-/- mice to examine the role of Adamts17 in skeletogenesis. Adamts17-/- mice recapitulated WMS, showing shorter long bones, brachydactyly, and thick skin. The hypertrophic zone of the growth plate in Adamts17-/- mice was shortened, with enhanced fibrillin-2 deposition, suggesting increased incorporation of fibrillin-2 into microfibrils. Comprehensive gene expression analysis of growth plates using laser microdissection and RNA sequencing indicated alteration of the bone morphogenetic protein (BMP) signaling pathway after Adamts17 knockout. Consistent with this, phospho-Smad1 levels were downregulated in the hypertrophic zone of the growth plate and in Adamts17-/- primary chondrocytes. Delayed terminal differentiation of Adamts17-/- chondrocytes, observed both in primary chondrocyte and primordial metatarsal cultures, and was prevented by BMP treatment. Our data indicated that Adamts17 is involved in skeletal formation by modulating BMP-Smad1/5/8 pathway, possibly through inhibiting the incorporation of fibrillin-2 into microfibrils. Our findings will contribute to further understanding of disease mechanisms and will facilitate the development of therapeutic interventions for WMS.

In the published article, the Fig. 4a was published incorrectly.

Background: Surgery often introduce inflammatory response, which may promote tumor growth and metastasis of residual cancer cells. We investigated the impacts of methylprednisolone on the tumor growth and peritoneal seedings in mice treated with lipopolysaccharide (LPS), which mimics systemic inflammation induced by surgical stress and postoperative complications., Methods: The serum interleukin-6 (IL-6) levels, tumor volume, tumor weight, and the number of peritoneal nodules were investigated in tumor growth model and peritoneal seeding model using BALB/c mice and murine CT26 cancer cell lines in vivo. We conducted functional analyses of IL-6 in Western blotting and proliferation assays in vitro. We also investigated whether preoperative administration of methylprednisolone decreased postoperative serum IL-6 levels in cancer patients in a randomized clinical study., Results: In the in vivo study, methylprednisolone inhibited the LPS-induced increase of serum IL-6 levels (mean, 33,756 pg/ml vs. 5917 pg/ml; P < 0.001), tumor volume (mean, 397 mm 3 vs. 274 mm 3 ; P = 0.019), tumor weight (mean, 0.38 g vs. 0.15 g; P = 0.020), and the number of peritoneal nodules (mean, 112 vs. 47; P = 0.002). In the in vitro study, IL-6 enhanced JAK/STAT signaling and increased the cell proliferation, and IL-6R-neutralizing antibody attenuated these effects. In the clinical study, serum IL-6 levels were significantly decreased by methylprednisolone (median, 97.5 pg/ml vs. 18.0 pg/ml; P = 0.030)., Conclusions: Surgical stress and postoperative complications may enhance tumor growth due to the increase of IL-6. However, methylprednisolone can decrease serum IL-6 levels, thus inhibiting tumor growth and peritoneal seeding.

Objective: The Surgical Apgar Score quantifies three intraoperative parameters: lowest heart rate, lowest mean arterial pressure, and estimated blood loss (EBL). This scoring system predicts postoperative complications based on these measured factors. The aim of this study was to investigate the value of modified Surgical Apgar Score (mSAS) in predicting postoperative complications in patients with rectal cancer treated with robotic surgery in order to improve the survival and quality of life of rectal cancer patients., Methods: The study included patients with rectal cancer who underwent robotic surgery in the Department of Gastrointestinal Surgery at the First Affiliated Hospital of Nanchang University from January 2015 to December 2023. In minimally invasive surgery, we developed a modified Surgical Apgar Score (mSAS) tailored for robotic rectal cancer surgery, incorporating an adjusted threshold for EBL. This threshold was derived from quartile analysis of a cohort of 524 patients, with a median EBL of 100 mL (IQR 80-130 mL). We analyzed the association of postoperative complications with low mSAS., Results: This study included 524 patients, of which 91 (17.4%) experienced complications and 22 (4.2%) suffered severe complications. mSAS of 6 provided maximal Youden index and were determined as the cut-off values. The area under the ROC curve for predicting complications using the mSAS was 0.740. Univariate and multivariate analyses indicated that an older age, lower tumor localization, longer operation time, radiotherapy alone, combined chemoradiotherapy, and lower mSAS as independent risk factors for complications. The AUC of the prediction nomogram was 0.834 (95% CI 0.774-0.867). The calibration curve demonstrated excellent concordance with the nomogram, indicating the prediction curve ft the diagonal well., Conclusion: This study suggests that mSAS might be a valuable predictive indicator for postoperative complications following robotic rectal cancer surgery, with potentially higher clinical utility., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

In-hospital outcomes of acute myocardial infarction (AMI) with cardiogenic shock (CS) were still not satisfactory even in the primary percutaneous coronary intervention (PCI) era. The aim of this study was to compare in-hospital outcomes of AMI with CS caused by right coronary artery (RCA) occlusion vs. left coronary artery (LCA) occlusion. Consecutive 894 AMI patients from January 2010 to March 2015 were screened for inclusion. A total of 114 AMI patients with CS were included as the final study population, and were divided into the RCA group (n = 56) and LCA group (n = 58). The patient characteristics were compared between the two groups. Multivariate logistic regression analysis was performed to show whether the RCA group was associated with better outcomes even after controlling confounding factors. In-hospital mortality was significantly lower in the RCA group (8.9%) than in the LCA group (46.6%) (P < 0.001). The RCA group (vs. the LCA group) was inversely associated with in-hospital death (OR 0.08, 95% CI 0.02-0.21, P < 0.001) after controlling covariates. Aspartate transaminase value (per 50 U/L incremental: OR 1.22, 95% CI 1.03-1.45, P = 0.02), aging (per 10-year-old incremental: OR 2.14, 95% CI 1.26-3.63, P = 0.01) and using VA-ECMO (OR 22.13, 95% CI 5.22-93.90, P < 0.001) were also significantly associated with in-hospital death. In conclusion, among AMI patients with CS, IRA of RCA was significantly associated with the better in-hospital outcome.

The aim of this study was to clarify the differences in thallium-201-chloride (thallium-201) myocardial perfusion imaging (MPI) scans evaluated by conventional anger-type single-photon emission computed tomography (conventional SPECT) versus cadmium-zinc-telluride SPECT (CZT SPECT) imaging in normal databases for different ethnic groups. MPI scans from 81 consecutive Japanese patients were examined using conventional SPECT and CZT SPECT and analyzed with the pre-installed quantitative perfusion SPECT (QPS) software. We compared the summed stress score (SSS), summed rest score (SRS), and summed difference score (SDS) for the two SPECT devices. For a normal MPI reference, we usually use Japanese databases for MPI created by the Japanese Society of Nuclear Medicine, which can be used with conventional SPECT but not with CZT SPECT. In this study, we used new Japanese normal databases constructed in our institution to compare conventional and CZT SPECT. Compared with conventional SPECT, CZT SPECT showed lower SSS (p < 0.001), SRS (p = 0.001), and SDS (p = 0.189) using the pre-installed SPECT database. In contrast, CZT SPECT showed no significant difference from conventional SPECT in QPS analysis using the normal databases from our institution. Myocardial perfusion analyses by CZT SPECT should be evaluated using normal databases based on the ethnic group being evaluated.

Background: The number of elderly dialysis patients in Japan is dramatically increasing. Receiving therapy with better satisfaction through home care is one of the important factors in their daily lives. Thus, the quality of life of elderly patients on hemodialysis (HD) or peritoneal dialysis (PD) was evaluated., Methods: Clinical information of patients aged ≥80 years who started dialysis at our hospital between January 2013 and December 2015 was retrospectively collected. The mortality rate, length of hospitalization, and place of death were identified to evaluate patient quality of life., Results: In total, 56 patients (14 PD and 42 HD) were enrolled. The mean age of study subjects was 85.2 ± 4.0 years. The proportion of PD patients who lived with their family or have professional caregivers who could assist them in their daily life was higher than that of HD patients (100 vs. 76.2%, respectively; p = 0.044). Mortality rate was higher in PD patients than in HD patients (p = 0.003), but long-term hospitalization of >180 days was observed only in HD patients (PD vs. HD: 0.0 vs. 16.7%; p = 0.102). In patients with Barthel index scores <100, the long-term hospitalization difference was significant (PD vs. HD: 0.0 vs. 30.4%; p = 0.040). Of note, 6 of 7 deceased PD patients and 1 of 10 deceased HD patients died at home (p = 0.002)., Conclusion: PD is a desirable home care therapy for elderly patients, but the burden on caregivers should be considered.

Background: Acute kidney injury (AKI) is a serious complication among hospitalized individuals and is closely associated with chronic kidney disease (CKD)., Methods: This retrospective cohort study evaluated the incidences of AKI according to CKD stage at Kochi Medical School hospital during 1981-2011. AKI was defined and staged according to the kidney disease improving global outcomes criteria, using serum creatinine levels., Results: We analyzed data from 122,653 Japanese patients (57,105 men, 46.6 %). The incidence of AKI was 7.8 % (95 % confidence interval 7.7-8.0 %). Compared to non-AKI patients, patients with stage 1-2 AKI were more likely to be men. Patients with stage 1-2 AKI were significantly older than non-AKI or stage 3 AKI patients. The incidences of AKI were 6.7, 5.9, 10.4, 18.4, 30.0, and 48.8 % among individuals with estimated glomerular filtration rates of ≥90, 60-89, 45-59, 30-44, 15-29, and <15 mL/min/1.73 m 2 , respectively; these were significantly different from the incidence for the baseline eGFR. The proportions of inpatients with AKI exhibited step-wise increases with more severe pre-existing reduced kidney function, and the proportions among outpatients exhibited step-wise increases with milder pre-existing reduced kidney function., Conclusions: CKD was a risk factor for AKI, and the incidence of AKI was positively associated with pre-existing reduced kidney function (CKD stage). We also found that the prevalence of AKI at early-stage CKD among outpatients was higher than expected. We suggest that outpatients should be monitored for AKI, given its unexpected incidence in that population.

This study investigates the distribution of total mercury (T-Hg) and methylmercury (MeHg) in the soil and water around the artisanal and small-scale gold mining (ASGM) area along the Cikaniki River, West Java, Indonesia. The concentration of T-Hg and MeHg in the forest soil ranged from 0.07 to 16.7 mg kg -1 and from <0.07 to 2.0 μg kg -1 , respectively, whereas it ranged from 0.40 to 24.9 mg kg -1 and from <0.07 to 56.3 μg kg -1 , respectively, in the paddy field soil. In the vertical variation of the T-Hg of forest soil, the highest values were observed at the soil surface, and these values were found to decrease with increasing depth. A similar variation was observed for MeHg and total organic carbon content (TOC), and a linear relationship was observed between them. Mercury deposited on the soil surface can be trapped and retained by organic matter and subjected to methylation. The slope of the line obtained for the T-Hg vs. TOC plot became larger near the ASGM villages, implying a higher rate of mercury deposition in these areas. In contrast, the plots of MeHg vs. TOC fell along the same trend line regardless of the distance from the ASGM village. Organic carbon content may be a predominant factor in controlling MeHg formation in forest soils. The T-Hg concentration in the river water ranged from 0.40 to 9.6 μg L -1 . River water used for irrigation can prove to be a source of mercury for the paddy fields. The concentrations of Hg 0 and Hg 2+ in river water showed similar variations as that observed for the T-Hg concentration. The highest Hg 0 concentration of 3.2 μg L -1 can be attributed to the waste inflow from work sites. The presence of Hg 0 in river water can become a source of mercury present in the atmosphere along the river. MeHg concentration in the river water was found to be 0.004-0.14% of T-Hg concentration, which was considerably lower than the concentrations of other Hg species. However, MeHg comprised approximately 0.2% of the T-Hg in paddy field soil. Mercury deposited from the atmosphere and the river water can be subjected to methylation. Paddy fields are very important ecosystems; therefore, the effect of MeHg on these ecosystems and human beings should be further investigated.

Competing Interests: Compliance with ethical standards Financial sources and conflict of interest The funds used in producing the guideline were supported by a Health and Labour Science Research Grant from the Ministry of Health, Labour, and Welfare and the Japan AMED for Practical Research Project for Renal Diseases. All committee members involved in producing the Clinical Practice Guideline submitted conflict-of-interest statements based on academic society rules, which are managed by the Japanese Society of Nephrology (JSN). Opinions were sought from related academic societies, including JSN, The Japanese Society of Nephrology and pharmacotherapy, The Japanese Society of Clinical Pharmacology and Therapeutics, and The Japan Geriatrics Society to prevent the guidelines from being influenced by any conflicts of interest. Drafts were shown to the society members, and revisions were made based on their opinions (public comments).

Background and Objectives: Recent studies have shown that both low and high levels of serum uric acid (SUA) before cardiovascular surgery are independent risk factors for postoperative acute kidney injury (AKI). However, these studies were limited by their small sample sizes. Here, we investigated the association between SUA levels and AKI by performing a retrospective database analysis of almost 30 years of data from 81,770 hospitalized patients., Design, Setting, Participants, and Measurement: Hospitalized patients aged ≥18 years were retrospectively enrolled. AKI was diagnosed according to the Kidney Disease: Improving Global Outcomes 2012 Clinical Practice Guideline (KDIGO) criteria. Multivariate logistic regression analyses were performed to investigate the independent association between SUA levels and the incidence of AKI. SUA levels were treated as categorical variables because the relationship between SUA and the incidence of AKI has been suggested to be J-shaped or U-shaped. In addition to stratified SUA levels, we considered kidney function and related comorbidities, medications, and procedures performed prior to AKI onset as possible confounding risk factors., Results: The final study cohort included 59,219 adult patients. Adjusted odds ratios of AKI incidence were higher in both the high- and low-SUA strata. Odds ratios tended to become larger in the higher range of SUA levels in women than in men. Additionally, this study showed that AKI risk was elevated in patients with SUA levels ≤7 mg/dL. An SUA level >7 mg/dL is considered the point of initiation of uric acid crystallization., Conclusions: SUA level could be an independent risk factor for AKI development in hospitalized patients. Additionally, our results might suggest that intervention to lower SUA levels is necessary, even in cases of moderate elevation that does not warrant hyperuricemia treatment. Results also showed that SUA levels that require attention are lower for women than for men.

We screened a library of 528 approved drugs to identify candidate compounds with therapeutic potential as preeclampsia treatments via their proangiogenic properties. Using human umbilical vein endothelial cells (HUVECs), we assessed whether the screened drugs induced placental growth factor (PIGF) and restored damaged endothelial cell function. Enzyme-linked immunosorbent assays (ELISAs) were carried out to measure levels of PlGF in conditioned media treated with each drug (100 µmol/L) in the drug library. Tube formation assays were performed using HUVECs to evaluate the angiogenic effects of drugs that induced PlGF. We also performed ELISA, quantitative reverse transcription polymerase chain reaction, and tube formation assays after treatment with a range of concentrations of the candidate drug. Of the drugs that induced PlGF, vardenafil was the only compound that significantly facilitated tube formation in comparison with the control cells (P < .01). Treatment with vardenafil at concentrations of 50, 100, and 250 µmol/L increased expression of PlGF in a dose-dependent manner. Vardenafil (250 µmol/L) significantly improved tube formation which was inhibited in the presence of soluble fms-like tyrosine kinase 1 (100 ng/mL) and/or soluble endoglin (100 ng/mL). Production of PlGF from HUVECs in the presence of sera derived from patients with preeclampsia was significantly elevated by administration of vardenafil (250 µmol/L). By assessing drug repositioning through screening a library of approved drugs, we identified vardenafil as a potential protective agent against preeclampsia. The therapeutic mechanism of vardenafil may involve inhibition of the systemic maternal antiangiogenic state that leads to preeclampsia, in addition to its vasodilating effect. As concentrations used are high and unlikely to be useful clinically, further work is needed before testing it in humans., (© The Author(s) 2015.)

The consequences of acute strut malapposition in everolimus-eluting stents (EES) are unknown. This study investigated the impact of strut-vessel (S-V) distance and plaque type underneath acute strut malapposition on the mid-term vessel response in EES. Twenty-nine patients (35 EES) underwent optical coherence tomography (OCT) immediately after percutaneous coronary intervention and at 8-month follow-up. S-V distance and plaque type (lipid, calcified, or fibrous) underneath acute strut malapposition were evaluated. Follow-up OCT classified acute strut malapposition as persistent or resolved. The S-V cutoff value for predicting resolved strut malapposition and the incidence of intra-stent thrombi were determined. Among 569 cases of acute strut malapposition, involving 29,168 struts, 139 (24.4 %) were persistent. Mean S-V distance was significantly longer in persistent than in resolved strut malapposition (600 ± 294 vs. 231 ± 95 μm; P < 0.0001). S-V distance ≤380 μm was the best cutoff value for predicting resolved strut malapposition (sensitivity 93.5 %, specificity 69.8 %, area under curve 0.878). Acute strut malapposition with S-V distance ≤380 μm remained persistent more frequently over lipid/calcified than over fibrous plaques (lipid: 13.4 %, calcified: 18.2 %, fibrous: 4.2 %; lipid vs. fibrous, P = 0.001; calcified vs. fibrous, P = 0.02). Intra-stent thrombi were more frequent in stents with ≥1 persistent strut malapposition than in those without [4/11 stents (36.3 %) vs. 0/24 (0 %); P = 0.006]. Lipid and calcified plaque, together with S-V distance, affect the resolution of acute strut malapposition in EES. Persistent strut malapposition is associated with the presence of thrombi at follow-up, which could be the substrate for late stent thrombosis.

Neurotrophins (NGF, BDNF, NT3, NT4) can decrease cell death, induce differentiation, as well as sustain the structure and function of neurons, which make them promising therapeutic agents for the treatment of neurodegenerative disorders. However, neurotrophins have not been very effective in clinical trials mostly because they cannot pass through the blood-brain barrier owing to being high-molecular-weight proteins. Thus, neurotrophin-mimic small molecules, which stimulate the synthesis of endogenous neurotrophins or enhance neurotrophic actions, may serve as promising alternatives to neurotrophins. Small-molecular-weight natural products, which have been used in dietary functional foods or in traditional medicines over the course of human history, have a great potential for the development of new therapeutic agents against neurodegenerative diseases such as Alzheimer's disease. In this contribution, a variety of natural products possessing neurotrophic properties such as neurogenesis, neurite outgrowth promotion (neuritogenesis), and neuroprotection are described, and a focus is made on the chemistry and biology of several neurotrophic natural products., (© 2024. The Author(s), under exclusive license to Springer Nature Switzerland AG.)

Background: Prorenin, the precursor of renin, binds to the (pro)renin receptor [(P)RR] and triggers intracellular signaling. The ligand binding sites of (P)RR are disconnected and are present in the soluble form of the receptor in serum. Given that the clinical significance of serum prorenin and soluble (P)RR in chronic kidney disease (CKD) is unclear, we investigated the relationship between serum prorenin, soluble (P)RR, and various clinical parameters in patients with CKD., Methods: A total of 374 patients with CKD were enrolled. Serum samples were collected, and the levels of soluble (P)RR and prorenin were measured using ELISA kits. Serum creatinine (Cr), blood urea nitrogen (BUN), uric acid (UA), hemoglobin (Hb), soluble secreted α-Klotho, and the urine protein/Cr ratio were also measured. Similarly, clinical parameters were also evaluated using serum and urine sample collected after 1 year (n = 204)., Results: Soluble (P)RR levels were positively associated with serum Cr (P < 0.0001, r = 0.263), BUN (P < 0.0001, r = 0.267), UA (P < 0.005, r = 0.168) levels, CKD stage (P < 0.0001, r = 0.311) and urine protein/Cr ratio (P < 0.01, r = 0.157), and inversely with estimated glomerular infiltration rate (eGFR) (P < 0.0001, r = -0.275) and Hb (P < 0.005, r = -0.156). Soluble (P)RR levels were inversely associated with α-Klotho levels (P < 0.001, r = -0.174) but did not correlate with prorenin levels. With respect to antihypertensive drugs, soluble (P)RR levels were significantly lower in patients treated with an angiotensin II receptor blocker (ARB) than in those without ARB therapy (P < 0.005). Soluble (P)RR levels were significantly lower in CKD patients with diabetes mellitus or primary hypertension than in those without these conditions (P < 0.05). In contrast, serum levels of prorenin did not correlate with parameters related to renal function. Serum prorenin levels were significantly higher in CKD patients with diabetes mellitus than in nondiabetic patients (P < 0.05), but not in CKD patients with hypertension (P = 0.09). Finally, with respect to the relationship between basal soluble (P)RR levels and the progression rates of renal function, soluble (P)RR levels were positively associated with ΔCr (P < 0.05, r = 0.159) and inversely associated with ΔeGFR (P < 0.05, r = -0.148)., Conclusion: Serum levels of soluble (P)RR correlated with the stage of CKD. Our findings suggest that soluble (P)RR may be involved in renal injury and influence the progression of CKD.