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Abstract Background A recent Phase 2/3 study in Japanese patients showed that caplacizumab was effective in treating immune-mediated thrombotic thrombocytopenic purpura (iTTP), with a low rate of iTTP recurrence. ADAMTS13 activity is monitored weekly during caplacizumab treatment to guide discontinuation of caplacizumab and consequently avoid exacerbations or relapse. The aim of this study was to assess changes in ADAMTS13 activity/inhibitor levels during caplacizumab treatment in this patient population. Methods A post hoc analysis of the Phase 2/3 study in Japanese patients was conducted. Patients ≥ 18 years old with confirmed iTTP received 10 mg of caplacizumab daily in conjunction with therapeutic plasma exchange (TPE) and immunosuppression for 30 days post-TPE. Outcomes included time to recovery of ADAMTS13 activity, ADAMTS13 activity level at treatment end, incidence of ADAMTS13 inhibitor re-elevation (ie, inhibitor boosting) during treatment, time to platelet count recovery, number of days of TPE, and safety. Outcomes according to presence of inhibitor boosting were also assessed. Results Nineteen patients had confirmed iTTP and were included in this analysis. Median (95% confidence interval) time to recovery of ADAMTS13 activity to ≥ 10%, ≥ 20%, and ≥ 60% was 14.6 (5.9–24.8), 18.5 (5.9–31.8), and 47.5 (18.5–60.9) days, respectively. Median (range) ADAMTS13 activity level at caplacizumab treatment end was 62.0% (29.0–101.0). Nine patients had ADAMTS13 inhibitor boosting. Delayed response of ADAMTS13 activity was observed in patients with inhibitor boosting. The median time to platelet count response and median number of TPE days were shorter in patients with inhibitor boosting compared with patients without inhibitor boosting. Rituximab was administered to almost all patients with inhibitor boosting (88.9%), after completion of TPE. Patients without inhibitor boosting who were treated with rituximab received it prior to completion of TPE. Only one patient experienced a recurrence, which occurred shortly after caplacizumab discontinuation due to an adverse event. Conclusions In patients with iTTP, caplacizumab with TPE and immunosuppression may reduce the risk of ADAMTS13 inhibitor boosting if rituximab is administered early in the iTTP treatment period. Early administration of rituximab in addition to caplacizumab may prevent iTTP recurrence with inhibitor boosting. Trial registration NCT04074187.

Abstract Background In the global ARASENS study (NCT02799602), darolutamide plus androgen‐deprivation therapy (ADT) and docetaxel significantly reduced risk of death by 32.5% versus placebo plus ADT and docetaxel (hazard ratio [HR] 0.68; 95% confidence interval [CI] 0.57–0.80; p

Abstract In addition to testosterone, various endocrine hormones, such as dehydroepiandrosterone sulfate (DHEA-S) and estradiol, may be involved in erectile function. However, the role of these sex hormones in the erectile function of men without hypoandrogenism remains unclear. This cross-sectional study included 398 community-dwelling men without hypoandrogenism. The participants were categorized into the non-ED and ED groups. Multivariable logistic regression analyses were performed to investigate the relationship between ED and serum sex hormone levels, including total testosterone, DHEA-S, estradiol, luteinizing hormone (LH), follicle-stimulating hormone (FSH), and prolactin. Among the 398 men, 66 (17%) and 332 (83%) were categorized into the non-ED and ED groups, respectively. In the multivariable analyses, serum DHEA-S and estradiol levels were significantly associated with ED (odds ratio [OR]: 0.996, P = 0.030; OR: 1.082, P = 0.002; respectively), whereas serum total testosterone, LH, FSH, and prolactin levels did not demonstrate significant association. After adjusting for age, none of neutrophil-to-lymphocyte ratio, serum plasminogen activator inhibitor-1 levels, and skin advanced glycation end-products levels demonstrated significant correlation with serum DHEA-S and estradiol levels. In conclusion, lower testosterone levels did not affect ED in men with normal testosterone levels, whereas serum DHEA-S and estradiol levels were significantly associated with ED.

Background: The benefits of novel androgen receptor axis-targeted agents (ARATs) on oncological outcomes in patients with non-metastatic castration-resistant prostate cancer (nmCRPC) in real-world settings are unclear. Methods: This multi-institutional retrospective study included 178 patients with nmCRPC treated between September 2003 and August 2022. Patients were divided into two groups: those who were treated with any novel ARATs, including apalutamide, enzalutamide, darolutamide, and abiraterone acetate, during any line of nmCRPC treatment (novel ARATs group) and those who were not (control group). Multivariable Cox proportional hazards regression analyses were performed to evaluate the effects of novel ARATs on metastasis-free survival (MFS) and overall survival (OS). Results: The median age and follow-up period after nmCRPC diagnosis were 76 years and 37 months, respectively. Of the 178 patients, 122 (69%) were treated with novel ARATs after nmCRPC diagnosis. The MFS and OS in the novel ARATs group were significantly longer than those in the control group (P

Abstract Endoscopic therapy has recently undergone remarkable progress, including the use of suturing procedures within the gastrointestinal tract using flexible endoscopes. However, existing suturing techniques primarily involve closure using instruments or continuous sutures using an endoscopic needle holder, leaving a gap in nodal suturing methods with extracorporeal ligation. This paper introduces a novel approach, the endoscopic ligation technique, wherein a flexible endoscope is utilized for nodal suturing through extracorporeal ligation.

Abstract The patient was a 49‐year‐old female with a submucosal tumor (12×12 mm) located in the lesser curvature side of the stomach. The diagnosis by endoscopic ultrasound fine‐needle aspiration was of a gastrointestinal stromal tumor. Computed tomography and endoscopic ultrasound showed gastrointestinal stromal tumor with an intra‐luminal growth type. Endoscopic full‐thickness resection was then performed. To achieve good counter traction, enough safety margin, and minimal defect of muscle, full‐thickness resection via creating a submucosal tunnel was performed as a new technique. The final histological diagnosis was gastrointestinal stromal tumor with R0 resection.

Purpose: To evaluate the impact of severe erectile dysfunction (ED) on future major adverse cardiovascular events (MACE) in men on dialysis. Materials and Methods: This prospective cohort study included 71 men on dialysis. ED was assessed using the Sexual Health Inventory for Men (SHIM). Men were divided into the mild/moderate ED (SHIM score ≥8) and severe ED (SHIM score ≤7) groups. The primary endpoint was MACE-free survival. MACE was a composite of myocardial infarction, cardiovascular death, and stroke. The secondary endpoints were cardiac event-free survival and overall survival (OS). Moreover, the predictive abilities of severe ED for 5-year MACE, 5-year cardiac events, and 5-year overall mortality were evaluated. Results: The median age and follow-up period of the included men were 64 years and 58 months, respectively. The median SHIM score was 4.0; all had a degree of ED, and 64.7% had severe ED. In the background-adjusted multivariable analyses, severe ED was not significantly associated with shorter MACE-free survival (hazard ratio [HR], 1.890; 95% confidence interval [CI], 0.533–6.706; p=0.324), cardiac event-free survival (HR, 2.081; 95% CI, 0.687–6.304; p=0.195), and OS (HR, 0.817; 95% CI, 0.358–1.863; p=0.630). Severe ED did not significantly improve the predictive abilities for 5-year MACE, 5-year cardiac events, and 5-year overall mortality (p=0.110, p=0.101, and p=0.740, respectively). Conclusions: ED severity was not associated with shorter MACE-free survival, cardiac event-free survival, or OS, and ED severity could not improve the predictive abilities for these outcomes in men undergoing dialysis.

Abstract We aimed to evaluate the humoral response after the second and third doses of SARS-CoV-2 mRNA vaccine in ABO blood type incompatible kidney transplant (KT) recipients treated with rituximab. This retrospective study conducted between June 2021 and June 2022 included 131 KT recipients and 154 nontransplant controls who had received mRNA vaccines. We compared the seropositivity (anti-SARS-CoV-2 spike IgG antibody titer ≥ 0.8 U/mL) after the second and third vaccinations. Furthermore, we evaluated the impact of pretransplant vaccination for seropositivity. Of the 131 KT recipients, 50 had received the third dose of mRNA vaccine. The antibody titer was significantly increased after the third dose of mRNA vaccine. The seropositivity rate after the third dose of mRNA vaccine increased from 36 to 70%. We observed no significant difference in seropositivity after the third dose of mRNA vaccine in ABO incompatibility, rituximab use, mycophenolate mofetil use, and age at KT. Of the nine recipients who had received the second or third dose of the mRNA vaccine prior to the KT, eight of the recipients were seropositive both before and after the KT. Our results suggest that ABO incompatibility or rituximab use was not significantly associated with seropositivity.

Purpose: To investigate the association between skin advanced glycation end-products (AGEs) levels, blood antioxidative vitamin and carotenoid concentrations, and severe erectile dysfunction (ED) in community-dwelling men. Materials and Methods: This cross-sectional study used the 5-Item International Index of Erectile Function to identify 335 community- dwelling men with ED. The accumulation of skin AGEs was assessed noninvasively by measuring skin autofluorescence. Background-adjusted multivariable logistic regression analyses using the inverse probability of treatment weighting method were performed to evaluate the effects of AGEs, vitamins, and carotenoids on severe ED. Moreover, multiple linear regression analyses were performed to assess the association between skin AGEs levels and serum carotenoid concentrations. Results: The median age of study participants was 57 years. Of the 335 men, 289 (86.3%) and 46 (13.7%) were classified into the mild/moderate and severe ED groups, respectively. Multivariable analyses revealed that skin AGEs levels, blood vitamins C and E, lutein, zeaxanthin, β-cryptoxanthin, α-carotene, β-carotene, total lycopene, and cis-lycopenes concentrations were significantly associated with severe ED, whereas all-trans lycopene concentrations were not. In the multiple linear regression analyses, serum zeaxanthin concentrations were negatively and significantly correlated with skin AGEs levels. Conclusions: Higher skin AGEs levels and lower blood antioxidative vitamin and carotenoid concentrations were significantly associated with severe ED. Serum zeaxanthin levels were negatively and significantly correlated with skin AGEs levels, suggesting the possible effects of zeaxanthin on ED by decreasing tissue AGEs levels.

Purpose: Accelerated atherosclerosis is a major complication in patients with end-stage renal disease and it plays an important role in the pathogenesis of erectile dysfunction (ED). However, the association between aortic calcification burden and the severity of ED remains unclear. The aim of the present study was to investigate this association in men undergoing dialysis. Materials and Methods: This cross-sectional study included 71 men undergoing peritoneal dialysis and/or hemodialysis between July 2016 and May 2018 at Mutsu General Hospital. ED was assessed with the Sexual Health Inventory for Men (SHIM). Patients were divided into the mild/moderate (SHIM score ≥8) and severe ED groups (SHIM score ≤7). Aortic calcification index (ACI) was examined as a clinical indicator of abdominal aortic calcification. Multivariable logistic regression analysis was performed to identify the significant factors associated with severe ED. Results: The median age of the study participants was 64 years; all had ED, with 64.8% having severe ED. In the multivariable analyses, a slight association was observed between ankle-brachial index and severe ED (odds ratio [OR], 0.058; p=0.072), whereas ACI was significantly associated with severe ED (OR, 1.022; p=0.022). Conclusions: Aortic calcification burden was independently associated with severe ED.

Abstract We compared the impact of treatment strategies on postoperative complications and prognosis between robot-assisted radical prostatectomy (RARP) plus extended pelvic lymph-node dissection (ePLND) and RARP plus neoadjuvant chemohormonal therapy (NCHT) without ePLND. We retrospectively evaluated 452 patients with high-risk prostate cancer (defined as any one of prostate-specific antigen ≥ 20 ng/mL, Gleason score 8–10, or cT2c–3) who were treated with RARP between January 2012 and February 2021. The patients were divided into two groups: RARP with ePLND (ePLND group) and NCHT plus RARP without ePLND (NCHT group). We compared the complication rate (Clavien–Dindo classification), biochemical recurrence-free survival, and castration-resistant prostate cancer (CRPC)-free survival between the groups. We performed multivariable Cox regression analysis using inverse probability weighting (IPTW) methods to assess the impact of the different treatments on prognosis. There were 150 and 302 patients in the ePLND and NCHT groups, respectively. The postoperative complication rate was significantly higher in the ePLND group than in the NCHT group (P

Objective To investigate the associations of impaired muscle strength and gait function with the severity of erectile dysfunction (ED) in men undergoing dialysis. Methods This cross-sectional study included 63 men undergoing dialysis. ED was assessed with the Sexual Health Inventory for Men (SHIM). Patients were divided into the mild/moderate (SHIM score ≥8) and severe ED groups (SHIM score ≤7). Correlations between variables were analyzed using Spearman’s rank correlation coefficient. Multivariable logistic regression analyses were performed to evaluate the impact of impaired grip strength and gait function on the severity of ED. Results The median age of the study participants was 62 years; all had ED, with 67% having severe ED. Spearman’s rank correlation test demonstrated significant negative and positive correlations between gait function and SHIM score (ρ = −0.257, p = 0.042) and between grip strength and SHIM score (ρ = 0.305, p = 0.015), respectively. In the multivariable analyses, impaired grip strength was significantly associated with severe ED (odds ratio [OR]: 4.965, p = 0.017), whereas gait function was not (OR: 3.147, p = 0.064). Conclusion Impaired muscle strength was significantly associated with severe ED, whereas impaired gait function had a marginal effect on this erectile condition.

Objectives To investigate the association between oxidative stress and erectile dysfunction (ED) in community-dwelling men and men on dialysis.Methods This cross-sectional study included 398 community-dwelling men and 42 men on dialysis. Oxidative stress was assessed using 8-hydroxy-2'-deoxyguanosine (8-OHdG). Univariable and multivariable logistic regression analyses were performed to evaluate the association between oxidative stress and ED.Results Spearman’s rank correlation test showed no significant correlation between urine 8-OHdG levels and the 5-Item International Index of Erectile Function scores in community-dwelling men (ρ = −0.005, p = 0.917) and between plasma 8-OHdG levels and the Sexual Health Inventory for Men scores in men on dialysis (ρ = 0.166, p = 0.295). In community-dwelling men, univariable and multivariable analyses revealed that urine 8-OHdG level was not significantly associated with ED (odds ratio [OR]: 1.005, 95% confidence interval [CI]: 0.884–1.144, p = 0.934; OR: 0.930, 95% CI: 0.798–1.084, p = 0.353; respectively). In men on dialysis, univariable analyses revealed that plasma 8-OHdG level was not significantly associated with severe ED (OR: 0.967, 95% CI: 0.876–1.066, p = 0.498).Conclusions Oxidative stress was not significantly associated with ED prevalence and severity in community-dwelling men and men on dialysis.

Introduction We examined the relationship between preferred daily smoking times and typical situations in which smoking occurs and aimed to determine the association between successful smoking cessation and preferred smoking time. Methods We conducted an internet survey and categorized participants based on their selected smoking status: ‘successful smoking cessation’, ‘failed smoking cessation’, or ‘currently smoking’. Ultimately, 3637 people (1854 men, 1789 women) aged 30–59 years were included in the study. Participants also described the time points at which smoking seemed to be the most appealing and those at which smoking seemed the most difficult to resist. Results Regarding times of tobacco cravings, the number of non-smokers for more than 1 year who chose ‘after dinner’ was significantly higher than the number who chose ‘after breakfast’ or ‘after waking up’. Regarding the time when smoking was the most difficult to resist, the proportion of people who chose ‘after dinner’ that had quit smoking for less than 3 months was significantly low. Conclusions Those who prefer smoking ‘after dinner’ are less likely to start smoking cessation, but when they do, the rate of continuation for more than 1 year is high. We suggest that smoking cessation support based on preferred smoking times may lead to a decrease in the smoking rate.

Abstract High-risk non-muscle-invasive bladder cancer (NMIBC) has a heterogeneity and intensive surveillances after transurethral resection of bladder tumor (TURBT) are major factors of increased costs. Therefore, we aimed to develop optimized surveillance protocols based on the risk score-based substratifications to improve surveillance costs. We retrospectively evaluated 428 patients with primary high-risk NMIBC who underwent TURBT. Patients were substratified into intra-lower, intra-intermediate, and intra-higher groups or UUT-lower, UUT-intermediate, and UUT-higher groups by summing each of the independent risk factors of intravesical and UUT recurrences, respectively. The optimized surveillance protocols that enhance cost-effectiveness were then developed using real incidences of recurrence after TURBT. The 10-year total surveillance costs were compared between the European Association of Urology (EAU) guidelines-based and optimized surveillance protocols. The Kaplan–Meier curves of intravesical and UUT recurrence-free survivals were clearly separated among the substratified groups. The optimized surveillance protocols promoted a 43% reduction ($487,599) in the 10-year total surveillance cost compared to the EAU guidelines-based surveillance protocol. These results suggest that the optimized surveillance protocols based on risk score-based substratifications could potentially reduce over investigation and improve surveillance costs after TURBT in patients with primary high-risk NMIBC.

ObjectivesThe purpose of this study was to deepen our understanding of pitches and to obtain basic knowledge about pitches by comparing 4-seam and other pitches in Major League Baseball (MLB).MethodsWe analyzed big data for 1,820 professional baseball pitchers of MLB on release speed, spin rate, release point 3D coordinates (X, Y, and Z axes), amount of change for 4-seam, and seven changing ball types (sinker, slider, changeup, cutter, curve, split finger, and knuckle curve), using PITCHf/x and TrackMan. We also evaluated three relationships: (1) between the release points and the ball types of pitch; (2) between the amount of change in the ball and the release speed; and (3) between the release speed and the spin rate.ResultsThe release speed was significantly slower in seven changing ball types than in the 4-seam (p

Abstract We aimed to determine the survival and staging benefit of limited pelvic lymph node dissection (PLND) during radical prostatectomy (RP) in high-risk prostate cancer (PC) patients treated with neoadjuvant chemohormonal therapy. We retrospectively analyzed 516 patients with high-risk localized PC (

Introduction We would like to present a rare case of metastatic renal tumor. Case presentation A 60‐year‐old woman presented to our department with a left renal tumor. She underwent a total hysterectomy and right adnexal resection for a stage IA ovarian granulosa cell tumor approximately 15 years ago, followed by left adnexal resection and postoperative chemotherapy with gemcitabine and paclitaxel 6 years ago. She received six courses of gemcitabine and carboplatin to treat a stage IC clear cell adenocarcinoma of the ovary. The patient was diagnosed with the left renal tumor and underwent a laparoscopic left nephrectomy. Immunostaining was positive for α‐inhibin and SF‐1 and showed FOXL2 402C→G (C134W) mutation. Finally, the patient was diagnosed with renal metastasis of a granulosa cell tumor. Conclusion To our knowledge, this is a very rare case of renal metastasis of a granulosa cell tumor with the FOXL2 mutation in an adult.

Abstract We aimed to evaluate the seroprevalence and investigated factors associated with seropositivity after the second SARS-CoV-2 mRNA vaccination in kidney transplant (KT) recipients. This retrospective study conducted between June and November 2021 included 106 KT recipients and 127 healthy controls who received the second dose of the BNT162b2 mRNA vaccine at least 7 days before the measurement of antibody titers. The antibody titer against the receptor-binding domain of SARS-CoV-2 spike (S) protein was determined. We compared seroprevalence rates (immunoglobulin G [IgG] level of ≥ 0.8 or ≥ 15 U/mL) between the healthy controls and KT recipients and identified factors associated with impaired humoral response. The seroprevalence rate of the healthy controls and KT recipients was 98% and 22%, respectively. Univariate logistic regression analysis revealed that age > 53 years, rituximab use, mycophenolate mofetil use, and KT vintage

Abstract Objective To evaluate the effects of the concomitant use of proton pump inhibitors (PPIs) and/or antibiotics (Abs) on oncological outcomes in patients with advanced urothelial carcinoma. Patients and methods We retrospectively evaluated 155 patients with advanced urothelial carcinoma who were treated with immune checkpoint inhibitors (ICIs) between August 2015 and April 2021. The concomitant use of PPI or Abs was defined as any PPI or Abs administered within 30 days before ICI initiation and during ICI therapy. The primary outcomes were the effect of PPI and/or Abs use on the objective response rate (ORR) and immune‐related adverse events (irAEs). The secondary outcomes were the effects of PPI and/or Abs use on progression‐free survival (PFS) and overall survival (OS) after ICI therapy analyzed using the inverse probability of treatment weighting‐adjusted Cox regression analysis. Results Of the 155 patients enrolled in the study, 99 (64%) were PPI users and 56 (36%) Abs users. PPI users were associated with a significantly poorer ORR than non‐PPI users (41% vs. 20%, respectively), whereas Abs use was not significantly associated with changes in ORR. The rate of irAEs was not significantly associated with the use of PPIs or Abs. Multivariate inverse probability of treatment weighting‐adjusted Cox regression analysis revealed significantly poorer PFS and OS in PPI users than in non‐PPI users, whereas Abs use was not associated with poorer outcomes. Conclusion The concomitant use of PPI may adversely affect oncological outcomes in patients with locally advanced or metastatic urothelial carcinoma treated with ICI therapy.

Abstract Objective To evaluate the effect of postoperative pathological findings related to the eligibility of adjuvant immunotherapy on oncologic outcomes in patients with localized and locally advanced muscle‐invasive bladder carcinoma (MIBC) and upper tract urothelial carcinoma (UTUC). Patients and methods We retrospectively evaluated 1082 patients treated with radical cystectomy (n = 597) and nephroureterectomy (n = 485) between January 2000 and April 2021. Patients were divided into two groups: pT3‐4 or pN+ without neoadjuvant chemotherapy and ypT2‐4 or pN+ treated with neoadjuvant chemotherapy (trial‐eligible group) or others (trial‐ineligible group). The primary outcome was the effect of trial eligibility for adjuvant immunotherapy on disease‐free survival (DFS) and overall survival (OS). Secondary outcomes included the additional effect of lymphovascular invasion (LVI) status to the clinical trial criteria on prognosis and a risk model development. Results The median ages of the patients were 69 and 72 years in the MIBC and UTUC groups, respectively. Fifty‐two percent of patients met the trial inclusion criteria. Trial eligibility was significantly associated with poor DFS and OS among patients with MIBC and UTUC. LVI‐positive status was significantly associated with poor prognosis among patients in the trial‐eligible group. A very high risk (LVI+ or pN+ among the pT3‐4 or ypT2‐4) was significantly associated with poor prognosis. Conclusion A total of 52% of patients were eligible for adjuvant immunotherapy. Trial eligibility was significantly associated with a poor prognosis. LVI+ and pN+ may play a key role in candidate selection for adjuvant immunotherapy.

Abstract Objectives To investigate the eligibility for maintenance immunotherapy and its impact on the prognosis of advanced urothelial carcinoma treated with first‐line chemotherapy, as the selection biases of the eligible population in the JAVELIN Bladder 100 trial remain unclear. Methods We retrospectively evaluated 213 patients (median age, 71 years) with unresectable locally advanced or metastatic urothelial carcinoma treated with platinum‐based first‐line chemotherapy between May 2003 and April 2021. The patients were categorized into the following two groups: progressive disease (PD) within four cycles (trial ineligible group) and non‐PD within four cycles (trial eligible group). The primary outcomes were the estimated proportion of trial eligible patients for maintenance immunotherapy. The secondary outcomes were the comparison of the overall survival in the trial eligible and ineligible groups and the impact of radiologic response at the second cycle on the fourth cycle. Results Among the 213 patients, 81 (38%) were included in the trial eligible group. The trial eligible group had a significantly longer overall survival than the trial ineligible group (P

Abstract Objective This study aimed to investigate the effect of advanced glycation end products (AGEs) on nocturia and sleep disorders in community‐dwelling adults. Materials and Methods This longitudinal study evaluated AGEs level, sleep disorders and nocturia frequency in 447 community‐dwelling adults between May 2011 and May 2016. Sleep disorders were evaluated using the Pittsburgh Sleep Quality Index (PSQI) score. Participants were divided into two groups: AGEs‐low (≤1.80) and AGEs‐high (>1.80). The longitudinal nocturia and PSQI changes for 5 years between the AGEs‐low and AGEs‐high groups were compared. The effect of baseline oxidative stress on worsening of nocturia or PSQI score 5 years later was evaluated using multivariable logistic regression analyses. Results There was no significant difference in PSQI score and nocturia frequency between the AGEs‐low (n = 223) and AGEs‐high (n = 224) groups at baseline. The PSQI score and nocturia frequency increased significantly over 5 years in both groups. However, the PSQI score increased significantly in the AGEs‐high group compared with the AGEs‐low group, although there was no difference in nocturia. Background‐adjusted multivariable analysis showed that the AGE‐high was significantly associated with PSQI score worsening, but AGE‐high was not significantly associated with nocturia worsening. Conclusions Oxidative stress may be significantly associated with worsening sleep disorders, although oxidative stress may not significantly worsen nocturia frequency.

ObjectivesThe optimal frequency and duration of surveillance in patients with high-risk non-muscle-invasive bladder cancer (NMIBC) remain unclear. The aim of the present study is to develop an optimal surveillance protocol based on the European Association of Urology (EAU) substratification in order to improve surveillance costs after transurethral resection of bladder tumor (TURBT) in patients with primary high-risk NMIBC.Materials and methodsWe retrospectively evaluated 428 patients with primary high-risk NMIBC who underwent TURBT from November 1993 to April 2019. Patients were substratified into the highest-risk and high-risk without highest-risk groups based on the EAU guidelines. An optimized surveillance protocol that enhances cost-effectiveness was then developed using real incidences of recurrence after TURBT. A recurrence detection rate ([number of patients with recurrence / number of patients with surveillance] × 100) of ≥ 1% during a certain period indicated that routine surveillance was necessary in this period. The 10-year total surveillance cost was compared between the EAU guidelines-based protocol and the optimized surveillance protocol developed herein.ResultsAmong the 428 patients with primary high-risk NMIBC, 97 (23%) were substratified into the highest-risk group. Patients in the highest-risk group had a significantly shorter recurrence-free survival than those in the high-risk without highest-risk group. The optimized surveillance protocol promoted a 40% reduction ($394,990) in the 10-year total surveillance cost compared to the EAU guidelines-based surveillance protocol.ConclusionThe optimized surveillance protocol based on the EAU substratification could potentially reduce over investigation during follow-up and improve surveillance costs after TURBT in patients with primary high-risk NMIBC.

Abstract The evaluation of surgical damage is challenging because of the lack of specific biomarkers. Total cell-free DNA (cfDNA) levels have been reported to increase with external trauma and may be a biomarker for tissue damage. To investigate the utility of perioperative total cfDNA levels in evaluating surgical damage in urological surgeries. This multicenter, prospective, observational study included 196 patients scheduled for urological surgeries between September 2020 and July 2021. The primary outcome was the change in total cfDNA levels before and after urological surgery. The secondary outcome was the effect of surgical type on total cfDNA ratio before and after urological surgery. The postoperative median total cfDNA level of the 196 patients was significantly increased 2.5-fold compared to the preoperative level (185.2 ng/mL vs. 406.7 ng/mL, P

IntroductionThe study investigated the baseball pitching performance in terms of release speed, spin rate, and 3D coordinate data of the release point depending on the ball and strike counts.MethodsWe used open data provided on the official website of Major League Baseball (MLB), which included data related to 580 pitchers who pitched in the MLB between 2015 and 2019.ResultsThe results show that a higher ball count corresponds to a slower release speed and decreased spin rate, and a higher strike count corresponds to a faster release speed and increased spin rate. For a higher ball count, the pitcher's release point tended to be lower and more forward, while for a higher strike count, the pitcher's release point tended to be to the left from the right pitcher's point of view. This result was more pronounced in 4-seam pitches, which consisted the largest number of pitchers. The same tendency was confirmed in other pitches such as sinker, slider, cut ball, and curve.DiscussionOur findings suggest that the ball count is associated with the pitcher's release speed, spin rate, and 3D coordinate data. From a different perspective, as the pitcher's pitching performance is associated with the ball and strike count, the ball and strike count is associated with pitching performance. With regard to the aforementioned factor, we propose a “performance-environment flow model,” indicating that a player's performance changes according to the game situation, and the game situation consequently changes the player's next performance.

The purpose of this study was to adapt a Japanese version of the Big Five Inventory-2 (BFI-2-J) to examine its factor structure, reliability, validity, and measurement invariance. The BFI-2-J assesses five domains and 15 facets of the Big Five personality traits. We analyzed two datasets: 487 Japanese undergraduates and 500 Japanese adults. The results of the principal component analysis and confirmatory factor analysis revealed that the domain-facet structure of the BFI-2-J was similar to that of other language versions. The reliability of the BFI-2-J is sufficient. The correlation coefficients between the BFI-2-J and the other Big Five and self-esteem measures supported convergent and discriminant validity. Moreover, we confirmed measurement invariance across age and sex groups in domain-level and facet-level models. The results suggest that the BFI-2-J is a good instrument for measuring the Big Five personality traits and their facets in Japan. The BFI-2-J is expected to be useful in Japanese personality research and international comparative research.

In the original publication [...]

Abstract Discriminating between urothelial carcinoma (UC), including bladder cancer (BCa) and upper urinary tract UC (UTUC), is often challenging. Thus, the current study evaluated the diagnostic performance of N‐glycosylation signatures of immunoglobulins (Igs) for detecting UC, including BCa and UTUC. N‐glycosylation signatures of Igs from serum samples of the training cohort, including 104 BCa, 68 UTUC, 10 urinary tract infection, and 5 cystitis cases, as well as 62 healthy volunteers, were measured retrospectively using automated capillary‐electrophoresis‐based N‐glycomics. UTUC or BCa scores were then established through discriminant analysis using N‐glycan signatures of Igs. Diagnostic performance was evaluated using the area under receiver operating characteristics curve (AUC) and decision curve analyses (DCA). Our result showed that BCa and UTUC scores for discriminating BCa (AUC: 0.977) and UTUC (AUC: 0.867), respectively, provided significantly better clinical performance compared to urine cytology, gross hematuria, or clinical T1 cases. DCA revealed that adding BCa and UTUC scores to gross hematuria status was the best combination for detecting UC and avoiding the need for more intervention without overlooking UC (risk threshold: 13%–93%). The UC nomogram based on the combination of gross hematuria, UTUC score, and BCa score could detect UC with an AUC of 0.891, indicating significantly better performance compared to gross hematuria status in the validation cohort (251 patients). The limitations of this study include its small sample size and retrospective nature. The UC nomogram based on gross hematuria and N‐glycosylation signatures of Igs can be a promising approach for the diagnosis of UC.

Abstract Objectives To evaluate the association between the use of local radiotherapy (RT) with the survival of patients with de novo metastatic prostate cancer and symptomatic local events (SLEs). Patients and methods Patients were initially diagnosed with metastatic prostate cancer between 2008 and 2017 at 30 institutes in Japan. Prostate‐specific antigen (PSA) progression‐free survival (PSA‐PFS) under initial androgen deprivation therapy and overall survival (OS) was compared between patients receiving local RT (RT group) and no RT (no‐RT group) by multivariate Cox proportional hazard analyses. The occurrence rate of grade ≥2 SLEs was compared by multivariate logistic regression analyses. Propensity score matching (PSM) analyses were performed to compare PSA‐PFS and OS of the groups in the high and low metastatic burden cohort. Results Two hundred and five (7%) of 2829 patients received RT before PSA progression. Median PSA‐PFS and OS were significantly longer in the RT group than in the no‐RT group and the difference was significant in multivariate analyses (HR = 0.44, 95% CI = 0.33‐0.57 and HR = 0.40, 95% CI = 0.27‐0.60, respectively). The occurrence rate of grade ≥2 SLEs was significantly lower in the RT group (2%) than the no‐RT group (9%) and the difference was significant in multivariate analyses (HR = 0.28, 95% CI = 0.10‐0.76). Using PSM analyses, PSA‐PFS and OS remained significantly different (HR = 0.64, 95% CI = 0.46‐0.89 and HR = 0.47, 95% CI = 0.30‐0.72, respectively), between the RT (n = 182) and the no‐RT (n = 182) groups. The difference in OS was significant in the high metastatic burden cohort (HR = 0.55, 95% CI = 0.37‐0.81). Conclusions Addition of local RT to standard treatment for de novo metastatic prostate cancer patients tends to have the potential to extend survival, even in patients with high metastatic burden, and to reduce SLEs.

Introduction Cell‐free DNA is suggested as a prognostic biomarker in metastatic castration‐resistant prostate cancer. However, it remains unknown which parameter of cell‐free DNA is correlated with the progression and prognosis of metastatic castration‐resistant prostate cancer. Case presentation A 75‐year‐old man with newly diagnosed prostate cancer (serum prostate‐specific antigen 4891 ng/mL, Gleason score 4 + 5 = 9, cT3bN1M1) was referred to our department. He first received sequential hormonal therapies and was consequently diagnosed metastatic castration‐resistant prostate cancer 64 months after initial treatment. He underwent serial examinations of plasma cell‐free DNA, including concentration, androgen receptor amplification, TP53 point mutation, and PTEN loss. Only the cell‐free DNA concentration increased along with disease progression and declined after the administration of abiraterone and enzalutamide. Conclusion This case presented that cell‐free DNA concentration was possibly correlated with response to castration‐resistant prostate cancer treatment and disease progression. Cell‐free DNA concentration was proposed as a potential prognostic biomarker of metastatic castration‐resistant prostate cancer.

Introduction Muscle‐invasive bladder cancer following radiotherapy for prostate cancer is rare. We reported a case of muscle‐invasive bladder cancer who underwent robot‐assisted radical cystectomy following radiotherapy for prostate cancer. Case presentation A 72‐year‐old man was referred to our division with a muscle‐invasive bladder cancer. He had a history of intensity‐modulated radiation therapy for localized prostate cancer. After three courses of platinum‐based neoadjuvant chemotherapy, he obtained a radiologic complete response. He elected for robot‐assisted radical cystectomy, standard lymph node dissection, and intracorporeal ileal conduit urinary diversion. Pathological findings revealed no residual tumor within the bladder and residual tumor in the prostate. He had discharged without any complications; and quality of life had improved. Conclusion A robot‐assisted approach might be a potential option for well‐selected patients with muscle‐invasive bladder cancer who have previously received radiotherapy for localized prostate cancer.

Iron is an essential nutrient in the body. However, iron generates oxidative stress and hence needs to be bound to carrier proteins such as the glycoprotein transferrin (Tf) in body fluids. We previously reported that cerebrospinal fluid contains Tf glycan-isoforms that are derived from the brain, but their origins at the cellular level in the brain have not yet been elucidated. In the present report, we described the localization of Tf protein and mRNA in mouse and human brain tissue. In situ hybridization of mouse brain tissue revealed that Tf mRNA is expressed by different cell types such as epithelial cells in the choroid plexus, oligodendrocyte-like cells in the medulla, and neurons in the cortex, hippocampus, and basal ganglia. In contrast, Tf protein was barely detected by immunohistochemistry in hippocampal and some cortical neurons, but it was detected in other types of cells such as oligodendrocyte-like cells and choroid plexus epithelial cells. The results showed that Tf mRNA is expressed by neural cells, while Tf protein is expressed in different brain regions, though at very low levels in hippocampal neurons. Low Tf level in the hippocampus may increases susceptibility to iron-induced oxidative stress, and account for neuron death in neurodegenerative diseases.

In this study, we report systematic investigations of the membership of galaxies inside a cluster using a machine learning (ML) neural network. By directly assigning the membership, rather than estimating the galaxy redshift as an intermediate step, we optimize the network structure to determine the membership classification. The cluster membership is determined by the Multi-Layer Perceptron (MLP) neural network trained using various observed photometric and morphological parameters of galaxies measured from I and V band images taken with the Subaru Suprime-Cam of 16 clusters at redshift ∼0.15–0.3. This dataset enables MLP to be applied to cluster galaxies in a wide range of cluster-centric distances, well into a field, and a wide range of galaxy magnitudes, into a regime of dwarf galaxies. We find: (1) With only two bands, our MLP model can achieve relatively high overall performance, obtaining high scores simultaneously in both the purity and the completeness of the classification; (2) The performance of MLP can be improved by including non-SED (Spectral Energy Distribution) parameters; (3) Faint galaxies are harder to assign their memberships even using our MLP model, though the performance is more robust than other photometric methods. ML can effectively combine various conventional methods of finding cluster membership, making it inherit advantages of each method. The overall good performance of the ML membership is vital to cluster studies in the era of faint and data-intensive galaxy survey in which the complete spectroscopic observation is out of reach.

The cerebrospinal fluid (CSF) plays an important role in homeostasis of the brain. We previously demonstrated that major CSF proteins such as lipocalin-type prostaglandin D2 synthase (L-PGDS) and transferrin (Tf) that are biosynthesized in the brain could be biomarkers of altered CSF production. Here we report that the levels of these brain-derived CSF proteins correlated well with each other across various neurodegenerative diseases, including Alzheimer’s disease (AD). In addition, protein levels tended to be increased in the CSF samples of AD patients compared with the other diseases. Patients at memory clinics were classified into three categories, consisting of AD (n = 61), mild cognitive impairment (MCI) (n = 42), and cognitively normal (CN) (n = 23), with MMSE scores of 20.4 ± 4.2, 26.9 ± 1.7, and 29.0 ± 1.6, respectively. In each category, CSF protein levels were highly correlated with each other. In CN subjects, increased CSF protein levels correlated well with those of AD markers, including amyloid-β and tau protein, whereas in MCI and AD subjects, correlations declined with AD markers except p-tau. Future follow-up on each clinical subject may provide a clue that the CSF proteins would be AD-related biomarkers.

A 42-year-old man visited a community hospital with chief complaints of lumbago and dyschesia. Computed tomography (CT) showed multiple lung, lymph node, and bone metastases and the irregular enlarged prostate with urinary bladder invasion. Serum prostate-specific antigen (PSA) was 544.0 ng/mL. Histological evaluation showed adenocarcinoma with the Gleason score 5+4, and the clinical stage was T4N1M1c as an initial diagnosis. Although androgen deprivation therapy was performed immediately, he had castration-resistant PCa after 3 months. Therefore, he received 6 courses of docetaxel chemotherapy every 3 weeks. Serum PSA was decreased to 0.2 ng/mL, and multiple metastases and prostate size were obviously reduced based on CT. He underwent robot-assisted radical prostatectomy and radiation therapy for prostatic fossa and multiple metastases. Although serum PSA level remained low, CT showed multiple liver metastases after 3 years from surgery. He received the combination therapy of cisplatin and etoposide (PE) every 4 weeks. Liver metastases had complete response. However, he visited our hospital with complaint of vomiting and a right drooping eyelid after 6 weeks from withdrawal of PE therapy. T2-weighted magnetic resonance imaging revealed multiple leptomeningeal metastases (LM). He received RT for the brain and was administered amrubicin. However, he died of PCa after 6 weeks from the diagnosis of LM.

Résumé Contexte Bien que l’extraction oncologique de spermatozoïdes testiculaires (onco-TESE) soit une pratique croissante, le bien-fondé de réaliser une onco-TESE chez des patients qui ont un cancer du testicule reste insuffisamment étayé. Par ailleurs, en cas de cancer bilatéral, qui représente 0,5–1% des cancers du testicule, l’onco-TESE est. plus difficile, et peu de cas ont été rapportés. Cas clinique Nous rapportons le cas d’un homme de 25 ans qui a bénéficié d’une onco-TESE pour tumeur à cellules germinales non séminomateuse sur testicule unique résiduel, survenant 5 ans après une orchidectomie controlatérale. Ont été réalisées simultanément une seconde orchidectomie et une TESE sur tissu testiculaire non tumoral. L’étude anatomopathologique a montré des tumeurs à cellules germinales de plus d’un type histologique (carcinome embryonnaire, tératome immature, tumeur vitelline, séminome, et choriocarcinome; pT1N0M0). Le patient a ensuite convolé en noces et le couple a souhaité avoir un enfant 3 ans plus tard. Alors que l’étude histologique du tissu testiculaire normal donnait un score de Johnsen à 6 (arrêt de maturation), des spermatozoïdes morphologiquement normaux et mobiles ont été retrouvés dans les échantillons de TESE décongelés; ces spermatozoïdes ont été utilisés pour réaliser plusieurs cycles d’injection intra cytoplasmique. Bien qu’aucune conception n’ait eu lieu à ce jour, les tentatives d’ICSI se poursuivent. Conclusions Ce cas montre l’efficacité de l’onco-TESE face à des cas tels qu’un cancer testiculaire bilatéral et non séminomateux.

Osteopontin (OPN) plays a pivotal role in cancer cell invasion and metastasis. Although OPN has a large number of phosphorylation sites, the functional significance of OPN phosphorylation in cancer cell motility remains unclear. In this study, we attempted to investigate whether phosphorylated OPN secreted from cancer cells affect cancer cell migration. Quantitative PCR and Western blot analyses revealed that MDA-MB435S, A549, and H460 cells highly expressed OPN, whereas the OPN expression levels in H358, MIAPaca-2, and Panc-1 cells were quite low or were not detected. Compared with the cancer cell lines with a low OPN expression, the high OPN-expressing cancer cell lines displayed a higher cell migration, and the cell migration was suppressed by the anti-OPN antibody. This was confirmed by the OPN overexpression in H358 cancer cells with a low endogenous OPN. Phos-tag ELISA showed that phosphorylated OPN was abundant in the cell culture media of A549 and H460 cells, but not in those of MDA-MB435S cells. Moreover, the A549 and H460 cell culture media, as well as the MDA-MB435S cell culture media with a kinase treatment increased cancer cell motility, both of which were abrogated by phosphatase treatment or anti-OPN antibodies. These results suggest that phosphorylated OPN secreted from cancer cells regulates cancer cell motility.

Glycosylation is a cell type-specific post-translational modification that can be used for biomarker identification in various diseases. Aim of this study is to explore glycan-biomarkers on transferrin (Tf) for Alzheimer’s disease (AD) in cerebrospinal fluid (CSF). Glycan structures of CSF Tf were analyzed by ultra-performance liquid chromatography followed by mass spectrometry. We found that a unique mannosylated-glycan is carried by a Tf isoform in CSF (Man-Tf). The cerebral cortex contained Man-Tf as a major isofom, suggesting that CSF Man-Tf is, at least partly, derived from the cortex. Man-Tf levels were analyzed in CSF of patients with neurological diseases. Concentrations of Man-Tf were significantly increased in AD and mild cognitive impairment (MCI) comparing with other neurological diseases, and the levels correlated well with those of phosphorylated-tau (p-tau), a representative AD marker. Consistent with the observation, p-tau and Tf were co-expressed in hippocampal neurons of AD, leading to the notion that a combined p-tau and Man-Tf measure could be a biomarker for AD. Indeed, levels of p-tau x Man-Tf showed high diagnostic accuracy for MCI and AD; 84% sensitivities and 90% specificities for MCI and 94% sensitivities and 89% specificities for AD. Thus Man-Tf could be a new biomarker for AD.