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The physical processes responsible for shaping how galaxies form and quench over time leave imprints on both the spatial (galaxy morphology) and temporal (star formation history; SFH) tracers that we use to study galaxies. While the morphology–SFR connection is well studied, the correlation with past star formation activity is not as well understood. To quantify this, we present Katachi (形), an interpretable convolutional neural network framework that learns the connection between the factors regulating star formation in galaxies on different spatial and temporal scales. Katachi is trained on 9904 galaxies at 0.02 < z < 0.1 in the SDSS-IV MaNGA DR17 sample to predict stellar mass ( M _* ; root mean square error (RSME) 0.22 dex), current star formation rate (SFR; RMSE 0.31 dex), and half-mass time ( t _50 ; RMSE 0.23 dex). This information allows us to reconstruct nonparametric SFHs for each galaxy from gri imaging alone. To quantify the morphological features informing the SFH predictions, we use SHAP (SHapley Additive exPlanations). We recover the expected trends of M _* governed by the growth of galaxy bulges, as well as those of SFR correlating with spiral arms and other star-forming regions. We also find that the SHAP maps of D4000 are more complex than those of M _* and SFR, and that morphology is correlated with t _50 even at fixed mass and SFR. Katachi serves as a scalable public framework to predict galaxy properties from large imaging surveys including Rubin, Roman, and Euclid, with large data sets of high signal-to-noise ratio imaging across limited photometric bands.

Selpercatinib is the first targeted therapy for rearranged during transfection (RET) fusion-positive unresectable non-small-cell lung cancer (NSCLC). The main adverse effects of selpercatinib include hypertension, liver dysfunction, diarrhea, and QT prolongation on electrocardiograms. However, instances of drug-induced interstitial lung disease (DI-ILD) are infrequently reported. We describe the first case of a patient with RET fusion-positive NSCLC treated with selpercatinib who developed DI-ILD, confirmed pathologically. The patient, a 72-year-old woman, initiated selpercatinib treatment following the postoperative recurrence of lung adenocarcinoma. After 15 months of treatment, computed tomography scans revealed multiple infiltrates and ground-glass opacities in both lungs. A thoracoscopic lung biopsy identified organizing pneumonia, attributed to DI-ILD caused by selpercatinib. Although she was asymptomatic, the patient's selpercatinib treatment was discontinued, leading to a gradual improvement in the lung infiltrates. Despite the lack of detailed reports, DI-ILD with selpercatinib represents a potentially serious adverse event and should be approached with caution., (© 2024 The Author(s). Thoracic Cancer published by John Wiley & Sons Australia, Ltd.)

There is no approved drug treatment for autoimmune pulmonary alveolar proteinosis (APAP), although traditionally requires complex treatments such as whole lung lavage (WLL). We herein report on a 67-year-old man diagnosed with APAP. Treatment with atorvastatin (5 mg daily) resulted in significant improvement in symptoms, lung function, and computed tomography findings, with enhanced oxygenation, although serum anti-GM-CSF antibody levels remained elevated. This case suggests that the remission observed in this case could potentially be attributed to a direct effect of atorvastatin within the pulmonary alveoli. Statins may be considered as one of the treatment options for APAP., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors.)

The process and molecular mechanisms underlying the formation and destruction of a pseudo-capsule (PC) in clear cell renal cell carcinoma (ccRCC) are poorly understood. In the present study, the PCs of surgical specimens from primary tumors and metastatic lesions in 169 patients with ccRCC, and carcinogen-induced ccRCC rat models were semi-quantified using the invasion of PC (i-Cap) score system. This was based on the relationship among the tumor, PC and adjacent normal tissue (NT) as follows: i-Cap 0, tumor has no PC and does not invade NT; i-Cap 1, tumor has a complete PC and does not invade into the PC; i-Cap 2, tumor with focal absences in the PC, which partially invades the PC but not completely through the PC; i-Cap 3, tumor crosses the PC and invades the NT; i-Cap 4, tumor directly invades the NT without a PC. The study suggested that PC formation was not observed without physical compression, and also revealed that tumor invasion into the PC was a prognostic factor for postoperative oncological outcomes. Higher i-Cap, Fuhrman grade and tumor size were independent poor prognostic factors for postoperative disease-free survival. mRNA expression arrays generated from carcinogen-induced ccRCC rat models were used to explore genes potentially associated with the formation and destruction of a PC. Subsequently, human ccRCC specimens were validated for four genes identified via expression array; the results revealed that collagen type 4A2, matrix metalloproteinase-7 and l-selectin were upregulated alongside the progression of i-Cap score. Conversely, endoglin was downregulated. In conclusion, the present study provides insights into the formation and destruction of a PC, and the results may aid the treatment and management of patients with ccRCC., Competing Interests: All authors confirm that they have no competing interests., (Copyright: © 2024 Shimizu et al.)

Complete metastasectomy (CM) in metastatic renal cell carcinoma (mRCC) has demonstrated efficacy in the cytokine era, but its effectiveness in the era of tyrosine kinase inhibitors (TKIs) and immune checkpoint inhibitors (ICIs) remains unclear. A multi-institutional database included clinicopathological data of 367 patients with mRCC. Patients were divided into two groups: the CM group and the non-CM group. These two groups were compared before and after propensity score matching (PSM). Cox proportional hazard models were used to detect factors associated with disease-free survival (DFS) and overall survival (OS) from mRCC diagnosis. The CM group showed a significant association with longer overall survival compared to the non-CM group in the PSM-unadjusted cohorts ( p < 0.001, hazard ratio 0.49, 95% confidence interval 0.35-0.69), but no superiority was noted in the adjusted cohorts. The median DFS after CM was 24 months, with no significant differences based on relapse timing. Notably, the international metastatic RCC database consortium risk categories and metastatic burden were associated with DFS. This study supports the potential of CM in mRCC management during the TKI/ICI era, although limitations including sample size and selection bias need to be considered.

(Purpose) We performed a clinical retrospective study on the evaluation of pembrolizumab treatment results for advanced urothelial cancer in our hospital. (Materials and Methods) Twenty-seven patients diagnosed with advanced or metastatic urothelial carcinoma who received pembrolizumab between April 2018 and December 2021 were included. We retrospectively reviewed medical records to examine treatment outcomes, immune-related adverse event (irAE), and prognostic factors. (Results) The median age of patients was 76 years, and the median number of pembrolizumab doses was 6. The median overall survival was 8.8 months, and the best treatment response according to RECIST version 1.1 was complete response 1, partial response 7, stable disease 5, and progression disease 14. Pre-pembrolizumab risk factors related to overall survival include the presence of liver metastasis, LDH ≥200 IU/L, and TSH <4 μIU/mL in univariate analysis. Grade 3 irAE was type 1 diabetes in only 1 case, and grade 2 were hypothyroidism in 4 cases, type 1 diabetes in 1 case, interstitial pneumonia in 1 case, and skin disorder in 1 case. Nine patients had a TSH of 4 μIU/mL or higher at the start of pembrolizumab, and four of them had hypothyroidism requiring oral levothyroxine, and none of the patients in the low TSH group required hormone replacement (p =0.013). (Conclusion) High TSH level before pembrolizumab administration for advanced urothelial cancer was associated with hypothyroidism, suggesting the possibility of improved prognosis.

Pulmonary neuroendocrine tumors are rare, accounting for approximately 1% to 2% of lung cancers. Atypical carcinoids account for approximately 10% of pulmonary neuroendocrine tumors and are categorized as moderately malignant. Treatment options for advanced-stage atypical carcinoids include everolimus, cytotoxic anticancer agents, and peptide receptor radionuclide therapy. In this report, we present the first case of KRAS G12C mutation-positive atypical carcinoid that was successfully treated with sotorasib. Therapeutically important mutations observed in non-small cell lung cancer are seldom found in atypical carcinoid tumors. Nonetheless, it is worthwhile to search for genetic mutations in atypical carcinoid tumors, considering the potential for molecular targeted therapy to be effective in their treatment as well., (© 2024 by the International Association for the Study of Lung Cancer.)

In this study, we conducted observational study to examine the effects of pharyngeal stimulation by a bolus of carbonated solution on repetitive voluntary swallowing in humans. Twelve healthy participants had a fine silicone tube inserted into their pharyngeal region, through which various solutions were slowly infused (0.2 mL/minute) to stimulate the pharyngeal mucosa without activating mechanoreceptors. The solutions included 0.3M NaCl (NaCl), carbonated 0.3M NaCl (NaCl + CA), 0.3M NaCl with acetic acid, distilled water, and carbonated distilled water. We used NaCl to inhibit water-sensitive neurons in the pharyngeal mucosa and enable the evaluation of the effects of carbonic acid stimulation on swallowing. Participants were instructed to repeat swallows as rapidly as possible during the infusion, and the swallowing interval (SI) was measured via submental surface electromyographic activity. SI was significantly shorter during the infusion of NaCl + CA, distilled water, and carbonated distilled water than during the infusion of NaCl. There was a significant positive correlation between SI with NaCl stimulation and the facilitative effects of the other solutions. Longer SIs with NaCl stimulation indicated potent facilitative effects. Thus, stimulation with NaCl + CA facilitated swallowing by reducing SI. Furthermore, the facilitative effects of SI were more pronounced in participants who had difficulty with repetitive voluntary swallowing. The sensation induced by carbonated solution may enhance the ability for repetitive voluntary swallowing, making it a potentially useful approach for rehabilitating patients with dysphagia., Competing Interests: The authors have no funding and conflicts of interest to disclose., (Copyright © 2023 the Author(s). Published by Wolters Kluwer Health, Inc.)

Background: Various donor characteristics have been reported as predictive factors for graft survival in kidney transplantations. The living kidney donor profile index (LKDPI) was established in 2016 to evaluate the quality of living donor kidneys. Herein, we verified whether the index score was associated with graft survival and analyzed various donor factors to identify predictors of graft survival in living donor kidney transplantations., Methods: This retrospective study included 130 patients who received a living donor kidney between 2006 and 2019 at our hospital. Clinical and laboratory data were obtained from the medical records. Living donor kidneys were categorized into 3 groups by LKDPI score, and the death-censored graft survival and predictors of graft survival were evaluated., Results: The median LKDPI score was 35 (IQR: 17-53). The index scores of the living donor kidneys in this study were higher than in previous studies. The groups with the highest scores (LKDPI >40) had significantly shorter death-censored graft survival compared with the group with the lowest scores (LKDPI <20; hazard ratio = 4.0, P = .005). There were no significant differences between the group with the middle scores (LKDPI, 20-40) and the other 2 groups. Donor/recipient weight ratio <0.9, ABO incompatibility, and 2 HLA-DR mismatches were identified as independent predictive factors for shorter graft survival., Conclusion: The LKDPI was correlated with death-censored graft survival in this study. However, more studies are required to establish a modified index that is more accurate for Japanese patients., Competing Interests: DISCLOSURES The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier Inc.)

Objectives: We investigated the diagnostic and therapeutic benefits of limited or extended pelvic lymph node dissection during a robot-assisted radical prostatectomy for localized prostate cancer., Methods: Diagnostic and therapeutic benefits were assessed according to the rates of pN1 and biochemical recurrence, respectively. The primary outcome was the biochemical recurrence-free rate, and secondary outcomes included the diagnostic and therapeutic benefits of pelvic lymph node dissection., Results: A total of 534 patients were analyzed. Out of the 534 patients, 207 (38.8%) received limited pelvic lymph node dissection while 134 (25.1%) received extended dissection. There were 297 patients with a Briganti index ≥5%. Extended dissections yielded significantly more resected lymph nodes (p < 0.0001), and 72.2% of cases of pN1 were located outside the obturator. The incidence rate of pN1 was 6.1%, and performance of extended lymph node dissection was an independent predictor for pN1 (odds ratio 9.0, 95% confidence interval 2.5-33.1). The rate of biochemical recurrence was 14.9%, and Cox proportional hazards regression analysis of the propensity score matched population revealed that patients with high or very-high risk tended to benefit from limited lymph node dissection (hazard ratio 8.4, 95% confidence interval 0.8-82.3) while the therapeutic benefit of extended dissection was unclear by comparison., Conclusions: Extended pelvic lymph node dissection significantly improves diagnostic accuracy; however, the therapeutic benefit of pelvic lymph node dissection was not observed in this study., (© 2022 The Japanese Urological Association.)

This longitudinal study aimed to compare 1-year mortality between users of home- and community-based services (HCBS) and residential facilities (nursing homes, group homes, and geriatric apartments) among non-hospitalized frail older adults in Japan. Using three nationwide data sources, we conducted a nationwide pooled cohort study of 1-year follow-up among certified users of long-term care insurance (LTCI) aged  65 years and older from 2007 through 2016 to compare 1-year mortality using a logistic regression model. Overall, compared to HCBS users, mortality was higher in residents in nursing homes and geriatric apartments but lower in group home residents. While mortality gradually increased over time among those in residential facilities, it remained at a level similar to that of HCBS users. Since 2006, Japan's public health policy has been to increase end-of-life care in residential facilities. Our results indicate that this policy resulted in an increase in mortality in residential facilities, possibly due to accommodation of more severely ill people there, or a shift in their focus from transferring dying residents to hospitals to preserve the dignity of residents., (© 2022. The Author(s), under exclusive licence to Springer Nature Limited.)

Background: First-line pembrolizumab is available for recurrent disease within 12 months after the receipt of platinum-based perioperative chemotherapy. However, the benefit of first-line pembrolizumab is unclear. This study evaluated the oncological outcome of patients treated with pembrolizumab compared with chemotherapy as first-line therapy for early relapsing disease after the receipt of platinum-based perioperative chemotherapy., Methods: Data from a multicenter study included 454 patients diagnosed with unresectable or metastatic UC from November 2006 to July 2021. We identified patients with early and non-early relapsing disease. Oncological outcomes were evaluated using progression-free survival, overall survival, and survival with disease control., Results: Fifty-three patients with early relapsing disease and 15 patients with non-early relapsing disease were identified. Of 53 patients with early relapsing disease, 26 (49.1%) were treated with pembrolizumab and 27 (50.9%) were treated with chemotherapy as first-line therapy. Fifteen patients with non-early relapsing disease were treated with chemotherapy. Early relapsing disease was associated with shorter progression-free survival and overall survival than non-early relapsing disease. Pembrolizumab was associated with longer progression-free survival and survival with disease control than chemotherapy in patients with early relapsing disease. There was no significant difference in overall survival between pembrolizumab and chemotherapy, but overall survival plateau with a long tail was observed in pembrolizumab., Conclusions: First-line pembrolizumab in earlier clinical settings for highly malignant tumors might improve the prognosis of patients with early relapsing disease after the receipt of platinum-based perioperative chemotherapy., (© 2022. The Author(s) under exclusive licence to Japan Society of Clinical Oncology.)

Objectives　The national database for long-term care insurance (LTCI) of Japan (Kaigo DB) enables researchers to access comprehensive data from its LTCI registry, eligibility assessment records, claims for service usage, and information about service providers. However, studies regarding the death or mortality of beneficiaries cannot be conducted because Kaigo DB does not contain death records, and researchers are not allowed to link Kaigo DB to other databases, such as national death records. Therefore, we aimed to assess the validity of using an insurer's disqualification from an LTCI beneficiary as a proxy of death.Methods　We used 510,751,798 monthly beneficiary records between April 2007 and March 2017 from the LTCI registry, while excluding data for ineligible persons for LTCI benefit or those younger than 65 years. We identified insurer cases disqualified from LTCI beneficiaries and linked them to national death records using deterministic linkage methods by dates of birth and death, sex, and residence. We considered the cases as positive if they were disqualified and their record was linked to a death. We used sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) as validity indices.Results　We identified 5,986,991 (1.17%) disqualified and 5,295,961 death cases. Sensitivity, specificity, PPV, and NPV of disqualification for death were 100%, 99.86%, 88.46%, and 100%, respectively. After stratification, PPV of disqualification was between 85% and 88% before 2012, 91% after 2012, 91.9% in men, and 85.9% in women. PPV increased with age (65-69 years: 80.6%, 70-74 years: 86.7%, 75-79 years: 86.4%, 80-84 years: 86.7%, 85-89 years: 88.0%, 90-94 years: 90.6%, and 95+ years: 93.4%) and level of care needed (support level: 72.2%, care level (CL) 1: 79.7%, CL2: 85.9%, CL3: 89.3%, CL4: 92.3%, and CL5: 94.0%).Conclusions　Disqualification from the LTCI registry is an inappropriate measure to estimate mortality accurately because it has a 10% false-positive rate. However, it appears sufficiently valid to use disqualification as a proxy outcome of death, although the main effect or confounding of a possible predictor of death could be slightly underestimated.

To investigate the organ-specific response and clinical outcomes of mixed responses (MRs) to immune checkpoint inhibitors (ICIs) for unresectable or metastatic urothelial carcinoma (ur/mUC), we retrospectively analyzed 136 patients who received pembrolizumab. The total objective response rate (ORR) and organ-specific ORR were determined for each lesion according to the Response Evaluation Criteria in Solid Tumors version 1.1 as follows: (i) complete response (CR), (ii) partial response (PR), (iii) stable disease (SD), and (iv) progressive disease (PD). Most of the organ-specific ORR was 30−40%, but bone metastasis was only 5%. There was a significant difference in overall survival (OS) between responders and non-responders with locally advanced lesions and lymph node, lung, or liver metastases (HR 9.02 (3.63−22.4) p < 0.0001; HR 3.63 (1.97−6.69), p < 0.0001; HR 2.75 (1.35−5.59), p = 0.0053; and HR 3.17 (1.00−10.0), p = 0.049, respectively). MR was defined as occurring when PD happened in one lesion plus either CR or PR occurred in another lesion simultaneously, and 12 cases were applicable. MR was significantly associated with a poorer prognosis than that of the responder group (CR or PR; HR 0.09 (0.02−0.35), p = 0.004). Patients with bone metastases benefitted less. Care may be needed to treat patients with MR as well as patients with pure PD. Further studies should be conducted in the future.

(Purpose) Our hospital plays the role of a prefectural core hospital for COVID-19 and mainly accepts moderate and severely ill patients. In addition, our hospital is also actively responsible for regional emergency medical care, and is designated as a cancer treatment cooperation base hospital. We started accepting patients with COVID-19 in April 2020, and 2 out of 10 wards of our hospital are in operation as exclusive wards for COVID-19 at the time of May 31, 2021. In this study, we compared the effects of the spread of COVID-19 on our urological practice with those before the spread. (Materials and methods) The number of urological operations, their types and average length of stay, the number of outpatients / inpatients, the unit cost of medical treatment income, the referral rate, and the reverse referral rate were calculated based on the in-hospital clinical statistics. (Results) The number of urological operations decreased to 847, 862, and 768 in fiscal year 2018, 2019, and 2020, respectively. There was no significant change in the number of surgeries for malignant tumors in fiscal year 2020, but the number of surgeries for benign diseases decreased. The number of emergency operations tended to increase in fiscal year 2020. The number of urological hospitalized patients in fiscal year 2018, 2019, and 2020 decreased to 653, 690, and 533, and the average length of stay was shortened to 8.4, 8.8, and 8.1 days, respectively. The outpatient and inpatient unit prices per patient when fiscal year 2018 was set to 100 were increasing to 119.5 and 104.9, 133.7 and 119.1 in fiscal year 2019 and 2020, respectively. (Conclusion) It is thought that the spread of COVID-19 has clarified the function and characteristics of our hospital in community medicine.

Extensive disease small cell lung cancer (ED-SCLC) is a systemic disease characterized by diffuse metastases and a poor prognosis. Oligometastatic cases in ED-SCLC are rare. This study reports the case of a 72-year-old Japanese male. A mass lesion was identified on chest computed tomography (CT). Fluorodeoxyglucose-positron emission tomography/computed tomography (FDG-PET/CT) revealed a solitary thyroid gland lesion with high FDG uptake as an extrapulmonary finding, suggesting thyroid cancer or a goiter. Upon confirmation of diagnosis, treatment of SCLC was prioritized, and chemoradiotherapy for limited disease SCLC was initiated without further examination of the thyroid gland. The thyroid nodule disappeared after treatment. Two years later, the disease recurred, and a thyroid nodule was found to have reappeared. Upon fine needle aspiration cytology of the thyroid, small cell carcinoma was detected. Therefore, in cases of SCLC, it is necessary to carefully investigate the thyroid for solitary lesions to consider the possibility of oligometastasis. KEY POINTS: SIGNIFICANT FINDINGS OF THE STUDY: Manifesting as a solitary lesion, oligometastasis, particularly in the thyroid, is rare in cases of ED-SCLC. WHAT THIS STUDY ADDS: In SCLC cases, it is necessary to carefully investigate the thyroid for solitary lesions to consider the possibility of oligometastasis., (© 2020 The Authors. Thoracic Cancer published by China Lung Oncology Group and John Wiley & Sons Australia, Ltd.)

Immune checkpoint inhibition is associated with a broad spectrum of immune toxicities referred to as immune-related adverse events (irAEs). Myositis is known to be a potentially fatal irAE. Here, we report a case of immune-related myositis after the administration of durvalumab. A 60-year-old man with stage IIIA lung adenocarcinoma was treated with durvalumab after concurrent chemoradiation therapy. After the third dose of durvalumab, his serum CK level was elevated, and soon thereafter myalgia of the proximal muscles and blepharoptosis were observed. We diagnosed immune-related myositis based on the results of pathological examination and initiated systemic corticosteroid therapy. His symptoms then improved and the serum CK level immediately dropped to within a normal range. Clinicians should be aware of possible myositis during the early phase of durvalumab therapy., (© 2020 The Authors. Thoracic Cancer published by China Lung Oncology Group and John Wiley & Sons Australia, Ltd.)

Priapism is defined as a full or partial erection for >4 hours without sexual stimulation or orgasm. Ischemic priapism is an emergency disease that urgently requires surgery to reduce pressure in the corpora cavernosa. We encountered a case of severe ischemic priapism that required a proximal shunt. The patient was a 71-year-old man who had been diagnosed with benign prostatic hyperplasia ; hence, oral administration of tamsulosin had been initiated at a local hospital. His penis became gradually rigid and presented with prolonged erection. Then he consulted our hospital. Penile aspiration was impossible, and phenylephrine injection was not effective. He was subsequently transferred to our hospital. He did not have severe pain but had complete erection. We could not correctly evaluate blood gas from the corpora cavernosa and color Doppler ultrasonography showed little blood flow in the corpora cavernosa. We judged that the patient had ischemic priapism. The erection could not be controlled by distal shunt plastic surgery performed using the T shunt and Al-Ghorab methods. Therefore, a proximal shunt plastic surgery as described by Sacher was performed. The surgery was effective, but it caused erectile dysfunction.

Introduction: Hypoparathyroidism, sensorineural deafness, and renal dysplasia syndrome is an autosomal dominant rare genetic disease. Some patients with hypoparathyroidism, sensorineural deafness, and renal dysplasia syndrome may present with renal calcification (nephrocalcinosis) and disorder. We report the first case of living-donor kidney transplantation for a patient with hypoparathyroidism, sensorineural deafness, and renal dysplasia syndrome., Case Presentation: This case pertains to a 26-year-old woman who was diagnosed with congenital hypoparathyroidism 1 month after birth, following which vitamin D supplementation was initiated. In 20XX, she developed nephrocalcinosis and was confirmed to have a GATA3 mutation; hence, she was diagnosed with hypoparathyroidism, sensorineural deafness, and renal dysplasia syndrome. In 20XX + 7, ABO-incompatible living-donor kidney transplantation was performed. Her renal function improved, and graft calcification was not observed., Conclusion: Over intake of vitamin D caused nephrocalcinosis. The renal function was improved after living-donor kidney transplantation and the patient's serum calcium levels normalized without vitamin D supplementation. Therefore, kidney transplantation should be considered a treatment option for patients with hypoparathyroidism, sensorineural deafness, and renal dysplasia syndrome., Competing Interests: The authors declare no conflict of interest., (© 2020 The Authors. IJU Case Reports published by John Wiley & Sons Australia, Ltd on behalf of the Japanese Urological Association.)

Background: Arterial reconstruction is one of the paramount procedures in kidney transplantation (KT) and greatly important if the procured kidney has multiple renal arteries (MRA). Despite various established techniques for arterial reconstruction, sometimes, the surgeon finds performing arterial anastomoses challenging in case of MRA. In our case, the donor's gonadal vein and recipient's internal iliac artery graft were used for arterial anastomoses, and 3 years after KT, the allograft did not present vascular complications., Case Presentation: A 34-year-old man underwent ABO-incompatible preemptive living KT. The allograft had three renal arteries and four renal veins. After donor nephrectomy, arterial reconstruction was performed on a back table. These arteries were reconstructed into one piece using the recipient's internal iliac artery graft. The two arteries at the middle of the renal hilum were reconstructed using the conjoined method. As the superior renal artery was too short to anastomose, the donor's gonadal vein was used for extension. The internal iliac artery graft was anastomosed to the original internal iliac artery. Intraoperative Doppler ultrasonography revealed that the blood flow in each renal artery was adequate, resulting in sufficient blood flow throughout the allograft. The allograft function was maintained with a serum creatinine level of approximately 0.9 mg/dL without vascular complications 3 years after KT., Conclusions: The donor's gonadal vein can be a candidate for extension of the renal artery in the allograft with MRA. Further follow-up is needed for the assessment of long-term outcomes.

Sarcopenia is a muscle loss syndrome known as a risk factor of various carcinomas. The impact of sarcopenia and sarcopenia-related inflammatory/nutritional markers in metastatic urothelial carcinoma (mUC) treated with pembrolizumab was unknown, so this retrospective study of 27 patients was performed. Psoas muscle mass index (PMI) was calculated by bilateral psoas major muscle area at the L3 with computed tomography. The cut-off PMI value for sarcopenia was defined as ≤6.36 cm 2 /m 2 for men and ≤3.92 cm 2 /m 2 for women. Neutrophil-to-lymphocyte ratio (NLR) ≥ 4.0 and sarcopenia correlated with significantly shorter progression-free survival (PFS) (hazard ratio (HR) 3.81, p = 0.020; and HR 2.99, p = 0.027, respectively). Multivariate analyses identified NLR ≥ 4.0 and sarcopenia as independent predictors for PFS (HR 2.89, p = 0.025; and HR 2.79, p = 0.030, respectively). Prognostic nutrition index < 45, NLR ≥ 4.0 and sarcopenia were correlated with significantly worse for overall survival (OS) (HR 3.44, p = 0.046; HR 4.26, p = 0.024; and HR 3.92, p = 0.012, respectively). Multivariate analyses identified sarcopenia as an independent predictor for OS (HR 4.00, p = 0.026). Furthermore, a decrease in PMI ≥ 5% in a month was an independent predictor of PFS and OS (HR 12.8, p = 0.008; and HR 6.21, p = 0.036, respectively). Evaluation of sarcopenia and inflammatory/nutritional markers may help in the management of mUC with pembrolizumab., Competing Interests: The authors declare no conflict of interest.

Introduction: Neuronal p3-Alcβ peptides are generated from the precursor protein Alcadein β (Alcβ) through cleavage by α- and γ-secretases of the amyloid β (Aβ) protein precursor (APP). To reveal whether p3-Alcβ is involved in Alzheimer's disease (AD) contributes for the development of novel therapy and/or drug targets., Methods: We developed new sandwich enzyme-linked immunosorbent assay (sELISA) systems to quantitate levels of p3-Alcβ in the cerebrospinal fluid (CSF)., Results: In monkeys, CSF p3-Alcβ decreases with age, and the aging is also accompanied by decreased brain expression of Alcβ. In humans, CSF p3-Alcβ levels decrease to a greater extent in those with AD than in age-matched controls. Subjects carrying presenilin gene mutations show a significantly lower CSF p3-Alcβ level. A cell study with an inverse modulator of γ-secretase remarkably reduces the generation of p3-Alcβ37 while increasing the production of Aβ42., Discussion: Aging decreases the generation of p3-Alcβ, and further significant decrease of p3-Alcβ caused by aberrant γ-secretase activity may accelerate pathogenesis in AD., (© 2019 The Authors.)

The assessor-blinded, parallel-design, quasi-randomized study (alternating allocation) aimed to determine the effects of the six-step method on postoperative numbers of oral bacteria, periodontal status, and atrial fibrillation (AF) among inpatients with heart diseases and periodontitis. Seventy inpatients who received preoperative periodontal treatment were quasi-randomly assigned to intervention and control groups at University Hospital. The intervention group received intensive oral hygiene instruction using a six-step method for 15 minutes per week and the control group received routine oral hygiene instruction. Significantly fewer oral bacteria were identified on the tongue at discharge compared with baseline in the intervention than the control group (ANCOVA) (large effect size, p = 0.02). Changes in scores for self-efficacy, plaque scores, probed pocket depth, and bleeding on probing between baseline and discharge were significantly greater in the intervention, than in the control group ( p < 0.05). The period of postoperative AF (days) was significantly shorter in the intervention, than in the control group ( p = 0.019). In conclusion, oral hygiene instruction using the six-step method decreased the numbers of oral bacteria on the tongue and improved self-efficacy, oral health behaviors, oral hygiene status, periodontal status, and period of postoperative AF among inpatients with periodontitis and heart diseases.

Objectives: To evaluate the clinical benefit of bone-modifying agents and identify the risk factors of skeletal-related events in patients with genitourinary cancer with newly diagnosed bone metastasis., Methods: This was a multicenter retrospective study including a total of 650 patients with bone metastasis of the following cancer types: hormone-sensitive prostate cancer (n = 443), castration-resistant prostate cancer (n = 50), renal cell carcinoma (n = 80) and urothelial carcinoma (n = 77). Clinical factors at the time of diagnosis of bone metastasis were analyzed. Early treatment with bone-modifying agents was defined as follows: administration of bone-modifying agents before the development of skeletal-related events and within 6 months from the diagnosis of bone metastasis., Results: During the follow-up period (median 19.0 months, interquartile range 6.0-43.8 months), skeletal-related events were reported in 88 (20%) patients with hormone-sensitive prostate cancer, 17 (34%) patients with castration-resistant prostate cancer, 58 (73%) patients with renal cell carcinoma and 34 (44%) patients with urothelial carcinoma. Early treatment with bone-modifying agents significantly prolonged the time to the first skeletal-related event in castration-resistant prostate cancer, renal cell carcinoma and urothelial carcinoma, but not in hormone-sensitive prostate cancer. Bone pain and elevated alkaline phosphatase levels were independent predictive risk factors of the first skeletal-related event. The subgroup analysis showed that early treatment with bone-modifying agents was associated with prolonged time to the first skeletal-related events in patients with bone pain or elevated alkaline phosphatase levels., Conclusions: Early treatment with bone-modifying agents should be considered, especially for patients with bone pain and elevated alkaline phosphatase levels, to prevent skeletal-related events in patients with genitourinary cancer with bone metastasis., (© 2019 The Japanese Urological Association.)

A 84-year-old female visited our hospital with the chief complaint of asymptomatic gross hematuria. The computed tomography and magnetic resonance imaging revealed a large invasive tumor in the right renal pelvis. Metastatic workup was negative. On imaging studies and voided urine cytology, diagnosis of right renal pelvic cancer (cT3N0M0) was made. Laparoscopic right nephroureterectomy was performed. Histopathological examinations revealed a small cell carcinoma of the renal pelvis. The patient declined adjuvant chemotherapy and died 5 months after surgery. Primary small cell carcinoma of the renal pelvis is a rare disease. To our knowledge, this is the 29th case of primary small cell carcinoma of the renal pelvis in the world literature.

Using a controlled pre/post study design, we investigated the effects of professional mechanical cleaning of the oral cavity with benzethonium chloride, interdental brushes, and hydrogen peroxide on the number of oral bacteria and postoperative complications among esophageal cancer patients in an intensive care unit. Before surgery, 44 patients with esophageal cancer were recruited at Okayama Hospital from January through August 2015. The control group (n = 23) received routine oral hygiene care in the intensive care unit. The intervention group (n = 21) received intensive interdental cleaning with benzethonium chloride solution and tongue cleaning with hydrogen peroxide. The number of oral bacteria on the tongue surface and plaque index were significantly lower in the intervention group than in the control group on postoperative days 1 and 2 (P < 0.05). Additionally, the number of days with elevated fever during a 1-week period was significantly lower in the intervention group than in the control group (P = 0.037). As compared with routine oral hygiene, a new oral hygiene regimen comprising benzethonium chloride, interdental brushes, and hydrogen peroxide significantly reduced the number of oral bacteria and days with elevated fever in patients with esophageal cancer.

(Objectives) Transurethral Ureterolithotripsy (TUL) has become an increasingly more common treatment for ureteric stones since the reduction in ureteroscope diameter and other device improvements. At the same time, TUL sometimes shows postoperative febrile urinary tract infection (fUTI) with severe complications. Therefore we investigated the occurrence and risk factors of fUTI in our hospital, and assessed the effect of antibiotic prophylaxis prior to TUL. (Materials and methods) The subjects were 260 patients who underwent TUL in our department during the period from January 2011 to October 2014. We retrospectively reviewed the data of those who developed postoperative fUTI and identified the risk factors of postoperative fUTI. From November 2014 to August 2016, we enrolled 110 patients undergoing TUL with one or more risk factors in a prospective clinical trial of prophylactic oral levofloxacin (500 mg) for 1 week before TUL. The chi-squared test, Mann-Whitney U-test, and logistic regression analysis were used for data analysis (significance level of 0.05). (Results) Postoperative fUTI occurred in 43 (16.5%) of 260 patients. The risk factors of postoperative fUTI included preoperative pyelonephritis (P=0.02), preoperative ureteral stent placement (P=0.017), and operative time >90 min (P=0.005). Operative time was correlated with and could be substituted for pre-TUL stone size (P<0.0001). Chemopreventive therapy before TUL in patients with preoperative pyelonephritis, preoperative ureteral stent placement, or stones of >20 mm significantly reduced their risk of fUTI (P=0.012). (Conclusions) The use of antibiotic prophylaxis significantly reduces the risk of postoperative fUTI in patients with preoperative pyelonephritis, preoperative ureteral stent placement, or stones of >20 mm.

Generation of amyloid-β peptides (Aβs) by proteolytic cleavage of the amyloid-β protein precursor (AβPP), especially increased production of Aβ42/Aβ43 over Aβ40, and their aggregation as oligomers and plaques, represent a characteristic feature of Alzheimer's disease (AD). In familial AD (FAD), altered Aβ production originates from specific mutations of AβPP or presenilins 1/2 (PS1/PS2), the catalytic subunits of γ-secretase. In sporadic AD, the origin of altered production of Aβs remains unknown. We hypothesize that the 'human chemical exposome' contains products able to favor the production of Aβ42/Aβ43 over Aβ40 and shorter Aβs. To detect such products, we screened a library of 3500 + compounds in a cell-based assay for enhanced Aβ42/Aβ43 production. Nine pyrazole insecticides were found to induce a β- and γ-secretase-dependent, 3-10-fold increase in the production of extracellular Aβ42 in various cell lines and neurons differentiated from induced pluripotent stem cells derived from healthy and FAD patients. Immunoprecipitation/mass spectrometry analyses showed increased production of Aβs cleaved at positions 42/43, and reduced production of peptides cleaved at positions 38 and shorter. Strongly supporting a direct effect on γ-secretase activity, pyrazoles shifted the cleavage pattern of another γ-secretase substrate, alcadeinα, and shifted the cleavage of AβPP by highly purified γ-secretase toward Aβ42/Aβ43. Focusing on fipronil, we showed that some of its metabolites, in particular the persistent fipronil sulfone, also favor the production of Aβ42/Aβ43 in both cell-based and cell-free systems. Fipronil administered orally to mice and rats is known to be metabolized rapidly, mostly to fipronil sulfone, which stably accumulates in adipose tissue and brain. In conclusion, several widely used pyrazole insecticides enhance the production of toxic, aggregation prone Aβ42/Aβ43 peptides, suggesting the possible existence of environmental "Alzheimerogens" which may contribute to the initiation and propagation of the amyloidogenic process in sporadic AD.

The activities of mitochondrial enzymes, which are essential for neural function, decline with age and in age-related disease. In particular, the activity of cytochrome c oxidase (COX/complex IV) decreases in patients with Alzheimer's disease (AD). COX, a mitochondrial inner membrane protein complex that contains heme, plays an essential role in the electron transport chain that generates ATP. Heme synthesis begins with 5-aminolevulinic acid (5-ALA) in mitochondria. 5-ALA synthetase is the rate-limiting enzyme in heme synthesis, suggesting that supplementation with 5-ALA might help preserve mitochondrial activity in the aged brain. We administered a diet containing 5-ALA to triple-transgenic AD (3xTg-AD) model mice for 6 months, starting at 3 months of age. COX activity and protein expression, as well as mitochondrial membrane potential, were significantly higher in brains of 5-ALA-fed mice than in controls. Synaptotagmin protein levels were also significantly higher in 5-ALA-fed mice, suggesting improved preservation of synapses. Although brain Aβ levels tended to decrease in 5-ALA-fed mice, we observed no other significant changes in other biochemical and pathological hallmarks of AD. Nevertheless, our study suggests that daily oral administration of 5-ALA could preserve mitochondrial enzyme activities in the brains of aged individuals, thereby contributing to the preservation of neural activity.

In patients with a bronchocutaneous fistula, positive pressure ventilation leads to air leakage and potential hypoxemia. A male patient with a right upper bronchocutaneous fistula was scheduled for esophageal reconstruction. His preoperative chest computed tomography image revealed aeration in the right middle and lower lobe, a large bulla in the left upper lobe, and pleural effusion and pneumonia in the left lower lobe. Therefore, left one-lung ventilation was considered to result in hypoxemia. Before anesthesia induction, the bronchocutaneous fistula was covered with gauze and film to prevent air leakage. After anesthesia induction, mask ventilation was performed with a peak positive pressure of 10 cmH 2 O. A left-sided double lumen endobronchial tube (DLT) was then inserted into the right main bronchus for occluding only the right superior bronchus, and two-lung ventilation was performed to minimize airway pressure and maintain oxygenation, which did not cause air leakage through the fistula. During anesthesia, no ventilation-related difficulty was faced. The method of inserting a left-sided DLT into the right main bronchus and occluding the right upper bronchus selectively by bronchial cuff is considered to be an option for mechanical ventilation in patients with a right upper bronchial fistula, as demonstrated in the present case.

Proteolytic cleavage of the amyloid-β protein precursor (AβPP) by secretases leads to extracellular release of amyloid-β (Aβ) peptides. Increased production of Aβ42 over Aβ40 and aggregation into oligomers and plaques constitute an Alzheimer's disease (AD) hallmark. Identifying products of the 'human chemical exposome' (HCE) able to induce Aβ42 production may be a key to understanding some of the initiating causes of AD and to generate non-genetic, chemically-induced AD animal models. A cell model was used to screen HCE libraries for Aβ42 inducers. Out of 3500+ compounds, six triazine herbicides were found that induced a β- and γ-secretases-dependent, 2-10 fold increase in the production of extracellular Aβ42 in various cell lines, primary neuronal cells, and neurons differentiated from human-induced pluripotent stem cells (iPSCs). Immunoprecipitation/mass spectrometry analyses show enhanced production of Aβ peptides cleaved at positions 42/43, and reduced production of peptides cleaved at positions 38 and lower, a characteristic of AD. Neurons derived from iPSCs obtained from a familial AD (FAD) patient (AβPP K724N) produced more Aβ42 versus Aβ40 than neurons derived from healthy controls iPSCs (AβPP WT). Triazines enhanced Aβ42 production in both control and AD iPSCs-derived neurons. Triazines also shifted the cleavage pattern of alcadeinα, another γ-secretase substrate, suggesting a direct effect of triazines on γ-secretase activity. In conclusion, several widely used triazines enhance the production of toxic, aggregation prone Aβ42/Aβ43 amyloids, suggesting the possible existence of environmental "Alzheimerogens" which may contribute to the initiation and propagation of the amyloidogenic process in late-onset AD.

Objective: Many cross-sectional studies have reported a relationship between overweight/obesity and eating quickly, but there have been few longitudinal studies to address this relationship in younger populations. The purpose of this prospective longitudinal study was to investigate whether eating quickly was related to being overweight in Japanese university students., Methods: Of 1,396 students who underwent a general examination and completed questionnaires at the start of university and before graduation, 1,314 students (676 male and 638 female) of normal body composition [body mass index (BMI) < 25 kg m(-2) ] at baseline were included in the analysis. The questionnaires included speed of eating and other lifestyle factors. After a 3-year follow-up, the students whose BMIs were ≥ 25 kg m(-2) were defined as overweight., Results: In this study, 38 participants (2.9%) became overweight. In the logistic regression analysis, the risk of being overweight was increased in males [adjusted odds ratio (OR): 2.77; 95% confidence interval (CI): 1.33-5.79; P < 0.01] and in those who ate quickly at baseline (OR: 4.40; 95% CI: 2.22-8.75; P < 0.001)., Conclusions: Eating quickly may predict risk of being overweight in Japanese university students., (Copyright © 2014 The Obesity Society.)

p3-Alcα is a metabolic fragment of Alcadeinα (Alcα). Similar to the generation of the p3 fragment from amyloid-β protein precursor (AβPP) processing, Alcα is cleaved by α- and γ-secretases, leading to the secretion of p3-Alcα peptides into cerebrospinal fluid (CSF). p3-Alcα is also detected in the plasma, similar to amyloid-β (Aβ), which is a metabolic fragment of AβPP cleaved by amyloidogenic β- and γ-secretases. Because p3-Alcα is a non-aggregatable and stable peptide, unlike aggregatable Aβ and metabolically labile p3 of AβPP, the changes of p3-Alcα in quality and/or quantity in CSF and plasma are expected to be a marker for assessing alteration of substrate cleavage by γ-secretase, such as Aβ generation from AβPP. The present study describes a sandwich enzyme-linked immunosorbent assay for quantifying levels of p3-Alcα35, the major form of the p3-Alcα species, and examines levels of p3-Alcα35 in the plasma of three independent Japanese cohorts. In two of the three cohorts, the p3-Alcα35 levels were significantly increased with a concomitant decrease in the Mini-Mental State Examination score, or in clinically diagnosed Alzheimer's disease (AD) patients, when compared with age-matched non-demented subjects. The values were significantly lower in AD subjects who were administered donepezil, when compared to AD subjects without donepezil treatment. The increase in plasma p3-Alcα35 levels may indicate an endophenotype in subjects in whom AD is due to a progressing cognitive impairment in subjects with a γ-secretase malfunction, or a disorder of the clearance of peptides.

Background: Patients with juvenile dermatomyositis (JDM) often present strong exercise intolerance and muscle weakness. However, the role of exercise training in this disease has not been investigated., Purpose: this longitudinal case study reports on the effects of exercise training on a 7-year-old patient with JDM and on her unaffected monozygotic twin sister, who served as a control., Methods: Both the patient who was diagnosed with JDM as well as her healthy twin underwent a 16-week exercise training program comprising aerobic and strengthening exercises. We assessed one repetition-maximum (1-RM) leg-press and bench-press strength, balance, mobility and muscle function, blood markers of inflammation and muscle enzymes, aerobic conditioning, and disease activity scores. As a result, the healthy child had an overall greater absolute strength, muscle function and aerobic conditioning compared to her JDM twin pair at baseline and after the trial. However, the twins presented comparable relative improvements in 1-RM bench press, 1-RM leg press, VO2peak, and time-to-exhaustion. The healthy child had greater relative increments in low-back strength and handgrip, whereas the child with JDM presented a higher relative increase in ventilatory anaerobic threshold parameters and functional tests. Quality of life, inflammation, muscle damage and disease activity scores remained unchanged., Results and Conclusion: this was the first report to describe the training response of a patient with non-active JDM following an exercise training regimen. The child with JDM exhibited improved strength, muscle function and aerobic conditioning without presenting an exacerbation of the disease.

There has been an increasing recognition of adverse short-, mid-, or long-term effects associated with the treatment as well as the disease itself that impair the health-related quality of life and functional capacity of children and adolescents with rheumatic diseases. Interestingly, cumulative evidence has suggested that exercise training may benefit patients with juvenile idiopathic arthritis, juvenile systemic lupus erythematosus, juvenile dermatomyositis and juvenile fibromyalgia, attenuating several clinical symptoms related to physical disability. Remarkably, recent evidence also suggests that exercise may have direct effects on the pathogenesis of autoimmune diseases by attenuating chronic low-grade systemic inflammation. It is also important to emphasize that no exercise-related adverse effects have been reported. This short review provides the evidence for physical training as a treatment of pediatric rheumatic diseases, introducing a novel concept that exercise is a treatment for these populations., (Copyright 2010 Elsevier B.V. All rights reserved.)

Study Objectives: To assess the quality of life (QOL) in patients with severe obstructive sleep apnea (OSAS), and the relationship between the QOL and severity of OSAS, excessive daytime sleepiness (EDS), and mood., Methods: Sixty patients with OSAS and 34 normal control subjects were assessed for QOL using the Medical Outcomes Study Short-Form 36 Health Survey questionnaire (SF-36), for EDS using the Epworth sleepiness scale (ESS), and for mood using the Zung self-rated depression scale (SDS). The associations between each domain and the total score on the SF-36 and the baseline characteristics, polysomnographic parameters, ESS score, and SDS score were examined by simple regression analysis and stepwise multiple regression analysis., Results: Six of eight domains and the total score on the SF-36 were significantly lower than those in the control subjects. The ESS and SDS scores were also more impaired in the patients than in the control subjects. There was no relationship between each domain on the SF-36 and the severity of OSAS and ESS score. Five of eight domains and the total score on the SF-36 were significantly correlated with the SDS score. Stepwise multiple regression analysis selected three variables, the SDS score (partial R(2) = 0.505), the lowest arterial oxygen saturation during sleep (partial R(2) = 0.064), and ESS score (partial R(2) = 0.053), as independent factors for predicting the total score on the SF-36. These three variables accounted for 62.2% of the total variance in the total score on SF-36 (R(2) = 0.622, p < 0.0001), Conclusions: The QOL of patients with severe OSAS was decreased compared with normal control subjects. The QOL of patients was strongly correlated with the depression scale on simple regression analysis. However, EDS score and oxygen desaturation during sleep also affected the QOL, although the magnitude of its effect was small.