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Abstract To establish a safer and more efficient treatment strategy with mini-endoscopic combined intrarenal surgery (ECIRS), the present study aimed to develop models to predict the outcomes of mini-ECIRS in patients with renal and/or ureteral stones. We retrospectively analysed consecutive patients with renal and/or ureteral stones who underwent mini-ECIRS at three Japanese tertiary institutions. Final treatment outcome was evaluated by CT imaging at 1 month postoperatively and stone free (SF) was defined as completely no residual stone or residual stone fragments ≤ 2 mm. Three prognostic models (multiple logistic regression, classification tree analysis, and machine learning-based random forest) were developed to predict surgical outcomes using preoperative clinical factors. Clinical data from 1432 ECIRS were pooled from a database registered at three institutions, and 996 single sessions of mini-ECIRS were analysed in this study. The overall SF rate was 62.3%. The multiple logistic regression model consisted of stone burden (P

Introduction: In the United States, a total of 268,490 men were found to have prostate cancer in 2022, thus making it the most common cancer in men, accounting for 27% of all cancers in the male population. Among all cancers in men, it was the fifth leading cause of death, with 34,500 deaths and a mortality rate of 11%. In 2019, the total number of cases was 94,748, making it the leading cancer in males, accounting for 11% of all male cancers. In terms of mortality, it ranked seventh, with 13,217 deaths and a mortality rate of 1.6%. However, new treatment options for metastatic castration-sensitive prostate cancer (mCSPC) have emerged. Docetaxel has been shown to be effective for both mCSPC and castration-resistant prostate cancer (CRPC). Upfront docetaxel has not been approved in Japan, nor has it been validated in large-scale studies. Furthermore, several agents can be used after docetaxel treatment, but it is unclear which is the most effective. We used a large Japanese health insurance database to determine which agent would be the most effective as a next-line therapy in patients who had received docetaxel. Materials and Methods: We used data from medical institutions using the Diagnosis Procedure Combination (DPC), which provides a comprehensive evaluation of medical classifications. The Medical Data Vision database covers approximately 23% of DPC hospitals in Japan. This study analyzed 2938 patients with mCSPC who received docetaxel, followed by CRPC, between April 2008 and December 2021. The study focused on three agents: enzalutamide, abiraterone acetate, and cabazitaxel. Other agents were excluded due to the small number of patients. The following data were analyzed: age, date of CRPC diagnosis, presence of bone metastasis, drug type, and prognosis. Results: This study included 1997 patients with CRPC after upfront docetaxel therapy for mCSPC (enzalutamide [ENZ] group, n = 998; abiraterone acetate [ABI] group, n = 617; and cabazitaxel [CBZ] group, n = 382). The overall survival (OS) time from drug initiation was 456 days in the enzalutamide group, which was significantly longer than that in the cabazitaxel group (p = 0.017, HR 0.94) (ENZ: ABI p = 0.54, HR 0.94; ABI: CBZ p = 0.14, HR 0.75). OS was also compared for the third-line drug in the group that received enzalutamide as the second-line drug, the group that used abiraterone acetate as the third-line drug (ENZ-ABI group), and the group that used abiraterone acetate as the second-line drug. OS from the start of the third-line drug was compared between the ENZ–ABI group and the ABI–ENZ group, which received enzalutamide as the third-line drug, but showed no significant difference (269 vs. 281 days, p = 0.85; HR 1.03). Conclusion: ENZ was shown to prolong OS relative to cabazitaxel after the cessation of docetaxel. ENZ was associated with a longer duration of drug use than ABI and CBZ.

Abstract Background To compare the efficacy and safety of bipolar transurethral vaporization of the prostate (B-TUVP) with holmium laser enucleation of the prostate (HoLEP) for moderate [prostate volume (PV) 30–80 ml] and large (≥ 80 ml) benign prostatic enlargement (BPE). Materials and methods Male patients with lower urinary tract symptom (LUTS) or urinary retention who underwent B-TUVP or HoLEP treatment in two regional centers were respectively enrolled. Patient characteristics and treatment outcomes were retrospectively compared between B-TUVP and HoLEP. Results In patients with moderate and large prostate volume,B-TUVP showed shorter operative time (P 80 ml.(P 80 ml.(P=0.08) The Incidence of postoperative stress incontinence(SUI) was higher in HoLEP than in B-TUVP for patients with moderate and large prostate volume. Conclusions There are few studies that investigated the short-term efficacy and safety of second-generation B-TUVP in comparison with HoLEP for moderate and large BPE. Improvement in LUTS and achievement of catheter-free status were predominant in HoLEP, and these outcomes were more prominent in patients with large BPE of PV > 80 ml. However, B-TUVP resulted in less blood loss, shorter operative duration, and less SUI suggesting that B-TUVP is also well-tolerated surgical modality.

Thrombocytopenia, anasarca, myelofibrosis, renal dysfunction, and organomegaly (TAFRO) syndrome is a rare condition with diverse clinical and pathological characteristics related to multi-organ damage. We report a case of TAFRO syndrome complicated by immune thrombocytopenia with prolonged fever and thrombocytopenia for several weeks. A 61-year-old man was transferred with sepsis caused by Enterococcus faecalis, and developed disseminated intravascular coagulation. Antibiotics treatment was initiated: however, low-grade fever and thrombocytopenia persisted despite the adequate antimicrobial treatment. Systemic edema, pleural effusion, and ascites had developed before hospitalization, and renal and liver function had deteriorated, resulting in progressive multi-organ damage. Prednisolone 40 mg/day was initiated based on the assumption of a condition in which excessive production of inflammatory cytokines would lead to systemic deterioration and fatal organ damage. Subsequently, the fever resolved, and renal function began to normalize. However, thrombocytopenia did not show much recovery trend after Helicobacter pylori eradication therapy and initiation of thrombopoietin receptor agonists. Bone marrow biopsy results showed normal bone marrow with no malignant findings. Alternatively, significant clinical signs met the diagnostic criteria for TAFRO syndrome, and a renal biopsy revealed thrombotic microangiopathy, which is also reasonable for renal involvement in TAFRO syndrome. The use of cyclosporine remarkably corrected the thrombocytopenia. We considered this a case of TAFRO syndrome that developed after sepsis with disseminated intravascular coagulation and performed the differential diagnosis of prolonged thrombocytopenia and excluded it. Although TAFRO syndrome is a unique disease concept, diagnostic criteria may consist of nonspecific elements such as generalized edema, thrombocytopenia, persistent fever, and elevated inflammatory response, and there are many differential conditions to exclude, requiring caution in diagnosing TAFRO syndrome.

We aimed to identify prognostic predictive factors of patients with penile squamous cell carcinoma (PSCC). This retrospective study reviewed the clinical and pathological data of patients with PSCC at 10 institutions in Japan between January 2008 and December 2019. The primary endpoint was cancer-specific survival (CSS). We also identified useful predictive factors for CSS in patients with PSCC. In total, 64 patients with PSCC were enrolled. At the end of the follow-up period, 15 patients (23.4%) died owing to PSCC and six (9.4%) died owing to other causes. The 2- and 3-year CSS rates were 78.9% and 76.6%, respectively. Using the Kaplan–Meier method, the Eastern Cooperative Oncology Group performance status 0, serum albumin levels ≥4.2 g/dL, hemoglobin levels ≥13.2 g/dL, C-reactive protein levels

Summary: Background: Birt-Hogg-Dubé (BHD) syndrome, caused by germline alteration of folliculin (FLCN) gene, develops hybrid oncocytic/chromophobe tumour (HOCT) and chromophobe renal cell carcinoma (ChRCC), whereas sporadic ChRCC does not harbor FLCN alteration. To date, molecular characteristics of these similar histological types of tumours have been incompletely elucidated. Methods: To elucidate renal tumourigenesis of BHD-associated renal tumours and sporadic renal tumours, we conducted whole genome sequencing (WGS) and RNA-sequencing (RNA-seq) of sixteen BHD-associated renal tumours from nine unrelated BHD patients, twenty-one sporadic ChRCCs and seven sporadic oncocytomas. We then compared somatic mutation profiles with FLCN variants and RNA expression profiles between BHD-associated renal tumours and sporadic renal tumours. Findings: RNA-seq analysis revealed that BHD-associated renal tumours and sporadic renal tumours have totally different expression profiles. Sporadic ChRCCs were clustered into two distinct clusters characterized by L1CAM and FOXI1 expressions, molecular markers for renal tubule subclasses. Increased mitochondrial DNA (mtDNA) copy number with fewer variants was observed in BHD-associated renal tumours compared to sporadic ChRCCs. Cell-of-origin analysis using WGS data demonstrated that BHD-associated renal tumours and sporadic ChRCCs may arise from different cells of origin and second hit FLCN alterations may occur in early third decade of life in BHD patients. Interpretation: These data further our understanding of renal tumourigenesis of these two different types of renal tumours with similar histology. Funding: This study was supported by JSPS KAKENHI Grants, RIKEN internal grant, and the Intramural Research Program of the National Institutes of Health (NIH), National Cancer Institute (NCI), Center for Cancer Research.

Case: A 59-year-old man presented with posterior sternoclavicular joint dislocation concomitant with fracture-dislocations of multiple thoracic costovertebral joints caused by traumatic injury. The posterior sternoclavicular joint dislocation was treated using an ultra-high molecular weight polyethylene fiber cable and the joint was stabilized. The degree of malpositioning of the thoracic costovertebral joints was difficult to reduce. Conclusion: The patient achieved an excellent shoulder range of motion at 12 months postoperatively; however, chronic shoulder stiffness and posterior neck discomfort persisted.

Objective. To identify risk factors for difficult ureters during ureteroscopic lithotripsy and to determine the appropriate indications for preoperative stenting. Methods. We retrospectively analyzed 156 ureteroscopic procedures for upper urinary tract stones after excluding those with preoperative stenting or percutaneous nephrostomy. Traceability of the ureter was assessed by two urologists. Traceability was defined as positive if either or both urologists discerned the ureter in all slices on preoperative plain computed tomography. Patients’ backgrounds were compared between the nondifficult ureter and difficult ureter groups. A multivariate logistic regression model was used to evaluate the relationships between difficult ureters and other clinical factors. Results. Of 156 patients, 31 (19.9%) were classified into the difficult ureter group. The positive traceability was higher in the nondifficult ureter group (48.3% vs. 83.2%, P

Abstract Pachyvessels are pathologically dilated large choroidal vessels and are associated with the pathogenesis of several pachychoroid-related disorders, including central serous chorioretinopathy. We aimed to investigate the prevalence of and risk factors for pachyvessels in the Japanese population. We included 316 participants (aged ≥ 40 years) with normal right eyes. The presence of pachyvessels (vertical diameter > 300 µm, distance to the retinal pigment epithelium

Summary: Our understanding of how each hereditary kidney cancer adapts to its tissue microenvironment is incomplete. Here, we present single-cell transcriptomes of 108,342 cells from patient specimens including from six hereditary kidney cancers. The transcriptomes displayed distinct characteristics of the cell of origin and unique tissue microenvironment for each hereditary kidney cancer. Of note, hereditary leiomyomatosis and renal cell carcinoma (HLRCC)-associated kidney cancer retained some characteristics of proximal tubules, which were completely lost in lymph node metastases and present as an avascular tumor with suppressed T cells and TREM2-high macrophages, leading to immune tolerance. Birt-Hogg-Dubé (BHD)-associated kidney cancer exhibited transcriptomic intratumor heterogeneity (tITH) with increased characteristics of intercalated cells of the collecting duct and upregulation of FOXI1-driven genes, a critical transcription factor for collecting duct differentiation. These findings facilitate our understanding of how hereditary kidney cancers adapt to their tissue microenvironment.

Background:: To investigate the treatment outcomes and postoperative complications of second-generation bipolar transurethral vaporization of the prostate (B-TUVP) using an oval-shaped electrode in older patients aged ≥80 years with benign prostatic enlargement (BPE). Materials and Methods:: Second-generation B-TUVP was performed in male patients with lower urinary tract symptoms (LUTS) or urinary retention between July 2018 and August 2021. Patient characteristics and surgical outcomes were retrospectively compared between patients aged

We conducted a multicenter, retrospective study to evaluate the efficacy and safety of combination nivolumab plus ipilimumab (NIVO+IPI) in 35 patients with advanced or metastatic renal cell carcinoma (mRCC). In this study, we focused on patients who received NIVO+IPI and were stratified into intermediate- or poor-risk disease according to the International Metastatic Renal Cell Carcinoma Database Consortium model at five institutions in Japan. The primary endpoint was overall survival (OS). Secondary endpoints were disease control rate (DCR), best overall response (BOR), objective response rate (ORR), and progression-free survival (PFS). In addition, we evaluated the role of inflammatory cell ratios, namely neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR), as predictive biomarkers in patients with mRCC. The median follow-up period was 1 year, and the 1-year OS rate was 95.8%. The ORR and DCR were 34.3% and 80.0%, respectively. According to BOR, four patients (11.4%) achieved complete response. According to NLR stratification, the 1-year PFS rates were 82.6% and 23.7% when the NLR was ≤4.6 and >4.6, respectively (p = 0.04). Based on PLR stratification, the 1-year PFS rates were 81.7% and 34.3% when the PLR was ≤188.1 and >188.1, respectively (p = 0.033). Although 71.4% of the patients experienced treatment-related adverse events (TRAEs) with NIVO+IPI, only four patients discontinued NIVO+IPI due to grade 3/4 TRAEs. Patients treated with NIVO+IPI as a first-line therapy for advanced or mRCC achieved relatively better oncological outcomes. Therefore, NIVO+IPI may have potential advantages and may lead to a treatment effect compared to those receiving targeted therapies. In addition, PLR >188.1 may be a useful predictive marker for mRCC patients who received NIVO+IPI.

This paper describes a case of renal pelvic cancer with a complete duplication of the renal pelvis and ureter, which is substantially rare. A 76-year-old man was referred to the hospital because of gross hematuria for 2 years. A tumor was detected in the upper right kidney using enhanced computed tomography and magnetic resonance imaging scan, and the downstream ureter was suspected to open into the prostate. Retrograde ureteroscopy via the ectopic ureter orifice showed a hemorrhagic papillary tumor consistent with imaging findings. Laparoscopic radical nephroureterectomy was performed and the prostate was preserved because the tumor was only in the renal pelvis. Histopathological examination showed the tumor as a high-grade urothelial carcinoma. There was no sign of recurrence at one and a half years after operation. Ureteroscopy was effective in detecting an upper urinary tract tumor, even via ectopic ureter orifice, and preserving the prostate was possible.

We propose a novel image transformation network for generating visually protected images for privacy-preserving deep neural networks (DNNs). The proposed transformation network is trained by using a plain image dataset so that plain images are converted into visually protected ones. Conventional perceptual encryption methods cause some accuracy degradation in image classification and are not robust enough against state-of-the-art attacks. In contrast, the proposed network not only enables us to maintain the image classification accuracy that using plain images achieves but is also strongly robust against attacks including DNN-based ones. Furthermore, there is no need to manage any security keys as the conventional methods require. In an image classification experiment, the proposed network is demonstrated to strongly protect the visual information of plain images while maintaining a high classification accuracy under the use of two typical classification networks: ResNet and VGG. In addition, it is shown that the visually protected images are robust enough against various attacks in an experiment in which we tried to restore the visual information of plain images.

To elucidate the unknown regulatory mechanisms involved in aluminum (Al)-induced expression of POLYGALACTURONASE-INHIBITING PROTEIN 1 (PGIP1), which is one of the downstream genes of SENSITIVE TO PROTON RHIZOTOXICITY 1 (STOP1) regulating Al-tolerance genes, we conducted a genome-wide association analysis of gene expression levels (eGWAS) of PGIP1 in the shoots under Al stress using 83 Arabidopsis thaliana accessions. The eGWAS, conducted through a mixed linear model, revealed 17 suggestive SNPs across the genome having the association with the expression level variation in PGIP1. The GWAS-detected SNPs were directly located inside transcription factors and other genes involved in stress signaling, which were expressed in response to Al. These candidate genes carried different expression level and amino acid polymorphisms. Among them, three genes encoding NAC domain-containing protein 27 (NAC027), TRX superfamily protein, and R-R-type MYB protein were associated with the suppression of PGIP1 expression in their mutants, and accordingly, the system affected Al tolerance. We also found the involvement of Al-induced endogenous nitric oxide (NO) signaling, which induces NAC027 and R-R-type MYB genes to regulate PGIP1 expression. In this study, we provide genetic evidence that STOP1-independent NO signaling pathway and STOP1-dependent regulation in phosphoinositide (PI) signaling pathway are involved in the regulation of PGIP1 expression under Al stress.

The treatment options are currently limited, and the oncological outcomes remain unclear, for patients with metastatic urothelial carcinoma (mUC) with or without third-line systemic therapy. We aimed to evaluate the oncological outcomes in real-world daily clinical practice after platinum-based chemotherapy followed by pembrolizumab for mUC. This retrospective, multicenter cohort study included patients with mUC who received second-line pembrolizumab in Japan. The patients were divided into the treatment group (those who received third-line treatment) and the BSC group (those who did not receive other treatments). The primary endpoint of this study was to evaluate the oncological outcomes. Of 126 patients enrolled in this study, 40 received third-line therapy. The median follow-up period was 8.0 months. The median overall survival (OS) times were nine months in the BSC group and 17 months in the treatment group (p < 0.001). The median progression-free survival (PFS) times were 4 months in the BSC group and 14 months in the treatment group (p < 0.001). In the multivariate analysis, performance status and liver metastasis were significantly associated with OS. Third-line therapy may have clinical potential advantages for improving the oncological outcomes in patients with mUC.

The effects of photosynthetic photon flux density (PPFD) fluctuations in sunlight have already been investigated; however, the spectral photon flux density distribution (SPD) has hardly been considered. Here, sunlight SPD fluctuations recorded for 200 min in October in Tokyo, Japan were artificially reproduced using an LED-artificial sunlight source system. The net photosynthetic rate (Pn) of cucumber leaves under reproduced sunlight was measured and compared with the Pn estimated from a steady-state PPFD–Pn curve for the same leaves. The measured and estimated Pn agreed except when the PPFD was low, where the measured Pn was lower than the estimated Pn. The ratio of measured Pn to estimated Pn was 0.94–0.95 for PPFD ranges of 300–700 μmol m–2 s–1, while the value was 0.98–0.99 for 900–1,300 μmol m–2 s–1, and the overall ratio was 0.97. This 3% reduction in the measured Pn compared with the Pn estimated from a steady-state PPFD–Pn curve was significantly smaller than the approximately 20–30% reduction reported in previous experimental and simulation studies. This result suggests that the loss of integral net photosynthetic gain under fluctuating sunlight can vary among days with different fluctuation patterns or may be non-significant when fluctuations in both PPFD and relative SPD of sunlight are taken into consideration.

It is unclear how some Drosophila neurons develop sex-specific neurites that contribute to dimorphic circuitries required for gendered behavior. The authors show that sex-specific cleavage by the E3 ubiquitin ligase Cullin1 and 26S proteasome of the pleiotropic BTB-ZF transcription factor Lola confers its sexual fate-inducing ability in these neurons.

We focused on the therapeutic effect of pembrolizumab for metastatic urothelial carcinoma (mUC) and evaluated predictive factors for improving clinical outcomes. We conducted a retrospective multicenter cohort study of patients with mUC who received pembrolizumab. The endpoint was to evaluate the association between clinicopathological features and oncological outcomes. A total of 160 patients were enrolled in this study and were divided into two groups: the responder and the non-responder group, according to the best response. They were followed up for a median period of 10 months. The median overall (OS) and progression-free survival (PFS) in this study were 17 and 4 months, respectively. The responder group did not achieve median OS and it was 10 months in the non-responder group (p < 0.001). Similarly, the responder group did not achieve PFS, and it was 2 months in the non-responder group (p < 0.001). Regarding the neutrophil-to-lymphocyte ratio (NLR) after two courses of administration of pembrolizumab, patients with NLR < 3.24 had significantly better oncological outcomes than those with NLR ≥ 3.24. Multivariate analysis showed a significant association between NLR after two courses of pembrolizumab and OS. Therefore, the absolute value of NLR after two courses of pembrolizumab was a significant predictive factor for oncological outcomes.

Abstract Background Bladder cancers have been characterized as a tumor group in which the immunological response is relatively well preserved. Programmed death ligand 1 (PD-L1, B7-H1, CD274) has been shown to be expressed in several malignancies, including bladder cancer. However, the clinicopathological impact of this biomarker has not yet been established. In the present study, a quantitative real-time polymerase chain reaction (qPCR) was performed using paired normal and cancerous bladder cancer tissue to investigate PD-1/PD-L1 gene expression. Methods We examined the mRNA expression of PD-1/PD-L1 by a qPCR using 58 pairs of normal and cancerous human bladder tissue specimens. We also examined the correlation with the expressions of the STAT1 and NFAT genes, which are thought to be upstream and downstream of the PD-L1 pathway, respectively. Results There were no significant differences between normal and cancerous tissue in the expression of the PD-1 and PD-L1 genes (p = 0.724 and p = 0.102, respectively). However, PD-1 and PD-L1 were both more highly expressed in high-grade bladder cancer than in low-grade bladder cancer (p

The shortage of doctors is a societal problem, especially in rural areas such as Akita Prefecture, Japan. Therefore, it is not unusual in Akita for orthopedic surgeons to perform upper and lower limb surgeries under ultrasound-guided peripheral nerve blocks managed by the operators themselves. Multicenter studies of ultrasound-guided peripheral nerve blocks performed by orthopedic surgeons have not been reported. The purpose of this study was to clarify the safety and reliability of ultrasound-guided peripheral nerve blocks performed by orthopedic surgeons in Akita. A total of 1,674 upper extremity surgery cases operated under ultrasound-guided peripheral nerve blocks at 8 hospitals in Akita prefecture from April 2016 to April 2018 were investigated retrospectively. These blocks were performed by a total of 37 orthopedic surgeons, including senior surgeons and residents. In 321 of the 1,674 cases (19%), local anesthetics were added to the surgical field. Two cases with special factors were converted to general anesthesia. There were 2 cases of complications associated with the nerve block, but they were all transient and recovered promptly. The block site and the hospital where the block was performed showed a significant relationship with the addition of local anesthetics to the surgical site (P

BackgroundTo investigate the efficacy and safety of a second-generation bipolar transurethral electro vaporization of the prostate (B-TUVP) with the new oval-shaped electrode for large benign prostatic enlargement (BPE) with prostate volume (PV) ≥100ml.Materials and methods100 patients who underwent second-generation B-TUVP with the oval-shaped electrode for male lower urinary tract symptom (LUTS) or urinary retention between July 2018 and July 2020 were enrolled in this study. The patients' characteristics and treatment outcome were retrospectively compared between patients with PV Results17/41 (41.5%) cases of PV ≥100ml and 24/59 cases (40.7%) of PV ConclusionsThis is the first study investigating short-term efficacy and safety of second-generation B-TUVP with the oval-shaped electrode on large BPE. B-TUVP appears to be effective and safe for treating moderate-to-severe lower urinary tract symptoms and urinary retention in patients with large BPE.

Background and Objectives: Peritoneal dialysis (PD)-related peritonitis is a critical problem. However, preoperative risk factors for PD-related peritonitis have not been established. Thus, we aimed to determine the preoperative risk factors for PD-related peritonitis. Materials and Methods: This is a single-center prospective observational study. All peritonitis episodes during the study period were recorded, and preoperative and intraoperative clinical parameters were compared between patients with and without peritonitis to examine risk factors for PD-related peritonitis. Furthermore, subcutaneous and abdominal fat volumes were evaluated using computed tomography. Results: Among a total of 118 patients, 24 patients developed peritonitis. The proportion of male patients (83% vs. 61%, p = 0.04), body mass index (25 vs. 22 kg/m2, p = 0.04), and subcutaneous fat area (120 vs. 102 cm2, p = 0.01) were significantly higher and the proportion of patients living with family members (75% vs. 94%, p = 0.02) was significantly lower in the peritonitis group than in the non-peritonitis group. There were no significant differences in age, operation method, surgeon experience, previous abdominal surgery, medical history of diabetic nephropathy, serum albumin level, and renal function between the two groups. Conclusions: Male patients with high subcutaneous fat who are living alone might be at higher risk of PD-related peritonitis. These characteristics might be useful in risk assessment and patient education before PD induction.

Micturition requires precise control of bladder and urethral sphincter via parasympathetic, sympathetic and somatic motoneurons. This involves a spino-bulbospinal control circuit incorporating Barrington’s nucleus in the pons (Barr). Ponto-spinal glutamatergic neurons that express corticotrophin-releasing hormone (CRH) form one of the largest Barr cell populations. BarrCRH neurons can generate bladder contractions, but it is unknown whether they act as a simple switch or provide a high-fidelity pre-parasympathetic motor drive and whether their activation can actually trigger voids. Combined opto- and chemo-genetic manipulations along with multisite extracellular recordings in urethane anaesthetised CRHCre mice show that BarrCRH neurons provide a probabilistic drive that generates co-ordinated voids or non-voiding contractions depending on the phase of the micturition cycle. CRH itself provides negative feedback regulation of this process. These findings inform a new inferential model of autonomous micturition and emphasise the importance of the state of the spinal gating circuit in the generation of voiding.

Zinc was discovered to be a novel second messenger in immunoreactive cells. We synthesized a novel free zinc chelator, IPZ-010. Here, we investigated the effects of IPZ-010 in a mouse postoperative ileus model and determined the effects of zinc signal inhibition as a new therapeutic strategy against postoperative ileus. Zinc waves were measured in bone marrow-derived mast cells (BMMCs) loaded with a zinc indicator, Newport green. Degranulation and cytokine expression were measured in BMMCs and bone marrow-derived macrophages (BMDMs). Postoperative ileus model mice were established with intestinal manipulation. Mice were treated with IPZ-010 (30 mg/kg, s.c. or p.o.) 1 h before and 2 h and 4 h after intestinal manipulation. Gastrointestinal transit, inflammatory cell infiltration, and expression of inflammatory mediators were measured. Free zinc waves occurred following antigen stimulation in BMMCs and were blocked by IPZ-010. IPZ-010 inhibited interleukin-6 secretion and degranulation in BMMCs. IPZ-010 inhibited tumor necrosis factor-α mRNA expression in BMMCs stimulated with lipopolysaccharide or adenosine triphosphate, whereas IPZ-010 had no effects on tumor necrosis factor-α mRNA expression in BMDMs stimulated with lipopolysaccharide or adenosine triphosphate. In postoperative ileus model mice, IPZ-010 inhibited leukocyte infiltration and cytokine expression, which ameliorated gastrointestinal transit. Furthermore, ketotifen (1 mg/kg) induced similar effects as IPZ-010. These effects were not amplified by co-administration of IPZ-010 and ketotifen. IPZ-010 inhibited zinc waves, resulting in inhibition of inflammatory responses in activated BMMCs in vitro. Targeting zinc waves in inflammatory cells may be a novel therapeutic strategy for treating postoperative ileus.

It is important to calculate the drug removal by hemodialysis (HD) for drug dosing regimens in HD patients. However, there are limited and inconsistent information about the dialyzability of drugs by HD. Therefore, the aim of our study is to evaluate drug removal by utilizing a rat model of HD (HD rat) and to extrapolate this result to the drug removal rate in HD patients. HD rats received bilateral nephrectomy and HD for 2 h. The dialysis removal of 6 drugs was evaluated in HD rats. Dialysis efficiency, plasma protein binding rate (PBR) and distribution volume (Vd) of drugs were also measured. Furthermore, we examined the correlation between the dialyzability of drug in HD rats and humans and constructed the prediction formula of the drug dialyzability in HD patients. The clearance of urea and creatinine and normalized dialysis dose in HD rats were 0.83 ± 0.07 mL/min, 0.70 ± 0.08 mL/min, and 0.13 ± 0.06, respectively. The drug dialyzability in HD rats was similar to reported clinical data except for doripenem. A higher correlation was observed between drug dialyzability in reported clinical data and HD rats which were adjusted for PBR (r2 = 0.936; p < 0.001) compared to unadjusted (r2 = 0.812; p = 0.009). Therefore, we constructed the prediction formula of the drug dialyzability in HD patients by utilizing the HD rat model and PBR. This study is useful for evaluating the dialyzability of high-risk drugs in a clinical setting and might provide appropriate preclinical dialyzability data for new drug.

Abstract Background Recently, sarcopenia has been reported as a new predictor for patient outcomes or likelihood of post-operative complications. The purpose of this study was to evaluate the association of the psoas muscle volume with the length of hospitalization among patients undergoing radical cystectomy. Methods A total of 63 (80.8%) male patients and 15 (19.2%) female patients who underwent radical cystectomy for their bladder cancer in our institution from 2000 to 2015 were analyzed. The psoas muscle index (PMI) was calculated by normalizing the psoas muscle area calculated using axial computed tomography at the level of the umbilicus (cm2) by the square of the body height (m2). Longer hospitalization was defined as hospitalization exceeding 30 days after surgery. Results The median PMIs (mean ± standard deviation) were 391 (394 ± 92.1) and 271 (278 ± 92.6) cm2/m2 in men and women, respectively. Thus, the PMIs of male patients were significantly larger than those of females (p

Abstract Quantum dots (QDs) were immobilized on an ultra-flat Au surface by using amide binding between the carboxyl groups on the QDs and the amino groups of the self-assembled monolayer on the surface. The number density of the QDs estimated by atomic force microscopy (AFM) agreed with the quantity of QDs estimated by X-ray photoelectron spectroscopy and fluorescence microscopy. QDs were also immobilized on dot patterns fabricated by e-beam lithography. AFM was able to identify clusters of just a few QDs on the dot patterns, whose minimum designed size was 50 nm × 50 nm per dot.

Atypical fractures commonly arise in the subtrochanteric region or the femoral shaft, whereas those of the upper extremities are rare. Only 15 fractures in 13 patients have been described in the English literature. The management of such fractures has not been established. We describe a patient with an atypical fracture of the ulnar diaphysis, which required revision surgery to achieve the union of the fracture site. Teriparatide together with low-intensity pulsed ultrasound contributed to bone healing. Further studies are needed to determine the optimal strategy for treating atypical fractures of the ulna.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

By genetic manipulations, we study the roles played by insulin-producing cells (IPCs) in the brain and their target, the corpora allata (CA), for reproductive dormancy in female Drosophila melanogaster, which is induced by exposing them to a combination of low temperature (11°C), short-day photoperiod (10L:14D) and starvation (water only) for 7 days immediately after eclosion (dormancy-inducing conditions). Artificial inactivation of IPCs promotes, whereas artificial activation impedes, the induction of reproductive dormancy. A transcriptional reporter assay reveals that the IPC activity is reduced when the female flies are exposed to dormancy-inducing conditions. The photoperiod sensitivity of reproductive dormancy is lost in pigment-dispersing factor (pdf), but not cry, mutants, suggesting that light input to IPCs is mediated by pdf-expressing neurons. Genetic manipulations to upregulate and downregulate insulin signaling in the CA, a pair of endocrine organs that synthesize the juvenile hormone (JH), decrease and increase the incidence of reproductive dormancy, respectively. These results demonstrate that the IPC-CA axis constitutes a key regulatory pathway for reproductive dormancy.

This study aimed to develop a prediction model for the operative time of flexible ureteroscopy (fURS) for renal stones. We retrospectively evaluated patients with renal stones who had been treated successfully and had stone-free status determined by non-contrast computed tomography (NCCT) 3 months after fURS and holmium laser lithotripsy between December 2009 and September 2014 at a single institute. Correlations between possible factors and the operative time were analyzed using Spearman's correlation coefficients and a multivariate linear regression model. The P value < 0.1 was used for entry of variables into the model and for keeping the variables in the model. Internal validation was performed using 10,000 bootstrap resamples. Flexible URS was performed in 472 patients, and 316 patients were considered to have stone-free status and were enrolled in this study. Spearman's correlation coefficients showed a significant positive relationship between the operation time and stone volume (ρ = 0.417, p < 0.001), and between the operation time and maximum Hounsfield units (ρ = 0.323, p < 0.001). A multivariate assessment with forced entry and stepwise selection revealed six factors to predict the operative time of fURS: preoperative stenting, stone volume, maximum Hounsfield unit, surgeon experience, sex, and sheath diameter. Based on this finding, we developed a model to predict operative time of fURS. The coefficient of determination (R2) in this model was 0.319; the mean R2 value for the prediction model was 0.320 ± 0.049. To our knowledge, this is the first report of a model for predicting the operative time of fURS treatment of renal stones. The model may be used to reliably predict operative time preoperatively based on patient characteristics and the surgeons' experience, plan staged URS, and avoid surgical complications.

Discolored ureteral stents are sometimes encountered in daily clinical practice; however, the mechanism(s) underlying the development of discolored ureteral stents remain unknown. In this study, we retrospectively analyzed the characteristics of discolored ureteral stents based on the results of a urinalysis and urine culture.We identified a total of 26 patients with discolored ureteral stents and compared the findings in the urinalyses and urine culture in 21 discolored versus 45 non-colored ureteral stents.The median and mean (± SD) duration of stenting time was 78.0 and 81.3 (± 21.3) days for the discolored ureteral stents and 69.0 and 74.9 (± 19.8) days for the non-colored ureteral stents, respectively (P = 0.25). The discolored ureteral stents were associated with a higher mean urine pH than the non-colored ureteral stents (mean: 6.4 vs 6.0, P< 0.05). There were no significant differences between the two groups in the RBC (P = 0.51) and WBC (P = 0.35) counts in the urinalyses. In addition, the rate of a positive culture in the patients with discolored stents [20 of 21 (95.2%)] was significantly (P

PURPOSE: To retrospectively assess the clinical utility in ureteroscopy (URS) planning of cumulative stone diameter (CSD), which does not account for stone width or depth, as a predictor of URS outcome and compare it with stone volume. MATERIALS AND METHODS: Patients with renal stones treated at a single institute by flexible URS were retrospectively evaluated. To assess the clinical utility of CSD, relationships between stone-free (SF) status and stone burden (CSD and volume) were analyzed using the area under the receiver operating characteristics (AUROC) curve. To identify stone number impact on CSD, the AUROC of CSD divided by stone number was evaluated. Correlation coefficients of CSD and stone volume were also calculated for groups by stone number. RESULTS: In cases with CSD

OBJECTIVE: To determine the impact of ureteroscopy-assisted retrograde nephrostomy (UARN) during percutaneous nephrolithotomy (PCNL). MATERIALS AND METHODS: From April 2009 to September 2011, a total of 50 patients underwent PCNL for large renal stones (stone burden >2 cm). We performed UARN in the Galdakao-modified Valdivia position for 27 patients (UARN PCNL) and ultrasonography-assisted percutaneous nephrostomy in the prone position for 23 patients (prone PCNL). RESULTS: UARN PCNL significantly improved the stone-free rate (81.5% vs 52.2%) and the rate of residual stones (

A 23-year-old female had bilateral ureteral stents placed due to bilateral renal stones and hydronephrosis. The bilateral ureteral stents were changed every 3 months. A kidney ureter bladder (KUB) film showed left encrustation along the ureteral stent thus necessitating removal; however, the ureteral stent could not be removed cystoscopically. The ureteral stent was, therefore, extracted using flexible ureteroscopy (URS) with a holmium (Ho): yttrium aluminum garnet (YAG) laser.

Introduction. Open surgical anatrophic nephrolithotomy (ANL) had been the standard treatment for large renal calculi prior to the development of endoscopic devices and endoscopic techniques. A previous report described the efficacy of ureteroscopy-assisted retrograde nephrostomy (UARN) and presented a case of renal calculi successfully treated with UARN during percutaneous nephrolithotomy (PCNL) in a patient after ANL. Case Presentation. A 61-year-old male with left renal calculi was referred for further treatment. The patient was placed under general and epidural anesthesia, in a Galdakao-modified Valdivia position. A flexible ureteroscope (URS) was inserted, and a Lawson retrograde nephrostomy puncture wire was advanced into the flexible URS. The puncture wire then followed the route from the renal pelvis to the exit skin. Calculus fragmentation was undertaken using a pneumatic lithotripter. Conclusions. UARN for PCNL was therefore found to be a safe, effective, and appropriate treatment for a patient presenting with renal calculi after undergoing ANL.

INTRODUCTION: We developed a method for ureteral stent removal in female patients that requires no cystoscopy or fluoroscopic guidance using a crochet hook. In addition, we also investigated the success rate, complications and pain associated with this procedure. METHODS: A total of 40 female patients (56 stents) underwent the removal of ureteral stents. All procedures were carried out with the patients either under anesthesia, conscious sedation, or analgesic suppositories as deemed appropriate for each procedure including Shock Wave Lithotripsy (SWL), Ureteroscopy (URS), Percutaneous Nephrolithotomy (PCNL), and ureteral stent removal. At the time of these procedures, fluoroscopy and/or cystoscopy were prepared, but they were not used unless we failed to successfully remove the ureteral stent using the crochet hook. In addition, matched controls (comprising 50 stents) which were removed by standard ureteral stent removal using cystoscopy were used for comparison purposes. RESULTS: A total of 47 of the 56 stents (83.9%) were successfully removed. In addition, 47 of 52 (90.4%) were successfully removed except for two migrated stents and two heavily encrusted stents which could not be removed using cystoscopy. Ureteral stent removal using the crochet hook technique was unsuccessful in nine patients, including two encrustations and two migrations. Concerning pain, ureteral stent removal using the crochet hook technique showed a lower visual analogue pain scale (VAPS) score than for the standard technique using cystoscopy. CONCLUSIONS: Ureteral stent removal using a crochet hook is considered to be easy, safe, and cost effective. This technique is also easy to learn and is therefore considered to be suitable for use on an outpatient basis.

This article discusses two rare cases of SAPHO syndrome involving the femur, a relatively uncommon occurrence. SAPHO syndrome is characterized by aseptic osteitis and pustular dermatitis. The patients in these cases showed femoral thickening without bone destruction, which aligns with previous reports. Treatment options for SAPHO syndrome include nonsteroidal anti-inflammatory drugs and methotrexate, although there are occasional treatment-resistant cases. Other drug therapies and biological agents have shown promise but require further research. Overall, appropriate drug therapy can lead to positive treatment outcomes and long-term clinical courses. [Extracted from the article]

Necrotizing fasciitis is a rapidly progressive, life-threatening soft tissue infection that needs acute surgical intervention and other types of supportive care. The upper extremities are a less frequent site for this infection than the lower extremities. Axillary necrotizing fasciitis is quite rare and bears a high risk of iatrogenic neurovascular injuries. We report a severe case of a 39-year-old man with a right axillary necrotizing fasciitis caused by Streptococcus pyogenes. While dealing with important nerves and blood vessels at the initial emergency surgery, we marked and preserved them with vascular tapes. The patient underwent several surgical interventions for infection control in addition to supportive care to avoid limb loss and to survive. Intraoperatively, the locations of nerves and vessels could be easily found by checking the vessel tapes. Twelve months after the initial admission, the patient had no symptoms of nerve injuries and resumed work. With necrotizing fasciitis, the risk of an iatrogenic nerve injury exists even if limb amputation is avoided due to repeated debridement. We report that marking and preserving nerves and blood vessels with vascular tapes at the initial surgery may make the subsequent ones easier and may reduce iatrogenic neurovascular injury. [ABSTRACT FROM AUTHOR]

Abstract In this study, plasma belimumab concentrations were measured over the course of treatment in systemic lupus erythematosus (SLE) patients on belimumab therapy, and intra‐ and interindividual variations in plasma belimumab concentration were evaluated. A single‐center prospective study was conducted at Oita University Hospital to evaluate trough plasma concentrations over the course of treatment in 13 SLE patients treated with intravenous belimumab. Plasma belimumab concentrations were measured by a validated ultra‐high performance liquid chromatography with tandem mass spectrometry method. The median age of the patients was 40 (interquartile range: 35–51) years and the median weight was 51.8 (47.0–58.1) kg. A mean of 9.4 (range: 1–13) blood samples was collected per patient at routine visits. The mean (± SD) plasma belimumab concentration was 33.4 ± 11.9 μg/mL in the patient with the lowest concentration and 170.0 ± 16.6 μg/mL in the patient with the highest concentration, indicating a 5‐fold difference between patients. On the other hand, the within‐patient coefficient of variation ranged from 7.1% to 35.7%, showing no large variations. No significant correlation was observed between plasma belimumab concentration and belimumab dose (mg/kg) (Spearman's rank correlation coefficient = 0.22, p = .54). Examinations of trough plasma belimumab concentrations over the course of treatment in patients with SLE showed small intraindividual variation but large interindividual variation. Plasma belimumab trough concentration varied widely among patients administered the approved dose.