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Introduction Although uterine perforation is a rare but serious complication, intrauterine devices are globally popular and effective contraceptive methods. Case presentation A 76‐year‐old female patient manifesting symptoms of vaginal leakage and lower abdominal discomfort was admitted to our hospital. Diagnostic imaging identified a vesicovaginal fistula and bladder calculi attributable to perforation of the bladder by an intrauterine device that had been inserted over four decades ago. The patient underwent open surgery for cystolith removal and vesicovaginal fistula repair. Conclusions If a patient with an intrauterine device complains of bladder stones or ongoing lower urinary tract symptoms, bladder perforation caused by the device should be considered in the differential diagnosis.

The action potential of cardiomyocytes is controlled by electrolytes in serum such as Na+, K+ and Ca2+. Hyperkalemia, which refers to an abnormally high concentration of K+ in the blood, can induce lethal arrythmia. In this study, the extracellular potentials on a sheet of chick embryonic cardiomyocytes were investigated at increasing K+ concentrations using a multielectrode array system. We observed that the interspike interval (ISI) was prolonged by approximately 3.5 times; dV/dt (the slope of a waveform) was decreased by more than five times; the field potential duration (FPD) was shortened by 20%, and the conduction velocity was about half at 12 mM K+ against the control (4 mM K+). In calcium therapy for hyperkalemia, although the prolongation of ISI under hyperkalemic conditions was restored, the slowing of conduction velocity, the decrease in dV/dt, and the shortening of FPD were not recovered by increasing the extracellular Ca2+ concentration. These findings provide a comprehensive understanding of cardiomyocytes in hyperkalemic conditions. Electrophysiological analysis by varying the extracellular concentrations of multiple types of electrolytes will be useful for the further discussion of the results of this study and for the interpretation of the waveforms obtained by measuring the extracellular potential.

Background: Salvage robot-assisted radical prostatectomy (sRARP) after PSA failure in patients who underwent initial radiotherapy or focal therapy has rarely been reported in Japan. We aimed to report the oncologic and functional outcomes of the first 10 cases of sRARP. Methods: Ten patients underwent sRARP after failing to respond to initial radiotherapy or focal therapy. Initial definitive treatment included volumetric modulated arc therapy, intensity-modulated radio therapy, stereotactic body radiotherapy, heavy-ion radiotherapy, low-dose-rate brachytherapy, and high-intensity focused ultrasound. We retrospectively investigated 10 cases on oncologic and functional outcomes of sRARP. Results: The median PSA level at sRARP, amount of blood loss, and console time were 2.17 ng/mL, 100 mL, and 136 min, respectively. Positive surgical margins were found in half of the cases. Median follow-up was 1.1 years. There were no 30-day major complications. No patients had erections after sRARP. Urinary continence and biochemical recurrence (BCR) rate were 40% and 30% at 1 year after sRARP, respectively. Conclusions: Salvage RARP may be a feasible option after PSA failure in patients who underwent radiotherapy or focal therapy as initial treatment, showing acceptable BCR rate.

Introduction Enfortumab vedotin is an antibody‐drug conjugate targeting Nectin‐4 for the treatment of advanced urothelial carcinoma in patients previously treated with platinum‐containing chemotherapy and immune checkpoint inhibitors. Common adverse events include rashes, peripheral neuropathy, and hyperglycemia. However, there are no reports on the development of myelodysplastic syndrome during enfortumab vedotin therapy in clinical settings. Case presentation A 72‐year‐old male patient experienced prolonged and severe thrombocytopenia 18 weeks after the start of enfortumab vedotin therapy for metastatic urothelial carcinoma, requiring daily platelet transfusions. Bone marrow examination and chromosomal analysis confirmed the diagnosis of myelodysplastic syndrome. Treatment with eltrombopag proved to be effective. Conclusion This is the first report of the development of myelodysplastic syndrome during enfortumab vedotin therapy in a clinical setting. Although rare, myelodysplastic syndrome can occur during enfortumab vedotin therapy.

Abstract A multicenter study of nonmetastatic castration-resistant prostate cancer (nmCRPC) was conducted to identify the optimal cut-off value of prostate-specific antigen (PSA) doubling time (PSADT) that correlated with the prognosis in Japanese nmCRPC. Of the 515 patients diagnosed and treated for nmCRPC at 25 participating Japanese Urological Oncology Group centers, 450 patients with complete clinical information were included. The prognostic values of clinical factors were evaluated with respect to prostate specific antigen progression-free (PFS), cancer-specific survival (CSS), and overall survival (OS). The optimal cutoff value of PSADT was identified using survival tree analysis by Python. The Median PSA and PSADT at diagnosis of nmCRPC were 3.3 ng/ml, and 5.2 months, respectively. Patients treated with novel hormonal therapy (NHT) showed significantly longer PFS (HR: hazard ratio 0.38, p

Background: In recent years, site-directed therapies (SDTs) targeting progressive lesions in patients with oligometastatic prostate cancer have attracted attention. However, whether they effectively treat oligoprogressive castration-resistant prostate cancer (CRPC) remains unclear. Here, we investigated the efficacy of SDT in patients with oligoprogressive CRPC and identified prognostic factors. Methods: We reviewed 59 patients with oligoprogressive CRPC who underwent SDT targeting prostate or metastatic lesions between April 2014 and March 2022. We evaluated the associations between several pretreatment clinical variables and treatment procedures and a >50% prostate-specific antigen (PSA) response, progression-free survival (PFS), and time to next treatment (TTNT). Results: A PSA response of >50% was observed in 66% of patients. The median PFS and TTNT were 8.3 months and 9.9 months, respectively. Patients with PSA doubling time ≥6 months showed a higher >50% PSA response rate (87% vs. 45%; P 50% PSA response, favorable PFS, and TTNT (P = 0.037, 0.025, and 0.017, respectively). Conclusion: PSA doubling time of ≥6 months may be a key indicator of the favorable efficacy of SDT for oligoprogressive CRPC.

Introduction Retroperitoneal tumors account for 0.2% of all neoplasms. Among these tumors, retroperitoneal vascular malformations are particularly rare, with most previously reported cases being venous malformations. Case presentation A 72‐year‐old woman was diagnosed with a retroperitoneal tumor on abdominal computed tomography. The 27‐mm diameter tumor was located away from the right kidney and major vessels in the right perirenal adipose tissue. Contrast‐enhanced computed tomography revealed a heterogeneously enhanced tumor with well‐defined borders. Dynamic contrast‐enhanced magnetic resonance imaging revealed rapid enhancement in the arterial phase and a progressive filling‐in pattern in the delayed phase. Although vascular malformation was suspected, a definitive diagnosis could not be established. The retroperitoneal tumor was excised laparoscopically for therapeutic and diagnostic purposes, and the histopathological diagnosis confirmed it as a capillary arteriovenous malformation. Conclusion Herein, we presented a rare case of retroperitoneal capillary arteriovenous malformation that was difficult to definitively diagnose preoperatively.

Introduction Primary prostate lymphomas are very rare; however, the incidence of malignant lymphoma is high among HIV‐infected patients. Herein, we report a case of primary diffuse large B‐cell lymphoma (DLBCL) of the prostate in an HIV‐infected patient. Case presentation A 47‐year‐old man presented with miction pain and back pain. Abdominal CT revealed a huge prostate mass extending to the left retroperitoneum. Serum sIL‐2R level was abnormally high (2896 U/mL), whereas PSA level was normal. HIV antigen and antibody tests were positive. The patient was diagnosed with DLBCL after a prostate biopsy. Systemic treatments were administered; however, the tumor was refractory, and the patient died 9 months after diagnosis. Conclusion Prostate malignant lymphomas are rare but should be considered in patients with enlarged prostates and normal PSA levels. It should be noted that HIV patients have a high incidence of malignant lymphomas.

We examined the effects of neurotensin (NTS) on the excitability of type II neurons in the rat dorsolateral bed nucleus of the stria terminalis (dlBNST) using whole-cell patch-clamp electrophysiology. Bath-application of NTS depolarized type II dlBNST neurons. Analyses of the steady-state I–V relationships implied that the depolarizing effect of NTS is due to potassium conductance blocking. The depolarizing effect of NTS was abolished in the presence of a PLC inhibitor, but not affected by a protein kinase C inhibitor. In the presence of a CaMKII inhibitor, NTS showed depolarizing effects via the increase in non-selective cation conductance in addition to the decrease in potassium conductance. Unexpectedly, in the presence of a PKA inhibitor, NTS hyperpolarized type II dlBNST neurons. These results reveal that diverse signaling pathways mediate the effects of NTS on the excitability of type II dlBNST neurons. The elevation of intracellular Ca2+ levels via the inositol phosphate-mediated signaling activates both Ca2+-dependent adenylate cyclase (AC) and CaMKII. Activation of the AC-cAMP-PKA pathway exerts depolarizing effects on type II dlBNST neurons by decreasing potassium conductance and increasing non-selective cation conductance, whereas activation of the CaMKII pathway exerts hyperpolarizing effects on dlBNST neurons by decreasing non-selective cation conductance.

Abstract Although the albumin-to-globulin ratio (AGR) is a promising biomarker, no study has investigated its prognostic significance for advanced urothelial carcinoma (UC). This study conformed to the REporting recommendations for tumor MARKer prognostic studies (REMARK) criteria. We retrospectively reviewed 176 patients with advanced UC treated with pembrolizumab between 2018 and 2020. We evaluated the associations between pretreatment clinicopathological variables, including the AGR and performance status (PS), with progression-free survival, cancer-specific survival, and overall survival. The Cox proportional hazards model was used for univariate and multivariable analyses. The AGR was dichotomized as

Introduction We present the case of a patient with penetrating penile injury caused by splintering floorboards in a gymnasium. Case presentation A 24‐year‐old man was brought to the emergency department of our hospital because of an unintentional penetrating penile injury sustained while playing volleyball at a gymnasium. He dove into the wooden floor to fly‐receive the ball. When sliding with his abdomen on the floor, a wooden splinter from the floorboard stuck from the base of his penis to near the glans penis. The splinter was gently removed without bleeding under local anesthesia. Conclusions Splintering floorboards in gymnasiums can cause serious trauma, including penile injuries. Health‐care workers and users of public facilities, such as gymnasiums, should be aware of the accident risk associated with wooden floors.

Background Several studies have reported the incidence of immune-related adverse events (irAEs) as a predictor of the efficacy of anti-programmed cell death protein 1 antibodies in patients with cancer. However, immortal time bias has not always been fully addressed in these studies. In this retrospective multicenter study, we assessed the association between the incidence of irAEs and the efficacy of pembrolizumab in urothelial carcinoma (UC) using time-dependent analysis, an established statistical method to minimize immortal time bias.Methods The study included 176 patients with advanced UC who underwent pembrolizumab treatment at seven affiliated institutions between January 2018 and July 2020. Patients with irAEs were compared with those without irAEs in terms of overall survival (OS) and cancer-specific survival (CSS). Immortal time bias was eliminated by using time-dependent analysis.Results Of the 176 patients, irAEs occurred in 77 patients (43.8%), with a median of 60 days. The irAEs (+) cohort showed significantly favorable OS and CSS compared with the irAEs (−) cohort (p=0.018 and p=0.005, respectively), especially in the cohort with grade 1–2 irAEs (OS and CSS; p=0.003 and p=0.002, respectively). Multivariate analyses identified any irAEs and grade 1–2 irAEs as independent favorable prognostic factors for OS and CSS.Conclusion Even after minimizing immortal time bias by time-dependent analysis, the incidence of irAEs, especially grade 1–2 irAEs, could be a significant predictor of favorable prognoses in patients with UC who have undergone pembrolizumab treatment.

Introduction Uretero‐arterial fistula is a rare life‐threatening condition. Its diagnosis and management remains a challenge for urologists. Case presentation A 64‐year‐old man presented to our hospital with gross hematuria. He had history of rectal cancer treated with neoadjuvant chemoradiotherapy followed by low anterior resection and chronic ureteral stenting for bilateral ureteral strictures. He developed recurrent hemorrhagic shocks due to sudden massive gross hematuria. Repeated computed tomography and angiography could not identify the source of bleeding. After prophylactic embolization of the right renal artery and right nephrectomy, angiography finally revealed a uretero‐arterial fistula from the right external iliac artery. Percutaneous balloon‐expandable covered stent graft was used to successfully treat the fistula. Conclusions Urologists should consider possible uretero‐arterial fistula in patients with recurrent hematuria along with several risk factors and convincing medical history.

We investigated electrophysiological properties of human induced-pluripotent-stem-cell-derived and embryonic-stem-cell-derived cardiomyocytes, and analyzed action potential parameters by plotting their frequency distributions. In the both cell lines, the distribution analysis revealed that histograms of maximum upstroke velocity showed two subpopulations with similar intersection values. Sub-populations with faster maximum upstroke velocity showed significant prolongation of action potential durations by application of E-4031, whereas others did not, which may be partly due to shallower maximum diastolic potentials. We described electrophysiological and pharmacological properties of stem-cell-derived cardiomyocytes in the respective sub-populations, which provides a way to characterize diverse electrical properties of stem-cell-derived cardiomyocytes systematically.

The dynamic properties of the heart differ based on the regions that effectively circulate blood throughout the body with each heartbeat. These properties, including the inter-beat interval (IBI) of autonomous beat activity, are retained even in in vitro tissue fragments. However, details of beat dynamics have not been well analyzed, particularly at the sub-mm scale, although such dynamics of size are important for regenerative medicine and computational studies of the heart. We analyzed the beat dynamics in sub-mm tissue fragments from atria and ventricles of hearts obtained from chick embryos over a period of 40 h. The IBI and contraction speed differed by region and atrial fragments retained their values for a longer time. The major finding of this study is synchronization of these fragment pairs physically attached to each other. The probability of achieving this and the time required differ for regional pairs: atrium–atrium, ventricle–ventricle, or atrium–ventricle. Furthermore, the time required to achieve 1:1 synchronization does not depend on the proximity of initial IBI of paired fragments. Various interesting phenomena, such as 1:n synchronization and a reentrant-like beat sequence, are revealed during synchronization. Finally, our observation of fragment dynamics indicates that mechanical motion itself contributes to the synchronization of atria.

A non-destructive method of collecting cultured cells after identifying their in situ functional characteristics is proposed. In this method, cells are cultivated on an alginate layer in a culture dish and released by spot application of a calcium chelate buffer that locally melts the alginate layer and enables the collection of cultured cells at the single-cell level. Primary hippocampal neurons, beating human embryonic stem (hES) cell-derived cardiomyocytes, and beating hES cell-derived cardiomyocyte clusters cultivated on an alginate layer were successfully released and collected with a micropipette. The collected cells were recultured while maintaining their physiological function, including beating, and elongated neurites. These results suggest that the proposed method may eventually facilitate the transplantation of ES- or iPS-derived cardiomyocytes and neurons differentiated in culture.

Background/Aim: We present a case of solitary fibrous tumor, arising from the diaphragm in the retroperitoneal space, that was resected with robotic assistance. Case Report: An 85-year-old female patient was referred to our hospital for evaluation of a suspected right renal tumor. Abdominal contrast-enhanced computed tomography revealed a tumor (maximum diameter, 36 mm) protruding from the superior pole of the right kidney. The patient was scheduled for robot-assisted, retroperitoneoscopic, partial nephrectomy based on a preoperative diagnosis of renal cell carcinoma. Intraoperative findings revealed that the tumor originated from the diaphragm and had no continuity with the renal parenchyma. Pathological examination revealed a solitary fibrous tumor. Conclusion: Solitary fibrous tumors are rare soft-tissue neoplasms with a distinct molecular feature of the fusion of nerve growth factor-inducible A genebinding protein 2 with signal transducer and activator of transcription 6 gene (NAB2::STAT6). We believe that this is the first reported case of a solitary fibrous tumor arising from the diaphragm in the retroperitoneal space. [ABSTRACT FROM AUTHOR]

Background/Aim: This study aimed to describe the voiding patterns of patients after surgical treatment of pelvic fractures and determine the predictive factors of lower urinary tract injuries (LUTIs) and spontaneous voiding failure among patients with surgically treated pelvic fractures at a tertiary trauma center in Japan. Patients and Methods: We retrospectively assessed patients with surgically treated pelvic fractures in our tertiary trauma center during May 2009-April 2021. We excluded patients who died during hospitalization and who had indwelling catheter prior to the injury. Patients' LUTIs and spontaneous voiding failure at discharge were recorded. Multivariate analysis was performed to assess the predictive factors of LUTIs and spontaneous voiding failure at discharge. Results: In total, 334 eligible patients were identified. Among them, 301 patients (90%) voided spontaneously with or without diapers at discharge. Thirty-three patients required some form of catheterization for bladder drainage. LUTIs were found to be associated with chronological age [odds ratio (OR)=0.96; 95% confidence interval (CI)=0.92-0.99; p=0.024] and pelvic ring fracture (OR=12.0; 95%CI=1.39-255.2; p=0.024). Spontaneous voiding failure was associated with intensive care unit admission (OR=7.17; 95%CI=1.49-34.4; p=0.004). Conclusion: Overall, 10% of patients with surgically treated pelvic fractures were not able to void spontaneously at discharge. Spontaneous voiding failure after pelvic fractures was related to injury severity. [ABSTRACT FROM AUTHOR]

Making decisions based on a good representation of the environment is advantageous in deep reinforcement learning (DRL). In this work, we propose a new network structure for DRL. Deep Residual Attention Reinforcement Learning (DRARL), by incorporating an attention-based structure into the network structure of Importance Weighted Actor-Learner Architecture (IMPALA). DRARL helps the model learn a better representation by helping the model focus on the crucial features. The effectiveness of DRARL was empirically evaluated in a subset of Atari games, with popular RL algorithms, IMPALA, PPO, and A2C. The experiments show that DRARL works robustly with the three algorithms and improves sample efficiency in seven out of ten games. Furthermore, the visualization of important features empirically shows that the DRARL helps the model concentrate on the crucial features and therefore improves the performance and sample efficiency. [ABSTRACT FROM AUTHOR]

The dynamic properties of the heart differ based on the regions that effectively circulate blood throughout the body with each heartbeat. These properties, including the inter-beat interval (IBI) of autonomous beat activity, are retained even in in vitro tissue fragments. However, details of beat dynamics have not been well analyzed, particularly at the sub-mm scale, although such dynamics of size are important for regenerative medicine and computational studies of the heart. We analyzed the beat dynamics in sub-mm tissue fragments from atria and ventricles of hearts obtained from chick embryos over a period of 40 h. The IBI and contraction speed differed by region and atrial fragments retained their values for a longer time. The major finding of this study is synchronization of these fragment pairs physically attached to each other. The probability of achieving this and the time required differ for regional pairs: atrium–atrium, ventricle–ventricle, or atrium–ventricle. Furthermore, the time required to achieve 1:1 synchronization does not depend on the proximity of initial IBI of paired fragments. Various interesting phenomena, such as 1:n synchronization and a reentrant-like beat sequence, are revealed during synchronization. Finally, our observation of fragment dynamics indicates that mechanical motion itself contributes to the synchronization of atria. [ABSTRACT FROM AUTHOR]

Abstract  This study examined the effects of contact with wood on the living human body using a physiological index and subjective evaluation. Consecutive blood pressure measurements were used as the physiological index, and sensory evaluation using the semantic differential (SD) method was used for subjective evaluation. Consideration was also given to cases in which materials were cooled and heated as well as kept at room temperature, to eliminate the effects of heat flux due to differences in thermal conductivity between wood and other materials. It was found that contact with wood produced coarse/natural sensations, with no associated increase in systolic blood pressure. Contact with cold wood created subjectively dangerous/uncomfortable but still coarse/natural sensations, also with no associated increase in blood pressure; therefore, there was no correspondence between subjective evaluation and physiological responses. Contact with aluminum kept at room temperature and cold acrylic plastic created flat/artificial and dangerous/uncomfortable sensations, with an associated significant increase in blood pressure; thus, there was a close correlation between subjective evaluation and physiological responses. It was therefore concluded that contact with wood, unlike artificial materials such as aluminum, induces no physiological stress even when kept at room temperature or cooled. [ABSTRACT FROM AUTHOR]

The calcium ion (Ca2+) concentrations in a cell are responsible for the control of vital cellular functions and have been widely studied as a means to investigate and control cell activities. Here, we demonstrate Ca2+ wave generation in HeLa cells by femtosecond laser irradiation and show unexpected properties of the Ca2+ release and propagation. When the laser was focused in the cell cytoplasm, Ca2+ release was independent of both external Ca2+ influx and the phosphoinositide-phospholipase C (PLC) signaling pathway. The nucleus was not a susceptible target for laser-induced Ca2+ release, whereas irradiation of the plasma membrane produced evidence of transient poration, through which the extracellular solution could enter the cell. By chelating extracellularCa2+, we found that laser-induced influx of ethylene glycol tetra-acetic acid (EGTA) can compete with calciuminduced calcium release and significantly delay or suppress the onset of the Ca2+ wave in the target cell. Intercellular Ca2+ propagation was adenosine triphosphate-dependent and could be observed even when the target cell cytosolic Ca2+ rise was suppressed by influx of EGTA. The irradiation effect on overall cell viability was also tested and found to be low (85% at 6 h after irradiation by 60 mW average power). Laser-induced Ca2+ waves can be reliably generated by controlling the exposure and focal position and do not require the presence of caged Ca2+. The technique has the potential to replace other methods of Ca2+ stimulation, which either require additional caged molecules in the cell or do not have an interaction that is as well localized. [ABSTRACT FROM AUTHOR]

To study cell communication, it is essential that single cell responses in cellular networks are analyzed. Cardiomyocyte networks are known to simultaneously change membrane potential with spontaneous excitation. To measure the extracellular potential change in single cardiomyocytes in networks, we developed a microelectrode array (MEA) chip consisting of 8-µm-diameter and 3-µm-thick platinum-black (Pt-B)-coated indium tin oxide (ITO) electrodes with agarose microchambers. Single cardiomyocytes were seeded individually on this MEA chip with a micropipette. The extracellular potential of a single cardiomyocyte could be measured with this MEA chip. The amplitude of the extracellular potential change in a single cardiomyocyte was very small (<100 µV) and the beating rate was not constant. We expected that these results would accelerate the measurement of membrane potential changes of single cardiomyocytes in cellular networks. [ABSTRACT FROM AUTHOR]

To investigate the optimal conditions for electrical stimulation, communities of lined-up chick embryonic cardiomyocytes were evaluated in terms of their threshold voltage for pacing (PVMin) and the half-maximum paced frequency (PF50), with a focus on the following factors: (1) the orientation of the major axis of cell communities to the electric field (EF) direction as the external factor; (2) the number of cells in a cell community, the length of the cell community, and the mean length of cells comprising the community as the internal factors. Firstly, PVMin decreased with increasing length of the cell network oriented parallel to the EF. PVMin was approximately 0.041 ± 0.025 V/mm when the community was sufficiently long. On the other hand, PVMin in the orthogonal orientation was constant at 1.7 ± 0.047 V/mm with no dependence on the length of the cell network. Secondly, we found that PF50 increased with increasing length of the cell network or the number of cells in the network; the PF50 values were 2.03 ± 0.05 and 3.39 ± 0.05 Hz when the respective cell network lengths were 100 µm (n = 43) and more than 300 µm (n = 6) and the cells were oriented parallel to the EF. These findings indicate that it is important to suppress ventricular fibrillation with minimal efficient stimulation by considering the EF direction with respect to the orientation of cardiomyocytes. Furthermore, expanded cells showed the loss of ability to respond to stimulation at higher frequencies. Cardiomyocytes combined with seeded fibroblasts as a cell network at a low density are a possible model of a ventricular remodeling heart. [ABSTRACT FROM AUTHOR]