Pharmacological effect of cepharanthine on SARS-CoV-2-induced disease in a Syrian hamster model.

BACKGROUND: Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), remains a global public health threat. Although several effective vaccines and therapeutics have been developed, continuous emergence of new variants necessitates development of drugs with different mechanisms of action. Recent studies indicate that cepharanthine, a chemical derivative purified from Stephania cepharantha, inhibits SARS-CoV-2 replication in vitro. METHODS: This study examined the in vivo effects of cepharanthine using a Syrian hamster SARS-CoV-2 infection model. To evaluate the prophylactic and therapeutic effects, cepharanthine was intranasally administered before or after SARS-CoV-2 infection. Effects were assessed by monitoring body weight changes, lung pathology, lung viral load, and inflammatory response in the lungs. RESULTS: Pre-infection administration of cepharanthine resulted in less weight loss, reduced virus titers, alleviated histopathological severity, and decreased lung inflammation. Furthermore, post-infection administration of cepharanthine also exhibited therapeutic effects. CONCLUSIONS: This study demonstrated that both prophylactic and therapeutic administration of cepharanthine reduces the pathogenesis of COVID-19 in a Syrian hamster SARS-CoV-2 infection model. Our findings suggest that cepharanthine is a potential therapeutic agent against COVID-19.

Effectiveness of dose-dense methotrexate, vinblastine, doxorubicin, and cisplatin as compared to gemcitabine-based regimens as neoadjuvant chemotherapy for oncologic outcomes in muscle-invasive bladder cancer cases-Single-center study in Japan.

OBJECTIVES: To compare the efficacy and safety of dose-dense methotrexate, vinblastine, doxorubicin, and cisplatin (dd-MVAC) with gemcitabine-based regimens for neoadjuvant chemotherapy (NAC) in muscle-invasive bladder cancer (MIBC) patients treated in Japan. METHODS: Data for MIBC patients who received NAC-dd-MVAC followed by a radical cystectomy from June 2019 to May 2023 performed at our hospital were analyzed. For comparisons, data for MIBC patients who received NAC gemcitabine and cisplatin (GC) or gemcitabine and carboplatin (GCarbo) therapy between January 2010 and March 2019 were also obtained. Rates of ypT1N0 or less, progression-free survival (PFS), overall survival (OS), and NAC adverse effects were compared between the GC/GCarbo and dd-MVAC regimens. RESULTS: Results for 32 patients who received dd-MVAC and 30 who received GC/GCarbo NAC therapy were analyzed. ypT1N0 or less was noted in 40.7% of the dd-MVAC and 40.0% of the GC/GCarbo groups, while ypT0N0 rates were 25% and 10%, respectively, with no statistical differences noted. However, Kaplan-Meier analysis of the total cohort demonstrated that dd-MVAC was associated with significantly better PFS and OS rates than GG/GCarbo (hazard ratios: 0.33, p = 0.0237, and 0.23, p = 0.0127, respectively). Propensity-matched models also showed similar results for both PFS and OS. Adverse effects of dd-MVAC were acceptable and the incidence of hematologic toxicity was lower as compared with GC/GCarbo therapy. CONCLUSION: The present study is the first to show that dd-MVAC as NAC can provide better survival as compared with a gemcitabine-based regimen for patients with MIBC treated in Japan.

Potential for artificial intelligence in medicine and its application to male infertility.

Background: The third AI boom, which began in 2010, has been characterized by the rapid evolution and diversification of AI and marked by the development of key technologies such as machine learning and deep learning. AI is revolutionizing the medical field, enhancing diagnostic accuracy, surgical outcomes, and drug production. Methods: This review includes explanations of digital transformation (DX), the history of AI, the difference between machine learning and deep learning, recent AI topics, medical AI, and AI research in male infertility. Main Findings Results: In research on male infertility, I established an AI-based prediction model for Johnsen scores and an AI predictive model for sperm retrieval in non-obstructive azoospermia, both by no-code AI. Conclusions: AI is making constant progress. It would be ideal for physicians to acquire a knowledge of AI and even create AI models. No-code AI tools have revolutionized model creation, allowing individuals to independently handle data preparation and model development. Previously a team effort, this shift empowers users to craft customized AI models solo, offering greater flexibility and control in the model creation process.

Significant inverse association of testosterone level with penile deformity severity in Japanese males with Peyronie's disease.

OBJECTIVES: We evaluated the relationship between penile curvature and testosterone in Peyronie's disease patients treated in Japan. METHODS: Data were obtained from 109 patients with Peyronie's disease treated with surgery at our hospital between April 2004 and December 2019. Penile deformity assessment was based on findings of a rigid erection induced by intracavernosal injection. Low total testosterone level was defined as <300 ng/dl. Patients were divided into two groups according to curvature severity (I, <60°; II ≥60°), then clinical factors including total testosterone were compared. Uni- and multivariate logistic regression analyses were performed to identify factors predicting severe penile deformity (≥60°). RESULTS: For all patients, mean total testosterone was 469 ng/dl and median curvature was 50°, with a significant inverse correlation found between curvature and testosterone level (p < 0.0001). Group I and II patients numbered 55 and 54, respectively. Mean total testosterone for Group II was 397 ng/dl, significantly lower than Group I (539 ng/dl). Median curvature in 15 patients with a low testosterone level was 80°, significantly higher than those with a normal testosterone range (50°). Univariable and multivariable logistic regression analysis indicated total testosterone, follicle stimulating hormone, and C-reactive protein as significant factors correlated with severe penile deformity, among which total testosterone was most relevant. CONCLUSION: The present findings confirmed that penile deformity severity is correlated with testosterone level in Japanese males with Peyronie's disease.

Molecular Mechanisms and Risk Factors Related to the Pathogenesis of Peyronie's Disease.

Peyronie's disease (PD) is a benign condition caused by plaque formation on the tunica albuginea of the penis. It is associated with penile pain, curvature, and shortening, and contributes to erectile dysfunction, which worsens patient quality of life. In recent years, research into understanding of the detailed mechanisms and risk factors involved in the development of PD has been increasing. In this review, the pathological mechanisms and several closely related signaling pathways, including TGF-ß, WNT/ß-catenin, Hedgehog, YAP/TAZ, MAPK, ROCK, and PI3K/AKT, are described. Findings regarding cross-talk among these pathways are then discussed to elucidate the complicated cascade behind tunica albuginea fibrosis. Finally, various risk factors including the genes involved in the development of PD are presented and their association with the disease summarized. The purpose of this review is to provide a better understanding regarding the involvement of risk factors in the molecular mechanisms associated with PD pathogenesis, as well as to provide insight into disease prevention and novel therapeutic interventions.

Bone biopsy findings in patients receiving long-term bisphosphonate therapy for glucocorticoid-induced osteoporosis.

INTRODUCTION: Bisphosphonates (BPs) have been shown to reduce the incidence of vertebral fractures during the first year or two of glucocorticoid (GC) treatments and are therefore recommended as a first-line treatment for GC-induced osteoporosis (GIO). However, there are theoretical concerns about the long-term use of BPs in low-turnover osteoporosis caused by chronic GC therapy. MATERIALS AND METHODS: We analyzed the trabecular microarchitecture, bone metabolism, and material strength of iliac crest bone biopsy samples from 10 female patients with rheumatoid arthritis who received an average of 6.7 years of BP therapy for GIO (GIOBP group), compared with those of 10 age- and bone mineral density (BMD)-matched non-rheumatoid arthritis postmenopausal women (reference group). RESULTS: Patients in the GIOBP group had a significantly greater fracture severity index, as calculated from the number and the extent of vertebral fractures compared with the reference patients. Micro-computed tomography analysis showed that the degree of mineralization and trabecular microarchitecture were significantly lower in the GIOBP group than in the reference patients. Patients in the GIOBP group exhibited lower bone contact stiffness, determined by micro-indentation testing, than in the reference group. The contact stiffness of the bone was negatively correlated with the fracture severity index and the daily prednisolone dosage. Immunohistochemistry and serum bone turnover markers showed decreased osteoclastic activity, impaired mineralization, and an increased fraction of empty lacunae in the GIOBP group. CONCLUSION: Our findings indicate that patients receiving long-term BP for GIO are still at high risk for fragility fractures because of poor bone quality.

Comparison of the Efficacy and Renal Safety of Bisphosphonate Between Low-Dose/High-Frequency and High-Dose/Low-Frequency Regimens in a Late-Stage Chronic Kidney Disease Rat Model.

The efficacy and renal safety of low-dose/high-frequency (LDHF) dosing and high-dose/low-frequency (HDLF) dosing of bisphosphonates (BPs) are comparable in patients with normal kidney function but might be different in patients with late-stage chronic kidney disease (CKD). This study aimed to compare the efficacy and renal safety of two different dosage regimens of a BP, alendronate (ALN), in stage 4 CKD using a rat model. Male, 10-week-old Sprague-Dawley rats were subjected to either 5/6 nephrectomy or sham surgery. The animals received subcutaneous administration of vehicle (daily) or ALN in LDHF dosage regimen (LDHF-ALN: 0.05 mg/kg/day) or HDLF dosage regimen (HDLF-ALN: 0.70 mg/kg/2 weeks). Medications commenced at 20 weeks of age and continued for 10 weeks. Micro-computed tomography, histological analysis, infrared spectroscopic imaging, and serum and urine assays were performed to examine the efficacy and renal safety of the ALN regimens. Both LDHF-ALN and HDLF-ALN increased bone mass, improved micro-structure, and enhanced mechanical properties, without causing further renal impairment in CKD rats. Histologically, however, HDLF-ALN more efficiently suppressed bone turnover, leading to more mineralized trabecular bone, than LDHF-ALN in CKD rats, whereas such differences between LDHF-ALN and HDLF-ALN were not observed in sham rats. Both LDHF-ALN and HDLF-ALN showed therapeutic effects on high bone turnover osteoporosis in CKD stage 4 rats without causing further renal impairment. However, as HDLF-ALN more efficiently suppressed bone turnover than LDHF-ALN in late-stage CKD, HDLF-ALN might be more appropriate than LDHF-ALN for fracture prevention in high bone turnover osteoporosis patients with late-stage CKD.

Novel prediction scoring system for simple assessment of stone-free status after flexible ureteroscopy lithotripsy: T.O.HO. score.

OBJECTIVES: To develop a novel simple quantitative scoring model for predicting stone-free status after a flexible ureteroscopy lithotripsy procedure by standardizing the complexity of ureteral stone characteristics. METHODS: We retrospectively reviewed 586 patients with renal or ureteral stones who underwent flexible ureteroscopy lithotripsy at Abiko Toho Hospital, Chiba, Japan, from 2015 to 2018. Multivariate regression was applied to examine the relationship between preoperative descriptors and stone-free status, and a nomogram was developed using significant predictors. Next, the individual components of the nomogram were assigned points to form a simple scoring system. The predictive performance of this new scoring system was compared with the STONE score at optimal cut-off values using receiver operating characteristic curve and area under the curve analyses. RESULTS: Multivariate logistic regression findings showed that factors associated with stone-free status were length, Hounsfield unit and stone location. A nomogram prediction model was developed with an area under the curve value of 0.845, then consequently used to develop a new simple score system termed the T.O.HO. score consisting of three stone characteristics: (T)allness (1-5 points), (O)ccupied lesion (1-3 points) and (HO)unsfield units evaluation (1-3 points). The T.O.HO. score was significantly higher in stone remaining (7.66) than stone-free (5.27; P < 0.001) cases. The area under the curve for the T.O.HO. score was 0.833 at an optimal cut-off value of 7, whereas that for the STONE score was 0.683 at an optimal cut-off value of 9, showing the superiority of this new scoring system. CONCLUSION: The T.O.HO. score is a useful tool for predicting stone-free status in patients who have undergone a flexible ureteroscopy lithotripsy procedure.

Temporary pacemaker insertion for severe bradycardia following pneumoperitoneum during robot-assisted radical prostatectomy: a case report.

BACKGROUND: Pneumoperitoneum to maintain a constant gas flow to assist various surgeries is known to cause severe bradycardia and has been linked to heart failure;; however, a recent study demonstrated that it is not linked to poorer surgical outcomes; accordingly, it does not require routine preventive measures. Thus, whether there is a link between sudden bradycardia development and surgical procedures is controversial. We report the case of severe bradycardia that occurred along with a complete atrioventricular block (CAVB) during peritoneum creation in robot-assisted radical prostatectomy (RARP). CASE PRESENTATION: A 72-year-old man presented at our hospital with prostate cancer and underwent RARP. After pneumoperitoneum, severe bradycardia and CAVB were observed; thus, the surgery was extended by inserting a temporary pacemaker (TPM). CONCLUSION: Because of the difficulty in performing emergency procedures in robot-assisted surgeries, the current case is reported to provide an awareness that surgeons should be cautious of the possible complication of bradycardia and CAVB during such operations, and thus should take steps necessary for managing induction of such conditions.

Nationwide survey of urological specialists regarding male infertility: results from a 2015 questionnaire in Japan.

Purpose: To investigate the incidence, etiology, treatment indications, and outcomes regarding infertile male patients in Japan. Methods: Between April, 2014 and March, 2015, the authors contacted 47 clinical specialists in male infertility who had been certified by the Japan Society for Reproductive Medicine. The participating clinicians were sent a questionnaire regarding information on their infertile patients, according to etiology and the number and success rates of male infertility operations that had been performed in their practice. Results: Thirty-nine specialists returned the questionnaire and provided information regarding 7268 patients. The etiology of infertility included testicular factors, sexual disorders, and seminal tract obstruction. During the study year, the clinicians performed varicocelectomies, testicular sperm extractions (TESEs), and re-anastomoses of the seminal tract. The rate of successful varicocelectomies was >70%. The sperm retrieval rates with conventional TESE and microdissection TESE were 98.3% and 34.0%, respectively, while the patency rates with vasovasostomy and epididymovasostomy were 81.8% and 61.0%, respectively. Conclusion: Surgical outcomes for infertile male patients are favorable and can be of great clinical benefit for infertile couples. To achieve this, urologists should work in collaboration with gynecological specialists in order to optimize the treatment of both partners.