Improvement of medication adherence for desmopressin by adjusting the prescription dosage in male patients with overactive bladder: A claims database analysis.

OBJECTIVES: Desmopressin is widely used for nocturia in patients with nocturnal polyuria. We investigated the continuation rate and adherence for desmopressin in patients with overactive bladder and nocturia using a claims database and evaluated factors that improved adherence. METHODS: Patients with nocturia in a Japanese claims database who started desmopressin between September 2019 and July 2021 were evaluated. Drug persistence was assessed using the Kaplan-Meier method for initial prescription of desmopressin. The proportion of days covered (PDC) was also evaluated among patients with prescription persistence. Multivariate analysis was performed using logistic regression analysis to identify factors predicting adherence to desmopressin. RESULTS: The study included 72,888 patients entered into Japan Medical Data Center (JMDC) database between September 2019 and July 2021. For the 236 patients prescribed desmopressin formulations, mean prescription duration was 114 days. Among the total cases, 90 (38.1%) cases were prescribed only once, mean PDC was 0.60, and the number of high-adherence patients (PDC ≥ 0.80) was 108 (45.8%). Desmopressin prescription doses were fixed in 216 patients and adjusted in 20 patients. Multivariate analysis identified prescription dose adjustment for desmopressin as significantly associated with high PDC. CONCLUSION: Desmopressin showed a 38% dropout rate after the first dose. However, high medication continuation and high medication adherence rates (PDC) could be maintained with prescription adjustments. Careful patient monitoring and appropriate adjustment of the desmopressin dosage appear to be important factors in improving nocturia.

Factors related to nocturia-specific quality of life in renal transplantation patients.

OBJECTIVES: Patients following renal transplantation (RTX) may experience nocturia exacerbation due to polyuria and reduced bladder capacity, thereby impacting the specific quality of life (QOL) associated with nocturia. The present study aims to investigate factors associated with the deterioration of nocturia-specific QOL in RTX patients. METHODS: The study cohort comprised 59 consecutive patients who had undergone successful RTX. Nocturia-related QOL questionnaires (N-QOL) were employed to evaluate the specific QOL related to nocturia. The Bother/Concern and Sleep/Energy domains of the N-QOL were also assessed. The primary outcome measure was to explore factors related to the aggravation of nocturia-specific QOL in patients post-RTX. RESULTS: The mean nocturia frequency post-RTX was 1.3 ± 1.0. Univariate and multivariate analyses revealed a significant reduction in the Bother/Concern domain score associated with increased nocturia (p = .042). Aging significantly decreased the total N-QOL score and the Sleep/Energy domain score (p = .001 and .0002, respectively). Prolonged duration after RTX significantly reduced the scores of both the Sleep/Energy domain and the Bother/Concern domain (p = .018 and .037, respectively). However, the duration of dialysis prior to RTX was not significantly associated with the total score or subdomains of N-QOL. CONCLUSIONS: Nocturia-specific QOL affected not only the nocturia itself, but also aging and the prolonged duration after RTX. Thus, comprehensive approaches to the RTX patients were needed to improve the Nocturia-specific QOL in RTX patients.

Optimal temperature for the long-term culture of adult porcine islets for xenotransplantation.

Porcine islet xenotransplantation represents a promising therapy for severe diabetes mellitus. Long-term culture of porcine islets is a crucial challenge to permit the on-demand provision of islets. We aimed to identify the optimal temperature for the long-term culture of adult porcine islets for xenotransplantation. We evaluated the factors potentially influencing successful 28-day culture of islets at 24°C and 37°C, and found that culture at 37°C contributed to the stability of the morphology of the islets, the proliferation of islet cells, and the recovery of endocrine function, indicated by the expression of genes involved in pancreatic development, hormone production, and glucose-stimulated insulin secretion. These advantages may be provided by islet-derived CD146-positive stellate cells. The efficacy of xenotransplantation using islets cultured for a long time at 37°C was similar to that of overnight-cultured islets. In conclusion, 37°C might be a suitable temperature for the long-term culture of porcine islets, but further modifications will be required for successful xenotransplantation in a clinical setting.

Factors Related to Overactive Bladder-like Symptoms in Bladder Cancer.

BACKGROUND/AIM: The aim of the present study was to investigate the factors related to overactive bladder (OAB)-like symptoms in patients with bladder cancer. PATIENTS AND METHODS: This study included 59 patients who underwent transurethral resection of bladder tumor (TURBT). OAB-like symptoms were identified based on the Overactive Bladder Symptom Score (OABSS) and International Prostate Symptom Score (IPSS) questionnaires. The main outcome measures were elucidation of bladder cancer-related factors that might induce OAB-like symptoms. RESULTS: Non-muscle invasive bladder cancer (NMIBC) was observed in 50 patients, and carcinoma in situ (CIS) was observed in 14 patients. OABSS total score, IPSS total score, and quality of life index were 5±3, 12±7 and 3±1, respectively. The OABSS question 1 score, indicating pollakisuria, was significantly higher in NMIBC patients with CIS than in those without CIS (presence of CIS vs. absence of CIS=1.0±0.6 : 0.5±0.6, p=0.02). IPSS question 4 score, indicating urgency (r=0.31, p=0.01), and OABSS question 4 score, indicating urgency incontinence (r=0.29, p=0.03), correlated significantly with the maximum bladder tumor diameter. Multivariate regression analysis demonstrated that presence of CIS in NMIBC cases correlated significantly with pollakisuria (p=0.02), and that maximum diameter of the bladder tumor correlated significantly with both urgency (p=0.04) and urgency incontinence (p=0.01). CONCLUSION: CIS induced pollakisuria in NMIBC. Larger diameter bladder tumors induced both urgency and urgency incontinence. Patients with bladder cancer who present with pollakisuria might have CIS.

Differentiation of human adipose tissue-derived mesenchymal stromal cells into steroidogenic cells by adenovirus-mediated overexpression of NR5A1 and implantation into adrenal insufficient mice.

BACKGROUND AIMS: Cell therapy for adrenal insufficiency is a potential method for physiological glucocorticoid and mineralocorticoid replacement. We have previously shown that mouse mesenchymal stromal cells (MSCs) differentiated into steroidogenic cells by the viral vector-mediated overexpression of nuclear receptor subfamily 5 group A member 1 (NR5A1), an essential regulator of steroidogenesis, and their implantation extended the survival of bilateral adrenalectomized (bADX) mice. METHODS: In this study, we examined the capability of NR5A1-induced steroidogenic cells prepared from human adipose tissue-derived MSCs (MSC [AT]) and the therapeutic effect of the implantation of human NR5A1-induced steroidogenic cells into immunodeficient bADX mice. RESULTS: Human NR5A1-induced steroidogenic cells secreted adrenal and gonadal steroids and exhibited responsiveness to adrenocorticotropic hormone and angiotensin II in vitro. In vivo, the survival time of bADX mice implanted with NR5A1-induced steroidogenic cells was significantly prolonged compared with that of bADX mice implanted with control MSC (AT). Serum cortisol levels, which indicate hormone secretion from the graft, were detected in bADX mice implanted with steroidogenic cells. CONCLUSIONS: This is the first report to demonstrate steroid replacement by the implantation of steroid-producing cells derived from human MSC (AT). These results indicate the potential of human MSC (AT) to be a source of steroid hormone-producing cells.

Procedure of Adult Porcine Islet Isolation.

Islet transplantation is a useful therapeutic choice for severe diabetes mellitus; however, limited donor supplies have interfered with the use of this treatment. Therefore, the establishment of alternative donor sources and engineered tissue, which enables to produce appropriate insulin for controlling blood glucose, is an important challenge. The adult pig is a promising and feasible donor source and materials for the engineered tissue for the clinical setting among various candidates. The recent progress of gene-editing technology contributes to possible clinical porcine xenotransplantation, including porcine islet xenotransplantation. For the success of future clinical porcine islet xenotransplantation, establishing an islet isolation technique for acquiring adequate, good-quality porcine islets is equally important to use a gene-edited pig. However, the characteristics of porcine islets are different from other species; therefore, establishing a suitable technique for porcine islets is challenging. Impact statement Recent technological progress promotes the feasibility of xenotransplantation, including islet xenotransplantation, for clinical setting. Adult pig is a promising and feasible donor source for islet xenotransplantation and engineered tissue, which enables to control blood glucose in recipients. It is important to acquire porcine islets in good qualities for the promotion, however, establishing a technique for adult porcine islet isolation is important but challenging because of the vulnerability of adult porcine islets. Deciding the proper timing of stopping pancreatic digestion is one of the important factors for obtaining adult porcine islets in good quality.

Successful Fowler-Stephens Orchiopexy for an Abdominal Testis Associated With Continuous Type of Splenogondal Fusion: A Case Report.

Splenogonadal fusion (SGF) is a rare congenital anomaly in which there is abnormal adhesion between splenic tissue and gonads. Several patients with cryptorchidism associated with this anomaly have undergone orchiectomy because of the suspicion of tumors. Preoperative computed tomography (CT) is useful in differentiating between SGF and tumors, and in evaluating the vasculature of the SGF. We report a boy with an abdominal testis associated with SGF. Based on the CT findings, we successfully performed Fowler-Stephens orchiopexy. To the best of our knowledge, no SGF cases in which Fowler-Stephens orchiopexy could salvage the testis without testicular atrophy have been previously reported.

Comprehensive approach for preserving cavernous nerves and erectile function after radical prostatectomy in the era of robotic surgery.

A nerve-sparing procedure during robot-assisted radical prostatectomy has been considered one of the most important techniques for preserving postoperative genitourinary function. The reason is that adequate nerve-sparing procedures could preserve both erectile function and lower urinary tract function after surgery. When a nerve-sparing procedure is carried out, the cavernous nerves themselves cannot be visualized, despite the magnified viewing field during robot-assisted radical prostatectomy. Thus, nerve-sparing procedures have been considered challenging operations, even now. However, because not all surgeons have carried out a sufficient number of nerve-sparing procedures, the development of new nerve-sparing procedures or new methods for mapping the cavernous nerves is required. Recently, various new operative techniques, for example, Retzius-sparing robot-assisted radical prostatectomy, transvesical robot-assisted radical prostatectomy and retrograde release of neurovascular bundle technique during robot-assisted radical prostatectomy, have been developed. In addition, new surgical devices, for example, biological/bioengineering solutions for cavernous nerve protection and devices for identifying the cavernous nerves during radical prostatectomy, have developed to preserve the cavernous nerves. In contrast, limitations or problems in preserving cavernous nerves and postoperative erectile function have become apparent. In particular, the recovery rate of erectile function, the positive surgical margin rate at the site of nerve-sparing and the indications for nerve sparing have become obvious with the accumulation of much evidence. Furthermore, predictive factors for postoperative erectile function after nerve-sparing procedures have also been clarified. In this article, the importance of a comprehensive approach for early recovery of erectile function in the robot-assisted radical prostatectomy era is discussed.

Extension of Survival in Bilaterally Adrenalectomized Mice by Implantation of SF-1/Ad4BP-Induced Steroidogenic Cells.

Mesenchymal stroma/stem cells (MSCs) exist in adult tissues, such as adipose tissue and bone marrow, and differentiate into cells of multiple lineages. In previous studies, we found that MSCs differentiate into steroidogenic cells by forced expression of steroidogenic factor 1 (SF-1)/adrenal 4 binding protein (Ad4BP), the master regulator of steroidogenesis and differentiation of pituitary gonadotrophs, adrenal glands, and gonads. In this study, SF-1/Ad4BP-induced steroidogenic cells derived from mouse adipose tissue-derived MSCs (ADSCs) were implanted under the kidney capsule of bilateral adrenalectomized (bAdx) mice. bAdx mice did not survive after 7 days. However, 4 of 9 bAdx mice implanted with SF-1/Ad4BP-induced steroidogenic cells, 1 of 10 bAdx mice transplanted with control ADSCs, and bAdx mice transplanted with an adrenal gland survived for 30 days. Plasma corticosterone levels in bAdx mice implanted with SF-1/Ad4BP-induced steroidogenic cells and control ADSCs were 5.41 ±â€…2.26 ng/mL (mean ±â€…SEM) and undetectable at 7 days after implantation, respectively. After removal of the kidney bearing the graft from the surviving mice at 30 days after implantation, plasma corticosterone was not detected in any of the samples. Immunohistochemical staining revealed SF-1/Ad4BP-positive cells under the capsule of the kidney. Although we performed an adrenocorticotropin (ACTH) loading test on bAdx mice implanted with SF-1/Ad4BP-induced steroidogenic cells, ACTH responsiveness was not observed. Implantation of steroidogenic cells derived from ADSCs into bAdx mice increased the basal plasma corticosterone level and extended the survival of bAdx mice, suggesting the capability of restoring steroidogenic cells by cell transplantation therapy for adrenal insufficiency.

[COMBINING MODALITY THERAPY WITH SURGERY CAN PROVIDE LONG-TERM SURVIVAL WITH IMPROVED QUALITY OF LIFE FOR PATIENTS WHO HAVE PROSTATE CANCER WITH INTRACRANIAL DURAL METASTASIS: A CASE REPORT].

A 61-year-old man visited our hospital with a headache and left visual field defect. A head MRI showed an intracranial dural tumor with cerebral compression, which was suspected to be metastatic. Analysis of the tumor markers revealed an increase in prostate-specific antigen (PSA) levels (172.8 ng/mL), and therefore prostate cancer was suspected as the primary tumor. Histological diagnosis of a prostatic tissue sample using a transrectal needle biopsy gave a prostate carcinoma with Gleason score of 5+4=9. Additional imaging examinations revealed metastatic lesions in the intra-pelvic lymph node and bones. These data indicated to us that curative surgery was unlikely to be successful, but finally we decided to perform a craniotomy for tumor resection for the intracranial dural tumor to remove his neurological symptoms. After surgery, his headache and visual field defect improved. The pathological finding was intracranial dural metastasis from prostate cancer and the clinical stage was diagnosed as T3bN1M1c in the UICC criteria (ver. 8). Endocrine therapy with degarelix and bicalutamide was started for the primary and residual metastatic prostate cancers. After one year of initial treatment, bicalutamide was changed to enzalutamide because of a tendency towards increased plasma PSA levels. The patient has survived for two and a half years after surgery with no new metastatic tumors or intracranial tumors. Our experience indicates that combined modality therapy with surgery can provide long-term survival with no cranial nerve disorders for patients who have prostate cancer with intracranial dural metastasis.

Role of Computed Tomography Volumetry in Preoperative Donor Renal Function Evaluation of Living Related Kidney Transplantation.

INTRODUCTION: Renal scintigraphy is used to evaluate split renal function. A computed tomography (CT) examination is also carried out for donor safety and appropriate transplantation surgery, and the renal volume (CT volumetry) can be obtained at that time. In this study, we evaluated donor kidney function by inulin clearance (Cin) before and after donor nephrectomy in living donor renal transplantation, and the predictive role of CT volumetry was compared with diethylenetriamine pentaacetic acid (DTPA). METHOD: From November 2005 to April 2018, 34 cases of living donor transplantation conducted at Fukuoka University Hospital were retrospectively studied. The donated kidney weight was measured in 25 cases, and postoperative Cin was measured in 19 cases. RESULTS: The average donor age was 51.7 years old (from 35 to 71). Preoperative Cin and postoperative Cin of donors were 86.3 mL/min/1.73 m2 (from 59.5 to 138.3) and 52.3 (from 40.5 to 76.6), respectively. The average CT volumetry of donated kidneys was 153.9 mL (from 107.8 to 219.3). Correlations of weight and DTPA and CT volumetry of donated kidneys were r = 0.033 (P = .8770) and r = 0.763 (P < .0001), respectively. Correlations of glomerular filtration rate of DTPA and CT volumetry and Cin of postoperative donor residual kidneys were r = 0.66 (P = .002) and r = 0.555 (P = .014). CONCLUSION: There was a significant correlation between CT volumetry and the weight of the removed kidneys, and a correlation between Cin after donor nephrectomy and CT volumetry of the remaining kidneys, but it did not exceed the predictive role of DTPA. However, it was suggested that it is worthy to use as a preoperative examination for split renal function equivalent to DTPA.