Comparison of mirabegron and vibegron for clinical efficacy and safety in female patients with overactive bladder: a multicenter prospective randomized crossover trial.

PURPOSE: To compare the efficacy and safety of mirabegron and vibegron in female OAB patients. METHODS: We conducted a multicenter, prospective, randomized crossover study of female patients with OAB. The patients were assigned to Group MV (mirabegron for 8 weeks, followed by vibegron for 8 weeks) or group VM (vibegron for 8 weeks, followed by mirabegron for 8 weeks). The primary endpoint was the change in OABSS from baseline, and the secondary endpoint was the change in FVC parameters. After completion of the study, each patient was asked which drug was preferable. RESULTS: A total of 83 patients were enrolled (40 and 43 in groups MV and VM, respectively). At 8th and 16th week, 33 and 29 in Group MV and 34 and 27 in Group VM continued to receive the treatment. The change in PVR was not significantly different between treatment with mirabegron and vibegron. The changes in OABSS, nighttime frequency, mean, and maximum voided volume were similar between mirabegron and vibegron. The mean change in the daytime frequency was greater in the vibegron than in the mirabegron. Of the 56 patients, 15 (27%) and 30 (53%) preferred mirabegron and vibegron, respectively. The remaining 11 patients (20%) showed no preference. The change in the urgency incontinence score during vibegron was better in patients who preferred vibegron to mirabegron. CONCLUSION: The efficacies of mirabegron and vibegron in female patients was similar. The patients' preference for vibegron could depend on the efficacy of vibegron for urgency incontinence.

Proteogenomic identification of an immunogenic antigen derived from human endogenous retrovirus in renal cell carcinoma.

CD8+ T cells can recognize tumor antigens displayed by HLA class I molecules and eliminate tumor cells. Despite their low tumor mutation burden, immune checkpoint blockade (ICB) is often beneficial in patients with renal cell carcinoma (RCC). Here, using a proteogenomic approach, we directly and comprehensively explored the HLA class I-presenting peptidome of RCC tissues and demonstrated that the immunopeptidomes contain a small subset of peptides derived from human endogenous retroviruses (hERV). A comparison between tumor and normal kidney tissues revealed tumor-associated hERV antigens, one of which was immunogenic and recognized by host tumor-infiltrating lymphocytes (TIL). Stimulation with the hERV antigen induced reactive CD8+ T cells in healthy donor-derived (HD-derived) peripheral blood mononuclear cells (PBMC). These results highlight the presence of antitumor CD8+ T cell surveillance against hERV3895 antigens, suggesting their clinical applications in patients with RCC.

Urodynamic Efficacy and Safety of Mirabegron Add-on Treatment with Tamsulosin for Japanese Male Patients with Overactive Bladder.

OBJECTIVES: To investigate urodynamic efficacy and safety of mirabegron add-on treatment with tamsulosin for Japanese male patients with overactive bladder (OAB). METHODS: A prospective study was conducted in 26 consecutive male patients with OAB who had been taking tamsulosin. OAB was diagnosed by overactive bladder symptom score (OABSS). Before and 8 weeks after mirabegron add-on treatment with preceding tamsulosin, we assessed OABSS, International Prostate Symptom Score (IPSS), free uroflowmetry (UFM), filling cystometry and pressure-flow study (PFS). RESULTS: Mean age and prostate volume of the study patients were 75 ± 7 years and 32 ± 19 mL, respectively. Mirabegron significantly improved OABSS (from 8.5 ± 2.3 to 4.7 ± 2.5, P < 0.001). On free UFM, mirabegron significantly increased voided volume (from 135 ± 47 to 182 ± 102 mL, P = 0.01), maximum (from 10.7 ± 3.7 to 13.5 ± 6.4 mL/sec, P < 0.01) and average flow rate (from 5.5 ± 1.9 to 7.1 ± 3.3 mL/sec, P < 0.01), while postvoid residual urine volume did not change significantly (from 47 ± 38 to 63 ± 61 mL, P = 0.23). Before mirabegron, 24 patients (92%) had detrusor overactivity (DO). After mirabegron add-on, maximum cystometric capacity significantly increased from 170 ± 98 to 212 ± 95 mL (P = 0.01) and DO disappeared in six patients (25%). In the other 18 patients with persistent DO, amplitude of involuntary contraction decreased and bladder volume at first involuntary contraction increased with statistical significance. On PFS, detrusor pressure at maximum flow rate (from 79 ± 31 to 68 ± 19 cmH2 O, P = 0.10) or bladder contractility index (from 126 ± 39 to 120 ± 27, P = 0.45) did not change significantly. CONCLUSIONS: Mirabegron add-on treatment with tamsulosin has efficacy and safety because it improves storage symptom without impairment of bladder contractility during voiding in male patients with OAB.

Micturition-suppressing region in the periaqueductal gray of the mesencephalon of the cat.

The periaqueductal gray (PAG) of the mesencephalon has been implicated to be involved in the control of micturition. We investigated the micturition-suppressing region in the PAG of the cat. Decerebrated 27 adult cats were used. A microelectrode was inserted stereotaxically into the PAG, and a region was searched where electrical stimulation suppressed isovolumetric bladder contractions. Simultaneous stimulation of the pontine micturition center (PMC) and micturition-suppressing region in the PAG was performed before and after an injection of bicuculline (GABA(A) blocker) into the PMC. The micturition-suppressing region was found at the dorsolateral margin of the rostral PAG. Bladder contractions were not provoked by simultaneous stimulation of the PMC and micturition-suppressing region in the PAG. However, after bicuculline injection into the PMC, partial bladder contractions were provoked by simultaneous stimulation of the PMC and the micturition-suppressing region in the PAG. These results suggest that the dorsolateral margin of the rostral PAG includes the micturition-suppressing region that seems to have neural connections with the PMC. GABA is assumed to be one of the neurotransmitters that are involved in the PMC inhibition from the micturition-suppressing region in the PAG.

[A case of perineal abscess due to urethral fistula in a patient with spinal cord injury].

We report a case of perineal subcutaneous abscess due to urethral fistula in a patient with spinal cord injury. A 39-year-old male visited our hospital complaining of left scrotal swelling and fever. The left scrotum and perineal skin were swollen to the size of a goose egg, and pus was discharged from the perineal swollen bump. Magnetic resonance imaging (MRI) suggested an urethral fistula with a large subcutaneous abscess. The abscess was resected with debridement of necrotic tissue, and a cystostomy was placed. Endoscopy revealed a fistula in the bulbar urethra. The characteristics of this rare entity are discussed.

[A case of amyloidosis of the renal pelvis].

We report a case of localized amyloidosis of the renal pelvis and upper ureter arising in a 74-year-old man who presented at our hospital with gross hematuria. The intravenous pyelogram showed right hydronephrosis and stenosis of right renal pelvis and upper ureter. The cystoscopy view was normal, but the right retrograde-ureteropyelogram showed a long irregular stricture of the renal pelvis. Ureteroscopy was performed and rubbing biopsy of edematous, bleeding lesion suggested class IIIb, transitional cell carcinoma. With the diagnosis of a right renal pelvic tumor, right nephroureterectomy was performed. The histology report stated "massive deposits of amyloids are seen in the segment of macroscopically abnormal renal pelvis". Amyloidosis of the renal pelvis is a rare entity and 12 cases were reported in the Japanese and English literature.

[Two cases of vesical nephrogenic adenoma].

Case 1: A 52-year-old man receiving regular treatment for quadriplegia due to Friedreich disease visited our hospital with the chief complaint of macroscopic hematuria. He had undergone cystostomy 12 years ago due to neurogenic bladder. The computed tomography and cystoscopic examination revealed a bladder tumor with a few bladder stones. Transurethral resection of bladder tumor (TUR-Bt) was performed after bladder stone removal in May 2000. The pathological diagnosis showed nephrogenic adenoma. Case 2: A 54-year-old man had been treated with bladder tumor by TUR-Bt in Nov. 1995. The pathological diagnosis showed transitional cell carcinoma, G3, pT2 and intravesical instillation therapy using THP was performed. The bladder tumor had recurred twice and the instillation therapy had been exchanged to BCG since Nov. 1997. A small bladder tumor was observed in Jan. 2001, and from the biopsy specimen it was diagnosed as nephrogenic adenoma. Forty-six cases of urothelial nephrogenic adenoma including our cases have been reported in Japan. Chronic stimulation such as bladder stone and infection is thought to induce nephrogenic adenoma. BCG instillation therapy is believed to be an initiation factors for nephrogenic adenoma.

Inguinal herniation in two patients with continuous ambulatory peritoneal dialysis.

We report two cases of subacute inguinal swelling in uremic patients on continuous ambulatory peritoneal dialysis (CAPD). Computed tomography, scintigraphy demonstrated a mass in the right groin. Surgical repair of an inguinal hernia resulted in complete resolution of the inguinal swelling. Both patients could restart continuous ambulatory peritoneal dialysis, without complication.