Urinary Recovery Research Articles

Prostate size ≥ 100g and its association with long-term outcomes of Retzius-sparing robot-assisted radical prostatectomy.

It is unknown whether perioperative and functional outcomes of Retzius-sparing robot-assisted radical prostatectomy (RS-RARP) may be affected by large prostate sizes (PS). All patients treated with RS-RARP were identified and compared according to PS. The definition of PS relied on the prostatic weight at final pathology (PS < 100g vs ≥ 100g). Multivariable logistic regression models tested immediate and 12-month urinary continence recovery (UCR, namely, 0-1 safety pad per-day), and positive surgical margins (PSM). Multivariable Poisson log-linear regression analyses tested operative time (OT), estimated blood loss (EBL), and length of stay (LOS). The analyses relied on the database of a high-volume European institution (2010-2022). Of 1,555 overall patients, 1503 (96.7%) had a PS < 100g and 52 (3.3%) had a PS ≥ 100g. No differences were recorded in LOS (3days), and intraoperative (1.9 vs 2.3%) as well as postoperative complications (13 vs 12%; all p values > 0.05). No significant difference was recorded in PSM (25 vs 23%, p = 0.6). In patients with PS ≥ 100g vs < 100g, immediate UCR rate was 42 vs 64% (p = 0.002), and 12-month UCR rate was 87 vs 88% (p = 0.3). PV ≥ 100g independently predicted worse immediate UCR (odds ratio 0.55, 95% CI 0.30-0.98, p = 0.044), but not worse 12-month UCR (p = 0.3) or higher PSM (p = 0.7). PV ≥ 100g independently predicted longer OT (incidence rate ratio [IRR] 1.12, 95% CI 1.10-1.15, p < 0.001) and higher EBL (IRR 1.26, 95% CI 1.24-1.28, p < 0.001), but not longer LOS (p = 0.3). RS-RARP is a valid option for prostate cancer treatment, even in case of very large prostates. Specifically, no significant association was recognized between PS ≥ 100g and PSM or 12-month UCR.

Anxiety, depression, urinary continence, and sexuality in patients undergoing radical prostatectomy: preliminary findings.

Evaluate the relationship between psychological distress, namely anxiety and depression, with urinary continence and recovery of erectile function in patients undergoing radical prostatectomy (RP). We retrospectively analyzed data from 33 consecutive patients who underwent RP in a single tertiary-referral academy between 01/2018 to 01/2019. We used the International Index of Erectile Function (IIEF-15), the Sexual Complaints Screener for Men (SCS-M), and the Hospital Anxiety and Depression Scale (HADS), validated questionnaires for the assessment of sexual function, anxiety, and depression experiences, respectively. These questionnaires were administered at the pre-surgical visit, after surgery, and at intermediate follow-ups (three, six, and twelve months). The analysis of the questionnaires completed during follow-up shows that erectile function is the most affected, with 90% erectile dysfunction (ED) at three months after surgery. In terms of emotional states, anxiety prevails in the first months following surgery and is statistically significantly associated with incontinence (p = 0.02). Depressive symptoms, on the other hand, appear later and prevail over anxiety at six months after surgery, although not statistically significant. In the early post-surgical phase anxiety and ED are the most frequently detected components, while depressive experiences and decreased desire, typical of later stages, have not yet fully emerged.

Is early continence recovery related to the length of spared urethra? A prospective multicenter study comparing preoperative MRI and histologic specimen measurements after robotic radical prostatectomy

BackgroundUrinary incontinence (UI) is a common complication after radical prostatectomy, significantly affecting patients' quality of life. This study aimed to correlate the length of preserved urethra in robotic radical prostatectomy (RALP) patients with short-term urinary continence rates within 90 days post-surgery. MethodsA prospective multicentric study enrolled 190 prostate adenocarcinoma patients undergoing RALP. Using preoperative magnetic resonance imaging (mpMRI), urethral length was measured from the external urethral sphincter to the bladder neck. After surgery, histological measurements of the removed urethra were compared to the preoperative mpMRI data. Patients were categorized into two groups at the three-month follow-up based on urinary continence assessed through Urodynamic Study (UDS): Group A (94 patients without UI) and Group B (96 patients with UI). ResultsResults revealed a significant difference in mean UI recovery time (Group A: 12.35 days, SD: 3.09 vs. Group B: 93.86 days, SD: 34.8, p < 0.0001). A ROC curve identified a 16.5% cut-off value (p < 0.000, sensitivity 87.5%, specificity 91.8%). Both groups showed a significant negative correlation between preserved urethral percentage and UI recovery time (Group A: r −0.655, p < 0.0001; Group B: r −0.340, p: 0.017). Group A had an average of 21.52% preserved urethra, while Group B had 13.86% (p < 0.0001). At one-year follow-up, 93.2% overall patients reported urinary continence without pads. ConclusionsThis study emphasizes the positive correlation between preserved urethra percentage in RALP and early urinary continence recovery, highlighting its surgical significance.

Association between 3D membranous urethral parameters and urinary continence recovery after RARP

ObjectivesTo evaluate whether the urinary continence (UC) recovery after robotic-assisted radical prostatectomy (RARP) relates to the membranous urethral length (MUL) and the membranous urethral complex volume (MUV).Materials and methods120 patients who underwent RARP were enrolled according to the different times of UC recovery and examined using prostate magnetic resonance imaging (MRI) before surgery. The membranous urethral (MU) parameters were measured using the three-Dimensional (3D) model reconstructed by holographic technology, such as total MUV (tMUV), exposed MUV (eMUV), full MUL (fMUL) and exposed MUL (eMUL). Statistical software SPSS 26.0 was used to analyze the data and compare the MU parameters and baseline data in different groups.ResultsPatients with larger tMUV (p = 0.038), eMUV (p = 0.003), longer fMUL (p = 0.025), eMUL (p = 0.044) had better UC after removal of the catheter, and eMUV (OR = 1.002, 95%CI = 1.001–1.004, p = 0.004) was a predictor; the patients with younger age (p = 0.021), lower VPSS score (p = 0.004) and larger eMUV (p = 0.012) and longer eMUL (p = 0.049) had better UC recovery one month after RARP while eMUV (OR = 1.002, 95% CI = 1.000–1.003, p = 0.008) and VPSS score (OR = 0.886, 95% CI = 0.806–0.973, p = 0.011) were independent risk factors; The patients with younger age (p = 0.018), larger tMUV (p = 0.029), eMUV (p = 0.016) had better UC recovery three months after RARP. eMUV (OR = 1.002, 95% CI = 1.000–1.004, p = 0.042) and age (OR = 0.904, 95% CI = 0.818–0.998, p = 0.046) were independent risk factors.ConclusionThis clinical study shows that patients with larger MUV and longer MUL can return to UC earlier after surgery. Among that, eMUV is a better predictor.

Effect of Renal Impairment on Pharmacokinetics and Safety of Ensitrelvir, a SARS-CoV-2 3CL Protease Inhibitor.

Ensitrelvir, a novel oral inhibitor of 3C-like protease of SARS-CoV-2, shows efficacy and safety in participants with mild to moderate COVID-19. Since urinary recovery of ensitrelvir ranged from 12.9% to 21.8% across dose groups given 20-1000mg in a single-ascending dose study, renal excretion contributes to the elimination of ensitrelvir. Therefore, the effect of renal impairment on the pharmacokinetics and safety of ensitrelvir needed to be evaluated. This study (NCT05363215) was a phase 1, open-label, nonrandomized, parallel-group study. The effect of renal function on the pharmacokinetics of ensitrelvir was investigated. Ensitrelvir was administered as a single dose of 375mg to participants with normal renal function and those with mild, moderate, and severe renal impairment. The participants with normal renal function were matched to each participant with moderate renal impairment with respect to sex, age, and body mass index. The unbound fractions in plasma after administration of ensitrelvir were also evaluated. For the safety assessment, the nature, frequency, and severity of treatment-emergent adverse events were evaluated and recorded. The plasma concentrations of participants with renal impairment were higher than those of participants with normal renal function. The ratios (90% confidence intervals) of the area under the plasma concentration-time curve from 0 to infinity (AUC0-inf) in participants with mild, moderate, and severe renal impairment compared to normal renal function were 1.4374 (1.1716-1.7636), 1.4885 (1.1883-1.8646), and 1.6021 (1.2782-2.0080), respectively. The plasma protein-unbound fraction was similar regardless of the plasma ensitrelvir concentration or renal function. Ensitrelvir was well tolerated in participants with mild to severe renal impairment and normal renal function. Ensitrelvir was well tolerated by participants with renal impairment. There was no clinically meaningful increase on exposure to ensitrelvir in participants with renal impairment, indicating that no dose adjustment would be required due to renal function.

The application of full-length urethral preservation without anastomosis in single-port laparoscopic radical prostate cancer

Objective: To preliminarily examine the feasibility and outcome of single-port laparoscopic radical prostatectomy with full-length urethral preservation (FLUP-SPRP). Method: This study was a prospective case series study. A total of 25 patients with prostate cancer who met the enrollment criteria and agreed to this surgical procedure from March 2022 to December 2022 were collected at the Department of Urology, the Second Affiliated Hospital of Nanjing Medical University. The age of the patients was (67.2±7.6) years (range: 61 to 76 years). This novel procedure was performed by an experienced surgeon who performed single hole radical prostatectomy skillfully. Patient urinary control, tumor control, and related surgical complications after surgery were regularly monitored. Postoperative urinary control was evaluated using the daily amount of urine pad, 0 to 1 piece of urine pad was to restore urinary control, and 0 to 1 piece of pad within 24 hours after catheter removal was immediate urinary control. Result: All prodecures were successfully completed without transit to open surgery. The surgical time was (128.4±22.4) minutes (range: 100 to 145 minutes), the intraoperative blood loss was (68.2±13.7) ml (range: 50 to 120 ml). The urethral injury occurred in 4 cases during surgery and was repaired by sutures. The urinary control recovery rates within 24 hours, 1 week, 4 weeks, and 7 weeks after surgery were 80.0%, 84.0%, 92.0% and 100%, respectively. Postoperative large section pathology revealed 1 case with a positive basal margin of the prostate and negative margins of all prostate glands around the urethra. Postoperative complications included urinary tract infection in 3 cases, urodynia in 2 cases, and acute urinary retention in 1 case. MRI follow-up 3 months after surgery showed normal anatomy of the bladder and urethra. The follow-up values of prostate specific antigen at 3 and 6 months after surgery were less than 0.1 μg/L. Conclusions: The preliminary results of this study indicate that the FLUP-SPRP procedure is safe and feasible. The early results of postoperative urinary control and oncology are as expected.

Does Retzius-Sparing robot-assisted radical prostatectomy guarantee optimal urinary continence recovery across all ages?

The association between age at surgery and urinary continence (UC) recovery after Retzius-sparing robot-assisted radical prostatectomy (RS-RARP) is not well established. We addressed this knowledge gap, relying on a large series of 1,417 patients treated with RS-RARP at a high-volume centre between 2010 and 2021. Multivariable logistic models, as well as LOESS plot functions were performed. The probability of immediate, as well as 12-month UC-recovery progressively declined with increasing age at surgery, and per 5-years age at surgery increase reached the independent predictor status for both immediate and 12-month UC-recovery. These findings may significantly improve the quality of patient counseling regarding RS-RARP.

Outcomes of lateral approach in robot-assisted radical prostatectomy: insights from a single-surgeon experience

In the era of robotic prostate surgery, various techniques have been developed to improve functional outcomes. Urinary continence has shown satisfactory results, but the preservation of lateral nerves to the periprostatic capsule is only achievable by sparing the pubovesical complex. This study aims to present the first cases of lateral-approach robot-assisted radical prostatectomy (LRRP) performed by a novice surgeon. We conducted a retrospective analysis of 70 prostate cancer patients who underwent LRRP between October 2019 and September 2021, analyzing the perioperative and functional outcomes. The median operative time and intraoperative blood loss were 102 (92–108) minutes and 150 (130–180) mL, respectively. Five minor postoperative complications were reported, and the median hospital stay was 2 (1–2) days. Eleven positive surgical margins occurred. Potency and urinary continence recovery were achieved in 59 (84%) and 66 (94%) patients, respectively, 12 months after surgery. Our analysis shows that LRRP is a safe and effective procedure for prostate cancer surgery. Continence and potency recovery required a short learning curve, with an acceptable recovery rate even in the initial cases.

Early recovery of urinary continence after robot-assisted radical prostatectomy is associated with membranous urethra and neurovascular bundle preservation.

We investigated the correlation between surgical outcomes and postoperative urinary continence recovery in robot-assisted radical prostatectomy (RARP). Patients who underwent RARP in our institution (n = 195) were included in this study. Preserved urethral length (PUL) was assessed during the procedure. Other outcomes of the surgical procedure were collected from operative records. Kaplan-Meier analysis with log-rank test was used to compare urinary continence recovery rate with the PUL, sparing of the neurovascular bundle (NVB), and other surgical procedures. Univariate and multivariate analyses were performed using Cox proportional hazards model, and p-values of <0.05 were considered significant. Patients with a PUL ≥26 mm had 10.0%, 24.7%, 36.6%, and 89.0% continence recovery rates at 30, 60, 90, and 365 days after surgery, respectively, while patients with a PUL <26 mm had 0%, 17.8%, 26.1%, and 80.9% recovery rates, respectively. Kaplan-Meier curves showed significantly better postoperative urinary continence recovery at 30 days after RARP in patients with a PUL ≥26 mm than those with a PUL <26 mm (p = 0.0028) and in patients with NVB preservation than those with no NVB preservation (p = 0.014). Urinary continence recovery within 30, 60, and 90 days after surgery was 90.6% for patients with a PUL of ≥26 mm and NVB preservation, while only 82.3% for patients with a PUL of <26 mm or no NVB preservation. Our results suggest that a PUL ≥26 mm and NVB preservation after RARP correlate with a significantly higher postoperative rate of recovery of urinary continence.

First-in-Human Assessment of Gut Permeability in Crohn’s Disease Patients Using Fluorophore Technology

Background and AimsThe dual sugar absorption test (DSAT) as a classic measure of human intestinal permeability has limited clinical utility due to lengthy and cumbersome urine collection, assay variability, and long turnaround. We aimed to determine if the orally administered fluorophore MB-102 (relmapirazin) (MW=372) compares to lactulose (L) (MW=342) and rhamnose (R) (MW=164)-based DSAT as a measure of gut permeability in people with a spectrum of permeability including those with Crohn’s disease (CD). MethodsWe performed a single center, randomized, open label, crossover study comparing orally administered MB-102 (1.5 or 3.0 mg/kg) to L (1000 mg) and R (200 mg). Adults with active small bowel CD on magnetic resonance enterography (cases) and healthy adults (controls) were randomized to receive either MB-102 or L and R on study day 1, and the other tracer 3-7 days later. Urine was collected at baseline and 1, 2, 4, 6, 8, 10, and 12 hours after tracer ingestion to calculate the cumulative urinary percent excretion of MB-102 and L and R. ResultsNine cases and 10 controls completed the study without serious adverse events. Urinary recovery of administered MB-102 correlated with recovery of lactulose (r-squared = 0.83) for all participants. MB-102 urine recovery also tracked with the L:R ratio urine recovery (r-squared=0.57). In controls, the percentages of L and MB-102 recovered were similar within a narrow range unlike in CD patients. ConclusionsThis first-in-human study of an orally administered fluorophore to quantify gastrointestinal permeability in adults with CD demonstrates that MB-102 is well tolerated, and its recovery in urine mirrors that of percent L and the L:R ratio.

Salvage robot-assisted radical prostatectomy after carbon ion radiotherapy to the prostate.

This study presents the surgical and oncological outcomes of salvage robot-assisted radical prostatectomy (RARP) after carbon ion radiotherapy at a single institution. Patients who underwent salvage RARP for local recurrence after carbon ion radiotherapy at Kyushu University Hospital between 2020 and 2023 were included. A single surgeon performed salvage RARP with extended pelvic lymph node dissection. Clinicopathological characteristics and perioperative and postoperative outcomes were prospectively collected and electronically recorded. Ten cases were included. The preoperative clinical T-stage was T2, except for one case with T3a. The median console time was 171 min (range, 135-226 min). No severe perioperative or postoperative complications were noted. The pathological T-stage was T2, T3a, and T3b in four, four, and two cases, respectively. Biochemical recurrence was observed in one patient at 31.2 months after surgery. For patients with more than 1 year of follow-up, urinary continence recovery with ≤1 pad was achieved in two cases within 1 year, whereas four cases did not recover urinary continence within 1 year. This case series demonstrated the feasibility of salvage RARP after carbon ion radiotherapy. Although the urinary continence recovery was modest, short-term disease control was favorable.

Effect of 3D laparoscopy versus traditional laparotomy on serum tumor markers and coagulation function in patients with early-stage endometrial cancer

ObjectivesTo investigate the impact of Three-Dimensional (3D) laparoscopy compared to traditional laparotomy on serum tumor markers and coagulation function in patients diagnosed with early-stage Endometrial Cancer (EC). MethodThe authors retrospectively analyzed the clinical data of 75 patients diagnosed with early-stage EC and categorized them into two groups based on the surgical techniques employed. The 3D group consisted of 36 patients who underwent 3D laparoscopic surgery, while the Laparotomy group comprised 39 patients who underwent traditional laparotomy. The authors then compared the alterations in serum tumor markers and coagulation function between the two groups. ResultsPostoperatively, serum levels of CA125, CA199, and HE4 were notably reduced in both groups on the third day, with the levels being more diminished in the 3D group than in the Laparotomy Group (p < 0.05). Conversely, FIB levels escalated significantly in both groups on the third-day post-surgery, with a more pronounced increase in the 3D group. Additionally, PT and APTT durations were reduced and were more so in the 3D group than in the laparotomy group (p < 0.05). ConclusionsWhen juxtaposed with traditional laparotomy, 3D laparoscopic surgery for early-stage EC appears to be more efficacious, characterized by reduced complications, and expedited recovery. It can effectively mitigate serum tumor marker levels, attenuate the inflammatory response and damage to immune function, foster urinary function recovery, and enhance the quality of life. However, it exerts a more significant influence on the patient's coagulation parameters, necessitating meticulous prevention and treatment strategies for thromboembolic events in clinical settings.

Urinoma mimicking pancreatic pseudocyst: Case report

Introduction. A urinoma is a localized urine collection in the retroperitoneum, occurring outside the urinary tract. Although relatively rare, traumatic urinomas in pediatric patients pose significant diagnostic and therapeutic challenges. Initial diagnosis primarily relies on ultrasonography, but computed tomography (CT) and magnetic resonance imaging (MRI) provide clearer differentiation and localization. The treatment strategy focuses on preventing potential complications and promoting urinary tract recovery. Case Report. We present the case of a seventeen-year-old male with a penetrating abdominal injury. Prompt abdominal exploration revealed and managed minor colon and spleen lacerations. Upon readmission due to the fever and abdominal pain, further diagnostics initially misinterpreted the formed traumatic urinoma as a pancreatic pseudocyst. Postoperative computed tomography, cystoscopy, and retrograde pyelography subsequently confirmed the existence of a urinoma. Conclusion. Through this case report and its atypical manifestation, we aim to highlight the importance of differential diagnosis, the complexity of abdominal injuries, and diagnostic and treatment protocols in pediatric populations. Emphasizing a multidisciplinary strategy is crucial to optimizing treatment outcomes.

The effects of a 6-week intervention with Limosilactobacillus reuteri ATCC PTA 6475 alone and in combination with L. reuteri DSM 17938 on gut barrier function, immune markers, and symptoms in patients with IBS-D-An exploratory RCT.

An increased intestinal permeability is a common feature in patients with diarrhoea-predominant irritable bowel syndrome (IBS-D). Probiotics have shown to improve IBS symptoms and might also affect intestinal barrier function. The aim of this study was to investigate the effects of a 6-week intervention with Limosilactobacillus reuteri ATCC PTA 6475 alone (single strain) or in combination with Limosilactobacillus reuteri DSM 17938 (dual strain) on gut barrier function, immune markers, and symptoms in IBS-D patients (ClinicalTrials.gov registration number: NCT03986476). 65 IBS-D patients were randomised into three groups (placebo, single strain, dual strain). Small and large intestinal permeability were assessed using a multi-sugar urinary recovery test. Blood, saliva, faecal samples, and several symptom scales were collected before, and after three and six weeks of intervention. Small and large intestinal permeability as well as other markers of gut barrier function were not significantly affected by the probiotic interventions. Serum IL-6 levels showed a tendency to be reduced in the single strain group (descriptive p = 0.052). In addition, high-sensitivity C-reactive protein was significantly reduced in the dual strain group (p = 0.041). The participants in both treatment groups reported less gastrointestinal symptoms after three weeks, but this reached significance only in the dual strain group (total score: p = 0.032, pain subscore: p = 0.028). After six weeks, none of the assessed symptoms were significantly different from the placebo. The probiotic compounds investigated in this study did not seem to affect IBS-D patients' gut barrier function, but showed potential anti-inflammatory and symptom-improving properties, which need to be confirmed in larger study cohorts.

Pharmacokinetics of collagen dipeptides (Gly-Pro and Pro-Hyp) and tripeptides (Gly-Pro-Hyp) in rats.

Although systemic exposure to peptides, such as Gly-Pro-Hyp, Pro-Hyp, and Gly-Pro, has been reported following administration of collagen hydrolysates from fish scale and porcine skin in vivo, the individual peptide pharmacokinetics remain unknown. We administered the three peptides individually to rats via the intravenous (5mg/kg) and intragastric (100mg/kg) routes and then monitored systemic exposure and urinary excretion. The peptides in biological samples were analyzed via liquid chromatography/tandem mass spectrometry. Gly-Pro-Hyp tended to exhibit higher first-pass metabolism than Pro-Hyp; the absolute oral bioavailabilities of Gly-Pro-Hyp and Pro-Hyp were 4.4% and 19.3%, respectively. Gly-Pro levels were very low in the systemic circulation. Pro-Hyp biotransformed from Gly-Pro-Hyp behaved similarly to Pro-Hyp alone when administered orally. Flip-flop kinetics (elimination rate ≫ absorption rate) were evident, probably reflecting transporter-mediated slow absorption. A double-peak phenomenon was observed for Gly-Pro-Hyp and Pro-Hyp when administered orally, and 5.9%±2.6% and 1.9%±0.3% of each dose were excreted in urine after intravenous administration, respectively. Urinary recovery of Gly-Pro was limited to 0.4%±0.5% of the intravenous dose. This work represents the first individual pharmacokinetics of Gly-Pro-Hyp, Pro-Hyp, and Gly-Pro in vivo.

Retzius-Sparing Robotic-Assisted Prostatectomy: Technical Challenges for Surgeons and Key Prospective Refinements.

Robotic-assisted radical prostatectomy (RARP) is the gold standard for localized prostate cancer. Several RARP approaches were developed and described over the years, aimed at improving oncological and functional outcomes. In 2010, Galfano et al described a new RARP technique, known as Retzius-sparing RARP (RS-RARP), a posterior approach through the Douglas space that spares the anterior support structures involved with urinary continence and sexual potency. This approach has been used increasingly in many centers around the world comparing its results with those of the most used standard anterior approach. Several randomized controlled trials, systematic reviews and meta-analyses demonstrated an important advantage relative to standard anterior RARP in terms of early urinary continence recovery, with comparable perioperative and long-term oncological outcomes. Several surgeons are concerned regarding RS-RARP because it appears to increase the risk of positive surgical margins (PSMs). However, this statement is based on low-certainty evidence. Indeed, the available studies compared the results of surgeons who had an initial experience with posterior RARP with those who had a solid experience with anterior RARP. Recent evidence strongly suggests that RS-RARP is feasible and safe not only in low- and intermediate-risk prostate cancer patient but also in challenging scenario such as high-risk setting, salvage prostatectomy and after transurethral resection of the prostate.

The case of urinary continence recovery after HoLEP.

The case of urinary continence recovery after HoLEP.

Single- and multiple-dose pharmacokinetics of sotalol hydrochloride in healthy cats

Introduction/objectivesThe objective of this study was to describe the single- and multiple-dose pharmacokinetics and urinary elimination of sotalol in healthy cats. AnimalsSix adult purpose-bred cats Materials and methodsCats were administered 2 mg sotalol/kg body weight as a single intravenous bolus and as a single oral dose in a randomized crossover study with a two-week washout period. The same cats then received 3 mg sotalol/kg orally every 12 h for two weeks. Blood samples were collected at predetermined time points for 48 h postdose for quantification of sotalol using ultra-high-pressure liquid chromatography with mass spectrometry. Non-compartmental analysis was used to obtain pharmacokinetic parameters. Data are presented as median (min–max). ResultsFollowing intravenous administration, plasma clearance and volume of distribution were 9.22 mL/min/kg (5.69–10.89 mL/min/kg) and 2175.56 mL/kg (1961–2341.57 mL/kg), respectively. Bioavailability was 88.41% (62.75–130.29) following a single oral dose. Peak plasma concentration (Cmax) and time to Cmax were 0.94 μg/mL (0.45–1.17 μg/mL) and 1.5 h (0.5–4 h) after a single oral dose (2 mg/kg), and 2.29 μg/mL (1.91–2.48 μg/mL) and 1.0 h (0.5–1.5 h) with chronic oral dosing (3 mg/kg), respectively. Elimination half-life was 2.75 h (2.52–4.10 h) and 4.29 h (3.33–5.53 h) for single and chronic oral dosing, respectively. Accumulation index was 1.17 (1.09–1.29) after chronic dosing. Urinary sotalol recovery was 81–108% of the intravenous dose. ConclusionsOral sotalol administration resulted in plasma concentrations reportedly efficacious in other species, with good to excellent oral bioavailability. Urinary excretion appears to be a major route of elimination. Following repeated oral dosing, minimal drug accumulation was estimated. Additional studies in cats are recommended due to the possibility of nonlinear kinetics.

Early and late urinary continence outcomes after unilateral and bilateral nerve-sparing robot-assisted radical prostatectomy: A retrospective multicentre cohort study in Japan (the MSUG94 group).

The impact of unilateral and bilateral nerve-sparing robot-assisted laparoscopic radical prostatectomy (NS-RARP) procedures on continence and the time to continence recovery have not been established. We retrospectively reviewed a total of 2801 patients who underwent RARP in 9 institutions. Procedures were classified as NS or non-NS; NS procedures were further classified as unilateral or bilateral. The recovery of continence was analysed using propensity score matching method. The pad-free rates at 12months after surgery were higher in the NS group (95% confidence interval of odds ratio, 1.06-1.51). Pad-free rates at all time points within 12months of surgery did not significantly differ between the unilateral and bilateral NS groups. NS-RARP resulted in better urinary continence outcomes than non-NS-RARP in the first 12months after surgery. Urinary recovery rates did not significantly differ between unilateral and bilateral NS-RARP.

Pharmacokinetics and Safety of the Tyrosine Kinase2 Inhibitor Deucravacitinib in Healthy Chinese Subjects.

Deucravacitinib, an oral, selective, allosteric tyrosine kinase2 inhibitor, blocks cytokine signaling involved in psoriasis pathogenesis. This ethnic-bridging study evaluated deucravacitinib pharmacokinetics, tolerability, and safety in healthy Chinese subjects. This phaseI, double-blind, single-/multiple-dose study randomized healthy Chinese subjects 4:1 to a single dose of deucravacitinib 6mg or placebo (group1) or deucravacitinib 12mg or placebo (group2) on day1; groups1 and 2 received deucravacitinib 6mg and 12mg once daily, respectively, or placebo on days5-19. Blood samples were collected on days1-5 (0 predose-96h postdose), day5 (0-24h postdose), days9 and 12 (0h), and day19 (0-24h postdose). Deucravacitinib and metabolite (BMT-153261, BMT-158170) concentrations were determined using liquid chromatography/mass spectrometry; pharmacokinetic parameters were calculated using noncompartmental analysis. Urine was collected on days1-4 (4h predose-96h postdose). Safety was monitored throughout. Forty healthy Chinese subjects (groups1 and 2: deucravacitinib, n = 32; placebo, n = 8) were enrolled. Deucravacitinib was rapidly absorbed after single-/multiple-dose administration, with median time to maximal plasma concentration of 1.5-2.3 h. Systemic exposure after single or multiple doses increased approximately twofold with twofold dose increase. Modest deucravacitinib accumulation was observed after multiple-dose administration (1.3- to 1.4-fold increase in area under the curve [AUC] under one dosing interval). Metabolite-to-parent ratios for maximal plasma concentration and AUC remained consistent in each dose group. Mean urinary percent recovery and renal clearance were similar between dose groups. Most adverse events (AEs) were mild/moderate, with no serious treatment-related AEs, deaths, or discontinuations due to AEs. Deucravacitinib was safe and well tolerated in healthy Chinese subjects. Deucravacitinib exhibited rapid absorption, dose-related increases in exposure, comparable half-life, and no evidence of time-dependent pharmacokinetics, suggesting minimal effect of Chinese ethnicity on deucravacitinib pharmacokinetics. NCT03956953.