Predictors of elaborated perineal or a combined abdominoperineal approach during repair for pelvic fracture urethral injury.

PURPOSE: A step-based anastomotic urethroplasty is a standard technique for repairing the posterior urethra in patients with pelvic fracture urethral injury (PFUI). We aim to identify pre-operative factors, including results of conventional radiological imaging, for prediction of elaborated perineal or a combined abdominoperineal procedure. METHODS: Retrospective observational study on 114 consecutive patients undergoing urethroplasty for PFUI between January 2020 and December 2022 was conducted. Surgical procedures were categorized according to the Webster classification into two groups: steps 1-2 (group 1) and steps 3-4 or a combined abdominoperineal repair (group 2). Pre-operative pattern results of RGU/VCUG were categorized regarding the relation between the proximal urethral stump with the pubic symphysis: posterior urethral stump below (pattern 1) or above (pattern 2) the lower margin of the pubic symphysis. Patient demographics were assessed. Univariate and multivariate logistic regression analyses were utilized. RESULTS: Overall, 102 patients were enrolled in the study for data analysis. On the multivariate logistic regression analysis, the presence of erectile dysfunction (OR 4.5; p = 0.014), prior combined treatment (endoscopic and urethroplasty) (OR 6.4; p = 0.018) and RGU/VCUG pattern 2 (OR 66; p < 0.001) significantly increased the likelihood of the need of step 3 or higher. CONCLUSIONS: The need of step 3 or higher during urethroplasty for PFUI can be predicted pre-operatively with conventional imaging (RGU/VCUG). Patients with proximal urethral stump above the lower margin of pubic symphysis were about 66 times more likely to need step 3 or higher during urethroplasty.

Novel single-stage preputial spiral graft for panurethral stricture: a step-by-step description of the technique.

PURPOSE: To report the 12-month results of a novel urethroplasty technique relying on a spiral preputial graft for panurethral stricture disease. MATERIALS AND METHODS: Twenty consecutive patients were treated between May and October 2021 at our center. A spiral preputial mucocutaneous graft is a foreskin-based graft, developed from a 5-cm-wide preputial skin, which is harvested using a helicoidal shape and can reach up to 20 cm in length. Stricture characteristics were assessed through preoperative retrograde and voiding cystourethrogram and maximum uroflowmetry data (Qmax). Complications were collected up to 30 days after surgery and graded using the Clavien-Dindo (C-D) classification. The patients were followed up to 12 months. RESULTS: Preoperative median Qmax was 6.5 ml/s [interquartile range (IQR): 4.0-8.7]. After a median follow-up of 12 months (IQR 12-13), six patients experienced at least one complication. Of them, two patients had grade 2 C-D complications, while only one developed a grade 3a C-D complication. The median postoperative Qmax was 16 ml/s (IQR: 13-18). Only one patient had early urethral stricture recurrence treated with dilatation after catheter removal. At one-year follow-up, no other patients had urethral stricture recurrence with an overall median Qmax of 15.1 ml/s (IQR 13.5-16.4). CONCLUSIONS: Our novel single-stage spiral preputial graft urethroplasty for panurethral stricture treatment appears to be safe and could be used as a valid alternative to two-stage procedures or even to single-stage buccal mucosa graft augmentation.

Advances in urethroplasty.

There has been rapid evolution in management of urethral strictures in the last 3 decades. From the era of dilatation, we have moved to urethral reconstruction. Reinvention of buccal grafts changed the outcomes of urethroplasty. Barbaglis dorsal onlay popularised stricture management across the globe. Kulkarni described a single stage surgery for panurethral stricture. Advances have taken place, and we have moved from transecting to the non-transecting approaches. We describe the various advances in urethral reconstruction in the last decade.

Mucosal-sparing augmented non-transected anastomotic (MsANTA) urethroplasty: a step forward in ANTA urethroplasty.

The surgical advancement of urethral reconstruction is a rapidly moving field. In the last decade, the technique for bulbar urethroplasty has evolved towards less invasive approaches with minimal transection and more tissue sparing in order to increase the patency rate. In this study, we provide a step forward in the augmented non-transected anastomotic (ANTA) urethroplasty proposed in 2012, with a true mucosa-sparing modification of the technique. In detail, the bulbar urethral lumen is approached with either a ventral or dorsal urethrotomy. Differently from previous techniques, the native urethral mucosa is neither transected nor resected but is reconstructed with a direct mucosa-to-mucosa anastomosis. This allows a complete sparing of communicant vessels that come from the corpus spongiosum to the urethral mucosa. The technique aims to preserve the native vascularity of the urethral mucosa by enlarging the native urethral plate with a direct anastomosis at the level of the stricture, and without the need for resection. In our hands the technique was easy and reproducible, and it carried promising results in the preliminary cohort where it was applied.

Comprehensive analysis of paediatric pelvic fracture urethral injury: a reconstructive centre experience.

OBJECTIVE: To analyse our experience in pelvic fracture urethral injury (PFUI) in children and adolescents, with various anastomotic urethroplasties (AUs) used to accomplish tension-free anastomosis described and their surgical outcomes evaluated. PATIENTS AND METHODS: From 2008 to 2019, 192 cases including both primary and redo PFUI, which comprised 181 boys and 11 girls aged ≤18 years. The results are presented separately according to gender. Moreover, the two populations were divided in two age-related sub-groups for sensitivity analyses: Group 1 (children) aged ≤11 years and Group 2 (adolescent) aged 12-≤18 years. RESULTS: The median (interquartile range [IQR]) age at presentation in our series was 14 (9-17) years for boys and 9 (6-10) years for girls. Primary vs redo cases were 85 (47%) vs 96 (53%) in boys and 10/11 vs one of 11 in girls. In the primary male cases (85), the bulbo-membranous junction was the commonest site of injury (63, 74.1%). In boys, transperineal AU (TPAU) was performed in 160 (88.4%) and transpubic urethroplasty (TPU) in 17 (9.4%). In girls, TPU was utilised in nine cases, where two received meatoplasty and vaginal episiotomy. In boys, the overall success rate for TPAU was 81.2% and in primary PFUI cases success for TPAU was 88.3%. Overall success for TPU was 64.7%. In girls, the success rate for TPU was 100%. In boys and girls, the success rates for various AUs utilised between the child and adolescent groups were comparable. The median (IQR) hospital stay was 3 (3-4) days for boys and girls. The median (IQR) follow-up duration was 25 (16-33) months and 20 (17-27) months for boys and girls, respectively. Secondary procedures were performed in 39 boys and one girl, which comprised laser optical internal urethrotomy in 26 (14.4%) boys and redo surgery in 13 (7.2%) boys and one (9.1%) girl. Of all patients, four of the 11 girls and 74 boys (38.5%) were lost to follow-up. CONCLUSIONS: Most paediatric PFUI can be addressed via a transperineal approach with reasonable long-term outcomes. In challenging cases salvage procedures utilising vascular-based flaps as a urethral substitute give satisfactory results. Even young children can be managed with a high success rate in expert hands and these injuries should be addressed by specialist reconstructive urologists.

Fertility and sexuality issues in congenital lifelong urology patients: male aspects.

PURPOSE: To review existing literature about fertility and sexuality of boys born with complex congenital genitourinary anomalies. METHODS: A Pubmed review was performed in December 2018 to identify the most relevant original manuscripts regarding male complex congenital conditions affecting the urogenital system in male patients including spina bifida (SB), bladder exstrophy-epispadias complex (BEEC) and hypospadias. A comprehensive review was drafted exploring sexual dysfunction from a medical, psychosexual, surgical and reproductive point of view during transition from childhood (or adolescence) to adulthood. RESULTS: About 75% of men with SB have erectile dysfunction (ED) (Gamé et al. in Urology 67(3):566-570, 2006; Diamond et al. in 58(4):434-435, 1986). Most SB patients have impaired sexual development mainly due to diminished self-esteem, dependence on caregivers and lack of privacy (Blum et al. in Pediatrics 88(2):280-285, 1991). Men with BEEC have fewer intimate relationships than women because of the greater difficulties with issues regarding their genitalia and sexual activities (Deans et al. in Am J Obstet Gynecol 206(6):496.e1-496.e6, 2012). However, a good quality of life is achievable with the effective use of coping strategies (Deng et al. in Transl Androl Urol 7:941, 2018; Rikken et al. in BMC Womens Health 18(1):163, 2018; Friedler et al. in Reprod Biomed Online 32(1):54-61, 2016). Chordee occurs in 25% of all hypospadias patients. More severe hypospadias is related to a greater risk for complications. The long-term sexual quality of life (QoL) in men who underwent hypospadias surgery is influenced by a lot of factors. Therefore, an interactive and dynamic biopsychosocial model of sexual QoL was proposed. CONCLUSIONS: The care of patients with congenital urologic conditions becomes a challenge especially in the period of 'transition'. The goal of follow-up is a holistic management viewed from a medical, psychosexual, surgical end reproductive point. All patients should be asked for specific urinary, fecal or sexual concerns.

Management of pelvic fracture urethral injuries in the developing world.

INTRODUCTION: Pelvic fracture causes urethral injury in about 10% of patients. The etiology of injury is different in developing and developed world. While high-velocity automobile accidents are common in developed countries, where patients are in the car and there is usually a side impact, in the developing world, significant number of injuries are caused by two-wheeler accidents, pedestrians, farming accidents, fall from height, fall from tractor, fall from tree, and other causes like earthquake. We share our experience which is the largest in the reported literature. MATERIALS AND METHODS: In our tertiary referral center, we get referrals from all across the globe. Since 1995 till 2018 we have performed 1307 surgeries for Pelvic fracture urethral injury. Our referrals are for complex urethroplasty. Our data from 1995-2018 was analyzed. Data after June 2018 was not included so as to have a minimum follow up of 6 months. RESULTS: 1296 patients were males and 11 were females. In the group of 1296 males, mean age was 32.4 years (range 1-79 years). The minimum follow-up was 6 months, and the median follow-up was 56.7 months (range 6.2-233.7). The overall success rate was 88.79% for primary cases while re-do urethroplasty patients had a success rate of 83.70%. The majority of our patients (more than 61.40%) needed inferior pubectomy: Of the total 1307 cases of urethroplasty for pelvic fracture urethral injury data was available for 1042 patients. Data were available for 1042 patients. The data from 2012 onwards were prospectively analyzed while the previous data were retrospectively analyzed. CONCLUSION: PFUI are common in the developing world. They tend to be more complex and have longer gaps as compared to developed world. This could be related to the anthropometric differences between races as well as nature of injury. They are best managed with delayed transperineal repair with excellent outcomes. Ancillary maneuvers are more frequently required. Re-do urethroplasty can achieve good results.

RE Re Do urethroplasty after multiple failed surgeries of pelvic fracture urethral injury.

INTRODUCTION: We quantify surgical success rate in the management of pelvic fracture urethral injury (PFUI) with repeat urethroplasty in the setting of two or more failed prior urethroplasties. MATERIALS AND MATERIALS: A retrospective analysis was completed of a single surgeon urethroplasty database from Jan 1, 2012 to June 31, 2018. Patients with a history of PFUI recurrent urethral stricture despite two or more failed prior urethroplasty procedures were included. RESULTS: We identified 87 patients that had two more more failed prior urethroplasties. These had 2 main categories. One requiring anastomotic urethroplasty and other requiring substitution urethroplasty. Total success rate was 74.75% for anastomotic group and 84.61% for substitution group with a median follow-up of 34 months (range 6-60). Overall success rate for re redo Urethroplasty was 82.70%. Bulbar urethral ischemic necrosis was identified in 14 of 64 patients (21.9%). In these cases urethral substitution measures were performed including 12 with preputial flap and tubularization, 1 sigmoid colon substitution, medial thigh flap. No significant difference was observed between the success or failure group with respect to age, BMI, stricture length, number of prior urethroplasty procedure or endoscopic procedures or comorbidities. CONCLUSIONS: Our findings demonstrate that high success rates can be achieved for repeat urethroplasty in recurrent PFUI urethral stricture after two or more failed prior urethroplasty procedures. Bulbar urethral ischemic necrosis is a common finding in this patient population. Patients should be managed at a tertiary high volume referral center.

Penile urethroplasty using Orandi's dorsal skin flap: a new technique.

OBJECTIVES: To describe, step by step, a new one-stage dorsal skin flap urethroplasty for penile stricture repair. MATERIALS AND METHODS: The surgery was accomplished through a midline incision on the ventral penile surface, the urethra was fully dissected from the corpora cavernosa and longitudinally opened along its dorsal surface. A penile skin island, based on the dartos fascia flap, was dissected and moved over the corpora cavernosa, and the urethra was moved and sutured over the penile skin flap. RESULTS: Out of the 12 cases, 10 were classified successful and there were two failures. The operating time was 60 min. There was no postoperative fistula or urethral diverticulum. CONCLUSION: Our modified Orandi's technique was easy and feasible, and avoided fistula and diverticulum formation after repair.

Management of post TURP strictures.

INTRODUCTION: Urethral stricture is a well-known complication after transurethral surgeries. The incidence of urethral stricture after transurethral resection of prostate (TURP) varies between 2.2 and 9.8%. Most of the cases present within 6 months of transurethral surgery. Presentation is likely with poor flow, urinary tract infection or acute retention. MATERIALS AND METHODS: A prospective study was undertaken from January 2010-June 2017 for the management of post TURP stricture. A total of 170 patients with stricture urethra due to TURP were studied. RESULTS: The age of patients was 54-87 years (mean age 67.34). The mean preop Qmax was 6.1 ml (range 0-15). The length of stricture varied from very short in the proximal bulbar to pan urethral stricture. Out of 170, 94 were treated with dorsal approach, 71 with ventral approach and 5 with simultaneous distal dorsal, proximal ventral approach. Five patients underwent endoscopic procedure. Mean BMG length was 6.25 cm (4-8) and width was 1.5 cm (1.3-1.8). Overall success rate was 82.43%. CONCLUSION: Urethral stricture is a well-known complication after transurethral surgeries. Post TURP can cause stricture at any part urethra. BMG mucosa Urethroplasty is the safe, feasible and offer long-term success in these patient and should be strongly considered over CIC and VIU. Ventral approach is best suited for proximal bulbar strictures close to membranous urethra. This is a continence preserving surgery.

Repair of sphincter urethral strictures preserving urinary continence: surgical technique and outcomes.

INTRODUCTION: Repair of post-TURP sphincter urethral strictures represents challenging problem, due to the risk of urinary incontinence after the repair. We described a surgical technique we use to repair these strictures preserving urinary continence in patients with incompetent bladder neck. MATERIALS AND METHODS: An observational, retrospective, study was conducted to include patients with post-TURP urethral strictures in the area of distal sphincter. We included only patients with complete clinical data and follow-up who previously underwent TURP or HOLEP or TUIP, and subsequently developed proximal bulbar urethral strictures close to the membranous urethra and the related distal urethral sphincter. Patients were included, if they were fully continent after TURP or other procedures to treat BPH. The primary outcome of the study was treatment failure, defined as the need for any post-operative instrumentation. Secondary outcome was post-urethroplasty urinary continence. Patients showing stricture recurrence or post-operative incontinence were classified as failure. RESULTS: Overall, 69 patients were included in the study. Median patient's age was 67 years; median stricture length was 4 cm. Thirty-tree patients (47.8%) underwent previous urethrotomy. Median follow-up was 52 months. Out of 69 patients, 55 (79.7%) were classified as success and 14 (20.3%) as failure. Out of the whole cohort, thus, 11/69 (16%) have a risk of recurrent strictures and 3/69 (4.3%) have incontinence. CONCLUSIONS: The use of modified ventral onlay graft urethroplasty, using particular non-aggressive steps, is a suitable surgical technique for repair of sphincter urethral stricture in patients who underwent BPH transurethral surgery, using different procedures (TURP, HOLEP, TUIP).

Cardiovascular safety of oral semaglutide in patients with type 2 diabetes: Rationale, design and patient baseline characteristics for the PIONEER 6 trial.

AIMS: To assess the cardiovascular (CV) safety of oral semaglutide, the first tablet formulation of a glucagon-like peptide-1 receptor agonist. MATERIALS AND METHODS: PIONEER 6 is a multinational, randomized, placebo-controlled, double-blind trial in patients with type 2 diabetes at high risk of CV events (defined as being aged ≥50 years and having established CV disease [CVD] or moderate [stage 3] chronic kidney disease [CKD], or being aged ≥60 years with ≥1 other CV risk factor). Patients were randomized to once-daily oral semaglutide (up to 14 mg) or placebo added to standard of care. The primary composite endpoint is time to first occurrence of CV death or non-fatal myocardial infarction or non-fatal stroke. The primary hypothesis was to exclude an excess in CV risk with oral semaglutide by assessing non-inferiority versus placebo for the primary endpoint (non-inferiority margin of 1.8 for the upper boundary of the 95% confidence interval of the hazard ratio). PIONEER 6 is event-driven, with follow-up continuing until accrual of at least 122 primary outcome events. There is no pre-defined minimal duration. RESULTS: Overall, 3183 patients have been enrolled (mean age 66.1 years, 31.6% females) in 214 sites across 21 countries. At baseline, the mean duration of diabetes was 14.9 years, mean glycated haemoglobin concentration was 66 mmol/mol (8.2%), and 84.6% of patients had established CVD/moderate CKD. CONCLUSIONS: PIONEER 6 will provide evidence regarding the CV safety of oral semaglutide in patients with type 2 diabetes and high CV risk.

Three-Dimensional Computerized Model Based on the Sonourethrogram: A Novel Technique to Evaluate Anterior Urethral Stricture.

PURPOSE: The sonourethrogram is a useful alternative to the traditional retrograde urethrogram to evaluate anterior urethral strictures. With the development of 3-dimensional reconstructive techniques 3-dimensional urethral imaging can provide more accurate and useful information to enable the surgeon to make the best surgical decisions. We evaluated the accuracy and efficacy of a 3-dimensional reconstructed digital model of the urethra based on the sonourethrogram to assess anterior urethral disease. MATERIALS AND METHODS: A total of 50 patients with an anterior urethral stricture and 10 healthy volunteers were enrolled in this study from April 2014 to January 2017. All patients and volunteers underwent sonourethrogram and retrograde urethrogram. Three-dimensional urethral models were reconstructed based on the sonourethrogram. Stricture length and location on retrograde urethrogram or sonourethrogram based images were compared with those found at operation. RESULTS: The 3-dimensional digital model revealed the entire anterior urethra, including the navicular fossa, and the penile and bulbar parts. The semitransparent model clearly demonstrated the structure of the corpus spongiosum and inside the urethral lumen. Further information on spongiofibrosis could also be seen in the 3-dimensional digital model. There was no significant difference in stricture length or location in the 3-dimensional model compared with retrograde urethrogram imaging and actual surgical findings. However, the latest technique could only reconstruct the short segment of the anterior urethra due to the probe width limitation. CONCLUSIONS: The 3-dimensional computerized model based on the sonourethrogram is a novel and effective technique of evaluating anterior urethral strictures.

Plastic Scintillator-Based Microfluidic Devices for Miniaturized Detection of Positron Emission Tomography Radiopharmaceuticals.

A miniaturized radio-HPLC detector has been developed comprising a microfluidic device fabricated from plastic scintillator in combination with a silicon photomultiplier light sensor, and tested with samples containing a positron-emitting radionuclide, [18 F]fluoride. This cost-effective, small footprint analytical tool is ideal for incorporation into integrated quality control systems for the testing of positron emission tomography (PET) radiopharmaceuticals to good manufacturing practice (GMP) standards.

Determination of permeability, plasma protein binding, blood partitioning, pharmacokinetics and tissue distribution of Withanolide A in rats: A neuroprotective steroidal lactone.

Preclinical Research & Development Withanolide A (WA), a steroidal lactone is a major bioactive constituent of Withania somnifera (L.) with remarkable neuropharmacological activity. In this study, we investigated the permeability, plasma protein binding (PPB), blood partitioning, intravenous (i.v.), and oral pharmacokinetics as well as i.v. tissue distribution (TD) of pure WA in a rat model. The PPB, RBCs partitioning, and permeability of WA were determined by Ultra Performance Liquid Chromatography (UPLC) method. However, the pharmacokinetics and TD of WA were evaluated by validated and sensitive liquid chromatography coupled mass spectrometry (LC-ESI-MS/MS) method. The PPB and permeability of WA were determined by equilibrium dialysis and parallel artificial membrane permeability assay method, respectively. The results demonstrated that WA has high PPB and passive permeability. Furthermore, WA was found to have fast equilibration between RBCs and plasma. Following i.v. (2 mg/kg) and per-oral (25 mg/kg) administration of WA, the max concentration (Cmax ) in plasma was found as 85.53 ± 6.54 and 48.04 ±5.78 ng/mL, respectively. The TD study results indicated that WA has a rapid and wide TD. The maximum concentration in various tissues was found in following order: Clung > Cliver > Ckidney ≈ Cspleen > Cheart > Cbrain . The preclinical in vitro, as well as pharmacokinetics and TD results, are anticipated to support the future preclinical and clinical application of WA.

Sonographic Measurement of Optic Nerve Sheath Diameter: How Steep is the Learning Curve for a Novice Operator?

BACKGROUND: Transbulbar sonography for measuring optic nerve sheath diameter (ONSD) is noninvasive bedside technique for detection of raised intracranial pressure. This study aims to evaluate the number of sonographic evaluations required for a novice operator to learn proper measurement of ONSD after a formal training and supervised scanning session. METHODS: Three novice operators and one expert operator measured ONSD of 27 healthy volunteers using linear array transducer HFL38x (frequency range of 6-13 MHz) (MicroMaxx®; SonoSite, USA). In each eye, ONSD was measured three times by each observer and mean value was determined. Correlation coefficient was calculated between the novice and the experienced operator and in between the novice operators. Number of scans, after which the significant correlation developed between novice and the experienced operator and between the novice operators, was analyzed. RESULTS: Cronbach's alpha was tested to evaluate the reliability of the values obtained from intra- and interobservations. For all 27 cases, the value of Cronbach's alpha was high: 0.80-0.99 for the right eye and 0.69-0.97 for the left eye. The mean interobserver variations were plotted on a graph which fluctuated largely in the first 17 cases but oscillated around 0.5-0.30 in the last 10 cases. CONCLUSION: Learning curve for novice operators to measure ONSD is steep and they can be taught to measure ONSD in healthy volunteers by sonography in supervised clinical session with an acceptable clinical precision and accuracy comparable to an experienced operator.