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Objectives Patients with urethral stricture due to any type of trauma, hypospadias or gender dysphoria suffer immensely from impaired capacity to urinate and are in need of a new functional urethra. Tissue engineering with decellularization of a donated organ recellularized with cells from the recipient patient has emerged as a promising alternative of advanced therapy medicinal products. The aim of this pilot study was to develop an ovine model of urethral transplantation and to produce an individualized urethra graft to show proof of function in vivo. Methods Donated urethras from ram abattoir waste were decellularized and further recellularized with autologous buccal mucosa epithelial cells excised from the recipient ram and expanded in vitro. The individualized urethral grafts were implanted by reconstructive surgery in rams replacing 2.5 ± 0.5 cm of the native penile urethra. Results After surgery optimization, three ram had the tissue engineered urethra implanted for one month and two out of three showed a partially regenerated epithelium. Conclusions Further adjustments of the model are needed to achieve a satisfactory proof-of-concept; however, we interpret these findings as a proof of principle and a possible path to develop a functional tissue engineered urethral graft with de- and recellularization and regeneration in vivo after transplantation.

Background Open surgical treatment of short bulbar urethral strictures (urethroplasty) is commonly performed as transecting excision and primary anastomosis (tEPA) or buccal mucosa grafting (BMG). Erectile dysfunction and penile complications have been reported, but there is an absence of randomised trials. Objective To evaluate sexual dysfunction and penile complications after urethroplasty with tEPA versus BMG. Design, setting, and participants Centres in Finland, Sweden and Norway participated. Patients with a bulbar urethral stricture of ≤2 cm without previous urethroplasty were randomised. The primary endpoints were the degree of erectile dysfunction and penile complications. Follow-up was 12 mo. Intervention Patients were randomised to either tEPA or BMG urethroplasty. Outcome measurements and statistical analysis Sexual dysfunction was measured using the International Index of Erectile Function, 5-item version (IIEF-5) and a penile complications questionnaire (PCQ) designed for this study. Continuous data were analysed using analysis of covariance and categorical data were compared using a χ2 test. Results and limitations A total of 151 patients were randomised to either tEPA (n = 75) or BMG (n = 76). The tEPA group reported more penile complications (p = 0.02), especially reduced glans filling (p = 0.03) and a shortened penis (p = 0.001). There were no differences in postoperative IIEF-5 total scores. Recurrence rates were similar in both groups (12.9%) but the study was not designed to detect differences in recurrence rates. The PCQ is not validated, which is a limitation. Conclusions More patients reported penile complications after urethroplasty with tEPA than with BMG. This should be considered when choosing the operative method, and patients should be informed accordingly. Patient summary This study compared two common operations for repair of narrowing of the male urethra. Neither of the two methods seems to cause worsened erections. However, penile problems are more common after the transection technique than after the grafting technique.

INTRODUCTION AND OBJECTIVE:The most common methods of bulbar urethral stricture surgery are resection and primary anastomosis or augmentation with onlay buccal mucosal graft. The effects on sexual ...

The aim of this study was to assess whether sclerosis in histology following bulbar urethroplasty is a predictive factor for failure of surgery.Resected stricture specimens from 45 patients undergoing open urethroplasty with excision and anastomosis were collected prospectively during 2011-2014. Histopathological characteristics, including fibrosis (grade I-III), inflammation and sclerosis, were evaluated using different routine staining. These specimens were compared to normal urethral resection specimens from patients undergoing sex-correction surgery. The uropathologist who conducted the analyses was blinded to the study design.The outcomes of the histological classifications were as follows: 19 patients had grade I fibrosis, of whom three had failures; 13 patients had grade II fibrosis, without any failures; and the most severe fibrosis, grade III, including sclerosis, was found in 13 patients (11 with sclerosis), with failure in eight. Sclerosis was a significant risk factor for restricture when comparing patients with sclerosis and those without sclerosis, and likewise when adjusting for age, inflammation and stricture length.Histological findings of sclerosis in the resected urethral stricture specimen indicate a significantly higher risk for restricture after urethroplasty surgery.

Even though more than 30 years have passed since the eradication of smallpox, high titers of smallpox-specific antibodies are still detected in the blood of subjects vaccinated in childhood. In fact, smallpox-specific antibody levels are maintained in serum for more than 70 years. The generation of life-long immunity against infectious diseases such as smallpox and measles has been thoroughly documented. Although the mechanisms behind high persisting antibody titers in the absence of the causative agent are still unclear, long lived plasma cells (LLPCs) play an important role. Most of the current knowledge on LLPCs is based on experiments performed in mouse models, although the amount of data derived from human studies is increasing. As the results from mouse models are often directly extrapolated to humans, it is important to keep in mind that there are differences. These are not only the obvious such as the life span but there are also anatomical differences, for instance the adiposity of the bone marrow (BM) where LLPCs reside. Whether these differences have an effect on the function of the immune system, and in particular on LLPCs, are still unknown. In this review, we will briefly discuss current knowledge of LLPCs, comparing mice and humans.

The aim of this study was to evaluate outcomes and possible risk factors for failure of open urethroplasty due to penile urethral strictures.A retrospective chart review was undertaken of 90 patients with penile stricture undergoing 109 open urethroplasties between 2000 and 2011. In 80 urethroplasties, a one-stage procedure was performed: 68 of these had a pediculated penile skin flap, nine had a free buccal mucosal graft and three had a free skin graft. A two-stage procedure using buccal mucosa was performed in 29 urethroplasties. Failure was defined as when further urethral instrumentation was needed.The mean age in the one-stage and two-stage groups were 50 and 54 years, respectively. The success rates in the corresponding groups were 65% and 72%, with follow-up times of 63 and 40 months, respectively. Multivariable analyses disclosed body mass index (BMI) and previous urethral surgery to be significant risk factors for failure in the one-stage group. Failure over time significantly decreased during the study period.Both one- and two-stage penile urethroplasty demonstrated success rates in line with previous reports. Limited experience, high BMI and previous urethral surgery appear to be associated with less favourable outcome.

Urethroplasty is a procedure that has a high success rate. However, there exists a small subgroup of patients who require multiple procedures to achieve an acceptable result. This study analyses the outcomes of a series of patients with failed urethroplasty.This is a retrospective review of 82 failures out of 407 patients who underwent urethroplasty due to urethral stricture during the period 1999-2013. Failure was defined as the need for an additional surgical procedure. Of the failures, 26 patients had penile strictures and 56 had bulbar strictures. Meatal strictures were not included.The redo procedures included one or multiple direct vision internal urethrotomies, dilatations or new urethroplasties, all with a long follow-up time. The patients underwent one to seven redo surgeries (mean 2.4 procedures per patient). In the present series of patients, endourological procedures cured 34% (28/82) of the patients. Ten patients underwent multiple redo urethroplasties until a satisfactory outcome was achieved; the penile strictures were the most difficult to cure. In patients with bulbar strictures, excision with anastomosis and substitution urethroplasty were equally successful. Nevertheless, 18 patients were defined as treatment failures. Of these patients, nine ended up with clean intermittent self-dilatation as a final solution, five had perineal urethrostomy and four are awaiting a new reintervention. Complicated cases need centralized professional care.Despite the possibility of needing multiple reinterventions, the majority of patients undergoing urethroplasty have a good chance of successful treatment.

Urethral stricture is a common disease that is characterised by fibrotic tissue arising from inflammation after urethral injury. Urination is inhibited when there is total obstruction, and the suffering is immense. Following the paradigm shift in treatments, from internal urethrotomy to open urethroplasty surgery, different surgical techniques have emerged. The aims of this thesis were to assess the outcomes of different reconstructive surgical techniques, including redo surgery, and to analyse the histopathology of urethral stricture disease. All consecutive patients subjected to urethroplasty at Sahlgrenska University Hospital during the period 1999–2014 were identified and data were retrieved from their medical charts. Papers I-III were retrospective studies and Paper IV was prospective. All the patients were subjected to a follow-up regimen of 3, 12, and 24 months, and more if deemed necessary. If the patient was satisfied with his micturition after 2 years of follow-up, he was discharged from follow-up and instructed to come back if micturition problems should re-appear. Failure or restricture were in all the studies defined as the need for a new surgical intervention, such as dilatation, internal urethrotomy, or a redo urethroplasty. For bulbar strictures, treated with either transection with excision followed by anastomosis (EA) or using a graft as an onlay, Paper I reported success rates of 91% and 71%, respectively, with a low risk of sexual dysfunction. This indicates that EA is a feasible method for treating bulbar strictures. In Paper II, penile strictures were studied; they were treated with one- and two-stage substitution urethroplasty, (SU) with success rates of 65% and 72%, respectively. Limited clinical experience, obesity and previous urethral surgery emerged as predictors for less favourable outcome. In Paper III, 195 re-interventions performed for 82 failures out of 407 consecutive primary urethroplasties, were analysed. EA and SU were equally successful interventions for bulbar restrictures. Twenty percent of the patients were cured with one single direct vision internal urethrotomy. After one or up to seven re-interventions in each patient, 18 patients remained as failures at the study end-point date, yielding an overall success rate of 78%. The most complex cases involved redo surgery for penile restrictures, these complicated strictures probably need to be centralised at a specialised clinic, to ensure an optimal outcome. Paper IV the histological findings of the resected part of the urethral stricture were analysed. The fibrosis was classified into Grades I–III, where III involved sclerosis. The occurrence of severe fibrosis with sclerosis was a strong predictor of failure after EA surgery for bulbar strictures. In summary, transection and non-transection surgical procedures entail low rates of sexual dysfunction. Overall, bulbar strictures have a higher success rate than penile strictures, the latter being the most complex ones. Two-stage procedures, involving grafting of buccal mucosa, appear to be the most successful treatment for penile strictures. There are several risk factors associated with urethroplasty surgery. Redo surgery was a relatively rewarding treatment in this cohort, even though several re-interventions were needed to achieve a satisfactory outcome. Sclerosis is a risk factor for failure of urethroplasty in bulbar strictures. The establishment of a classification system for fibrosis pave the way for extended investigations into the origin how strictures develop on the cellular level, as well as novel therapeutic regimens.

Open urethroplasty is the preferred treatment for recurrent bulbar urethral stricture. However, there are still some controversies regarding the optimal technique and the consequences of transecting the urethra in terms of sexual dysfunction, such as erectile dysfunction, penile shortening, impaired glans filling, decreased glans sensibility and ejaculatory function. We performed a retrospective analysis with long-term followup of anastomotic and substitution onlay urethroplasty in bulbar strictures with an emphasis on postoperative sexual function.A total of 169 patients with bulbar stricture were treated with urethroplasty via the onlay technique (75) or resection followed by end-to-end anastomosis (94) during 1999 to 2009. Mean followup in the transection and onlay groups was 41 and 69 months, respectively (range 12 to 132). All patients were asked verbally about sexual function during followup. Failure was defined as the need for new surgical intervention.Erectile dysfunction developed in 1 patient (1%) per group. In the transection group 5 patients (5%), including 4 with longer and more distal strictures, had penile shortening/downward angulation. However, this did not interfere with sexual ability during intercourse. No patient reported impaired glans or ejaculatory function. The success rate in the transection and onlay groups was 91% and 71%, respectively.Transection with resection and end-to-end anastomosis is a good method for bulbar stricture with a low rate of sexual dysfunction and a high success rate postoperatively. To avoid penile angulation/shortening, it might be wise to use the onlay technique for longer and distal strictures.

Multi-Processor Systems on Chip (MPSoC) run multiple independent applications, often developed by different parties. The applications share the hardware resources, e.g. processors, memories and interconnect. The sharing typically causes interference between the applications, which severely complicates system integration and verification. Even if the applications are verified in isolation, the system designer must verify the combined behaviour, leading to an explosion in design complexity. Composable MPSoCs have no interference between applications, thus allowing independent design and verification. For an MPSoC to be composable, all the hardware resources must offer composability. A particularly challenging resource is the processors, often purchased as off-the-shelf intellectual property. In this work we present the design and implementation of CompOSe, a light-weight (only 1500 lines of code) composable operating system for MPSoCs. CompOSe uses fixed-size time slices, coupled with a composable scheduler, to enable composable processor sharing. Using instances of ARM7, ARM11 and the Xilinx MicroBlaze we experimentally demonstrate the ability to provide temporal composability, even in the presence of dynamic application behaviour and multiple use cases. We do so using a diverse set of processor architectures, without requiring any hardware modifications. We also show how CompOSe allows slack to be distributed within and between applications through a novel two-level scheduler and slack-distribution system.