Delayed repair of pelvic fracture urethral injuries: Preoperative decision-making.

Pelvic fracture urethral injuries comprise one of the most challenging reconstructive procedures in urology. The obliterated or stenosed urethra can usually be effectively repaired by an end-to-end anastomosis (bulbomembranous anastomosis). To achieve this, a progression of surgical steps can be used to make a tension-free anastomosis. Before undertaking surgery it is important to comprehensively assess the patient to define their anatomical defects, in particular the site of the stenosis, the length of the distraction injury and the integrity of the bladder neck, and thus guide preoperative decision-making. Contemporary reports suggest that most pelvic fracture urethral distraction defects (PFUDD) can be adequately managed by a perineal approach. Nevertheless it is essential that all surgeons treating these injuries are familiar with the whole spectrum of operative steps that are necessary to repair PFUDD

Efficacy and safety of upadacitinib for active ankylosing spondylitis refractory to biological therapy: a double-blind, randomised, placebo-controlled phase 3 trial

Objectives: To evaluate the efficacy and safety of upadacitinib, a Janus kinase inhibitor, in patients with active ankylosing spondylitis (AS) with an inadequate response (IR) to biological disease-modifying antirheumatic drugs (bDMARDs). Methods: Adults with active AS who met modified New York criteria and had an IR to one or two bDMARDs (tumour necrosis factor or interleukin-17 inhibitors) were randomised 1:1 to oral upadacitinib 15 mg once daily or placebo. The primary endpoint was Assessment of SpondyloArthritis international Society 40 (ASAS40) response at week 14. Sequentially tested secondary endpoints included Ankylosing Spondylitis Disease Activity score, Spondyloarthritis Research Consortium of Canada MRI spine inflammation score, total back pain, nocturnal back pain, Bath Ankylosing Spondylitis Functional Index, Bath Ankylosing Spondylitis Metrology Index and Maastricht Ankylosing Spondylitis Enthesitis Score. Results are reported from the 14-week double-blind treatment period. Results: A total of 420 patients with active AS were randomised (upadacitinib 15 mg, n=211; placebo, n=209). Significantly more patients achieved the primary endpoint of ASAS40 at week 14 with upadacitinib vs placebo (45% vs 18%; p<0.0001). Statistically significant improvements were observed with upadacitinib vs placebo for all multiplicity-controlled secondary endpoints (p<0.0001). Adverse events were reported for 41% of upadacitinib-treated and 37% of placebo-treated patients through week 14. No events of malignancy, major adverse cardiovascular events, venous thromboembolism or deaths were reported with upadacitinib. Conclusion: Upadacitinib 15 mg was significantly more effective than placebo over 14 weeks of treatment in bDMARD-IR patients with active AS. No new safety risks were identified with upadacitinib.</p

Tissue-engineered buccal mucosa urethroplasty - Clinical outcomes

INTRODUCTION Whilst buccal mucosa is the most versatile tissue for urethral replacement, the quest continues for an ideal tissue replacement for the urethra when substantial tissue transfer is needed. Previously we described the development of autologous tissue-engineered buccal mucosa (TEBM). Here we report clinical outcomes of the first human series of its use in substitution urethroplasty. METHODOLOGY: Five patients with urethral stricture secondary to lichen sclerosus (LS) awaiting substantial substitution urethroplasty elected to undergo urethroplasty using TEBM, with full ethics committee support. Buccal mucosa biopsies (0.5 cm) were obtained from each patient. Keratinocytes and fibroblasts were isolated and cultured, seeded onto sterilised donor de-epidermised dermis, and maintained at air-liquid interface for 7-10 d to obtain full-thickness grafts. These grafts were used for urethroplasty in a one-stage (n=2) or a two-stage procedure (n=3). Follow-up was performed at 2 and 6 wk, at 3, 6, 9, and 12 mo, and every 6 mo thereafter. RESULTS: Follow-up ranged from 32 to 37 mo (mean, 33.6). The initial graft take was 100%, as assessed by visual inspection. Subsequently, one patient had complete excision of the grafted urethra and one required partial graft excision, for fibrosis and hyperproliferation of tissue, respectively. Three patients have a patent urethra with the TEBM graft in situ, although all three required some form of instrumentation. CONCLUSIONS: Whilst TEBM may in the future offer a clinically useful autologous urethral replacement tissue, in this group of patients with LS urethral strictures, it was not without complications, namely fibrosis and contraction in two of five patients

Baseline Results from Proof – A 5-Year Observational Study of Long-Term Disease Outcome in Axial Spondyloarthritis

Background Axial spondyloarthritis (axSpA), encompassing ankylosing spondylitis (AS) and non-radiographic axSpA (nr-axSpA) without advanced structural lesions in the sacroiliac joints (SIJ), is a relatively new disease concept. The natural disease course of axSpA, including progression of structural damage over time, has not yet been systematically studied in large patient (pt) groups. Objectives To report the baseline data of PROOF, a large study currently being conducted in 29 countries across the world, evaluating long-term outcomes in pts with axSpA classified by ASAS criteria. Methods PROOF is a multi-country prospective observational study evaluating axSpA pts in rheumatology clinical practice over 5 years. Pts with axSpA fulfilling ASAS classification criteria were eligible, if diagnosed ≤12 months prior to study enrolment. Investigator's confidence with the diagnosis of axSpA is ascertained on a numeric rating scale (NRS 0–10) at enrolment and end of follow-up. Assessments of disease activity (BASDAI, ASDAS-CRP), physical function (BASFI), quality of life (SF-12v2), productivity (WPAI-SHP), and pelvic X-ray are scheduled at yearly follow-up visits. X-rays are graded according to NY criteria by local and central readers. Results 2084 pts with axSpA fulfilling ASAS criteria have been enrolled in PROOF study, 1259 pts with AS (60%) and 825 pts with nr-axSpA (40%) according to the investigators. The level of confidence with the diagnosis of axSpA was 8.7±1.8. The imaging criterion was fulfilled by 85% of pts (40% MRI, 51% X-ray, 9% both), 15% of pts were classified through the clinical arm. HLA-B27 was tested in 85% of pts and found to be positive in 68% of cases (70% with AS and 60% with nr-axSpA). Overall, pts were in their mid-thirties, had a long delay in referral to rheumatologist and recently diagnosed axSpA. Comparison of demographic and clinical characteristics between pts with AS and nr-axSpA is shown in Table 1. Pelvic x-rays were reportedly done in 1635 (78%) pts within 6 months of the baseline visit; to date both local and central readers have scored x-rays of 1344 pts (82% of available). Of the 1344 pts, 83.3% retained their classification (AS or nr-axSpA) after the central reading, while 16.7% were classified differently. Based on the kappa value, there was a substantial agreement on the grading of x-rays between the local and central readers: kappa=0.63 (95% CI, 0.59–0.68).Sin financiación12.811 JCR (2016) Q1,1/30 RheumatologyUE

Comparison of three methods for calculating the Bath Ankylosing Spondylitis Metrology Index in a randomized placebo-controlled study

Pathophysiology and treatment of rheumatic disease