Complications of Synthetic Midurethral Slings: Is There a Relevant Discrepancy Between Observational Data and Clinical Trials?

CONTEXT: The complications of synthetic midurethral slings (MUSs) in women with stress urinary incontinence (SUI) have become a globally debated issue. OBJECTIVE: To systematically review the short- and long-term complications of mesh slings reported in observational data compared with clinical trial data, to determine whether the complication rates from clinical trials reflects "real-world" observational data. EVIDENCE ACQUISITION: PubMed and Cochrane Library were searched. Methods as detailed in Preferred Reporting Items for Systematic Reviews and Meta-analyses and Cochrane Handbook for Systematic Reviews of Interventions were followed. EVIDENCE SYNTHESIS: Thirty registries/databases including 709 335 MUS procedures (1-22 yr of follow-up) were identified. MUS procedures were associated with intraoperative bladder perforation in 0.86-3.6%, urethral perforation in 0-0.1%, vascular injury in 0.04-0.1%, voiding lower urinary tract symptoms (LUTS) in 1.47-3.5%, vaginal exposure in 0.2-1.9%, and reoperation in up to 9% of cases. Forty-three randomised clinical trials were identified, including 6284 women who underwent MUS procedures and 2177 women who underwent other interventions (1-10 yr of follow-up). MUS procedures were associated with urinary tract perforation in 2.58%, vaginal injury in 1.43%, de novo voiding LUTS in 4.37%, de novo storage LUTS in 5.41%, mesh extrusion/exposure (vaginal/urinary tract) in 2.54%, dyspareunia in 2.26%, pain (pelvic/suprapubic/perineal) in 2.83%, and reoperation for complications required in 1.82% of cases. Meta-analyses of the randomised controlled trials revealed that retropubic MUSs were associated with more events of urinary tract perforation (risk ratio [RR] 9.81, 95% confidence interval [CI] 5.05-19.04, high certainty of evidence [COE]) and voiding LUTS (RR 1.57, 95% CI 1.19-2.07, high COE) than transobturator MUSs. MUSs were associated with more events of pain than mini-slings (RR 1.72, 95% CI 1.04-2.87, moderate COE). CONCLUSIONS: Short- and long-term data on complications of polypropylene mesh used for female SUI are fairly comparable when using outcome data from well-designed clinical trials or from less structured prospective or retrospective registries. Comparisons have to be made with caution since the two systems of data collection are inherently incomparable. This knowledge should be incorporated in the discussion on how to implement polypropylene mesh for female stress incontinence. PATIENT SUMMARY: In order to know whether mesh tapes used for treating stress incontinence work well and are safe, high-quality information is important. It appears that well-designed clinical studies give similar results to large registration databases. These data should be interpreted with caution in view of the different ways the information was collected. These results will help physicians and patients understand the risks of mesh tapes.

Tissue engineered buccal mucosa for urethroplasty: progress and future directions.

PURPOSE: Autologous buccal mucosa is commonly utilized in the surgical treatment of urethral strictures. Extensive strictures require a larger quantity of tissue, which may lead to donor site morbidity. This review assesses progress in producing tissue engineered buccal mucosa as an alternative graft material. RESULTS: Few clinical studies have introduced cells onto biological or synthetic scaffolds and implanted resulting constructs in patients. The available studies show that buccal mucosa cells on acellular human dermis or on collagen matrix lead to good acute stage tissue integration. Urothelial cells on a synthetic substrate also perform well. However while some patients do well many years post-grafting, others develop stricture recurrence. Acellular biomaterials used to treat long urethral defects in animals commonly lead to fibrosis. CONCLUSIONS: Tissue engineered buccal mucosa shows promise as a substitute for native tissue. The fibrosis which occurs months post-implantation may reflect the underlying disease process recurring in these patients.

Nocturia: current concepts and future perspectives.

Nocturia is a prevalent highly bothersome urinary symptom that may significantly detriment the health and well-being of sufferers. It is characterized by waking at night to void, each void preceded and followed by sleep, hence leading to fragmentation of sleep and day-time tiredness. This may result in reduced productivity in the workplace, which contributes to the significant burden to the wider society that nocturia incurs. Nocturia was traditionally viewed as one of the many urinary tract symptoms that occur due to lower urinary tract dysfunction. However, recently it has been recognized that due to its multi-factorial aetio-pathogenesis, nocturia should be viewed as distinct clinical condition in its own right. Careful assessment of the nocturic patient is essential so that treatment strategies are guided by the likely causes. Much research is currently being undertaken into the underlying causes and the optimal management approaches. This review will explore the contemporary status of research on nocturia with a focus on the current and newly available pharmacotherapies.

Regulation of SDF-1 (CXCL12) production by osteoblasts; a possible mechanism for stem cell homing.

Stromal derived factor-1 (SDF-1 or CXCL12) controls many aspects of stem cell function including trafficking and proliferation. Previously, it was demonstrated that DNA-damaging agents such as irradiation, cyclophosphamide or 5-fluorouracil increase the expression of SDF-1 by osteoblasts in murine marrow. Here, the production of SDF-1 by osteoblasts in vitro in response to cytokines known to be particularly important in bone physiology was examined using primary human osteoblasts (HOBs), mixed marrow stromal cells (BMSCs), and by, mouse, rat and human osteoblast-like cell lines. From these studies, it was determined that the expression of SDF-1 is an early feature of osteoblastic induction that may be modulated by IL-1beta, PDGF-BB, VEGF, TNF-alpha and PTH. Each of these factors increased SDF-1 synthesis, while TGF-beta1 decreased SDF-1 secretion. Of note, the biodistribution of SDF-1 in culture was equally distributed between the medium and detergent-soluble and -insoluble fractions of the cultures. Immunohistochemistry of developing bones demonstrated that SDF-1 was also a feature of early bone development first beginning in the perichondrium and moving into the marrow cavity of the developing bone analogue. As SDF-1 expression increases in response to PTH in vitro, animals were treated with an anabolic regime of PTH for 21 days. Under these conditions, significant increases in SDF-1 mRNA expression were observed near the growth plate and epiphysis regions of the long bones. Yet, in serum, immunodetectable SDF-1 levels were significantly reduced (24%) in the PTH-treated animals (Vehicle: 408 +/- 25 vs. PTH 308 +/- 20 SDF-1 pg/ml). Together, these data suggest a possible mechanism for localizing stem cells into a developing marrow where increased expression of SDF-1 in the local marrow environment along with decreased SDF-1 in the serum may create a homing gradient.

The effects of breed, neonatal age and pregnancy on the plasma copper status of goats in Oman.

There is a history of copper deficiency in grazing Omani livestock and the copper status of three economically important goat breeds, Jabal Akhdar (JA), Batina (B) and Dhofari (D) were therefore compared in October/November (cool season) and June (dry season) in a penned flock given a plentiful dietary supply of copper. In the cool season, 62 lactating does (5 JA, 12 B and 33 D), their 0-5-day-old kids (17 JA, 19 B and 22 D) and 25 dry does (17 JA, 5 B and 3 D) were blood sampled. In the dry season, the does sampled were either barren (15 JA, 16 B and 13 D) or pregnant (9 JA, 13 B and 33 D). The samples were analysed for total copper (TCu) and trichloroacetic acid (TCA)-soluble copper (TCA-sol Cu). There were no effects of breed on TCu or TCA-sol Cu in the cool season, the overall means being 0.75 (SE 0.049) and 0.59 (SE 0.052) mg/L. The mean TCu was low in kids at birth (0.59 mg/L) but had increased to 0.86 mg/L by 4 days of age (p < 0.001); breed differences were found (p < 0.002), the pooled values for JA, B and D being 0.77, 0.59 and 0.68 (SE 0.033-0.044) mg/L, respectively. By the dry season, the mean TCu had risen in barren does to 0.96 (0.045) mg/L but not in pregnant does (0.76 (0.047) mg/L: p < 0.002) and breed differences had emerged, the mean for D being 20% lower than those for JA and B (p < 0.05). The highest TCu values were found in the 7-month-old kids in June ( 1.17 (0.039) mg/L) but the breeds did not then differ. Some effects on TCA solubility were found but were considered unreliable. Breed effects may have been diminished by the generous supply of copper and early stage of lactation studied.