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    ABSTRACT: ● To validate the Bladder Control Self-Assessment Questionnaire (B-SAQ), a short screener to assess LUTS / OAB in men. ● Lower urinary tract symptoms (LUTS) and overactive bladder (OAB) are highly prevalent. Case finding tools such as the B-SAQ have been developed to raise awareness of LUTS, possible bladder problems and prompt people to seek treatment. ● Prospective, single centre study, urology outpatient setting. N=211. ● All patients completed the B-SAQ and Kings Health questionnaire (KHQ) prior to consultation, and the consulting urologist made an independent assessment of LUTS and need for treatment. ● Psychometric properties of the B-SAQ were analysed. ● 98% of respondents completed all items correctly in less than 5 min. ● Mean B-SAQ scores were 12 and 3.3, respectively for cases (n=101) and controls (n=108) (p<0.00001). ● Good correlation was evident between the B-SAQ and the KHQ. ● The agreement between the individual B-SAQ items and the KHQ symptom severity scale was 86%, 85%, 84% and 79% for frequency, urgency, nocturia and urinary incontinence. ● Using a B-SAQ symptom threshold of ≥ 4 alone had a sensitivity, specificity and positive predictive value of 75%, 86% and 84%, respectively, for detecting LUTS with an area under the curve of 0.88. However, in combination with a bother score threshold of ≥ 1 this changed to 92%, 46% and 86%. ● The B-SAQ is an easy and quick valid case finding tool for LUTS / OAB in men. ● The B-SAQ has the potential to raise awareness of LUTS. ● It appears to be less specific in men compared to women. ● Further validation in a community setting is required.
    BJU International 10/2013;
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    ABSTRACT: In systemic endotoxaemia, bacterial lipopolysaccharide causes the rapid expression of tissue factor (TF) and disseminated intravascular coagulation and in animal models, anticoagulants limit pathology and promote survival. Recent studies have emphasised the importance of TF expressed by mononuclear cells for initiating thrombin generation during endotoxaemia and suggested that endothelial cell TF is of little relevance. However, the precise importance of endothelium for intravascular thrombin generation has not been established. In this study, we compared the effect of equivalent levels of hirudin tethered to either endothelium or platelets and monocytes. CD31-Hir-Tg mice express a vesicle-targeted, membrane-tethered hirudin fusion protein on endothelium, platelets and monocytes. Bone marrow chimeras between these mice and C57BL/6 were generated The level of intravascular hirudin expressed during endotoxaemia was quantified by inhibition studies using an anti-hirudin antibody and reference to the circulating thrombin anti-thrombin complexes generated in control mice given soluble hirudin. Antibody inhibition studies indicated that individual chimeras expressed similar levels of hirudin fusion protein on endothelium alone as on platelets and leukocytes combined and accordingly, the levels of thrombin anti-thrombin complexes and fibrinogen in each chimera were similar, indicating equivalent inhibition of thrombin generation. However, mice with hirudin on endothelium alone developed significantly less thrombocytopenia. These results suggest a hitherto unrecognized role of endothelium in thrombin-dependent platelet sequestration during endotoxaemia. The data have implications for the development of therapeutic strategies based on targeted anticoagulation to limit disseminated intravascular coagulation.
    Thrombosis Research 10/2013;
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    ABSTRACT: Intracorporeal urinary diversion (ICUD) has the potential benefits of a smaller incision, reduced pain, decreased bowel exposure, and reduced risk of fluid imbalance. To compare the perioperative outcomes of patients undergoing extracorporeal urinary diversion (ECUD) and ICUD following robot-assisted radical cystectomy (RARC). We reviewed the database of the International Robotic Cystectomy Consortium (IRCC) (18 international centers), with 935 patients who had undergone RARC and pelvic lymph node dissection (PLND) between 2003 and 2011. All patients within the IRCC underwent RARC and PLND as indicated. The urinary diversion was performed either intracorporeally or extracorporeally. Demographic data, perioperative outcomes, and complications in patients undergoing ICUD or ECUD were compared. All patients had at least a 90-d follow-up. The Fisher exact test was used to summarize categorical variables and the Wilcoxon rank sum test or Kruskal-Wallis test for continuous variables. Of 935 patients who had RARC and PLND, 167 patients underwent ICUD (ileal conduit: 106; neobladder: 61), and 768 patients had an ECUD (ileal conduit: 570; neobladder: 198). Postoperative complications data were available for 817 patients, with a minimum follow-up of 90 d. There was no difference in age, gender, body mass index, American Society of Anesthesiologists grade, or rate of prior abdominal surgery between the groups. The operative time was equivalent (414min), with the median hospital stay being marginally longer for the ICUD group (9 d vs 8 d, p=0.086). No difference in the reoperation rates at 30 d was noted between the groups. The 90-d complication rate was not significant between the two groups, but a trend favoring ICUD over ECUD was noted (41% vs 49%, p=0.05). Gastrointestinal complications were significantly lower in the ICUD group (p ≤ 0.001). Patients with ICUD were at a lower risk of experiencing a postoperative complication at 90 d (32%) (odds ratio: 0.68; 95% confidence interval, 0.50-0.94; p=0.02). Being a retrospective study was the main limitation. Robot-assisted ICUD can be accomplished safely, with comparable outcomes to open urinary diversion. In this cohort, patients undergoing ICUD had a relatively lower risk of complications.
    European Urology 10/2013;
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    ABSTRACT: Botulinum toxin injections into the bladder have become established in the management of refractory detrusor overactivity and overactive bladder. Mechanism of action of the toxin appears to involve both efferent and afferent nerve pathways, as well as having an antinociceptive effect. Over the years, several reports of its use in refractory bladder pain syndrome and interstitial cystitis have emerged. We review the literature with a view to assessing efficacy and adverse events in this setting. Small open-labelled studies have suggested botulinum neurotoxin serotype A (BoNT-A) to be an effective treatment for the majority of patients with refractory bladder pain syndrome/interstitial cystitis. A single set of injections result in demonstrable improvements in symptom scores and bladder pain, although some studies suggest repeated injections may be better. BoNT-A is more effective in nonulcer-type patients. In chronic pelvic pain syndrome, a recent placebo-controlled trial showed only a modest benefit for BoNT-A over placebo with a response rate of 30%. Although botulinum neurotoxin for refractory bladder pain syndrome/interstitial cystitis appears promising, larger-scale studies with adequate follow-up and in particular randomized placebo-controlled studies are required to confirm these findings.
    Current opinion in urology 09/2013;
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    ABSTRACT: Objectives To describe how learning curves are measured and what procedural variables are used to establish a ‘learning curve’ (LC). To assess whether LCs are a valuable measure of competency. Patients and Methods A review of the surgical literature pertaining to LCs was conducted using the Medline and OVID databases. Results Variables should be fully defined and when possible, patient-specific variables should be used. Trainee's prior experience and level of supervision should be quantified; the case mix and complexity should ideally be constant. Logistic regression may be used to control for confounding variables. Ideally, a learning plateau should reach a predefined/expert-derived competency level, which should be fully defined. When the group splitting method is used, smaller cohorts should be used in order to narrow the range of the LC. Simulation technology and competence-based objective assessments may be used in training and assessment in LC studies. Conclusions Measuring the surgical LC has potential benefits for patient safety and surgical education. However, standardisation in the methods and variables used to measure LCs is required. Confounding variables, such as participant's prior experience, case mix, difficulty of procedures and level of supervision, should be controlled. Competency and expert performance should be fully defined
    BJU International 07/2013;
  • BJU International 07/2013; 112(1):9-10.
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    ABSTRACT: Complement receptors are expressed on cells of the innate and the adaptive immune system. They play important roles in pathogen and danger sensing as they translate the information gathered by complement fluid phase sensors into cellular responses. Further, they control complement activation on viable and apoptotic host cells, clearance of immune complexes and mediate opsonophagocytosis. More recently, evidence has accumulated that complement receptors form a complex network with other innate receptors systems such as the Toll-like receptors, the Notch signaling system, IgG Fc receptors and C-type lectin receptors contributing to the benefit and burden of innate and adaptive immune responses in autoimmune and allergic diseases as well as in cancer and transplantation. Here, we will discuss recent developments and emerging concepts of complement receptor activation and regulation with a particular focus on the differentiation, maintenance and contraction of effector and regulatory T cells.
    Molecular Immunology 06/2013;
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    ABSTRACT: ● To determine the number of cases a urological surgeon must complete to achieve proficiency for different urological procedures. ● The MEDLINE(®) , EMBASE(TM) and PsycINFO(®) databases were systematically searched until December 2011. ● Studies pertaining to learning curves of urological procedures were included. ● Two reviewers independently identified potentially relevant articles. ● Procedure name, statistical analysis, number of participants, procedure setting, level of participants, outcomes and learning curves were analysed. ● Forty-nine studies described the learning curve (LC) for different urological procedures. ● The LC for open radical prostatectomy (ORP) ranged from 250 - 1000 cases and laparoscopic radical prostatectomy (LRP) from 200-750 cases. ● The LC for robot assisted laparoscopic prostatectomy (RALP) has been reported to be 40 procedures as a minimum number. ● Robot assisted radical cystectomy has a documented LC of 16-30 cases, depending on which outcome variable is measured. ● Irrespective of prior laparoscopic experience, there is a significant reduction in operative time (p 0.008), blood loss (p 0.008) and complication rates (p=0.042) after 100 RALP's. ● The available literature can act as a guide for LC's of trainee urologists. Although the LC may vary amongst individual surgeons, a consensus should exist for minimal number of cases to achieve proficiency. ● The complexities associated with defining procedural competence are vast. ● The majority of learning curve trials have focussed on the latest surgical techniques with paucity in data pertaining to basic urological procedures.
    BJU International 06/2013;
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    ABSTRACT: CD4(+) CD25(+) Foxp3(+) T regulatory (Treg) cells maintain immunological tolerance. In this study the possibility that Treg cells control immune responses via the production of secreted membrane vesicles, such as exosomes, was investigated. Exosomes are released by many cell types, including T cells, and have regulatory functions. Indeed, TCR activation of both freshly isolated Treg cells and an antigen-specific Treg-cell line resulted in the production of exosomes as defined morphologically by electron microscopy (EM) and by the presence of tetraspanin molecules LAMP-1/CD63 and CD81. Expression of the ecto-5-nucleotide enzyme CD73 by Treg cells has been shown to contribute to their suppressive function by converting extracellular AMP to adenosine, which, following interaction with adenosine receptors expressed on target cells, leads to immune modulation. CD73 was evident on Treg-cell-derived exosomes, accordingly when these exosomes were incubated in the presence of AMP production of adenosine was observed. Most importantly, CD73 present on Treg-cell-derived exosomes was essential for their suppressive function hitherto exosomes derived from a CD73-negative CD4(+) T-cell line did not have such capabilities. Overall our findings demonstrate that CD73-expressing exosomes produced by Treg cells following activation contribute to their suppressive activity through the production of adenosine. This article is protected by copyright. All rights reserved.
    European Journal of Immunology 06/2013;
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    ABSTRACT: OBJECTIVES: To identify and assess potential hazards in robot-assisted urological surgery. To develop a comprehensive checklist to be used in operating theatres with robotic technology. METHODS: Healthcare Failure Mode and Effects Analysis (HFMEA), a risk assessment tool, was used in a urology operating theatre with innovative robotic technology in a UK teaching hospital between June and December 2011. A 15-member multidisciplinary team identified 'failure modes' through process mapping and flow diagrams. Potential hazards were rated according to severity and frequency and scored using a 'hazard score matrix'. All hazards scoring ≥8 were considered for 'decision tree' analysis, which produced a list of hazards to be included in a surgical safety checklist. RESULTS: Process mapping highlighted three main phases: the anaesthesia phase, the operating phase and the postoperative handover to recovery phase. A total of 51 failure modes were identified, 61% of which had a hazard score ≥8. A total of 22 hazards were finalised via decision tree analysis and were included in the checklist. The focus was on hazards specific to robotic urological procedures such as patient positioning (hazard score 12), port placement (hazard score 9) and robot docking/de-docking (hazard score 12). CONCLUSIONS: HFMEA identified hazards in an operating theatre with innovative robotic technologies which has led to the development of a surgical safety checklist. Further work will involve validation and implementation of the checklist.
    BJU International 04/2013;
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