Recognition of pulmonary hypertension in the rheumatology community: lessons from a Quality Enhancement Research Initiative.

OBJECTIVES: The aim of this study was to utilise the Quality Enhancement Research Initiative in Systemic Sclerosis (QuERI-SSc) to measure and reduce a perceived gap in the diagnosis of pulmonary arterial hypertension (PAH) associated with systemic sclerosis (SSc). METHODS: Rheumatologists enrolled patients with SSc (aged ≥ 18 years) and provided data on a panel of diagnostic tests over 3 years. Pulmonary function testing, echocardiography, 6-minute walk distance, N-terminal pro-brain natriuretic peptide assays, high-resolution computed tomography of the lungs, and ventilation/perfusion scan plus right heart catheterisation (RHC; when appropriate) were emphasised. Exclusion criteria included previously documented PAH, interstitial lung disease, and SSc overlapping with other connective tissue disease. RESULTS: Participating rheumatologists enrolled 207 patients with SSc (90% female; 80% white), with a median age of 57 years and median disease duration of 5 years. A total of 82% of patients were classified as New York Heart Association functional class I and II; of these patients, 177 had an echocardiogram at enrolment and 191 at any time during the study. Of those who met study-specified criteria for RHC at enrolment, only 3 of 7 patients underwent RHC. CONCLUSIONS: The screening algorithm was successful in identifying patients with mild impairment. Although specific tools were recommended for screening PAH in patients with SSc, results indicate that significant diagnostic care gaps still exist in the general rheumatology community. Better understanding and adherence to guidelines could improve the care and, ideally, outcomes of these high-risk patients.

Cost effective laparoendoscopic single-site surgery with a reusable platform.

BACKGROUND AND OBJECTIVES: Many disposable platforms have been applied in laparoendoscopic single-site surgery (LESS). Besides technical issues, cost is one of the limiting factors for its widespread acceptance. The current study describes the first completely reusable LESS-platform. METHODS: We performed LESS-procedures in 52 patients including nephrectomy (18), adrenalectomy (2), partial nephrectomy (3), pyeloplasty (4), renal cyst ablation (4), pelvic lymphadenectomy (15), and lymphocele ablation (6). All procedures were conducted using a novel reusable single-port device (X-Cone, Karl-Storz) with a simplified set of instruments. We obtained perioperative and demographic data, including a visual analogue pain scale (VAS), and a complication reporting system based on Clavien grading. RESULTS: Mean age was 50.04 y. Conversion to standard laparoscopy was necessary in 3 cases and addition of a needlescopic instrument in 6 cases. There was no open conversion. Intra- and postoperative complications occurred in 3 (Clavien II in 2 and III in 1) cases. Mean operative time was 110, 90, and 89 min, and hospital stay was 4.9, 3.1, and 3.6 d for nephrectomy, pelvic lymphadenectomy, and pyeloplasty, respectively. Mean VAS was 2.13, 1.07, and 1.5 while blood loss was 81.3 mL, 25.67 mL, and 17.5 mL, respectively. Mean lymph node yield was 15 (range, 8 to 21). CONCLUSIONS: A completely reusable LESS-platform is applicable to various uses in urology, yielding favorable functional and cosmetic results. Reusable materials are useful to reduce the cost of LESS, further increasing its acceptance. LESS with a completely reusable platform is more cost effective than standard laparoscopy.

[Primary monosymptomatic enuresis: diagnostics and therapy]. / Primäre Monosymptomatische Enuresis: Diagnostik und Therapie.

Nocturnal enuresis is one of the most common problems in childhood. In this article a standardized terminology for basic diagnostics additionally to extended diagnostics will be presented. Depending on the findings a specialized therapy can be performed. Besides drug therapy with antidiuretic hormone (ADH) sleep arousal devices can be used and the combination of both approaches also shows excellent results. At the end of therapy a protracted withdrawal shows better results than abrupt cessation.

[Laparoendoscopic single-site surgery in urology using reusable systems]. / Laparoendoskopische Single-site-Chirurgie in der Urologie durch Einsatz eines wieder verwendbaren Systems.

PURPOSE: Many disposable platforms have been available for laparoendoscopic single-site surgery (LESS) for a long time. Besides technical challenges cost remains the limiting factor for the widespread use of LESS. We present our experiences with the first completely reusable LESS platform. METHODS: We performed LESS procedures in 52 patients, including nephrectomy (n=18), adrenalectomy (2), partial nephrectomy (3), pyeloplasty (4), renal cyst ablation (4), pelvic lymphadenectomy (15) and lymphocele ablation (6). All procedures were carried out using a novel reusable single-port device (X-ConeR, Karl-Storz) with a simplified combination of standard and preformed instruments. Perioperative and demographic data including a visual analogue pain scale (VAS) were obtained. Complications were recorded using the Clavien classification. RESULTS: The mean age of the patients was 50.04 years. Conversion to standard laparoscopy was necessary in 3 cases and the additional use of a 3 mm needle instrument in 6 cases. There were no open conversions. Intraoperative and postoperative complications occurred in 3 (Clavien II in 2 and III in 1) cases. Mean operating time was 110, 90, and 89 min and hospital stay was 4.9, 3.1 and 3.6 days for nephrectomy, pelvic lymphadenectomy, and pyeloplasty, respectively. The mean VAS was 2.13, 1.07 and 1.5 while blood loss was 81.3 ml, 25.67 ml and 17.5 ml, respectively. CONCLUSIONS: The LESS technique with a completely reusable platform is applicable to various indications in urology yielding favorable functional and cosmetic results. This novel simplified combination of instruments facilitates handling and shortens the learning curve. Reusable materials may help to reduce cost leading to a wider acceptance of LESS.

Patterns and predictors of change in outcome measures in clinical trials in scleroderma: an individual patient meta-analysis of 629 subjects with diffuse cutaneous systemic sclerosis.

OBJECTIVE: To examine the range and responsiveness to change of clinical outcome measures and study predictors of clinical response in patients with diffuse cutaneous systemic sclerosis (dcSSc) in the context of clinical trials. METHODS: Data were combined from 629 patients with dcSSc who participated in 7 multicenter clinical therapeutic trials. Trials used common outcome measures: modified Rodnan skin thickness score (MRSS), Health Assessment Questionnaire disability index (HAQ DI), patient's global assessment of disease activity, pulmonary function tests (forced vital capacity, diffusing capacity for carbon monoxide), hand span, and oral aperture. RESULTS: The combined database included 629 patients (82% women, mean ± SD age 46.5 ± 11.8 years, mean ± SD disease duration 19.4 ± 15.9 months). Outcomes tended to improve during trials for patients with more severe disease at study entry and to worsen for patients with less severe disease at entry. Disease duration was mildly negatively predictive of change in MRSS at 6 months (r = -0.27, P < 0.001), and substantial bidirectional variation in change in MRSS and HAQ DI score was seen across the spectrum of disease duration. Sixty-three percent of patients with "early" disease (disease duration <18 months) had a decline in MRSS, and 37% had an increase in MRSS. Eighty-one percent of patients with "late" disease (disease duration ≥ 18 months) had a decline in MRSS, and 19% had an increase in MRSS. Multivariate mixed models did not demonstrate that any baseline variables were strongly predictive of subsequent outcome. CONCLUSION: Among patients with dcSSc enrolled in clinical trials, standard outcome measures tend to improve in those with more severe disease at study entry and to worsen in those with less severe disease at entry. Overall, the MRSS improves during trials, while HAQ DI scores and lung function are mostly static. None of these variables, including disease duration, reliably identifies groups of subjects whose MRSS will predictably increase or decrease in the course of a clinical trial. These findings have important implications for clinical trial design in scleroderma.

Introducing a large animal model to create urethral stricture similar to human stricture disease: a comparative experimental microscopic study.

PURPOSE: In this tissue engineering study we investigated urethral stricture formation to evaluate different treatment modalities in the large animal model and validate the most current, comparable effect of human stricture development for successful human clinical application. MATERIALS AND METHODS: In 12 male minipigs stricture formation was evaluated by urethrography 1, 8 and 12 weeks after stricture induction by ligation, urethrotomy or thermocoagulation. Normal human urethral and scar tissue of 6 patients was harvested and compared to animal specimens. The effect of urethral damage was investigated for microvessel density and collagen I:III ratio. RESULTS: A week after urethrotomy urothelium covered the spongiosum tissue, showing minimal infiltration of lymphocytes and macrophages, and sporadic eosinophil granulocytes. However, increased connective tissue was observed with time as well as urethral luminal narrowing, vascular network loss (decreased microvessel density) and significantly increased collagen with a favorably revised collagen type I:III ratio. The 3 methods of stricture induction resulted in different stricture severity in the animal model (thermocoagulation >ligation >urethrotomy). Porcine urethral samples after thermocoagulation showed a significantly increased collagen I:III ratio (p <0.001), almost equal to that of human urethral stricture specimens. CONCLUSIONS: We successfully developed a large animal model in which to study urethral stricture formation by defined iatrogenic intervention. The established animal model advances investigation to evaluate new therapy modalities in a preclinical setting to treat urethral stricture and predict clinical outcome.

Development of a porcine animal model for urethral stricture repair using autologous urothelial cells.

OBJECTIVE: To present a versatile large animal model for endoscopic stricture repair using autologous urothelial cells. MATERIALS AND METHODS: 12 male minipigs were used. An artificial stricture model was established using suture-ligation, thermo-coagulation and internal urethrotomy. A vesicostomy served for urinary diversion. Stricture formation was confirmed radiologically and histologically. Autologous urothelial cells were harvested from bladder washings, cultivated and labeled. Internal urethrotomy was done in all, and the cultivated cells were injected into the urethrotomy wound. All animals were sacrificed after 4 or 8 weeks. Immunohistology was done to confirm the presence of autologous urothelial cells within the reconstituted urethra. RESULTS: Stricture formation was verified with all three methods. Histologically, no significant differences in the severity of stricture development could be observed with regard to the method used. The autologous urothelial cells in the area of the urethrotomy could be detected in the urothelium and the corpus spongiosum until 8 weeks after re-implantation. CONCLUSIONS: We created a reliable and reproducible porcine model for artificial urethral strictures. Autologous urothelial cells can be implanted into an artificial stricture after urethrotomy. These cells retain their epithelial phenotype and are integrated in the resident urothelium. Further comparative studies are needed to ultimately determine a superior efficacy of this novel approach.

Videourodynamic changes of botulinum toxin A in patients with neurogenic bladder dysfunction (NBD) and idiopathic detrusor overactivity (IDO) refractory to drug treatment.

PURPOSE: To document the videourodynamic changes and the efficacy and safety profile of botulinum toxin A (BoNT-A, Dysport(®)) in neurogenic bladder dysfunction (NBD) including neurogenic detrusor overactivity, low-compliance and break-low-compliance and idiopathic detrusor overactivity (IDO), in patients refractory to drug treatment. METHODS: Sixty-four patients with NBD and 170 patients with IDO were treated between 2002 and 2007. Diagnostic approach included medical history, bladder diary, standardised questionnaire rating quality of life, sonography, videourodynamic and temporary sacral nerve block. All patients received BoNT-A-injection under local anaesthesia. Patients with NBD received 500 mouse units (MU) and patients with IDO received 250 MU BoNT-A, injected into ten sites including the trigonum. Patients were followed up 6 weeks after injection. RESULTS: For NBD, 58/64 (91%) patients achieved satisfactory continence during the day as well as significant reduction in incontinence episodes and improvement in quality of life. For IDO, 158/170 (93%) were responders with regard to urgency and urge incontinence. Urodynamical changes included significant improvement in the following parameters in both groups: increase in maximum cystometric capacity and decrease in detrusor pressure. BoNT-A was well tolerated; no drug-related side effects were documented. No de novo vesicoureteral reflux was induced. Long-term follow-up revealed a mean duration effect of BoNT-A of 5.7 months in NBD and 4.9 months in IDO. CONCLUSIONS: BoNT-A is highly effective in NBD as well as in IDO suggesting that this is a good treatment option for patients with detrusor overactivity. Furthermore, intratrigonal injection is safe and not associated with vesicoureteral reflux.

Long-term biochemical evaluation of the androgen receptor pathway in males with disorders of sex development.

PURPOSE: Disorders of sex (DSD) development represent a serious condition. Most of the underlying mechanisms remain unclear. Disturbances within the androgen receptor (AR) pathway frequently account for 46 XY-DSDs. The individual gender-related outcome often is unsatisfactory. We present a long-term AR gene-mutation-associated follow-up in a group of 46 XY-DSD patients. METHODS: Twenty patients (46 XY) who underwent genitoplasty in infancy or early childhood were retrospectively identified. Median follow-up after surgery was 16 years. All were undervirilized at initial presentation. Thirteen had female gender assignment, and 7 were raised as males. A genital skin biopsy and subsequent fibroblast cultures were done. The specific binding of dihydrotestosterone, the thermostability of the receptor hormone complex, and 5-α-reductase activity were measured. AR gene mutations were detected by direct sequencing. The individual outcome was correlated with specific AR mutations. RESULTS: AR point mutations were detected in 12, 7 were previously unknown. There was no specific androgen binding in 3, reduced affinity in 9, and normal binding in 8 patients. 5-α-Reductase activity was normal in 15, reduced in 4 and completely absent in 1 patient. CONCLUSIONS: Retrospective evaluation revealed previously unknown and established AR gene mutations being associated with a distinct long-term outcome. Identification of the molecular mechanisms causing DSD will likely improve timely diagnosis and therapy. Exact characterization of AR activation and function may offer a treatment modality in affected patients. These data may allow us to give prognostic estimations on the individual outcome adding objective criteria for gender assignment in 46 XY-DSD patients.

Desmopressin treatment regimens in monosymptomatic and nonmonosymptomatic enuresis: A review from a clinical perspective.

OBJECTIVE: To evaluate outcomes of desmopressin treatment in monosymptomatic enuresis (ME) and nonmonosymptomatic enuresis (NME). MATERIALS AND METHODS: PubMed was searched for all studies investigating enuresis, up to July 2009, in which desmopressin was administered alone or combined with other treatments. Each study was graded according to its respective level of evidence. RESULTS: Altogether, 99 studies enrolling 7422 patients were identified as fulfilling the inclusion criteria. In 76 studies, desmopressin was administered as monotherapy; in 29 it was combined with other treatments such as antimuscarinics and enuresis alarm. CONCLUSION: Studies incorporating a minor invasive versus a non-invasive diagnostic approach seem to achieve superior long-term success rates. Primary efficacy outcomes following desmopressin treatment are more favourable in ME than NME. Desmopressin administered with adjunct measures achieves superior outcomes compared to monotherapy, especially in NME. Compared to sudden withdrawal, the structured withdrawal programs show better long-term success and lower relapse rates. So far, no superiority has been shown for either time- or dose-dependent structured withdrawal programs. Most studies incorporated only small case series; only 25 studies with level of evidence 1 or 2 have been conducted. The broad range of mono- and adjunct treatments were evaluated according to the evidence based criteria recommended by the European Association of Urology.

Differences in presentation of younger and older systemic sclerosis patients in clinical trials.

OBJECTIVES: To compare the characteristics of younger and older subjects with diffuse cutaneous systemic sclerosis (SSc) entering clinical trials. METHODS: Subjects were participants in three randomised interventional trials that shared relative uniformity of demographics and disease characteristics. Only subjects with diffuse cutaneous systemic sclerosis were evaluated. To maximise possible differences, the lowest (age<38 years) and highest quartiles (age>53 years) were used, and a total of 264 diffuse cutaneous SSc (dcSSc) subjects were identified. For the comparison between the two age groups, generalised linear mixed or linear models with adjustment for population norms, demographics and medications were employed to assess differences attributable to subject age. RESULTS: After adjustment for population norms and study effects, differences in diastolic blood pressure, alkaline phosphatase, AST, and creatinine phosphokinase (CK) were found between the two age groups. After further adjustment for demographics, disease duration and medications, older SSc patients still had significantly higher alkaline phosphatase (11 U/L higher), and lower CK (76 U/L lower) than younger patients (p<0.003 for all). All other variables were not significantly different in the two age groups. CONCLUSIONS: Clinical baseline differences exist between younger and older patients with SSc. However, after adjustment for population norms and potential confounders, including medications, only differences in alkaline phosphatise (only 11U/L) and CK (76 U/L) remain. Overall, older patients with SSc in clinical trials seem to be more similar to younger patients than was previously thought.

Randomized, prospective, placebo-controlled trial of bosentan in interstitial lung disease secondary to systemic sclerosis.

OBJECTIVE: Endothelin is implicated as a participatory pathway in systemic sclerosis (SSc). We tested this hypothesis in a 12-month trial of bosentan, a nonselective endothelin receptor antagonist, as a therapy for SSc-related interstitial lung disease (ILD). METHOD: Patients with SSc and significant ILD were recruited to this prospective, double-blind, randomized, placebo-controlled, parallel group study. The inclusion criteria were designed to select a cohort enriched for patients with active and progressive disease. Exclusion factors included significant pulmonary hypertension. Patients with a diffusing capacity for carbon monoxide of <80% predicted and a 6-minute walk distance of 150-500 meters or a 6-minute walk distance of > or = 500 meters with a decrease in oxygen saturation received bosentan or placebo. The primary efficacy end point was a change in the 6-minute walk distance from baseline up to month 12. Secondary end points included time to death or worsening results of pulmonary function tests (PFTs). The safety and tolerability of bosentan were also assessed. RESULTS: Among the 163 patients, 77 were randomized to receive bosentan, and 86 were randomized to receive placebo. No significant difference between treatment groups was observed for change in the 6-minute walk distance up to month 12. No deaths occurred in this study group. Forced vital capacity and diffusing capacity for carbon monoxide remained stable in the majority of patients in both groups. Significant worsening of PFT results occurred in 25.6% of patients receiving placebo and 22.5% of those receiving bosentan (P not significant). CONCLUSION: No improvement in exercise capacity was observed in the bosentan-treated group compared with the placebo group, and no significant treatment effect was observed for the other end points. Although many outcome variables were stable, bosentan did not reduce the frequency of clinically important worsening. These data do not support the use of endothelin receptor antagonists as therapy for ILD secondary to SSc.

[Long-term results after endoscopic subureteral injection for VUR using dextranomer/hyaluronic acid copolymer : a five years experience]. / Endoskopische Unterspritzung des vesikoureteralen Refluxes mit Dextranomer/Hyaluronsäure : 5-Jahres-Langzeitergebnisse.

BACKGROUND: A number of bulking agents have been used for the endoscopic correction of vesicoureteral reflux in children. We present the long-term results of endoscopic use of dextranomer/hyaluronic acid copolymer (Deflux) for VUR grade I-IV in children. PATIENTS AND METHODS: Between 2004 and 2008, 21 children underwent endoscopic subureteral injection of Deflux in 30 ureters as an outpatient procedure. Twelve children had a unilateral reflux (two duplicated systems) and nine had a bilateral reflux. The median age was 5 years (6 months to 14.9 years). Six weeks postoperatively a voiding cystourethrogram (VCUG) was performed. This study examined the disappearance of VUR and urinary tract infection (UTI) as well as the quality of life (parents' questionnaire) during long-term follow-up. RESULTS: No intra- and postoperative complications were noticed. In 25 ureters (83%) VCUG showed no VUR 6 weeks postoperatively. In three children a second injection was done (two were successful). After a median follow-up of 2.5 years 27 ureters in 17 children (90%) had no UTI and VUR. The results of the questionnaire regarding quality of life were very good in the successfully treated children and the parents would choose the same treatment option again. CONCLUSION: Subureteral injection of Deflux for children with VUR is an effective treatment option for VUR with a low complication rate.

Junctional adhesion molecule-A is abnormally expressed in diffuse cutaneous systemic sclerosis skin and mediates myeloid cell adhesion.

OBJECTIVE: To investigate the role of junctional adhesion molecule-A (JAM-A) in the pathogenesis of systemic sclerosis (SSc). METHODS: Biopsy specimens from proximal and distal arm skin and serum were obtained from patients with SSc and normal volunteers. To determine the expression of JAM-A on SSc dermal fibroblasts and in SSc skin, cell surface ELISAs and immunohistology were performed. An ELISA was designed to determine the amount of soluble JAM-A (sJAM-A) in serum. Myeloid U937 cell-SSc dermal fibroblast and skin adhesion assays were performed to determine the role of JAM-A in myeloid cell adhesion. RESULTS: The stratum granulosum and dermal endothelial cells (ECs) from distal arm SSc skin exhibited significantly decreased expression of JAM-A in comparison with normal volunteers. However, sJAM-A was increased in the serum of patients with SSc compared with normal volunteers. Conversely, JAM-A was increased on the surface of SSc compared with normal dermal fibroblasts. JAM-A accounted for a significant portion of U937 binding to SSc dermal fibroblasts. In addition, JAM-A contributed to U937 adhesion to both distal and proximal SSc skin. CONCLUSIONS: JAM-A expression is dysregulated in SSc skin. Decreased expression of JAM-A on SSc ECs may result in a reduced response to proangiogenic basic fibroblast growth factor. Increased JAM-A expression on SSc fibroblasts may serve to retain myeloid cells, which in turn secrete angiogenic factors.

Sexual activity and functioning in female scleroderma patients.

OBJECTIVE: Few studies exist on sexual activity and functioning in female patients with systemic sclerosis (SSc, scleroderma). We studied the patient-reported impact of SSc on sexual functioning among female patients. METHODS: 101 SSc patients completed the Short Form-36 (SF-36), the Female Sexual Functioning Index (FSFI) and the Female Sexual Function in Scleroderma (FSFS) questionnaires. RESULTS: Sixty patients reported being sexually active (59.4%). Reasons for sexual inactivity included lack of a partner (36.6%), personal choice (31.7%), and health status of the respondent's partner (19.5%). Only 7 subjects (17%) listed scleroderma as the primary reason for sexual inactivity. The mean FSFI score in the sexually active population was 24.9 (SD=6.7, range = 4.5-34.8) which is significantly lower than the mean score of 30.5 reported for the general population. Sexual functioning was significantly correlated with the Mental Component Score of the SF-36 (r=0.54, p<0.001) but surprisingly not with the Physical Component Score of the SF-36, age, and disease classification or duration. Several scleroderma-related problems including fatigue, body pain, vaginal dryness, and vaginal discomfort were cited as contributing to sexual difficulties. CONCLUSION: Women with scleroderma do remain sexually active overall in spite of several disease-related physical and psychological difficulties. Many of their problems are amenable to health interventions and should be addressed during health care visits.

EULAR recommendations for the treatment of systemic sclerosis: a report from the EULAR Scleroderma Trials and Research group (EUSTAR).

PURPOSE: The optimal treatment of systemic sclerosis (SSc) is a challenge because the pathogenesis of SSc is unclear and it is an uncommon and clinically heterogeneous disease affecting multiple organ systems. The aim of the European League Against Rheumatism (EULAR) Scleroderma Trials and Research group (EUSTAR) was to develop evidence-based, consensus-derived recommendations for the treatment of SSc. METHODS: To obtain and maintain a high level of intrinsic quality and comparability of this approach, EULAR standard operating procedures were followed. The task force comprised 18 SSc experts from Europe, the USA and Japan, two SSc patients and three fellows for literature research. The preliminary set of research questions concerning SSc treatment was provided by 74 EUSTAR centres. RESULTS: Based on discussion of the clinical research evidence from published literature, and combining this with current expert opinion and clinical experience, 14 recommendations for the treatment of SSc were formulated. The final set includes the following recommendations: three on SSc-related digital vasculopathy (Raynaud's phenomenon and ulcers); four on SSc-related pulmonary arterial hypertension; three on SSc-related gastrointestinal involvement; two on scleroderma renal crisis; one on SSc-related interstitial lung disease and one on skin involvement. Experts also formulated several questions for a future research agenda. CONCLUSIONS: Evidence-based, consensus-derived recommendations are useful for rheumatologists to help guide treatment for patients with SSc. These recommendations may also help to define directions for future clinical research in SSc.

European League Against Rheumatism (EULAR) Scleroderma Trial and Research group (EUSTAR) recommendations for the treatment of systemic sclerosis: methods of elaboration and results of systematic literature research.

OBJECTIVE: To describe methods and procedures used for the development of the European League Against Rheumatism (EULAR)/EULAR Scleroderma Trial and Research group (EUSTAR) recommendations for the treatment of systemic sclerosis. In particular, the results of a web-based Delphi exercise aimed at selection of research questions and evidence from systematic literature research, as parts of the development of these recommendations, are presented in detail. METHODS: In agreement with the EULAR standard operating procedures a Task Force was created that consisted of the EUSTAR board members, 10 systemic sclerosis (SSc) experts invited from outside the EUSTAR board and representing Europe, the USA and Japan, a clinical epidemiologist, 2 patients with SSc and 3 fellows for literature research. All EUSTAR centres were invited to contribute to the development of recommendations through submission and preliminary selection of the research questions. The systematic literature research was performed using the Pubmed, Medline, EMBASE and Cochrane databases. Retrieved trials were evaluated according to the Jadad classification, and the level of evidence was graded from 1 to 4. Outcome data for efficacy and adverse events were abstracted and effect size, number needed to treat (NNT) and number needed to harm (NNH) were calculated when appropriate. RESULTS: In all, 65 EUSTAR Centres provided 304 research questions concerning SSc treatment. These questions were aggregated, subdivided into 19 treatment categories and then subjected to preliminary selection by a web-based Delphi technique. The final set of 26 research questions was created by the Expert Committee based on the results of the Delphi exercise and the expert's experience. CONCLUSIONS: This paper is a comprehensive summary of the methods we used to build recommendations for the drug treatment of systemic sclerosis, combining an evidence based approach and expert opinion.

Laparoscopic heminephroureterectomy for duplex kidney anomalies in the pediatric population.

OBJECTIVE: Despite increasing acceptance of laparoscopy in pediatric urology, few published data are available on laparoscopic heminephroureterectomy in patients with duplex kidney anomalies. In the present study, we report our own experiences with this technique. PATIENTS AND METHODS: From August 2003 to January 2006, five laparoscopic heminephroureterectomies were performed in four girls with a mean age of 41 (9-67) months. In all cases, a non-functioning upper pole with an obstructive (n=4) or refluxing (n=1) megaureter was found. The upper pole was resected laparoscopically en bloc with the megaureter using three to four trocars. RESULTS: Mean follow-up was 42.4 (+/-7.9) months. All procedures were performed successfully without conversion to open surgery with a mean operative time of 190 (170-210)min. Blood loss was minimal and no intraoperative complications occurred. Despite chronic inflammation in the resected specimens, the patients showed no clinical signs of infection postoperatively. The average length of hospital stay was 5.6 (4-7) days. All patients were followed using duplex sonography. CONCLUSIONS: These data demonstrate that, even in infants, laparoscopic heminephroureterectomy is feasible and associated with minimal morbidity, a better cosmetic result and a shorter hospital stay compared to open surgery. The main disadvantage of the laparoscopic approach is a longer operative time. Laparoscopic heminephroureterectomy is a technically demanding procedure and should be performed only in specialized centers.