Peritoneal flap for lymphocele prophylaxis following robotic-assisted laparoscopic radical prostatectomy with pelvic lymph node dissection: study protocol and trial update for the randomized controlled PELYCAN study.

BACKGROUND: Data from interventional studies suggest that a peritoneal flap after pelvic lymph node dissection (LND) during laparoscopic, robotic-assisted radical prostatectomy (RARP) may reduce the rate of symptomatic lymphoceles in transperitoneal approach. However, most of these studies are not conducted in a randomized controlled fashion, thus limiting their scientific value. A recent prospective, randomized, controlled trial (RCT) did not show superiority of a peritoneal flap while further trials are lacking. Therefore, the aim of the presented RCT will be to show that creating a peritoneal flap decreases the rate of symptomatic lymphoceles compared to the current standard procedure without creation of a flap. METHODS/DESIGN: PELYCAN is a parallel-group, patient- and assessor-blinded, phase III, adaptive randomized controlled superiority trial. Men with histologically confirmed prostate cancer who undergo transperitoneal RARP with pelvic LND will be randomly assigned in a 1:1 ratio to two groups-either with creating a peritoneal flap (PELYCAN) or without creating a peritoneal flap (control). Sample size calculation yielded a sample size of 300 with a planned interim analysis after 120 patients, which will be performed by an independent statistician. This provides a possibility for early stopping or sample size recalculation. Patients will be stratified for contributing factors for the development of postoperative lymphoceles. The primary outcome measure will be the rate of symptomatic lymphoceles in both groups within 6 months postoperatively. Patients and assessors will be blinded for the intervention until the end of the follow-up period of 6 months. The surgeon will be informed about the randomization result after performance of vesicourethral anastomosis. Secondary outcome measures include asymptomatic lymphoceles at the time of discharge and within 6 months of follow-up, postoperative complications, mortality, re-admission rate, and quality of life assessed by the EORTC QLQ-C30 questionnaire. DISCUSSION: The PELYCAN study is designed to assess whether the application of a peritoneal flap during RARP reduces the rate of symptomatic lymphoceles, as compared with the standard operation technique. In case of superiority of the intervention, this peritoneal flap may be suggested as a new standard of care. TRIAL REGISTRATION: German Clinical Trials Register DRKS00016794 . Registered on 14 May 2019.

The comprehensive complication index (CCI): proposal of a new reporting standard for complications in major urological surgery.

PURPOSE: The comprehensive complication index (CCI) is a new tool for reporting the cumulative burden of postoperative complications on a continuous scale. This study validates the CCI for urological surgery and its benefits over the Clavien-Dindo-Classification (Clavien). MATERIAL AND METHODS: Data from a prospectively maintained data base of all consecutive patients at a university care-center was analyzed. Complications after radical cystectomy (RC), radical prostatectomy (RP), and partial nephrectomy (PN) were classified using the CCI and Clavien system. Differences in complications between the CCI and the Clavien were assessed and correlation analyses performed. Sample size calculations for hypothetical clinical trials were compared between CCI and Clavien to evaluate whether the CCI would reduce the number of required patients in a clinical trial. RESULTS: 682 patients (172 RC, 297 RP, 213 PN) were analyzed. Overall, 9.4-46.6% of patients had > 1 complication cumulatively assessed with the CCI resulting in an upgrading in the Clavien classification for 2.4-32.4% of patients. Therefore, scores between the systems differed for RC: CCI (mean ± standard deviation) 26.3 ± 20.8 vs. Clavien 20.4 ± 16.7, p < 0.001; PN: CCI 8.4 ± 14.7 vs. Clavien 7.0 ± 11.8, p < 0.001 and RP: CCI 5.8 ± 11.7 vs. Clavien 5.3 ± 10.6, p = 0.102. The CCI was more accurate in predicting LOS after RC than Clavien (p < 0.001). Sample size calculations based in the CCI (for future hypothetical trials) resulted in a reduction of required patients for all procedures (- 25% RC, - 74% PN, - 80% RP). CONCLUSION: The CCI is more accurate to assess surgical complications and reduces required sample sizes that will facilitate the conduction of clinical trials.

Early recovery after surgery for radical cystectomy: comprehensive assessment and meta-analysis of existing protocols.

PURPOSE: Different enhanced recovery after surgery (ERAS) protocols (EP) for radical cystectomy (RC) have been published. Protocols highly differ in number of included items and specific measures. MATERIALS AND METHODS: A systematic review and meta-analysis on EPs in RC were performed using the databases MedLine, Cochrane Library, Web of science, and Google Scholar. The specific ERAS measures of the protocols were extracted, analyzed, and compared. Pooling of available outcome data was performed for length of stay, complications, readmission rate, and time to defecation. RESULTS: The search yielded a total of 860 studies of which 25 studies were included in qualitative and 22 in quantitative analysis. Oral bowel preparation (BP) was omitted in 24/25 (96%) EPs, optimized fluid management was administered in 22/25 (88%) EPs and early mobilization (postoperative day 1) in 21/25 (84%). Gum chewing (n = 12, 46%), metoclopramide (n = 11, 44%), and alvimopan (n = 6, 24%) were the most common measures to prevent postoperative ileus. Our meta-analysis revealed a significant benefit in favor of EPs for the outcome parameters length of stay [mean difference (MD) - 3.46 d, 95% confidence interval (CI) - 4.94 to - 1.98, p < 0.01], complications [Odds ratio (OR) = 0.76, 95% CI 0.61-0.94, p = 0.01] and time to defecation (MD - 1.37 d, 95% CI - 2.06 to - 0.69, p < 0.01). Readmission rate did not show a significant difference (OR = 0.73, 95% CI 0.52-1.03, p = 0.07). CONCLUSION: Current EPs focus on omitting oral BP, early mobilization, and optimized fluid management while they differ in methods preventing postoperative ileus. Our meta-analysis revealed a benefit in introducing these protocols into clinical practice.

Prophylactic abdominal or retroperitoneal drain placement in major uro-oncological surgery: a systematic review and meta-analysis of comparative studies on radical prostatectomy, cystectomy and partial nephrectomy.

PURPOSE: To systematically analyze the impact of prophylactic abdominal or retroperitoneal drain placement or omission in uro-oncologic surgery. METHODS: This systematic review follows the Cochrane recommendations and was conducted in line with the PRISMA and the AMSTAR-II criteria. A comprehensive database search including Medline, Web-of-Science, and CENTRAL was performed based on the PICO criteria. All review steps were done by two independent reviewers. Risk of bias was assessed with the Cochrane tool for randomized trials and the Newcastle-Ottawa Scale. RESULTS: The search identified 3427 studies of which eleven were eligible for qualitative and ten for quantitative analysis reporting on 3664 patients. Six studies addressed radical prostatectomy (RP), four studies partial nephrectomy (PN) and one study radical cystectomy. For RP a reduction in postoperative complications was found without drainage (odds ratio (OR)[95% confidence interval (CI)]: 0.62[0.44;0.87], p = 0.006), while there were no differences for re-intervention (OR[CI]: 0.72[0.39;1.33], p = 0.300), lymphocele OR[CI]: 0.60[0.22;1.60], p = 0.310), hematoma (OR[CI]: 0.68[0.18;2.53], p = 0.570) or urinary retention (OR[CI]: 0.57[0.26;1.29], p = 0.180). For partial nephrectomy no differences were found for overall complications (OR[CI]: 0.99[0.65;1.51], p = 0.960) or re-intervention (OR[CI]: 1.16[0.31;4.38], p = 0.820). For RC, there were no differences for all parameters. The overall-quality of evidence was assessed as low. CONCLUSION: The omission of drains can be recommended for standardized RP and PN cases. However, deviations from the standard can still mandate the placement of a drain and remains surgeon preference. For RC, there is little evidence to recommend the omission of drains and future research should focus on this issue. REVIEW REGISTRATION NUMBER (PROSPERO): CRD42019122885.

Radical cystectomy under continuous antiplatelet therapy with acetylsalicylic acid.

INTRODUCTION: Aim of this study was to analyse the perioperative outcome of patients undergoing radical cystectomy under continuous antiplatelet therapy with acetylsalicylic acid. MATERIALS AND METHODS: Using prospectively maintained databases of two departments of urology, we identified 461 consecutive patients who underwent radical cystectomy for bladder cancer (2011-2017). Patients were divided into three groups: 1) on-going antiplatelet therapy with acetylsalicylic acid (n = 50), 2) discontinuing antiplatelet therapy (n = 65) and 3) no antiplatelet therapy (n = 346). Perioperative outcome was compared between the three groups using ANOVA, likelihood ratio or Kruskal Wallis test with post-hoc testing. Uni- and multivariate analyses were performed to identify predictor for perioperative complications and transfusion. RESULTS: Group 1 showed an average estimated blood loss of 732 ±â€¯424, group 2 752 ±â€¯488 and group 3 810 ±â€¯544 ml (p = 0.51). There was no significant difference in transfusion rate (44% in group 1, 45% and 39% in groups 2 and 3, p = 0.63). Severe complications occurred in 26%, 15% and 15% in groups 1-3 (p = 0.19). Ischemic complications were more often observed in group 1 (n = 4, 8%) and 2 (n = 5, 8%) than group 3 (n = 7, 2%), p = 0.02. 90-day readmission (n = 99, 22%) and mortality rate (n = 10, 2.2%) were low and did not show any significant differences between the groups. In uni- and multivariate analysis ongoing therapy with acetylsalicylic acid was no independent risk factor for transfusion or severe complications. CONCLUSION: Perioperative continuation of therapy with acetylsalicylic acid in radical cystectomy is safe with no difference in intraoperative blood loss, transfusion rate, complications or mortality.

Influence of symptomatic pseudoaneurysms on postoperative renal function after partial nephrectomy: results of a matched pair analysis.

PURPOSE: A symptomatic pseudoaneurysm (SPA) is a rare but severe complication after partial nephrectomy (PN). Selective trans-arterial embolization (TAE) is the treatment of choice with high success rates. However, the influence of this intervention on postsurgical renal function has not been studied. METHODS: Between 2005 and 2016 we performed 1047 PNs at our institution. Postsurgical SPA occurred in 40 patients (3.8%). Patients with and without SPA were matched in a 1:2 ratio concerning tumor complexity (RENAL) and pre-operative renal function (CKD stage). Any CKD upstage and a relevant CKD progression (CKD ≥ III) were defined as endpoints. Furthermore, the influence of the amount of contrast agent applied during TAE was assessed. RESULTS: All patients with SPA were treated successfully with TAE. No significant difference could be detected concerning clinical, functional and surgical aspects. Median follow-up time accounted for 12.5 (6.75-27.5) months. Kaplan-Meier analyses detected an increased rate of any CKD upstage (p = 0.066) and relevant CKD progression (p = 0.01) in patients with SPA. Multivariate analysis identified post-operative SPA to be an independent predictor for a relevant CKD progression (HR 4.15, p = 0.01). The amount of contrast agents used did not have an impact on the development of a relevant CKD progression (p = 0.72). CONCLUSION: Patients treated with TAE after PN show an additional risk for an impairment of renal function over time. Hence, those patients should explicitly be informed about possible consequences and closely monitored by nephrologists.

Wide-field autofluorescence-guided TUR-B for the detection of bladder cancer: a pilot study.

PURPOSE: The aim of this pilot study was to assess the feasibility and value of wide-field autofluorescence imaging (AFI) for the detection of bladder cancer during transurethral resection of the bladder (TUR-B). METHODS: For imaging, the D-Light/AF System (Karl Storz GmbH, Tuttlingen, Germany) and a customized band pass filter (≈ 480-780 nm) at the eyepiece of the endoscope were used. The excitation light wavelength was 440 nm. Representative spectral measurements of tissue autofluorescence (AF) were performed using a spectrometer attached behind the AF band pass filter in selected patients. During TUR-B, cystoscopy was performed in white light (WL) followed by wide-field AFI. Lesions were classified as suspicious or normal using either modality. RESULTS: Representative spectral measurements using excitation at a wavelength of 440 nm resulted in significantly lower fluorescence intensity of malignant versus non-malignant tissue. Overall, 56 lesions (30 cancerous and 26 non-malignant) in 25 patients were assessed and classified by wide-field AFI. Papillary tumors as well as flat lesions lacked the green fluorescence seen in normal urothelium, thus emerging as "brown-reddish" areas. When compared with histopathological findings, the pooled per-lesion sensitivity and specificity for AF were 96.7 and 53.8%, respectively. For WL these values were 86.7 and 69.2%, respectively. CONCLUSION: Wide-field AFI imaging during TUR-B is simple and easy to use. Our preliminary data suggest that AFI has the potential to increase the detection rates of bladder tumors compared with WL without the need of intravesical instillation prior to the procedure.

[An alternative continence mechanism for continent catheterisable micturation]. / Ein alternativer Kontinenzmechanismus für kontinente katheterisierbare Harnableitungen.

PURPOSE: The creation of a stable, reliable, continent and easily catheterisable continence mechanism is an essential prerequisite for the construction of a continent cutaneous urinary reservoir. Although a substantial number of surgical methods has been described, construction is still a complex surgical procedure. The aim of this study was the evaluation of a new method for a continence mechanism using stapled small or large intestine. MATERIAL AND METHODS: Small and large pig intestine was used for construction. For stapling the tube a 3 cm or 6 cm double row stapling system was used. Two variations using small and large intestine segments were constructed (IL 1, COL 1, COL 2). A 3 or 6 cm long stapler line was placed alongside a 12 Fr catheter positioned at the antimesenterial side creating a partially two-luminal segment. The open end of the non-catheterised lumen and the opposite intestinal end were closed by continuous sutures. The created tube was then embedded into the pouch. Pressure evaluation was performed for each variation. Intermittent external manual compression was used to simulate sudden pressure exposure. RESULTS: Construction times for the IL 1 and COL 1 variations were 10 +/- 1.5 min and 6.2 +/- 1.3 min for COL 2. All variations showed no leakage during filling or external compression. The maximum capacity was lower for the IL 1 compared to the COL variation. The maximum pressure levels reached did not differ significantly. CONCLUSION: The described technique is an easy and fast method to construct a continent and easy to catheterize continence mechanism using small or large intestine.

[Medical treatment of metastatic renal cell carcinoma after the approval and market entry of multitargeted tyrosine kinase inhibitors in Germany]. / Medikamentöse Therapie des metastasierten Nierenzellkarzinoms: eine Standortbestimmung nach Einführung der Multi-Tyrosinkinaseinhibitoren in Deutschland.

PURPOSE: To describe the current use and administration of multitargeted tyrosine kinase inhibitors (sunitinib and sorafenib) in the management of metastatic renal cell carcinoma (RCC) and to characterise frequent adverse events. MATERIALS AND METHODS: A questionnaire was sent to 104 urologists and medical oncologists having their own practice. The common use of medical treatment with sunitinib and sorafenib in patients with metastatic RCC was recorded. Data on the most frequent drug-associated adverse events were registered and described in a preliminary patient cohort. RESULTS: Medical oncologists in private practice treat over twice as many patients with metastatic RCC (8/year) as established urologists. Most medical oncologists but not urologists already use multitargeted tyrosine kinase inhibitors. For the initiation of treatment, most urologists admit patients to a hospital, whereas medical oncologists start and carry out medical treatment themselves. In all patients adverse events occurred due to medical treatment, leading to therapy stop or pause in 53% of patients. The most frequent adverse events were abnormal fatigue, arterial hypertension, diarrhoea and the hand-foot skin syndrome. CONCLUSIONS: Multitargeted tyrosine kinase inhibitor therapy in Germany is currently done predominantly by medical oncologists rather than urologists. Adverse events caused by sunitinib and sorafenib frequently required medical care, and in our initial series of patients prompted physicians to pause treatment.

New endourologic technology for simultaneous holmium:YAG laser lithotripsy and fragment evacuation for PCNL: ex-vivo comparison to standard ultrasonic lithotripsy.

Percutaneous nephrolithotomy (PCNL) is a well established procedure and accepted as the standard of care for the treatment of large renal calculi. Since the introduction of the holmium:yttrium-aluminum-garnet (Ho:YAG) laser into clinical practice in 1990, it has been used successfully to treat various urologic conditions. Today it is the modality of choice for retrograde intracorporeal stone disintegration ureteroscopically, and has also been used successfully for PCNL. One disadvantage when using the Ho:YAG laser for disintegration of renal calculi is the need for graspers to extract fragments and the mobilization of fragments due to the lack of simultaneous suction. We present our experience with a Ho:YAG laser in combination with simultaneous suction in an in-vitro model using a new endourologic technique in comparison to conventional ultrasonic lithotripsy.

[Solitary fibrous tumour of the testes (SFT)]. / Solitärer fibröser Tumor des Hodens (SFT).

INTRODUCTION: Testicular masses in adults are most likely seminomatous or non-seminomatous germ cell tumours. Paratesticular tumours are far less frequent. Most lesions within this category are variants of fibrous pseudotumours. Solitary fibrous tumours (SFT) with characteristic (hemangiopericytoma-like) vascular structures are rare neoplasms that in the vast majority arise in the pleura, although extrapleural localisations in virtually every organ have been reported. CASE REPORT: A 64-year-old male nursing case was presented with a testicular swelling on the left side and recurrent testicular pain. Physical examination revealed a distinct mass at the left spermatic cord. The tumour marker levels were normal. The patient's history included an HIV infection as well as neurosyphilis. The sonographic examination showed a heterogeneous and hyperperfused tumour, MRI examination a 3.2 x 4.3 cm measuring heterogeneous tumour above the left epididymis. An inguinal orchiectomy was performed due to the unclear dignity. The histological examination revealed a solitary fibrous tumour. CONCLUSIONS: In cases of paratesticular tumours, rare tumours like solitary fibrous tumours have to be considered. Certainty regarding the dignity of the tumour can only be achieved by surgical exposure and excision.

[Technical innovations in endourological stone therapy]. / Technische Innovationen in der endoskopischen Steintherapie.

Endoscopic stone management is a field of consistent technical innovation. For ureterorenoscopy, flexible scopes capable of 270 degrees deflection have allowed access to the complete urinary tract, including the lower-pole renal calculi. To counter the flaw of high repair costs, new-generation flexible ureterorenoscopes feature significantly greater durability and a less frequent need for repair. The development and improvement of auxiliary instruments such as access sheaths has facilitated the procedures, reduced complications, and improved the stone-free rates. A similar trend is seen for percutaneous nephrolitholapaxy (PCNL). Development is directed at miniaturised instruments such as the mini-PCNL. Especially in combination with a tubeless procedure in which a routine nephrostomy after PCNL is omitted and the nephrostomy tract is closed using hemostyptic sealant, similar success rates are achieved, with fewer complications and shorter hospital stays.

[The role of perineal ultrasound compared to lateral cysturethrogram in urogynecological evaluations]. / Die Perinealsonographie im Vergleich zum lateralen Zysturethrogramm bei der Inkontinenzdiagnostik der Frau.

PURPOSE: The aim of this study was to evaluate prospectively whether perineal ultrasound is comparable to the lateral cysturethrogram in the evaluation of incontinent women. PATIENTS AND METHODS: Following urodynamic investigations, a lateral cysturethrogram and perineal ultrasound (5 MHz probe, bladder filling 300 mL) were performed in 98 incontinent women. In women with detrusor overactivity and consecutively reduced bladder capacity, ultrasound was performed at maximum capacity. To evaluate differences between perineal ultrasound and the cysturethrogram, the difference between bladder neck and lower border of symphysis and the retrovesicle angle beta were determined at rest and during the Valsalva manoeuvre. RESULTS: Using perineal ultrasound, the differences between bladder neck and symphysis could be determined at rest and during the Valsalva manoeuvre in all patients. The determination of the retrovesical angle beta was possible in all patients at rest and in 89 of the 98 women during the Valsalva manoeuvre. The lateral cysturethrogram enabled the determination of difference between bladder neck and symphysis and the retrovesicle angle beta at rest in 81 of 98 women. During the Valsalva manoeuvre, the difference between bladder neck and symphysis and retrovesicle angle beta could be determined in 72 of the 98 women. In the 26 remaining women, the determination was impossible due to severe adiposity or cystoceles of the second or third degree. CONCLUSIONS: Perineal ultrasound provides comparable data to the lateral cysturethrogram. In patients with adiposity, perineal ultrasound seems to be superior. Within the routine evaluation of women suffering from incontinence, the lateral cysturethrogram can be replaced by perineal ultrasound without any limitations of the diagnostic value.

[New techniques for surgical treatment of postoperative male stress incontinence]. / Neue Verfahren zur operativen Therapie der postoperativen Belastungsinkontinenz beim Mann.

The impact of minimally invasive techniques for the treatment of postoperative male incontinence has significantly improved in recent years. These techniques are based on the continuous increase in urethral resistance. This resistance can be readjusted with balloons placed paraurethrally or with readjustable suburethral slings. The success rates depend on the preoperative degree of incontinence. With bulking agents that are transurethrally injected into the submucosa of the sphincter, continence rates between 12 and 90% can be seen. Severe complications are rare. The impact of the studies is often limited due to a short follow-up. After implantation of adjustable balloons that are placed paraurethrally close to the bladder neck, continence rates up to 70% can be seen. The overall improvement of incontinence is observed in up to 90% of the treated patients. Complications such as balloon migration or mechanical disorders can cause operative revision. Suburethral sling systems are available as bone-anchored slings or as readjustable slings. Continence can be seen in up to 90% of the patients postoperatively. Severe complications such as sling erosion or sling infection are rare. In cases of mild and moderate incontinence, these minimally invasive techniques are good alternatives to the fascial sling or alloplastic sphincter implantation. To improve the evaluation and to compare these techniques with the conventional methods, further investigations with a longer follow-up are necessary.

[Georg Kelling (1866-1945): the man who introduced modern laparoscopy into medicine]. / Georg Kelling (1866-1945): Der Erfinder der modernen Laparoskopie.

On 23 September 1901, Georg Kelling (1866-1945) from Dresden performed a celioscopy with a Nitze cystoscope on a dog in Hamburg. This was the beginning of the era of laparoscopy.His doctoral thesis already reflected his early interest in the anatomy and physiology of the gastrointestinal tract. This experience, together with his knowledge on air insufflation of the abdomen, enabled him to be the first to develop the procedure he named "celioscopy." During this pioneer time of laparoscopy, he developed various basic principles that are still valid today and demonstrated astonishingly visionary skills. Although his pioneering achievements have hardly been acknowledged to this day, modern laparoscopy has confirmed Kelling's visions and scientific work in almost all aspects. His name and achievements have most definitely earned a place in the history of endoscopy.

Shock wave lithotripsy versus ureteroscopy for distal ureteral calculi: a prospective study.

We performed a prospective, non-randomised study to determine the appropriate first-line treatment modality for distal ureteral stones. Between 2003 and 2004, a total of 124 patients with distal ureteral calculi were entered into the study (mean age 48 years, 35 women and 99 men). Sixty-two patients were treated with shock wave lithotripsy (SWL) and 62 patients with ureteroscopy (URS). The average stone size was 6.9 mm (3-33 mm) for SWL and 7.2 mm (3-30 mm) for URS. The treatment decision depended on the patients' preference and clinical parameters (i.e. contraindications for anaesthesia). URS was performed under general anaesthesia, using semirigid 8 Fr instruments. SWL was performed under analgo-sedation using a Modulith SLX. Of patients treated with SWL, 84% had a treatment success within 7 days, 98% after URS. These results show a significant success (P=0.005) in favour of URS. The average in-patient stay after SWL was 3 days and for URS 4 days (not significant). The results show a high efficacy and a low complication rate for both modalities. The attained stone-free rate shows a significant advantage for primary URS.

Assisted procreation in cases of hepatitis B, hepatitis C or human immunodeficiency virus infection of the male partner.

Guidelines for assisted procreation impose a special responsibility upon physicians for the health of the expected child because of their active role in inducing pregnancy. Therefore, careful clinical evaluation of both partners has to precede every application of these methods. Risks for the mother's health or the development of the child count as a relative contraindication for a treatment. To balance these relative contraindications, the existing risk factors have to be recognized through screening examination. If a chronic infection occurs in the male partner, prevention for the female partner is theoretically possible by using a condom. As this inhibits a pregnancy, at least in cases of human immunodeficiency virus and hepatitis C virus infections, realization of a pregnancy requires assisted procreation. The main question in these cases is whether infectious particles can be eliminated by sperm processing to ensure the safe treatment of the healthy female partner.

[Wolfgang Amadeus Mozart. A urological pathography]. / Wolfgang Amadeus Mozart. Eine urologische Pathographie.

The death of Wolfgang Amadeus Mozart was mysterious from the very first day, and cause of wildest speculation and adventurous assertions. Over the last 100 years, medical science has investigated the physical sufferings and the mysterious death of Mozart with increasing intensity. By means of letters from his father Leopold, his sister "Nannerl", himself and reports from his physicians and contemporaries, we would like to create a medical pathography. The rumour that Mozart was poisoned appeared soon after his early death at the age of 35 on December 5th 1791, and was kept up persistently. Accused were the physician van Swieten, Mozart's freemason's loge and the royal band master Salieri. Mozart, however, died due to chronic kidney disease and ultimately due to uraemia. Once the renal damage has reached a certain point, a minimum of additional stress leads to decompensation. This catastrophe occurs typically within the fourth decade of life. When listening to Mozart's music, we should remember that this apparently happy person was actually a premature adult robbed of his childhood, whose short life was an endless chain of indisposition, over fatigue, misery, concern and illness.

Reproducibility of a four-point clinical severity score for glabellar frown lines.

BACKGROUND: Focal injections of botulinum toxin A are used successfully for the treatment of hyperkinetic facial wrinkles. Efficacy can be measured by several methods. However, so far none has been investigated for its reproducibility. Objectives To investigate the reproducibility of a clinical 0-3 score for glabellar frown lines. METHODS: In the first part of the study, a standardized photographic documentation of glabellar frown lines was produced. Based on the results of this phase, a consensus atlas of glabellar frown lines was developed and participants were trained using this atlas. In the main study, 50 standardized photographs were shown on two consecutive days to 28 dermatologists. The reproducibility of the score was investigated by conventional kappa statistics. RESULTS: In the main study, we found an unweighted kappa according to Fleiss of 0.62 for interobserver reproducibility. Intraobserver reproducibility showed an unweighted kappa according to Cohen of between 0.57 and 0.91 for each observer, and a weighted kappa according to Cicchetti and Allison of between 0.68 and 0.94. CONCLUSIONS: The clinical 0-3 score for glabellar frown lines shows a good inter- and intraobserver reproducibility.