Vesico-urethral anastomotic stenosis following radical prostatectomy: a multi-institutional outcome analysis with a focus on endoscopic approach, surgical sequence, and the impact of radiation therapy.

OBJECTIVES: To investigate the predictors of recurrence and of de novo incontinence in patients treated by transurethral incision or resection for vesico-urethral anastomotic stenosis (VUAS) after radical prostatectomy. MATERIAL AND METHODS: All patients undergoing endoscopic treatment for VUAS between March 2009 and October 2016 were identified in our multi-institutional database. Digital chart reviews were performed and patients contacted for follow-up. Recurrence was defined as any need for further instrumentation or surgery, and de-novo-incontinence as patient-reported outcome. RESULTS: Of 103 patients undergoing endoscopic VUAS treatment, 67 (65%) underwent transurethral resection (TR) and 36 (35%) transurethral incision (TI). TI was performed more frequently as primary treatment compared to TR (58% vs. 37%; p = 0.041). Primary and repeated treatment was performed in 46 (45%) and 57 patients (55%), respectively. Overall, 38 patients (37%) had a history of radiation therapy. There was no difference in time to recurrence for primary vs repeat VUAS treatment, previous vs no radiation, TR compared to TI (all p > 0.08). Regarding treatment success, no difference was found for primary vs. repeat VUAS treatment (50% vs. 37%), previous radiation vs. no radiation (42% vs. 43%), and TR vs. TI (37% vs. 53%; all p ≥ 0.1). Postoperative de novo incontinence was more common after TI vs. TR (31% vs. 12%; p = 0.032), no difference was observed for previous radiation therapy vs. no radiation therapy (18% vs. 18%; p > 0.9) or primary vs. repeat VUAS treatment (22% vs. 16%; p = 0.5). CONCLUSION: VUAS recurrence after endoscopic treatment is not predictable. Endoscopic treatment with TI showed a higher risk for de novo incontinence than TR, and previous irradiation and the number of treatments do not influence incontinence.

DFTB+, a software package for efficient approximate density functional theory based atomistic simulations.

DFTB+ is a versatile community developed open source software package offering fast and efficient methods for carrying out atomistic quantum mechanical simulations. By implementing various methods approximating density functional theory (DFT), such as the density functional based tight binding (DFTB) and the extended tight binding method, it enables simulations of large systems and long timescales with reasonable accuracy while being considerably faster for typical simulations than the respective ab initio methods. Based on the DFTB framework, it additionally offers approximated versions of various DFT extensions including hybrid functionals, time dependent formalism for treating excited systems, electron transport using non-equilibrium Green's functions, and many more. DFTB+ can be used as a user-friendly standalone application in addition to being embedded into other software packages as a library or acting as a calculation-server accessed by socket communication. We give an overview of the recently developed capabilities of the DFTB+ code, demonstrating with a few use case examples, discuss the strengths and weaknesses of the various features, and also discuss on-going developments and possible future perspectives.

Testicular epidermoid cysts: a reevaluation.

BACKGROUND: Testicular epidermoid cysts (TECs) are rare benign testicular neoplasms. As TECs are rarely associated with germ cell tumours (GCTs), the understanding of biological behaviour and clinical management of TEC is unresolved. METHODS: We retrospectively searched the files of patients treated for testicular neoplasms and germ cell cancer in the time from 2000 to 2017. Those with TEC were subjected to closer review looking to clinical and histological features, and to results from imaging with ultrasonography (US), contrast enhanced sonography (CEUS) and magnetic resonance imaging (MRI). RESULTS: Among 589 patients undergoing surgery for testicular tumour, nine simple TECs were identified (1.5, 95% confidence intervals 0.53-2.50%). Median age was 26 years. Imaging revealed sharply demarcated roundish lesions with avascular central areas. Eight patients underwent testis-sparing excision with no recurrence ensuing. One had orchiectomy because of large size of the mass. Histologically, TECs consisted of cornifying squamous cell epithelium and no accompanying germ cell neoplasia in situ. Two additional cases (0.3% of all) required orchiectomy because these TECs were associated with ipsilateral GCT. CONCLUSIONS: TEC is usually a benign lesion that can safely be diagnosed with US, CEUS and MRI due to its roundish shape and its avascular centre. Histologically, this TEC corresponds to the prepubertal-type teratoma unrelated to germ cell neoplasia in situ of the 2016 WHO classification. The other subtype of TEC that is associated with invasive GCT represents a teratoma of postpubertal-type. From a clinical point of view it could be easier to differentiate between a "simple TEC" which is benign (prepubertal type) and a "complex TEC" which is malignant because of its association with invasive GCT.

Psychometric properties of the German version of the Diabetes Eating Problem Survey-Revised: additional benefit of disease-specific screening in adolescents with Type 1 diabetes.

AIM: To examine the psychometric properties of the German version of the abbreviated 16-item Diabetes Eating Problem Survey-Revised in a sample of young people with Type 1 diabetes. METHODS: A total of 246 young people, aged 11-19 years, with Type 1 diabetes from six pediatric diabetes centres in Germany were assessed using the Diabetes Eating Problem Survey-Revised. In addition, they underwent screening with two generic tools as well as the WHO five-question well-being index. A clinician's report was also obtained. RESULTS: The Diabetes Eating Problem Survey-Revised was found to have good internal consistency (Cronbach's α = 0.84). The Diabetes Eating Problem Survey-Revised scores significantly correlated with those provided by the non-specific screening tools (r = 0.37, P ≤ 0.000 and r = 0.50, P ≤ 0.000 for boys and r = 0.62, P ≤ 0.000 and r = 0.79, P ≤ 0.000 for girls), indicating convergent validity. The mean (sd) total of the scores was 12.0 (9.6). Criterion validity was confirmed against HbA1c value, BMI standard deviation score and expert (clinician) report. Of the boys included in the study, 11 scored higher than the threshold score on the Diabetes Eating Problem Survey-Revised, of whom only three (27%) were classified as 'suspected to have a disordered eating behaviour' by their clinicians. CONCLUSIONS: The Diabetes Eating Problem Survey-Revised delivered more specific information than generic screening instruments and identified more young people with eating disorders than did clinician report, especially regarding the detection of boys at risk. The results of this study support the utility of the German version of the Diabetes Eating Problem Survey-Revised to identify eating disorders in young people with Type 1 diabetes at an early stage. (German Clinical Trials Registry no.: DRKS00004699).

Brain penetration of emodepside is increased in P-glycoprotein-deficient mice and leads to neurotoxicosis.

The antiparasitic drug emodepside (EMO) is a substrate of the P-glycoprotein multidrug efflux carrier (P-gp; syn. MDR1, ABCB1), which has an important function in protecting the brain from potentially toxic compounds by functional drug efflux at the blood-brain barrier (BBB). Many dogs of the Collie breed and even dogs of many other breeds have a loss-of-function 4-bp deletion mutation in the MDR1 gene. In these dogs, brain penetration of many P-gp-transported drugs is increased and so their therapeutic usage is restricted. To elucidate the role of P-gp at the BBB for the brain penetration of EMO, we applied EMO at 1 mg/kg to mdr1-deficient (PGP(mut) ) and mdr1-intact (PGP(WT) ) CF1 mice. Whereas in the brain of the PGP(WT) mice, EMO was below the detection level of 10 ng/g, its concentration was at 43.7 ng/g in the PGP(mut) mice. Furthermore, appearance of neurological toxicity was analyzed in these mice after application of 1 mg/kg EMO using a rotarod setup. In all PGP(mut) mice, but not in the PGP(WT) mice, the walking performance on the rotarod was impaired by EMO with clear differences in the degree and duration of neurological toxicity. Some of the mice were completely unable to walk on the rotarod already at 2 h after drug application and showed long-lasting ataxia over >24 h. Others even showed significantly reduced walking performance, but completely recovered within 1 day. In conclusion, P-gp restricts brain penetration of EMO and prevents neurological toxicity of this drug in mice.

Genome-wide significant associations in schizophrenia to ITIH3/4, CACNA1C and SDCCAG8, and extensive replication of associations reported by the Schizophrenia PGC.

The Schizophrenia Psychiatric Genome-Wide Association Study Consortium (PGC) highlighted 81 single-nucleotide polymorphisms (SNPs) with moderate evidence for association to schizophrenia. After follow-up in independent samples, seven loci attained genome-wide significance (GWS), but multi-locus tests suggested some SNPs that did not do so represented true associations. We tested 78 of the 81 SNPs in 2640 individuals with a clinical diagnosis of schizophrenia attending a clozapine clinic (CLOZUK), 2504 cases with a research diagnosis of bipolar disorder, and 2878 controls. In CLOZUK, we obtained significant replication to the PGC-associated allele for no fewer than 37 (47%) of the SNPs, including many prior GWS major histocompatibility complex (MHC) SNPs as well as 3/6 non-MHC SNPs for which we had data that were reported as GWS by the PGC. After combining the new schizophrenia data with those of the PGC, variants at three loci (ITIH3/4, CACNA1C and SDCCAG8) that had not previously been GWS in schizophrenia attained that level of support. In bipolar disorder, we also obtained significant evidence for association for 21% of the alleles that had been associated with schizophrenia in the PGC. Our study independently confirms association to three loci previously reported to be GWS in schizophrenia, and identifies the first GWS evidence in schizophrenia for a further three loci. Given the number of independent replications and the power of our sample, we estimate 98% (confidence interval (CI) 78-100%) of the original set of 78 SNPs represent true associations. We also provide strong evidence for overlap in genetic risk between schizophrenia and bipolar disorder.

[Urinary bladder microbiome analysis and probiotic treatment options for women with recurrent urinary tract infections]. / Mikrobiomanalyse der Harnblase und probiotische Therapieoptionen bei Frauen mit rezidivierenden Harnwegsinfektionen.

Novel preventive measures and therapeutic approaches are needed to reduce the frequency of recurrent urinary tract infections (rUTI) and the associated emergence of multidrug-resistant uropathogens. The aim of this review is to systematically present the available evidence on the urinary bladder microbiome of healthy women and those with rUTIs. In addition, relevant studies on the efficacy of probiotics in rUTIs are presented in a structured manner. This will provide an overview on the current state of research and an outlook on treatment strategies beyond the usual antimicrobial options.

[Does structural and process quality of certified prostate cancer centers result in better medical care?] / Resultiert aus Struktur- und Prozessqualität zertifizierter Prostatakarzinomzentren eine bessere medizinische Versorgung?

BACKGROUND: An improved structural and process quality could be demonstrated 13 years after certification of the first German prostate cancer center. The question of optimization of the functional quality by establishing organ cancer centers arises. OBJECTIVE: A critical benefit-risk analysis of organ cancer centers was carried out to evaluate an improved quality of results. MATERIAL AND METHODS: Based on published results from individual centers and the individual annual reports of the German Cancer Society (DKG), the data for evaluating the quality of results were checked. For the issuing of certificates, the focus is on quality indicators for oncological surgery. The functional quality of results is assessed exclusively by a questionnaire-based survey. RESULTS: An improvement in the quality of functional results after radical prostatectomy has not yet been demonstrated. The functional quality features of urinary continence and erectile function that are essential for the quality of life and patient satisfaction are only insufficiently assessed due to the lack of objective measuring instruments and are not relevant for certification. There is no reliable evidence for improved overall survival, reduction in tumor-specific mortality, and optimization of functional results in certified centers. CONCLUSION: The relationship between certification and excellence cannot be proven without individual consideration of a surgeon-specific pentafecta analysis. For this reason, certification-relevant surgeon-related quality assurance is recommended.

[Testicular sperm extraction in male infertility : Indications, success rates, practical implementation, and possible complications]. / Testikuläre Spermienextraktion bei männlicher Infertilität : Indikationen, Erfolgsraten, praktische Durchführung und mögliche Komplikationen.

BACKGROUND: Unwanted childlessness is a burden on a couple's relationship. The therapeutic spectrum of male infertility has increased significantly in recent years so that even azoospermia patients can be given biological paternity by testicular sperm extraction (TESE). OBJECTIVES: The indications, success rates, practical implementation, and possible complications of conventional and microscopic TESE in male infertility are presented in this review. METHODS: A nonsystematic search of the relevant literature was carried out. RESULTS: In obstructive azoospermia (OA), primarily desobstructive surgical procedures are used, while TESE is the surgical procedure of choice in nonobstructive azoospermia (NOA). In the latter, sperm extraction can be performed conventionally or microscopically (mTESE) assisted, whereby the latter offers an advantage in terms of sperm detection rate in the case of small testicular volumes (<12 ml), chemotherapy, Klinefelter's disease and AZFc microdeletions. The sperm detection rate of TESE is about 50%. Postoperative controls are useful because of the possible induction of symptomatic hypogonadism. CONCLUSION: Before performing TESE, determining the hormone status and human genetic clarification are necessary. Any costs incurred and the possibility of missing sperm proof must be discussed. Close cooperation between andrologists, gynecologists, reproductive physicians, and human geneticists is necessary. All in all, TESE is a safe surgical procedure with a low complication rate.

[Continence and pelvic floor centers-Meaningful certification requirements?] / Kontinenz- und Beckenbodenzentren ­ sinnvolle Zertifizierungsvorgaben?

As a consequence of the demographic change, the prevalence of female and male bladder and bowel dysfunction, functional pelvic floor disorders and pelvic organ prolapse are steadily increasing. Continence and pelvic floor centers are interdisciplinary facilities that focus on these functional disorders, including malformations, tumors and functional disorders resulting from neurogenic diseases, injuries or surgery. The affected patient clientele includes children, women, and men of all ages. The certification is carried out by the accredited certification company CERT iQ Certification Services. In addition to structural requirements, personal quality criteria are also implemented in the novel harmonized and standardized certification system. The assessment of treatment quality is also a component of the procedure, although it is currently limited to the midurethral sling tracer procedure for the treatment of female stress urinary incontinence. Regarding the other conservative and surgical treatment options for pelvic floor, bladder and bowel functional disorders, no quality of outcome has so far been recorded. Internationally recognized and validated questionnaires to assess preoperative and postoperative quality of life would be valuable tools to define the quality of treatment and outcome. Similarly, supplementary thresholds should be established for complication rates and quality of the success of treatment to identify centers with high expertise. In this context, it is crucial to consider the individual complexity of the patient groups and to distinguish between primary and recurrent interventions.

[Types of evidence syntheses]. / Formen der Evidenzsynthese.

This manuscript outlines various types of review articles as forms of evidence synthesis with special regard to their strengths and limitations. Review articles not only present summarised data, but also offer an evaluation of the quality of the individual studies included in it. The validity and the reliability of outcomes of reviews is strongly dependent on the quality of the data included. For this reason, a comprehensive literature selection process is paramount. Fundamental knowledge of bias and literature assessment is also necessary when reading reviews. This article presents selected tools for evidence appraisal and evaluation of bias risk.

[Complicated urinary tract infections]. / Komplizierte Harnwegsinfektionen.

Urinary tract infections (UTIs) are among the most common bacterial infections in Germany, both in outpatient and inpatient settings. The clinical spectrum is heterogeneous and ranges from benign, often self-limiting, uncomplicated infections to complicated urinary tract infections (cUTIs) with life-threatening courses. Complicated urinary tract infections have a higher risk of chronicity, recurrence and/or progression than uncomplicated infections and may be associated with severe disease progression. Stratification of patients with urinary tract infections is, therefore, of utmost importance. Host factors rather than pathogen attributes determine the pathophysiology and therapy of complicated urinary tract infections and pyelonephritis. Complicated UTIs and pyelonephritis are also associated with high rates of antimicrobial resistance in the causative pathogens, so they should be given particular emphasis.

[Vascular injuries during urologic surgery]. / Gefäßverletzungen während urologischer Operationen.

This review article summarizes the epidemiology of vascular injuries during urologic surgery and discusses intraoperative strategies to control bleedings. Techniques of vascular approaches (arteries and veins) are discussed and tricks for vascular repair are explained. Generally, vascular injuries during urologic surgery are rare. However, hemorrhage due to vascular injury is a common cause of critical morbidity and mortality in the perioperative period. Susceptibility to vascular complications such as oncological debulking and revision surgery increase risk for damage. As vascular injuries range from arrosion to avulsion, treatment is also broad, ranging from vascular suture to open or endovascular repair. Prevention of exsanguination requires visual control to stop the bleeding. The surgeon must act quickly to initiate appropriate repair, aiming for damage control and stabilization of the patient. Planning the surgery and consulting an experienced surgeon are decisive for successful management. Catastrophic bleeding has to be controlled and in the case of arterial injury it is often necessary to reconstitute perfusion. Reconstructions such as vascular anastomoses, patch angioplasty or interposition grafts are the preferred surgical techniques which are influenced by the nature of the injury. Vessels have to be thoroughly prepared before cross clamping to prevent injury by vascular clamps. Veins can often be ligated. Endovascular repair is also a possibility to control the bleeding, but nowadays it is often a definitive therapy method. For example, resuscitative endovascular balloon occlusion is useful to stabilize the patient and then to initiate vascular repair. Depending on the type of surgery performed, different vessels are concerned. Severe bleeding is usually located retroperitoneal affecting the aorta, renovisceral and iliac vessels. Predisposing urologic operations are lymphadenectomy, nephrectomy and (cysto)prostatectomy and also the laparoscopic approach can cause bleeding complications.

[Penile paraffinoma-Treatment strategies]. / Penile Paraffinome ­ therapeutische Strategien.

BACKGROUND: Penile paraffinomas are a consequence of an injection of mineral oils for augmentation. As an result of the foreign body reaction local complications regularly occur, which require a plastic reconstructive intervention. So far 8 cases have been treated in our clinic over the last 20 years. OBJECTIVE: Presentation of the operative treatment techniques for penile paraffinoma as well as the indications and complications. MATERIAL AND METHODS: After reviewing the relevant literature, we analyzed the data of our own patient cohort. Since 1999 a total of 8 patients with lipogranuloma underwent surgical treatment at the St. Antonius Hospital in Eschweiler. RESULTS: The choice of a plastic reconstructive treatment depends on the extent of the paraffinoma. If it is limited to the foreskin, a radical circumcision is sufficient but if it extends to the skin of the penile shaft, a plastic defect coverage with a mesh graft, a full skin graft or a scrotal skin flap is required. In cases with additional pathologies, such as urethral fistulas, auxiliary reconstructive procedures should be performed. CONCLUSION: For optimal cosmetic and functional results, the surgeon must master a broad spectrum of plastic reconstructive techniques. In selected complex cases an interdisciplinary approach consisting of urologists and plastic surgeons can be necessary.

[Use of synthetic slings and mesh implants in the treatment of female stress urinary incontinence and prolapse : Statement of the Working Group on Urological Functional Diagnostics and Female Urology of the Academy of the German Society of Urology]. / Einsatz von synthetischen Band- und Netzimplantaten bei der Behandlung von Belastungsinkontinenz und Descensus genitalis der Frau : Stellungnahme des Arbeitskreises Urologische Funktionsdiagnostik und Urologie der Frau der Akademie der Deutschen Gesellschaft für Urologie.

Due to a safety alert issued by the US Food and Drug Administration (FDA) in 2011 for transvaginal mesh implants to treat female prolapse as a result of numerous reports of complications such as infection, chronic pain, dyspareunia, vaginal erosion, shrinkage and erosion into other organs nearly all industrial products have been withdrawn from the market in the meantime. The United Kingdom, Australia, and New Zealand extended warnings and prohibitions even on the implantation of midurethral slings (TVT, TOT). In view of these current international controversies regarding the use of implanted materials for the treatment of stress incontinence and prolapse and the lack of clear guidelines for the use of biomaterials, the opinion of the Working Group on Urological Functional Diagnostics and Female Urology should provide clarity. The Opinion is based on the SCENIHR Report of the "European Commission's Scientific Committee on Emerging and Newly Identified Health Risks", the "Consensus Statement of the European Urology Association and the European Urogynaecological Association on the Use of Implanted Materials for Treating Pelvic Organ Prolapse and Stress Urinary Incontinence" and in compliance with relevant EAU and national guidelines and the opinion of the Association for Urogynaecology and Plastic Pelvic Floor Reconstruction (AGUB eV). In addition, recommendations are given for the future handling of implants of slings and meshes for the treatment of stress incontinence and prolapse from a urologic viewpoint.

[Actively living a medical safety (error) culture-what does urology need to learn?] / Gelebte Sicherheits(fehler)kultur ­ was muss die Urologie lernen?

Patient safety is the basic quality of every medical treatment. Scientifically sound knowledge on the necessary structures of a safety management system and experience from effectively implementing those are aplenty. Yet, even 30 years after the first successful steps, it is still difficult for healthcare to implement a comprehensive, system-wide approach. Cultural changes at the level of attitudes and the consistent creation of the necessary structures might accelerate this transformation process.

[Old wine in new bottles-proven open-surgical procedures for the treatment of pelvic organ prolapse]. / Alter Wein in neuen Schläuchen ­ bewährte offen-operative Verfahren zur Behandlung des Urogenitalprolaps.

Urinary incontinence and pelvic organ prolapse (POP) are increasing due to demographic factors. Increasing life expectancy and sociocultural demands of women require successful treatments that also have low complication rates. Classic open procedures such as colposuspension or colposacropexy (native tissue repair as well as mesh procedures) are experiencing a renaissance due to the current critical view of mesh-repair pelvic floor surgery and continue to be of great importance. With suitable patient selection, long-term results of abdominal procedures are on a par with minimally invasive techniques. Cosmetically acceptable results can be achieved with optimized incisions. The therapeutically relevant target for apical fixation is the elevation angle of the vagina (EAV). Minimally invasive mesh-based primary reconstructions and interventions for POP recurrence proved to be superior to conventional procedures due to good long-term results, lower recurrence rates and reduced early and late complication rates when anatomically correct and gentle surgery is performed with a critical selection of textile implants. Abdominal procedures are not inferior to minimally invasive techniques when instrumental suturing techniques and modern instruments are used. Adequate and critical information about surgical options and possible risks of complications should be provided in a timely manner. Education and training in modern diagnostics as well as in abdominal and current minimally invasive techniques and complication management should be implemented according to the guidelines and recommendations of professional societies, the Food and Drug Administration and the European Network of Information Centres.

[Barriers to guideline adherence : Identification of barriers to guideline adherence using a survey on the AWMF S3 guideline epidemiology, diagnosis, treatment, and management of uncomplicated bacterial, community-acquired urinary tract infections in adult patients]. / Barrieren der Leitlinienadhärenz : Identifizierung von Barrieren der Leitlinienadhärenz am Beispiel einer Umfrage zur AWMF-S3-Leitlinie Epidemiologie, Diagnostik, Therapie und Management unkomplizierter bakterieller ambulant erworbener Harnwegsinfektionen bei erwachsenen Patienten.

BACKGROUND: Several studies have shown that nonadherence to guidelines is pretty common in the treatment of urinary tract infections (UTI). However, no urological study has raised the question, what are barriers or reasons for this nonadherence, yet. OBJECTIVES: Consequently, we performed a survey among German urologists with the primary endpoint identification of barriers for nonadherence to German guidelines on UTI. MATERIALS AND METHODS: A 19-item questionnaire was developed and transferred to the online portal "Survey Monkey®" (Private Equity, San Mateo, CA, USA) and tested for usability by our study group. The link for the survey was sent twice to the members of the German Society of Urology (DGU). RESULTS: Overall, 307 questionnaires were completed. The mean age of the study population was 46.7 years (standard deviation 11.5). The majority (34.9%) followed guidelines in 80% of the cases. Main reasons for nonadherence on the physicians' side were 23.4% personal experience and lacking practicality of UTI guidelines on the individual complex patient. On the open questions urologists mostly stated (11.7%) that the main reason on the physician side for nonadherence is ignorance. Therefore they, in open questions, suggest to promote guidelines more in meetings and more designed practically with shortcuts and simple layout. Patient-associated factors mentioned were mostly in 26.7%. Furthermore, German urologists stated that guidelines should also have a patient section, where the main recommendations are explained in plain language. CONCLUSION: We performed the first survey on identifying barriers for nonadherence to guidelines in urology. Despite some limitations, our results are very important for the further design of guidelines. This has the potential to improve guideline adherence.