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Purpose: We aimed to assess the impact of GATA3 binding protein (GATA3) gene copy number alterations on tumor aggressiveness, patient prognosis, and GATA3 protein expression in a large urothelial bladder cancer cohort., Methods: A tissue microarray containing over 2,700 urothelial bladder cancers (pTa-pT4) was analyzed retrospectively using dual-labeling fluorescence in-situ hybridization (FISH) with probes for GATA3 (10p14) and centromere 10. GATA3 copy number gains were categorized as GATA3 elevation (ratio GATA3/centromere ≥ 2/≤4), low-level amplification (ratio > 4/≤12), and high-level amplification (ratio > 12) and deletions were divided between homozygous and heterozygous., Results: GATA3 copy number gain was detected in 9.9% of 2,213 interpretable tumors, including 2.0% with GATA3 elevation, 3.2% with low-level amplification, and 4.7% with high-level amplification. The frequency of high-level amplification increased from pTa G2 low (0%) to pTa G3 tumors (12% [CI 0.07;0.21]; p < 0.0001 pTa G2 low vs. pTaG2 high) but decreased in advanced-stage carcinomas pT2-4 with 5.4% [CI 0.07;0.21] (p < 0.0001, pTa vs. pT2-4). In muscle-invasive carcinomas, GATA3 amplification was not linked to tumor aggressiveness or patient survival. Overall, no homozygous GATA3 deletion was detected and heterozygous GATA3 deletion was only observed in 1.1%; of 1,432 pT2-4 tumors without any association to cancer progression. While GATA3 copy number was significantly correlated with GATA3 expression (p < 0.0001), the relationship was not strong. Only 2.3% of GATA3-negative cancers had a deletion, and 42.1% of strong GATA3-expressing cancers exhibited high-level amplification., Conclusion: High-level GATA3 amplification is common in urothelial bladder cancer and correlates with grade progression in pTa tumors, while GATA3 deletion is rare. Neither amplification nor deletion appears to be the primary driver of GATA3 expression dysregulation., Clinical Trial Number: Not applicable., Competing Interests: Declarations. Ethical approval: The use of archived remnants of diagnostic tissues for manufacturing of TMAs and their analysis for research purposes as well as patient data analysis has been approved by local laws (HmbKHG, § 12) and by the local ethics committee (Ethics commission Hamburg, WF-049/09). All work has been carried out in compliance with the Helsinki Declaration. Competing interests: The authors declare no competing interests., (© 2025. The Author(s).)

Background: The shortage of skilled labor in medicine is one of the most pressing challenges in healthcare. The increasing number of women in medicine, particularly in the field of urology, raises questions about the compatibility of family and career, especially concerning the work environment and working time models., Objective: The aim of this study is to capture the impact of motherhood on the professional lives of female physicians and scientists in the field of urology in Germany. Specific challenges in this surgical specialty and the compatibility of family and career will be highlighted., Methods: The working group "Female Physicians and Scientists in Urology" of the German Society of Urology (DGU) surveyed its 1343 female members regarding demographic data, professional status, and aspects of work-life balance., Results: Among 487 female urologists in Germany, 53.4% had children. Mothers tended to be older, less frequently in training, less often in inpatient settings, and less frequently engaged in surgical activities. Notably, the proportion of full-time working mothers (36.2%) was significantly lower compared to female urologists without children (92.4%). Among female urologists with children, 32.3% reported having changed their workplace because of their children, while 10.7% indicated that their responsibilities had changed at least once after pregnancy. Additionally, 76.9% of mothers had reduced their weekly working hours due to family commitments. Multivariate analysis showed an influence of motherhood on professional status and parttime work., Conclusion: The fact that starting a family for women in urology in Germany is associated with a reduction in working hours and the end of clinical careers suggests a need for optimizing the compatibility of family and career in Germany. The increasing feminization of the medical profession exacerbates the existing shortage of skilled workers due to the exit of mothers from professional life. To meet the needs of working parents, particularly mothers, urgent adjustments in the work environment are necessary. Promoting flexible working time models and creating supportive conditions are crucial to preventing the loss of skilled professionals and maintaining job satisfaction in this field., Competing Interests: Einhaltung ethischer Richtlinien. Interessenkonflikt: L. Wiemer, S. Knipper, A. Herlemann, M.-N. Welte, C. Siech, E.M. Greiser, K. Müller, L. Bellut, S. Schönburg, M. Walach, R. Pompe und S. Weinberger geben an, dass kein Interessenkonflikt besteht. Da es sich um ein Forschungsvorhaben handelt, dass kein Risiko oder keine vermehrte Belastung für die Teilnehmenden darstellte, war ein Ethikantrag nicht erforderlich., (© 2024. The Author(s).)

Purpose: The objective of this study was to evaluate the perioperative outcomes and complications associated with the use of acetylsalicylic acid (ASA) in deceased donor kidney transplantation (KTX), with a particular focus on bleeding events., Methods: We retrospectively analyzed 157 kidney transplant recipients (KTRs) who underwent KTX at Charité Berlin, Department for Urology, between February 2014 and December 2017. Patients were divided into two groups: patients with ASA in their preoperative medication (Group A, n = 59) and patients without ASA use (Group B, n = 98). Data on demographic information, medical conditions, surgical details, and postoperative outcomes were analyzed. Complications were classified using the Clavien-Dindo classification. Statistical analyses included t-tests, chi-square tests, and multivariate logistic regression., Results: Group A had significantly older donors (59.7 ± 12.9 years vs. 52.0 ± 14.1 years, p < 0.001) and a higher incidence of coronary artery disease (42.4% vs. 3.1%, p = 0.001). There were no significant differences in perioperative hemoglobin loss and perioperative bleeding events between the groups, but a tendency towards higher rates of intraoperative bleeding (15.3% vs. 8.2%, p = 0.17) and postoperative transfusions (22% vs. 13.3%, p = 0.15) in Group A. Mortality was higher in Group A (18.6% vs. 4.1%, p = 0.003), with one death attributed to a cardiac event. Kaplan-Meier analysis revealed significantly inferior overall survival for Group A (p = 0.02), but no significant difference in graft survival (p = 0.18)., Conclusion: ASA use is associated with a trend towards increased intraoperative bleeding and postoperative blood transfusion but does not significantly increase major postoperative bleeding complications. Careful perioperative monitoring of patients with ASA is recommended., Competing Interests: Declarations. Ethical approval: This study has been conducted according to the Declaration of Helsinki; all organs were donated voluntarily with written informed consent, and this was conducted in accordance with the Declaration of Istanbul. The article is exempt from the local Ethical Committee approval (Institutional Review Board of Charité Hospital Berlin) because of this study’s retrospective, noninterventional design and because patient data confidentiality and privacy were always maintained. Conflict of interest: Authors disclose, that there are no interests that are directly or indirectly related to the work submitted for publication., (© 2024. The Author(s).)

Homozygous 9p21 deletions usually result in a complete loss of S-methyl-5'-thioadenosine phosphorylase (MTAP) expression visualizable by immunohistochemistry (IHC). MTAP deficiency has been proposed as a marker for predicting targeted treatment response. A tissue microarray including 2,710 urothelial bladder carcinomas were analyzed for 9p21 deletion by fluorescence in situ hybridization and MTAP expression by IHC. Data were compared with data on tumor phenotype, patient survival, intratumoral lymphocyte subsets, and PD-L1 expression. The 9p21 deletion rate increased from pTaG2 low (9.2% homozygous, 25.8% heterozygous) to pTaG2 high (32.6%, 20.9%; p < 0.0001) but was slightly lower in pTaG3 (16.7%, 16.7%) tumors. In pT2-4 carcinomas, 23.3% homozygous and 17.9% heterozygous deletions were found, and deletions were tied to advanced pT (p = 0.0014) and poor overall survival (p = 0.0461). Complete MTAP loss was seen in 98.4% of homozygous deleted while only 1.6% of MTAP negative tumors had retained 9p21 copies (p < 0.0001). MTAP loss was linked to advanced stage and poor overall survival in pT2-4 carcinomas (p < 0.05 each). The relationship between 9p21 deletions/MTAP loss and poor patient prognosis was independent of pT and pN (p < 0.05 each). The 9p21 deletions were associated with a noninflamed microenvironment (p < 0.05). Complete MTAP loss is strongly tied to homozygous 9p21 deletion, aggressive disease, and noninflamed microenvironment. Drugs targeting MTAP-deficiency may be useful in urothelial bladder carcinoma. MTAP IHC is a near perfect surrogate for MTAP deficiency in this tumor type., (© 2024 The Author(s). The Journal of Pathology: Clinical Research published by The Pathological Society of Great Britain and Ireland and John Wiley & Sons Ltd.)

Background: According to the European Association of Urology guidelines, the limit for monopolar, transurethral resection (M-TURP) in BPH- therapy is a volume of 80 g. However, whether larger prostates can also be resected transurethrally might also depend on the experience of the surgeon and especially the resected volume and speed of the resection. Little is known about the latter, and this paper aims to these factors., Methods: This study included 540 patients who received a single-stage M-TURP. Based on the postoperative resection weight, these were divided into four groups: group 1 with 10 to 59.9 g, group 2 with 60 to 79.9 g, group 3 with 80 to 99.9 g, and group 4 with ≥ 100 g. We examined patient age, the ASA-score, the IPSS, quality of life, resection weight, time and speed, pre- and postoperative hemoglobin and serum sodium values, complications, and surgeon experience., Results: The mean resection weight was 41.6 g, and the mean values for resection time and speed were 61.3 min and 0.7 g/min, respectively. The resection speed increased significantly with resection weight (from 0.7 to 1.3 g/min) as well as with the surgeon's level of experience (from 0.4 to 0.9 g/min). The number of serious complications (Clavien-Dindo ≥ IIIb) increased significantly from a resection volume of 59.5 g (cut-off value). The resection speed of M-TURP increased significantly with the resection weight and the surgeon's level of experience. Regardless of speed, resection weight of more than 60 g might increase the risk of severe complications., Competing Interests: Declarations. Conflict of interest: The authors declare no competing interests. All authors declare that there is no conflict of interest., (© 2024. The Author(s).)

Protein phosphorylation is a crucial regulatory mechanism in cellular homeostasis. The human cytomegalovirus (HCMV) incorporates protein phosphatase 1 (PP1) into its tegument, yet the biological relevance and mechanisms of this incorporation remain unclear. Our study offers the first characterization of the PP1 interactome during HCMV infection and its alterations. Using co-immunoprecipitation, mass spectrometry, and quantitative proteomics, we identified 159 high-confidence interacting proteins (HCIPs) in the PP1 interactome, consisting of 126 human and 33 viral proteins. We observed significant temporal changes in the PP1 interactome following HCMV infection, including the altered interactions of PP1 regulatory subunits. Further analysis highlighted the central roles of these PP1 interacting proteins in intracellular trafficking, with particular emphasis on the trafficking protein particle complex and Rab GTPases, which are crucial for the virus's manipulation of host cellular processes in virion assembly and egress. Additionally, our study on the noncatalytic PP1 inhibitor 1E7-03 revealed a decrease in PP1's interaction with key HCMV proteins, supporting its potential as an antiviral agent. Our findings suggest that PP1 docking motifs are critical in viral-host interactions and offer new insights for antiviral strategies.

Purpose: Placental alkaline phosphatase (PLAP) is a protein with a poorly understood function that is normally only expressed in the placenta. In cancer, PLAP expression is a hallmark of germ cell neoplasms, but it can also occur in urothelial carcinoma. To evaluate the potential clinical significance of PLAP expression in bladder cancer, METHODS: PLAP protein was analyzed by immunohistochemistry in more than 2500 urothelial bladder carcinomas in a tissue microarray format., Results: PLAP staining was absent in normal urothelial cells but was observed in 15.9% of urothelial carcinomas, including 282 (11.5%) with weak, 57 (2.3%) with moderate, and 51 (2.1%) with strong staining. PLAP positivity occurred in 4.1% of 413 pTa G2 low-grade, 10.2% of 176 pTa G2 high-grade, and 7.2% of 97 pTa G3 tumors (p = 0.0636). As compared to pTa tumors, the PLAP positivity rate was markedly higher in 1341 pT2-4 carcinomas (19.8%, p < 0.0001). Within pT2-4 carcinomas, PLAP staining was unrelated to pT, pN, grade, L-status, V-status, overall survival, recurrence-free survival, and cancer-specific survival (p > 0.25). However, PLAP positivity was linked to p16 positivity (p = 0.0185), GATA3 positivity (p < 0.0001), and p63 expression loss (p = 0.0456)., Conclusion: In summary, these data show that PLAP is expressed in a significant fraction of pT2-4 urothelial carcinomas, unrelated to cancer aggressiveness but associated with specific molecular features. Once anti-PLAP cancer drugs become effective, urothelial carcinoma is a candidate tumor entity for clinical evaluation., Competing Interests: Declarations. Conflict of interest: The authors declare no competing interests. Ethical approval: The use of archived remnants of diagnostic tissues for manufacturing of TMAs and their analysis for research purposes as well as patient data analysis has been approved by local laws (HmbKHG, §12) and by the local ethics committee (Ethics commission Hamburg, WF-049/09). All work has been carried out in compliance with the Helsinki Declaration., (© 2024. The Author(s).)

Background : The onabotulinumtoxinA detrusor injection (OnabotA DI) was approved a decade ago for the treatment of patients with idiopathic overactive bladder (iOAB) or neurogenic detrusor overactivity (nDO) dysfunction who had not been treated successfully otherwise. The procedure is usually performed under local anesthesia (LA), and various approaches have been investigated to make the procedure as painless as possible. We examined the level of anxiety and pain experienced by patients who wanted to have the procedure performed under LA or general anesthesia (GA). Material and Methods : Patients scheduled for OnabotA DI were able to choose the anesthesia procedure (LA or GA). The Amsterdam Preoperative Anxiety and Information Scale (APAIS) was used to grade anxiety before anesthesia or before the procedure itself. Intra- and postoperative pain was determined using the Visual Analogue Scale (VAS). Various established questionnaires (including the Urinary Distress Inventory UDI-6), as well as a postoperative satisfaction questionnaire, were used to evaluate the success of the therapy. Results : In total, 104 patients (93 F, 11 M; age 64.0 (22-89) years; 80× iOAB, 24× nDO) were evaluated. OnabotA-DI was performed with LA in 72 patients and GA in 32. Stratified by first versus repeat injection in the LA group, there was a significant decrease in the Anxiety Score in the first vs. repeat injection group ( p = 0.038). The LA group showed higher concerns in the anesthesia questions of the Amsterdam Preoperative Anxiety and Information Scale (APAIS) than the GA group (OR: 0.29, 95%CI: 0.02-1.74). The VAS Pain Score during the procedure was significantly lower in the GA group compared to the LA group (LA: 3.3 ± 2.2, GA group 1.5 ± 1.5; p < 0.001). There were no differences in the success of therapy. Despite the fear and pain, patients preferred LA to GA. Conclusions : This study shows that the anxiety and pain burden of patients undergoing OnabotA-DI under LA is significant in comparison to GA during the first injection, but insignificant for following injections. Overall, LA is favored over GA.

Overactive bladder (OAB) has a significant impact on the quality of life; thus, it requires treatment that can be adhered to over a long period without undue side effects. The current treatment which uses an anticholinergic or β-3 agonist may fail to improve symptoms and has side effects, leading to high discontinuation rates. OnabotulinumtoxinA (OnabotA) detrusor injection has been approved for idiopathic OAB as a second-line treatment with good effectiveness and tolerability. This study used a visual analog scale (VAS) to assess the impact of the type of needle used for OnabotA detrusor injections under local anesthesia on the pain levels after each injection. This study included 68 female patients. We used three different needles with thicknesses ranging from 22 to 27 gauge, lengths between 4 and 5 mm, and different cuts. The sensation of pain was rated at each standardized injection location. Regardless of the needle used, the patients' perceptions of pain at the beginning of the procedure were rated as being less than the subsequent injections. Most pain sensations were rated as low to moderate. The mean pain sensation on the VAS was 2.5 ± 0.3 overall, i.e., for all patients and needles used. Statistically significant differences in pain sensation were rated only at some locations of the bladder (on the back wall and the right side of the bladder). The single needles averaged the following pain scores: 2.8 ± 0.3 for needle A (20 G, 4 mm), 2.1 ± 0.3 for needle B (27 G, 5 mm), and 2.6 ± 0.4 for needle C (20 G, 4 mm, sharp cut 15°). The 27-gauge needle caused significantly less pain, and it had no negative impact due to its length, which was 1 mm longer than the other needles. Thus, the needle thickness was a decisive factor in the patients' perceptions of pain.

Objective: There is a shortage of established prognostic biomarkers in bladder cancer. One candidate is tumour protein 63 (p63), a transcription factor of the p53 gene family that is expressed in the normal urothelium. Recently proposed RNA expression-based molecular classifiers of bladder cancer identified high p63 expression as a component of a basal/squamous subtype linked to poor patient prognosis., Methods: In this study, p63 protein expression was analysed by immunohistochemistry on more than 2500 urothelial bladder carcinomas in a tissue microarray format to determine its relationship with clinicopathological parameters of disease progression and patient outcome., Results: Nuclear p63 staining was seen in all cells of normal urothelium and at elevated levels in pTaG2 tumours. The rate of p63 positive cases and the staining intensity was lower in pTaG3 tumours (93.2%, p  < 0.0001 for pTaG3 vs. pTaG2) and markedly lower in pT2-4 carcinomas (83.5%, p  = 0.0120 for pT2-4 vs. pTaG3). Within 1018 pT2-4 carcinomas treated by cystectomy, low p63 expression was linked to nodal metastasis ( p  = 0.0028) and overall survival ( p  = 0.0005). The association with survival was independent of pT and pN ( p  = 0.0081). p63 expression was associated with GATA3 expression ( p  < 0.0001), a luminal cell type marker associated with favourable disease. A joint analysis of p63 and GATA3 did not suggest that GATA3 could provide additional prognostic information., Conclusion: The independent prognostic role of reduced p63 expression in advanced urothelial carcinomas suggests that p63 could be a useful biomarker to distinguish pT2-4 urothelial carcinomas., Competing Interests: The recombinant rabbit monoclonal p63 antibody, clone MSVA‐063R, was obtained from MS Validated Antibodies GmbH, Hamburg, Germany (owned by a family member of GS)., (© 2024 The Author(s). BJUI Compass published by John Wiley & Sons Ltd on behalf of BJU International Company.)

17p13 deletions including TP53 and other genes represent a common cause for reduced/lost p53 function in tumor cells. In this study, we analyzed the impact of 17p13 (TP53) deletions and p53 expression on tumor aggressiveness and patient prognosis in urothelial carcinoma. The 17p13 copy number status was analyzed by fluorescence in situ hybridization (FISH) on more than 2700 urothelial bladder carcinomas in a tissue microarray format. 17p13 deletion data were compared to p53 expression data measured by immunohistochemistry (IHC) in a previous study. Different types of p53 alterations were compared with tumor phenotype and clinical outcome data. Deletions of 17p13 occurred in 23% of 2185 analyzable carcinomas. The fraction of tumors with 17p13 deletions increased from pTa G2 low (9%) to pTa G3 (24%, p < 0.0001). In muscle-invasive carcinomas, 17p13 deletions were associated with advanced pT stage (p = 0.0246), but unrelated to patient prognosis (p > 0.5). 17p13 deletions were significantly related to p53 immunostaining (p = 0.0375). 17p13 deletions were most common in tumors with complete lack of p53 staining (31%), which supports the concept that many of these tumors have a complete loss of p53 function (p53 null phenotype). 17p13 deletions were also increased in tumors with high p53 staining (25%). In conclusion, 17p13 deletions were most commonly seen in p53 negative cancers, supporting their role as a cause for the p53 null phenotype in urothelial cancer. The association of 17p13 deletions with high grade and advanced pT stage may reflect increasing genomic instability going along with stage and grade progression., (© 2024 The Author(s). Genes, Chromosomes and Cancer published by Wiley Periodicals LLC.)

Background and Objective: Quantity and the spatial relationship of specific immune cell types can provide prognostic information in bladder cancer. The objective of the study was to characterize the spatial interplay and prognostic role of different immune cell subpopulations in bladder cancer., Methods: A total of 2463 urothelial bladder carcinomas were immunostained with 21 antibodies using BLEACH&STAIN multiplex fluorescence immunohistochemistry in a tissue microarray format and analyzed using a framework of neuronal networks for an image analysis. Spatial immune parameters were compared with histopathological parameters and overall survival data., Key Findings and Limitations: The identification of > 300 different immune cell subpopulations and the characterization of their spatial relationship resulted in numerous spatial interaction patterns. Thirty-nine immune parameters showed prognostic significance in univariate analyses, of which 16 were independent from pT, pN, and histological grade in muscle-invasive bladder cancer. Among all these parameters, the strongest association with prolonged overall survival was identified for intraepithelial CD8 + cytotoxic T cells (time-dependent area under receiver operating characteristic curve [AUC]: 0.70), while stromal CD8 + T cells were less relevant (AUC: 0.65). A favorable prognosis of inflamed cancers with high levels of "exhaustion markers" suggests that TIM3, PD-L1, PD-1, and CTLA-4 on immune cells do not hinder antitumoral immune response in tumors rich of tumor infiltrating immune cells., Conclusions and Clinical Implications: The density of intraepithelial CD8 + T cells was the strongest prognostic feature in muscle-invasive bladder cancer. Given that tumor cell killing by CD8 + cytotoxic T lymphocytes through direct cell-to-cell-contacts represents the "terminal end route" of antitumor immunity, the quantity of "tumor cell adjacent CD8 + T cells" may constitute a surrogate for the efficiency of cancer recognition by the immune system that can be measured straightaway in routine pathology as the CD8 labeling index., Patient Summary: Quantification of intraepithelial CD8 + T cells, the strongest prognosticfeature identified in muscle-invasive bladder cancer, can easily be assessed by brightfield immunohistochemistry and is therefore "ready to use" for routine pathology., (Copyright © 2024. Published by Elsevier B.V.)

This randomized controlled trial tested the Family Assessment and Feedback Intervention (FAFI), a new intervention to enhance family engagement with emotional and behavioral health services. The FAFI is a guided conversation with families about results of their multidimensional assessment that is set in the context of motivational enhancement. It differs from other assessment-with-feedback interventions by extending the focus of assessment beyond the target child to parents and the family environment, addressing parental emotional and behavioral problems and competencies, spanning a broad range of children's and parents' strengths and difficulties, and being generalizable to many settings and practitioners. Participants were 81 families in primary care pediatrics. The FAFI was associated with a significant increase in parental mental health literacy and with an increase in parental attitudinal engagement with health supports and services that closely approached statistical significance (p = .052), while controlling for children's age and gender and family socioeconomic status., (© 2024. The Author(s).)

Background: A high level of PD-L1 expression is the most relevant predictive parameter for response to immune checkpoint inhibitor (CPI) therapy in urinary bladder cancer. Existing data on the relationship between PD-L1 expression and the natural course of disease are controversial and sparse., Methods: To expand our understanding of the relationship between PD-L1 expression and parameters of cancer aggressiveness, PD-L1 was analyzed on tissue microarrays containing 2710 urothelial bladder carcinomas including 512 patients with follow-up data who underwent radical cystectomy and follow-up therapies in the pre-immune checkpoint inhibitor therapy era., Results: Tumor cell positivity in ≥10% of cells were seen in 513 (20%) and an immune cell positivity occurred in 872 (34%) of 2566 interpretable cancers. PD-L1 positivity in tumor cells increased from pTaG2 low grade (0.9% positive) to pTaG3 high grade (4.1%; p = 0.0255) and was even higher in muscle-invasive (pT2-4) carcinomas (29.3%; p < 0.0001). However, within pT2-4 carcinomas, PD-L1 positivity was linked to low pT stage (p = 0.0028), pN0 (p < 0.0001), L0 status (p = 0.0005), and a better prognosis within 512 patients with cystectomy who never received CPIs (p = 0.0073 for tumor cells and p = 0.0086 for inflammatory cells). PD-L1 staining in inflammatory cells was significantly linked to PD-L1 staining in tumor cells (p < 0.0001) and both were linked to a positive p53 immunostaining (p < 0.0001)., Conclusion: It cannot be fully excluded that the strong statistical link between PD-L1 status and favorable histological tumor features as well as better prognosis could influence the outcome of studies evaluating CPIs in muscle-invasive urothelial carcinoma., (© 2024. The Author(s).)

Objectives: Carcinoembryonic antigen (CEA) is a cell surface glycoprotein that represents a promising therapeutic target. Serum measurement of shedded CEA can be utilized for monitoring of cancer patients., Material and Methods: To evaluate the potential clinical significance of CEA expression in urothelial bladder neoplasms, CEA was analysed by immunohistochemistry in more than 2500 urothelial bladder carcinomas in a tissue microarray format., Results: CEA staining was largely absent in normal urothelial cells but was observed in 30.4% of urothelial bladder carcinomas including 406 (16.7%) with weak, 140 (5.8%) with moderate, and 192 (7.9%) with strong staining. CEA positivity occurred in 10.9% of 411 pTaG2 low-grade, 32.0% of 178 pTaG2 high-grade, and 43.0% of 93 pTaG3 tumours ( p  < 0.0001). In 1335 pT2-4 carcinomas, CEA positivity (34.1%) was lower than in pTaG3 tumours. Within pT2-4 carcinomas, CEA staining was unrelated to pT, pN, grade, L-status, V-status, overall survival, recurrence free survival, and cancer specific survival ( p  > 0.25)., Conclusion: CEA increases markedly with grade progression in pTa tumours, and expression occurs in a significant fraction of pT2-4 urothelial bladder carcinomas. The high rate of CEA positivity in pT2-4 carcinomas offers the opportunity of using CEA serum measurement for monitoring the clinical course of these cancers. Moreover, CEA positive urothelial carcinomas are candidates for a treatment by targeted anti-CEA drugs., Competing Interests: The rabbit recombinant CEA antibody, clone MSVA‐465R was obtained from MS Validated Antibodies GmbH, Hamburg, Germany (owned by a family member of GS)., (© 2024 The Authors. BJUI Compass published by John Wiley & Sons Ltd on behalf of BJU International Company.)

Purpose: Management of a failed kidney allograft, and the question whether it should be removed is a challenging task for clinicians. The reported risks for transplant nephrectomy (TN) vary, and there is no clear recommendation on indications or surgical approach that should be used. This study gives an overview of indications, compares surgical techniques, and identifies risk factors for higher morbidity., Methods: Retrospective analysis was conducted on all transplant nephrectomies performed between 2005 and 2020 at Charité Hospital Berlin, Department of Urology. Patient demographics, laboratory parameters, graft survival data, indication for TN, and surgical complications were extracted from medical reports., Results: A total of 195 TN were performed, with graft intolerance syndrome being the most common indication in 52 patients (26.7%), acute rejection in 36 (18.5%), acute infection in 30 (15.4%), and other reasons to stop immunosuppression in 26 patients (13.3%). Rare indications were vascular complications in 16 (8.2%) and malignancies in the allograft in six (3.1%) cases. Extracapsular surgical approach was significantly more often used in cases of vascular complications and earlier allograft removal, but there was no difference in complication rates between extra- and intracapsular approach. Acute infection was identified as an independent risk factor for a complication grade IIIb or higher according to Clavien-Dindo classification, with a HR of 12.3 (CI 2.2-67.7; p = 0.004)., Conclusion: Transplant nephrectomy should only be performed when there is a good indication, and non-elective surgery should be avoided, when possible, as it increases morbidity., (© 2024. The Author(s).)

Background: Uroplakin-1a (Upk1a) and uroplakin-1b (Upk1b) have recently been identified as diagnostic markers for the distinction of urothelial carcinomas from other solid tumor entities. Both proteins play an important role in the stabilization and strengthening of epithelial cells that line the bladder., Methods: To evaluate the prognostic role of uroplakin expression in urothelial carcinomas, more than 2700 urothelial neoplasms were analyzed in a tissue microarray format by immunohistochemistry. To further assess the diagnostic role of uroplakin immunohistochemistry, results were compared with preexisting GATA3 data., Result: The fraction of Upk1a/Upk1b positive cases decreased slightly from pTaG2 low-grade (88% positive for Upk1a/87% positive for Upk1b) and pTaG2 high-grade (92%/89%) to pTaG3 (83%/88%; p > 0.05) and was lower in muscle-invasive (pT2-4) carcinomas (42%/64%; p < 0.0001/p < 0.0001 for pTa vs. pT2-4). Within pT2-4 carcinomas, high expression of Upk1a and Upk1b was linked to nodal metastasis and lymphatic vessel infiltration (p < 0.05) but unrelated to patient outcome. There were significant associations between Upk1a, Upk1b and GATA3 immunostaining (p < 0.0001 each), but 11% of GATA3 negative cancers were Upk1a/b positive and 8% of Upk1a/b negative cancers were GATA3 positive. Absence of GATA3/Upk1a/b staining was significantly linked to poor patient survival in the subgroup of 126 pT4 carcinomas (p = 0.0004) but not in pT2 and pT3 cancers., Conclusions: In summary, the results of our study demonstrate that Upk1a and/or Upk1b immunohistochemistry can complement GATA3 for the distinction of urothelial carcinomas. Furthermore, a progressive loss of Upk1a/b expression during stage progression and a prognostic role of the combination GATA3/Upk1a/Upk1b in pT4 carcinomas is evident., (© 2023. The Author(s).)

Introduction: Trophoblast cell surface antigen 2 (TROP2; EpCAM2) is a transmembrane glycoprotein which is closely related to EpCAM (EpCAM; EpCAM1). Both proteins share partial overlapping functions in epithelial development and EpCAM expression but have not been comparatively analyzed together in bladder carcinomas. TROP2 constitutes the target for the antibody-drug conjugate Sacituzumab govitecan (SG; TrodelvyTM) which has been approved for treatment of metastatic urothelial carcinoma by the United States Food and Drug administration (FDA) irrespective of its TROP2 expression status., Methods: To evaluate the potential clinical significance of subtle differences in TROP2 and EpCAM expression in urothelial bladder cancer, both proteins were analyzed by multiplex fluorescence immunohistochemistry in combination with a deep-learning based algorithm for automated cell detection on more than 2,700 urothelial bladder carcinomas in a tissue microarray (TMA) format., Results: The staining pattern of TROP2 and EpCAM were highly similar. For both proteins, the staining intensity gradually decreased from pTa G2 low grade (TROP2: 68.8±36.1; EpCAM: 21.5±11.7) to pTa G2 high grade (64.6±38.0; 19.3±12.2) and pTa G3 (52.1±38.7; 16.0±13.0, p<0.001 each). In pT2-4 carcinomas, the average TROP2 and EpCAM staining intensity was intermediate (61.8±40.9; 18.3±12.3). For both proteins, this was significantly lower than in pTa G2 low grade (p<0.001 each) but also higher than in pTa G3 tumors (p=0.022 for TROP2, p=0.071 for EpCAM). Within pT2-4 carcinomas, the TROP2 and EpCAM staining level was unrelated to pT, grade, UICC-category, and overall or tumor-specific patient survival. The ratio TROP2/EpCAM was unrelated to malignant phenotype and patient prognosis., Conclusion: Our data show that TROP2 and EpCAM expression is common and highly interrelated in urothelial neoplasms. Despite of a progressive loss of TROP2/EpCAM during tumor cell dedifferentiation in pTa tumors, the lack of associations with clinicopathological parameters in pT2-4 cancer argues against a major cancer driving role of both proteins for the progression of urothelial neoplasms., Competing Interests: The recombinant EpCAM antibody clone MSVA-326R, the recombinant TROP2 antibody clone MSVA-733R, the recombinant panCK antibody clone MSVA-000R were provided by MS Validated Antibodies GmbH owned by a family member of GS., (Copyright © 2024 Müller, Plage, Elezkurtaj, Mandelkow, Huang, Lurati, Raedler, Debatin, Vettorazzi, Samtleben, Hofbauer, Furlano, Neymeyer, Goranova, Ralla, Weinberger, Horst, Roßner, Schallenberg, Marx, Fisch, Rink, Slojewski, Kaczmarek, Ecke, Hallmann, Koch, Adamini, Lennartz, Minner, Simon, Sauter, Zecha, Schlomm and Bady.)

Tissue-resident lymphocytes provide organ-adapted protection against invading pathogens. Whereas their biology has been examined in great detail in various infection models, their generation and functionality in response to vaccination have not been comprehensively analyzed in humans. We therefore studied SARS-CoV-2 mRNA vaccine-specific T cells in surgery specimens of kidney, liver, lung, bone marrow, and spleen compared with paired blood samples from largely virus-naive individuals. As opposed to lymphoid tissues, nonlymphoid organs harbored significantly elevated frequencies of spike-specific CD4+ T cells compared with blood showing hallmarks of tissue residency and an expanded memory pool. Organ-derived CD4+ T cells further exhibited increased polyfunctionality over those detected in blood. Single-cell RNA-Seq together with T cell receptor repertoire analysis indicated that the clonotype rather than organ origin is a major determinant of transcriptomic state in vaccine-specific CD4+ T cells. In summary, our data demonstrate that SARS-CoV-2 vaccination entails acquisition of tissue memory and residency features in organs distant from the inoculation site, thereby contributing to our understanding of how local tissue protection might be accomplished.

Background: Most inactivating p53 mutations result in a nuclear p53 accumulation - detectable by immunohistochemistry (IHC). p53 alterations leading to a complete lack of p53 protein and absence of immunostaining do also occur - not easily detectable by IHC. p16 is upregulated in p53 inactivated cells. We hypothesized that a positive p16 IHC may help to distinguish p53 inactivation in IHC negative cases., Material and Methods: We investigated p53 and p16 immunostaining on 2710 urothelial bladder carcinomas in a tissue microarray format to understand their impact in relation to clinicopathological parameters of disease progression and patient outcome., Results: p16 immunostaining was absent in normal urothelium but occurred in 63.5% (30.4% strong) of cancers. p16 strongly positive cases increased from pTaG2 low-grade (9.6%) to pTaG3 high-grade tumors (46.5%, p  < .0001) but decreased from pTaG3 to pT4 (33.3%; p  = .0030). Among pT2-4 carcinomas, p16 positivity was linked to high-grade ( p  = .0005) but unrelated to overall survival. p53 staining was negative in 8.4%, very weak in 15.4%, weak in 55.3%, strong in 4.7%, and very strong in 16.2% cancers. p53 negative (potentially p53 null phenotype), strong, and very strong p53 positivity increased from pTaG2 low-grade to pTaG3 high-grade tumors ( p  < .0001) and from pTaG3 to pT2-4 cancers ( p  = .0007). p53 staining was largely unrelated to histopathological parameters or patient prognosis among pT2-4 carcinomas, except of p53 strong/very strong immunostaining. p16 expression predominated in tumors with very strong, strong, and negative p53 staining and the combination of p53 negative/p16 strongly positive cancers was linked to features of tumor aggressiveness., Conclusion: Aberrant p53 and p16 immunostaining increases during grade and stage progression although p53 negative and p16 positive immunostaining lack prognostic significance in pT2-4 carcinomas. Potential diagnostic features are that high level p16 expression is limited to neoplastic urothelium and p53 null phenotype to aggressive cancers (grade 3 and invasive).

Introduction: Job satisfaction is a valuable good. However, literature on job satisfaction of female and male physicians, especially in the field of urology, is scarce. Therefore, the aim of this study was to evaluate job satisfaction among female members of the German Society of Urology (DGU)., Materials and Methods: An online questionnaire was sent to 1343 female members of the DGU in Germany, Austria, and Switzerland. The responses of 521 female physicians were statistically analyzed regarding baseline characteristics and in relation to job satisfaction and satisfaction with the choice of specialty., Results: The median age of the participants was 37 (IQR 33; 45) years. While 91% of the respondents were rather or very satisfied with their choice of specialty-urology-only about 54% of the female urologists were satisfied with their job situation. Of the female urologists satisfied (vs. not satisfied) with their professional situation, 95% (vs. 87%) were also satisfied with their choice of urology as their specialty. Satisfaction with the working time model (odds ratio [OR] 9.61) and feeling unequal treatment (OR: 0.18) were independent predictors of satisfaction with the professional situation., Conclusion: Considering the increasing proportion of women in the health sector, it is important to identify factors influencing decisions on career and choice of specialty as well as career progression. Achieving career goals, increasing satisfaction with the working time model, and reducing unequal treatment or discrimination are central arguments for sustainably increasing the job satisfaction of female urologists., (© 2023. The Author(s), under exclusive licence to Springer Medizin Verlag GmbH, ein Teil von Springer Nature.)

Purpose: Female urologists are distinctly underrepresented in leading positions. The reasons behind this inequity remain unclear, with some suggesting factors such as family responsibilities, part-time work and insufficient mentorship. This study aimed to explore and characterize the working conditions of female urologists in Germany, with a focus on factors influencing the working time model., Methods: A questionnaire was developed and distributed to 1343 female members of the German Society of Urology between February and March 2022. The survey consisted of 43 questions covering the categories demographics, occupation situation, satisfaction at work, family situation, career aspects and research activity., Results: Of the 487 female German urologists who participated in the survey, 167 (34.3%) worked part-time. Doctors in training were significantly less likely to work part-time than colleagues who had completed their specialist training (p < 0.001). Only 10% of female doctors in training reported working part-time. Similarly, having children (p < 0.001) and engaging in scientific activities (p = 0.03) were independent factors influencing part-time work, with children increasing the likelihood of working part-time as expected, while scientifically active female urologists were more likely to work full-time., Conclusion: This study provides the largest survey on the situation of female urologists in German-speaking countries to date. Part-time work during specialist training is rare, while more than 50% of female urologists with children work part-time. With the projected decline in the number of practicing physicians and the increasing demand for medical attention, it is crucial to find ways to retain and support healthcare professionals, particularly female urologists., (© 2023. The Author(s).)

This randomized controlled trial tested the Vermont Family Based Approach (VFBA) in primary care pediatrics. The VFBA is a model of healthcare delivery that shifts the focus from the individual to the family, emphasizes emotional and behavioral health, and uses evidence-based health promotion/prevention along with the treatment of emotional and behavioral problems. Participants were 81 families of 3-15-year-olds. For children, the VFBA was associated with greater reductions than the Control condition on the Child Behavior Checklist Emotionally Reactive, Withdrawn, Sleep Problems, Aggressive Behavior and Total Problems scales. For parents, the VFBA was associated with greater reductions than the Control condition on the Adult Self-Report Anxious/Depressed, Rule-Breaking Behavior, Internalizing Problems and Total Problems scales. The VFBA was also associated with greater improvement than the Control condition in the parents' health-related quality of life, as indicated by all scales of the Medical Outcomes Study Health Survey., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Objective: We investigated whether pathological outcomes improved with experience and surgeon generation after robot-assisted laparoscopic prostatectomy (RALP). Materials and Methods: The study included 1338 patients who underwent RALP between February 2010 and April 2020. We created learning curves for pelvic lymph node dissection (PLND), number of lymph nodes (LNs) removed, and positive surgical margin (PSM) after adjustment for confounders. We compared the outcomes between the first and second generation of surgeons in regression models. Results: The learning curve regarding PLND indications showed a significant increase with experience for the first generation, whereas the second generation had a learning curve that remained flat at a higher level (92.3%) and significantly better than the first generation ( p  < 0.001). Similarly, the number of LN removed showed a significant increase with experience in both generations, but the overall median number of LN removed was significantly higher in the second generation compared with the first generation (12 vs 10, p  < 0.001). However, the learning curve for PSM remained flat at ∼20% after adjustment and did not show improvement with experience in both generations of surgeons ( p  = 0.794). Conclusions: Surgeons showed improvement with experience and education with RALP with respect to the indications for PLND and number of LNs removed. However, there was no improvement over time and generations for PSM. Experience based solely on the number of patients operated on is not an intrinsic factor in the pathological quality of RALP. Factors other than experience may also play a role in oncologic improvement.

Objective: To compare outcomes of monopolar incision and Allium Round Posterior Stent (RPS) insertion for the treatment of recurrent vesicourethral anastomosis stricture., Methods: Having a suprapubic catheter and an obstructed pattern with a peak flow rate (PFR) ≤12 mL/s on uroflowmetry were the indications for the surgery. Once the fibrotic vesicourethral anastomosis was incised, RPS was inserted at the level of vesicourethral anastomosis under fluoroscopic guidance. All the stents were removed at postoperative first year. Patients were evaluated 3months after stent removal. Objective cure was defined as no need to further treatments and PFR ≥12 mL/s while subjective cure was defined as having points <4 on Patient Global Impression of Improvements scale., Results: Of the 30 patients with a median age 66 (52-74) enrolled in the study, 18 had a suprapubic catheter, remaining 12 had median PFR 5.2 (2-10) mL/s. Stent migration was noted in two patients, these stents were replaced by new ones. Stone formation was diagnosed in one patient, a pneumatic-lithotripsy was performed. The median follow-up time was 28 (4-60) months following stent removal. Six cases needed further treatment after removal. The median PFR of remaining 24 patients was 20 (16-30) mL/s (P = .001). The objective cure rate was 24/30(80%), the Patient Global Impression of Improvements scores varied from 1 to 2, meaning subjective cure rate was 24/30(80%). For the six failed cases, according to patient preferences a lifetime RPS insertion was planned., Conclusion: With its minimally invasive nature, reversibility, and acceptable success and complication rates, incision of anastomosis and insertion of the RPS for a 1-year duration is a promising option for the treatment of recurrent vesicourethral anastomosis stricture., Competing Interests: Declaration of Competing Interest The authors have no conflict of interest to declare., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Cytokeratin 20 (CK20) expression is limited to umbrella cells in the normal urothelium. Since CK20 is often upregulated in neoplastic urothelial cells including dysplasia and carcinoma in situ, immunohistochemical CK20 analysis is often used for the assessment of bladder biopsies. CK20 expression is a feature of luminal bladder cancer subtype, but its prognostic relevance is disputed. In this study, we investigated CK20 on >2700 urothelial bladder carcinomas in a tissue microarray format by immunohistochemistry. Cytoplasmic and membranous CK20 staining was seen in 1319 (51.8%) cancers. The fraction of CK20 positive and especially strongly positive cases increased from pTaG2 low grade (44.5% strongly positive) and pTaG2 high grade (57.7%) to pTaG3 high grade (62.3%; p = 0.0006) but was lower in muscle-invasive (pT2-4) carcinomas (51.1% in all pTa vs. 29.6% in pT2-4; p < 0.0001). Within pT2-4 carcinomas, CK20 positivity was linked to nodal metastasis and lymphatic vessel invasion (p < 0.0001 each) and to venous invasion (p = 0.0177). CK20 staining was unrelated to overall patient survival if all 605 pT2-4 carcinomas were jointly analyzed but subgroup analyses revealed a significant association of CK20 positivity with favorable prognosis in 129 pT4 carcinomas (p = 0.0005). CK20 positivity was strongly linked to the expression of GATA3 (p < 0.0001), another feature of luminal bladder cancer. The combined analysis of both parameters showed best prognosis for luminal A (CK20+/GATA3+, CK20+/GATA3-) and worst outcome for luminal B (CK20-/GATA3+) and basal/squamous (CK20-/GATA3-) in pT4 urothelial carcinomas (p = 0.0005). In summary, the results of our study demonstrate a complex role of CK20 expression in urothelial neoplasms including neoexpression in pTa tumors, a subsequent loss of CK20 expression in a subset of tumors progressing to muscle-invasion, and a stage dependent prognostic role in muscle-invasive cancers., Competing Interests: Declaration of Competing Interest The rabbit recombinant CK20 antibody, MSVA-620R was purchased from MS Validated Antibodies GmbH (owned by a family member of GS)., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Ureteral complications such as urinary leak, ureteral necrosis or ureteral stenosis are common complications after renal transplantation with major short- and long-term issues, including graft impairment and graft loss. At present, there is no agreement on the optimal management of ureteral complications. The aim of the current study was to evaluate the safety and efficacy of the self-expanding, large-caliber Allium ureteral stent in patients with ureteral complications following renal transplantation. In this retrospective study, the electronic database of Charité University Hospital was screened for patients receiving the self-expandable Allium ureteral stent in the transplant ureter after kidney transplantation between January 2016 and March 2022. Descriptive statistics were used to describe the outcomes. There were six men and four women with a median age of 61 years (interquartile range, 55 to 68 years). Nine out of 10 patients had ureteric stenosis, which was diagnosed at a median of two years (interquartile range 10 months to 9 years) following renal transplantation. The median operating time was 49 min (interquartile range, 30 to 60 min). Endoscopic Allium stent placement was successful in all patients with ureteric stenosis. The median length of stay in the hospital was four days (interquartile range 2 to 7 days). Only one patient (#5) had a postoperative grade IIIb Clavien-Dindo complication. Patients had follow-ups every 3 months with ultrasound and serum creatinine. Dislocation of the Allium stent was seen in four patients; all occurred within three months. Ultimately, three patients required ureteric re-implantation, two of which had early dislocation of the stent. Six patients are managed with a permanent Allium stent. The median dwell time was 11 months (interquartile range 3 to 20 months) and maximum dwell time was 23 months. The overall success rate was 60% (6 out of 10). According to our data, the Allium stent represents a safe and minimally invasive option with a success rate of 60%. It might, therefore, represent an alternative to DJ stents, nephrostomies or immediate re-implantation. As all dislocations occurred within three months, frequent early postoperative follow-up is required.

Background: OnabotulinumtoxinA (Botox) has been approved in Germany since 2013 for the second-line treatment of idiopathic overactive bladder in the form of a detrusor injection (OnabotA DI) after failure of anticholinergic therapy. Until 2018, however, its application lagged far behind the demand due to billing hurdles. Since the beginning of 2018, there has been an EBM (German Uniform Evaluation Standard) approval number in Germany for the transurethral application of Botox in urology., Question: The aim of a survey performed in 2019 among course participants of regular injection workshops (WS-P) in our institution was to evaluate whether billability has changed user behaviour in Germany in line with the demand. A similar survey was carried out in 2021 to show the developments over the past two years., Material and Methods: In 2019, 88 consecutive participants in a user workshop that had been held regularly since 2013 were asked about their OnabotA DI practice anonymously via questionnaire. The survey was repeated in 2021 in an anonymous online survey of 55 course participants in order to evaluate changes in user behaviour over the past two years., Results: Evaluation 2019: Response rate 35/88 of the questionnaires (39.8%); a large majority (82%) of the WS-P attended the workshop AFTER the establishment of the EBM code. Only 54.5% of the WS-P performed two or more (12% more than 10) OnabotA DIs per quarter after the workshop. Most users (85%) always or predominantly performed the procedure on an outpatient basis, 63% always or predominantly under local anesthesia. The majority (84%) administered no or only a perioperative antibiotic treatment, 13% for one week. 89% stated that at least 70% of their patients had no or only mild symptoms under the LA. In the 2021 evaluation, the users tended to perform the procedure more often on an outpatient basis and in LA, and more often without any antibiotics., Conclusions: The results of our user survey indicate that the implementation of the OnabotA DI has gained significant impetus since the EBM approval in Germany in January 2018. In most cases, the procedure can be performed easily on an outpatient basis under local anesthesia., Competing Interests: H. Schulte-Baukloh: Fa. Allergan-Abbvie: Beratung und Workshops, (Thieme. All rights reserved.)

Introduction: According to the EAU guidelines, botulinum toxin type A (BoNT-A) detrusor injections are one of the last options in the management of overactive bladder before opting for invasive surgery. So far, there have been no studies dedicated exclusively to such patients who have undergone this treatment and in whom this treatment has presumably failed. From the patient's point of view, there are questions regarding what reasons led to discontinuation, how patients perceive their BoNT-A treatment in hindsight, what further treatment do these patients receive, and how satisfied such patients are with their current situation., Methods: A database of clinical and inpatient records was searched, and 695 records from 406 patients were identified in a 6-year period, who had received BoNT-A detrusor injections. There were 255 cases that were treated with BoNT-A injections into the detrusor muscle where the therapy was not repeated for at least 12 months (= suspected treatment failures). Interviews with these patients were conducted by mail and phone, and 115 questionnaires could be included in the analysis., Results: From the subjective and prospective points of view of the patients, the most common reason for stopping the therapy was a lack of efficacy of BoNT-A injections (39.1%). For 26.1% of all patients, side effects were a reason for dissatisfaction but never a reason for discontinuation. For 10.4%, the reason for stopping the therapy was spontaneous improvement. 35.6% of the respondents had no follow-up therapy. Those with a follow-up therapy mostly returned to anticholinergic treatment (33%). Operations were carried out on 13%, of which about half were highly invasive. For 71.3% of those patients, who were under any current therapy, this therapy led to no improvement or only some improvement of the symptoms. Surprisingly, 50.4% of the respondents would choose to undergo BoNT-A injection therapy again., Discussion/conclusion: The majority of patients who did not continue BoNT-A therapy are still suffering from lower urinary tract symptoms. The lack of efficacy was the reason for stopping the BoNT-A injection therapy for less than half of the patients. From the patient's point of view, reasons other than the effectiveness also seem to be relevant in the choice of the treatment. When changing therapy, most returned to drug treatment. However, for the majority of patients with any follow-up therapy, this therapy could not improve the symptoms., (© 2022 S. Karger AG, Basel.)

Introduction: Detrusor injection with onabotulinumtoxin A (OnabotA-DI) is an established therapy for overactive bladder (OAB). Little is known about the exact onset and course of the effect in the days after the injection therapy. By using a new type of app-controlled automated diary pod, for the first time, the precise onset of the effect of OnabotA-DI can be documented in real time. Materials and methods: Patients due for OnabotA-DI were asked to document voiding 3 days before and up to 3 weeks after therapy using the Diary Pod app. The detrusor injection was performed with onabotulinumtoxin A (Botox®), 100 units, at 20 sites of the detrusor muscle in a standardized manner. Voiding on the injection day itself was not documented. Results: A total of 17 patients (15 women, 2 men; aged 33−83 (mean 64.6; median 70) years) were included in the study. The handling of the Diary Pod app was user-friendly, and elderly patients did not encounter technical problems. The results of patients with reliably documented micturitions showed a continuous reduction in micturition frequency every day from the first day and significantly from day 5. For 24 h voiding, from 12.83 ± 5.54 in the 3 days before injection, the following mean values were found with significant (p < 0.05) changes after the intervention: 9.17 ± 3.19 on day 5, 8.75 ± 3.69 on day 10, 7.17 ± 2.04 on day 15, and 5.75 ± 0.5 on day 20. These changes were in similar proportions during the daytime and nighttime. Conclusions: Contrary to previous knowledge, the effect of the OnabotA-DI set in from the first postoperative days and was reflected a similar extent in day and night micturition. This study is the first to document the onset of action of OnabotA-DI in real time.

The transcription factor GATA binding protein 3 (GATA3) is commonly used in surgical pathology as a diagnostic marker to distinguish urothelial carcinomas from other cancer entities. However, the clinical relevance of GATA3 expression in urothelial bladder cancer is not completely clarified. In this study, we investigated GATA3 immunostaining on 2710 urothelial bladder carcinomas on a tissue microarray platform by using two different antibodies to better understand its impact in relation to pathological parameters of disease progression and patient outcome. Nuclear GATA3 immunostaining was regularly seen in normal urothelium and found in 74%/82% of interpretable urothelial neoplasms depending on the antibody used. Within pTa tumors, the rate of GATA3 positive tumors decreased with advancing grade. GATA3 positivity was seen in 98.6%/99.8% of pTaG2 low-grade, 98.6%/100% of pTaG2 high-grade, and 94.9%/99.2% of pTaG3 high-grade tumors (P = .0002). As compared to pTa tumors, GATA3 positivity was markedly less common in muscle-invasive urothelial carcinoma (59.9%/71.6%; P < .0001). Within pT2-4 cancers, high-level GATA3 immunostaining was associated with the presence of lymph node metastasis (P = .0034), and blood vessel (P = .0290) or lymphatic invasion (P = .0005) but unrelated to pT stage. GATA3 immunostaining results for both antibodies were not associated with overall survival in 586 patients treated by cystectomy for pT2-4 urothelial carcinoma. The results of our study identify GATA3 expression as a frequent event in noninvasive urothelial carcinomas with favorable tumor features. Loss of GATA3 immunostaining is linked with muscle-invasive disease but is largely unrelated to pathological parameters and patient prognosis., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Background and Objective: The aim of this study was to evaluate gender aspects and trends in urological clinics, research and private practice. The focus was on the objectification of gender-specific changes in the field of urology at the current time and in the future., Material and Methods: A digital survey among urological physicians in Germany was conducted with the SurveyMonkey© portal, which was sent to all registered members via the email distribution lists of the German Society of Urology (DGU) and the Professional Association of German Urologists (BvDU). Baseline data were collected in the outpatient and inpatient sectors, as were gender-specific data related to job distribution, goals, satisfaction, and reasons for career decisions., Results: The analysis of 398 responses revealed that urological colleagues in private practice were less likely to be female (23.6%) and significantly older (mean age 53 years) than in the inpatient sector (female proportion 47.2%, mean age 43 years). More men (49.4%) than women (29.9%) were in private practice and this was indicated as a career aspiration by more men than women (28.1% vs. 22.8%). The reasons for setting up a practice were more often family-related for women than for men (main reasons good opportunity or career aspiration). Women were more likely to work part-time (27.0% vs. 11.5%) and more likely to aspire to a career as a senior physician (29.1% of women, 9.4% of men). Correspondingly, the desire for a postdoctoral position or professorship was more common among women than among men (20.5% vs. 15%). Significantly more female urologists perceived inequality in career advancement opportunities (59.7% vs. 17.5%, p < 0.001) and 73.3% (vs. 18.5% of men, p < 0.001) perceived their gender as a cause of disadvantage. This resulted in significantly lower satisfaction of women with their professional status (p = 0.008) as well as a lower feeling of being valued (p < 0.001)., Conclusion: In order to prepare our specialty field for the future, it is essential to give even greater consideration to gender aspects. The path taken to offer the next generation of urologists a modern specialty in which all physicians, regardless of their gender, enjoy working, are valued and where equal opportunities prevail, should definitely be pursued and intensified in order to position urology well for the future., (© 2022. The Author(s).)

Background: The proportion of female urologists is steadily increasing, yet they continue to be underrepresented in academic leadership positions. A postdoctoral lecture qualification (habilitation), which is mandatory for a successful scientific career, is achieved significantly less often by female urologists in Germany than by their male colleagues., Objective: To identify factors to effectively promote female urologists into academic leadership positions, the current situation, as well as factors influencing successful habilitation of women who are members of the German Society of Urology (Deutsche Gesellschaft für Urologie [DGU]) were investigated., Methods: An online questionnaire was distributed to 1343 female members of the DGU in Germany, Austria, and Switzerland. The responses of 521 women were statistically analyzed with respect to baseline characteristics and in relation to research funding. The primary endpoint of our study was the habilitation rate., Results: The average age of the 521 participating female urologists who completed the questionnaire was 37 years (range 21-67 years). Of these, most female physicians were in postgraduate training (n = 168, 32%), worked full-time (n = 324, 62%), and had children (n = 277, 53%). Overall, 359 (69%) of the participants had a PhD and 63 (12%) were still working on their PhD. Thirty (5.8%) female urologists had a habilitation. In univariable logistic regression models, age (odds ratio [OR] 1.06), working time model (part-time OR 0.19), a research fellowship (OR 21.4), release from clinical work for research purposes (OR 13.7), and participation in a funding program (OR 6.9) or mentoring program (OR 7.0) were independent predictors of achieving habilitation. Whether a urologist had children was not an independent predictor of achieving habilitation. In multivariable logistic regression models, age (OR 1.08), and a research fellowship (OR 9.04) were independent predictors of achieving habilitation., Conclusions: Promoting habilitation among female urologists is required in order to increase the proportion of women in leading academic positions. The results of the data analysis show that the promotion of research fellowships explicitly for women could be a promising approach., (© 2022. The Author(s).)

Polymerase chain reaction (PCR) based methods are a fast and sensitive approach to detect and monitor viral load in Cytomegalovirus (CMV) patients. Letermovir (LMV) acts at a late stage during the CMV replication cycle and does not inhibit CMV DNA replication per se. Therefore, quantitative nucleic acid amplification testing might lead to the overestimation of viral load in patients treated with LMV and underestimate treatment success. To study this discrepancy, we treated infected cells with LMV or Ganciclovir (GCV) and compared viral progeny DNA levels. Prior to nucleic acid extraction and qPCR measurements we pretreated cell lysates and cell culture supernatants from infected cells with DNase I. This step assumes the degradation of DNA which is not protected from a viral capsid. LMV treatment did not reduce genomic copies (GC) in samples from whole cell lysates compared to samples treated with GCV. DNase treatment prior to DNA extraction, decreased GC in the LMV treated group to comparable levels as seen in the GCV group. In cell culture supernatants, LMV or GCV treatment led to an equivalent reduction of CMV GC. In this case, DNase treatment exerted a negligible effect on both groups. We conclude that the accumulation of concatemeric DNA within cells seems to be a confounding variable when monitoring LMV efficacy via qPCR. However, qPCR shows to be a reliable method to evaluate antiviral efficacy of LMV in cell free specimens. These results have strong clinical implications for the monitoring of CMV therapy during LMV treatment., (Copyright © 2022 The Authors. Published by Elsevier B.V. All rights reserved.)

In the past 20 years, scientific research focused on the identification of valid alternatives to materials of fossil origin, in particular, related to biobased polymers. Recently, the efforts led to the synthesis of thiophene-based polymers (TBPs), a new class of polyesters based on 2,5-thiophenedicarboxylic acid (TPCA) that can be industrially produced using biomass-derived molecules. In this study, TBPs were synthesized using diols with different chain length (from C4 to C6) leading to poly(butylene 2,5-thiophenedicarboxylate) (PBTF), poly(pentamethylene 2,5-thiophenedicarboxylate) (PPeTF), and poly(hexamethylene 2,5-thiophenedicarboxylate) (PHTF), respectively, that were processed to thin films. To investigate enzymatic hydrolysis of these polymer films, cutinase 1 (Thc&#95;cut1) and cutinase 2 (Thc&#95;cut2) from Thermobifida cellulosilytica were recombinantly expressed in the host E. coli and purified. After 72 h of incubation at 65°C with 5 µM Thc&#95;cut1, weight loss and HPLC analysis indicated 9, 100, and 80% degradation of PBTF, PPeTF, and PHTG with a concomitant release of 0.12, 2.70, and 0.67 mM of TPCA. The SEM analysis showed that tiny holes were formed on the surface of the films and after 72 h PPeTF was completely degraded. The LC-TOF/MS analysis indicated that Thc&#95;cut2 in particular released various oligomers from the polymer during the reaction. In addition, the FTIR analysis showed the formation of novel acid and hydroxyl groups on the polymer surfaces. The results showed that the two used thermostable cutinases are promising biocatalysts for the environmentally friendly degradation of TPCA-based polyesters, in view of a possible sustainable recycling of plastic waste through resynthesis processes., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Bertolini, Soccio, Weinberger, Guidotti, Gazzano, Guebitz, Lotti and Pellis.)

The World Health Organization declared the novel coronavirus, or COVID-19, a pandemic in March 2020. Given the severity of COVID-19, appropriate use criteria have been implemented for fetal echocardiography. Screening low risk pregnancies for critical congenital heart disease has typically been a shared responsibility by pediatric cardiologists, obstetricians, and maternal fetal medicine (MFM). Currently, many of the fetal echocardiograms for low risk pregnancies for critical congenital heart disease have been deferred or cancelled with the emphasis on suspected abnormalities by MFMs and obstetricians. In this review, we discuss the literature that has been the basis of screening of low risk pregnancies by pediatric cardiologists. A new approach to more widespread usage of fetal tele-echocardiography may play a large part during COVID-19 and may continue after the pandemic., Competing Interests: None., (© 2020 Elsevier B.V. All rights reserved.)

The production of polyhydroxybutyrate (PHB) by autotrophic fermentation of cyanobacteria has received increasing interest in the light of carbon emission reducing process strategies. Biotechnological approaches are in development to optimize the yield of PHB, including adapted cultivation media, characterized by a limitation of key nutrients: cyanobacteria accumulate PHB as energy storage molecules under limited growth conditions. Since there is an increasing demand for fast, simple and reliable analytics, we report the establishment of surface enhanced Raman spectroscopy (SERS) as a suitable monitoring tool for up scaled PHB production processes. Both, pure Ag-colloids mixed with bacterial culture, and in situ prepared colloids (Ag-Synechocystis), generated on the cell surface directly, were successfully applied and evaluated for this purpose. SERS measurements with in situ prepared Ag-colloids improved the reproducibility of Raman signals from 54.8% to 93.9%. The measurement time could be reduced significantly, completing our secondary goal. The quality of classically and in situ prepared Ag-colloids was monitored by zeta potential measurements and scanning electron microscopy (SEM) respectively. For data interpretation and statistical model-building an in house written code in the open source software RStudio was implemented. It was applied for the differentiation of PHB producers at the cellular level, revealing heterogeneities within sample groups regarding the PHB amount accumulated. The results obtained using the statistical model were validated as well and were complementary to the reference HPLC analysis. Therefore, a fast and reliable identification in situ SERS tool for the selection of the most promising cyanobacterial PHB production was established.

There is a strong need for novel and more efficient polyester hydrolyzing enzymes in order to enable the development of more environmentally friendly plastics recycling processes allowing the closure of the carbon cycle. In this work, a high throughput system on microplate scale was used to screen a high number of fungi for their ability to produce polyester-hydrolyzing enzymes. For induction of responsible enzymes, the fungi were cultivated in presence of aliphatic and aromatic polyesters [poly(1,4-butylene adipate co terephthalate) (PBAT), poly(lactic acid) (PLA) and poly(1,4-butylene succinate) (PBS)], and the esterase activity in the culture supernatants was compared to the culture supernatants of fungi grown without polymers. The results indicate that the esterase activity of the culture supernatants was induced in about 10% of the tested fungi when grown with polyesters in the medium, as indicated by increased activity (to >50 mU/mL) toward the small model substrate para -nitrophenylbutyrate (pNPB). Incubation of these 50 active culture supernatants with different polyesters (PBAT, PLA, PBS) led to hydrolysis of at least one of the polymers according to liquid chromatography-based quantification of the hydrolysis products terephthalic acid, lactic acid and succinic acid, respectively. Interestingly, the specificities for the investigated polyesters varied among the supernatants of the different fungi., (Copyright © 2020 Weinberger, Beyer, Schüller, Strauss, Pellis, Ribitsch and Guebitz.)

Purpose of Review: In the setting of kidney transplantation, the ureter is a common source for complications. As a result, prevention of ureteral complications and their management is of crucial importance. In this context, the purpose of this review is to summarize recent literature on the ureter in the kidney transplant setting with a special focus on new findings. We conducted a PubMed and Medline search over the last 10 years to identify all new publications related to ureteroneoimplantations, stents and management of complications in the kidney transplant setting., Recent Findings: Performance of the "Lich-Gregoir" technique for ureteroneocystostomy seems to be favourable in regard to postoperative complications when compared with other methods described in the literature. Moreover, major urologic complications can be further reduced by ureteral stenting. A new approach for management of ureteral strictures in renal transplants is presented. We discussed the usage of a ureteral stent covered with a biostable polymer aiming to prevent tissue ingrowth into the lumen as a new option for management of ureteral stricture in the kidney transplant setting.

The enzymatic synthesis of polyesters in solventless systems is an environmentally friendly and sustainable method for synthetizing bio-derived materials. Despite the greenness of the technique, in most cases only short oligoesters are obtained, with limited practical applications or requiring further chemical processing for their elongation. In this work, we present a catalyst-free thermal upgrade of enzymatically synthesized oligoesters. Different aliphatic and aromatic oligoesters were synthesized using immobilized Candida antarctica lipase B (iCaLB) as the catalyst (70 °C, 24 h) yielding poly(1,4-butylene adipate) (PBA, M w = 2200), poly(1,4-butylene isophthalate) (PBI, M w = 1000), poly(1,4-butylene 2,5-furandicarboxylate) (PBF, M w = 600), and poly(1,4-butylene 2,4-pyridinedicarboxylate) (PBP, M w = 1000). These polyesters were successfully thermally treated to obtain an increase in M w of 8.5, 2.6, 3.3, and 2.7 folds, respectively. This investigation focused on the most successful upgrade, poly(1,4-butylene adipate), then discussed the possible effect of di-ester monomers as compared to di-acids in the thermally driven polycondensation. The herein-described two-step synthesis method represents a practical and cost-effective way to synthesize higher-molecular-weight polymers without the use of toxic metal catalysts such as titanium(IV) tert -butoxide, tin(II) 2-ethylhexanoate, and in particular, antimony(IV) oxide. At the same time, the method allows for the extension of the number of reuses of the biocatalyst by preventing its exposure to extreme denaturating conditions.

We report 2 cases of de novo renal cell carcinoma (RCC) in renal grafts after transplantation. Both patients underwent nephron sparing surgery (NSS) 211 and 167 months after transplantation, revealing papillary RCC with a tumour size >4 cm (pT1a). Within a follow-up of 25 and 32 months after NSS, a stable renal function without indication for dialysis was present. No recurrence of RCC in both cases was reported within the yearly routine examinations. NSS in kidney allografts is a safe procedure with preservation of renal function., (© 2020 S. Karger AG, Basel.)

Purpose: The adoption of abdominal negative pressure therapy (NPT) during urgent laparotomy has shown to be helpful to control abdominal sepsis, improve morbidity and increase anastomosis rate. The aim of this study was to compare feasibility and outcome of two different abdominal negative pressure devices. Methods: The retrospective two-center study includes 78 consecutive patients with perforated sigmoid diverticulitis, who underwent urgent laparotomy using the ABThera™ (KCI, Wien, Austria) abdominal NPT device (Group A, n  = 51) or the Suprasorb® CNP (Lohmann & Rauscher, Wien, Austria) abdominal NPT device (Group B, n  = 27). Results: The mean length of abdominal NPT was 3.6 days in Group A and 2.8 days in Group B. Revisional surgery after closure of the abdomen was necessary due to surgical site infections, fascial dehiscence or anastomotic insufficiency in 25% and 29%, respectively. NPT-associated complications like fistula formation or acute bleeding were not observed. Mortality was 15% (Group A) and 7% (Group B). Conclusion: Despite the good feasibility and the well-known positive effect of abdominal NPT, perforated diverticulitis is still associated with high morbidity. However, the analysis did not show significant differences between the two abdominal NPT devices.

Management of infected wounds is one of the most costly procedures in the health care sector. Burn wounds are of significant importance due to the high infection risk that can possibly lead to severe consequences such as sepsis. Because antibiotic wound treatments have caused increasing antibiotic resistance in bacteria, there is currently a strong need for alternative strategies. Therefore, we developed new antimicrobial wound dressings consisting of pH-responsive human serum albumin/silk fibroin nanocapsules immobilized onto cotton/polyethylene terephthalate (PET) blends loaded with eugenol, which is an antimicrobial phenylpropanoid. Ultrasound-assisted production of eugenol-loaded nanocapsules resulted in particle sizes (hydrodynamic radii) between 319.73 ± 17.50 and 574.00 ± 92.76 nm and zeta potentials ranging from -10.39 ± 1.99 mV to -12.11 ± 0.59 mV. Because recent discoveries have indicated that the sweat glands contribute to wound reepithelialisation, release studies of eugenol were conducted in different artificial sweat formulas that varied in pH. Formulations containing 10% silk fibroin with lower degradation degree exhibited the highest release of 41% at pH 6.0. After immobilization, the functionalized cotton/PET blends were able to inhibit 81% of Staphylococcus aureus and 33% of Escherichia coli growth. Particle uniformity, silk fibroin concentration, and high surface-area-to-volume ratio of the produced nanocapsules were identified as the contributing factors leading to high antimicrobial activities against both strains. Therefore, the production of antimicrobial textiles using nanocapsules loaded with an active natural compound that will not contribute to antibiotic resistance is seen as a potential future alternative to commercially available antiseptic wound dressings.

Size trade-offs of visual versus olfactory organs is a pervasive feature of animal evolution. This could result from genetic or functional constraints. We demonstrate that head sensory organ size trade-offs in Drosophila are genetically encoded and arise through differential subdivision of the head primordium into visual versus non-visual fields. We discover that changes in the temporal regulation of the highly conserved eyeless/Pax6 gene expression during development is a conserved mechanism for sensory trade-offs within and between Drosophila species. We identify a natural single nucleotide polymorphism in the cis-regulatory region of eyeless in a binding site of its repressor Cut that is sufficient to alter its temporal regulation and eye size. Because eyeless/Pax6 is a conserved regulator of head sensory placode subdivision, we propose that its temporal regulation is key to define the relative size of head sensory organs., (Copyright © 2019 Elsevier Inc. All rights reserved.)

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.

Following concerns over increasing global plastic pollution, interest in the production and characterization of bio-based and biodegradable alternatives is rising. In the present work, the synthesis of a series of fully bio-based alternatives based on 2,4-, 2,5-, and 2,6-pyridinedicarboxylic acid-derived polymers produced via enzymatic catalysis are reported. A similar series of aromatic-aliphatic polyesters based on diethyl-2,5-furandicarboxylate and of the petroleum-based diethyl terephthalate and diethyl isophthalate were also synthesized. Here we show that the enzymatic synthesis starting from 2,4-diethyl pyridinedicarboxylate leads to the best polymers in terms of molecular weights (M n  = 14.3 and M w of 32.1 kDa when combined with 1,8-octanediol) when polymerized in diphenyl ether. Polymerization in solventless conditions were also successful leading to the synthesis of bio-based oligoesters that can be further functionalized. DSC analysis show a clear similarity in the thermal behavior between 2,4-diethyl pyridinedicarboxylate and diethyl isophthalate (amorphous polymers) and between 2,5-diethyl pyridinedicarboxylate and diethyl terephthalate (crystalline polymers).

The Vermont Family Based Approach (VFBA) is an innovative approach to healthcare delivery that addresses challenges of the healthcare system in the United States. The authors conducted a randomized controlled trial of the VFBA at a primary care pediatric clinic. The goal of the trial was to test the feasibility of the VFBA in pediatrics and to improve healthcare engagement and health outcomes for families. This article presents initial results of the trial on feasibility and engagement. The VFBA was found feasible and was associated with a significant increase in engagement with health and wellness supports and services., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Infections are a severe health issue, and the need for an early point-of-care diagnostic approach for wound infections is continuously growing. Lysozyme has shown a great potential as a biomarker for rapid detection of wound infection. In this study, spray-drying of labeled and derivatized chitosans was investigated for the production of small particles responsive to lysozyme. Therefore, various chitosans, differing in their origin (snow crab, Chionoecetes sp. , with medium and low molecular weight or shrimp) were N -acetylated, labeled with reactive black 5, and tested for solubility and spray-drying suitability. Reactive black-5-stained N -acetylated chitosan (low molecular weight, origin crab) was successfully spray-dried, and the obtained particles were characterized regarding size, ζ potential, and morphology. The particles showed an average hydrodynamic radius of 612.5 ± 132.8 nm. ζ potential was measured in the context of a later application as an infection detection system for wound infections in artificial wound fluid (-6.14 ± 0.16 mV) and infected wound fluid (-7.93 ± 1.35 mV). Furthermore, the aggregation behavior and surface structure were analyzed by using scanning electron microscopy and confocal laser scanning microscopy revealing spherical-shaped particles with explicit surface topologies. Spray-dried N -acetylated chitosan particles showed a 5-fold increase in lysozyme-responsive release of dyed chitosan fragments due to the enhanced surface area to volume ratio when compared to non-spray-dried N -acetylated chitosan flakes. On the basis of these results, the study showed the improved properties of N -acetylated spray-dried chitosan particles for future applications for early and rapid infection detection., Competing Interests: The authors declare no competing financial interest.

Urogynaecology is a highly specialised interdisciplinary medical field. It aims to investigate and treat functional, static, endocrine and sexual disorders of the genitourinary system and pelvic area in a sustainable and holistic manner.The "Urological Functional Diagnostics and Female Urology" working group of the German Urologist Academy was founded in 1977. It focuses on developing and updating diagnostics and clinical therapy, contributing to urogynaecological guidelines as well as establishing programmes for further education.Urinary incontinence and other pelvic floor disorders are increasing for demographic reasons. Rising socio-cultural expectations of women require more effective treatments using methods that guarantee success and a low level of complications.Milestones in urogynaecology include the introduction and further development of minimally-invasive surgical procedures such as tension-free vaginal tape (TVT) systems, laparoscopic and robot-assisted techniques, the development of a modern complication management, more targeted drug therapies, and the possibilities of modern functional diagnostics including pelvic floor sonography and MRI examinations.Classic surgical techniques such as colposuspension or colposacropexy and vaginal native tissue repair continue to be very important. In special cases, e. g. recurrent pelvic organ prolapse, mesh-based repair has proven to be superior to conventional procedures because of good long-term success and low recurrence rates. However, this method requires an anatomically correct surgical technique, critical selection of textile implants, and adequate patient education. Suturing devices and robot-assisted surgery may be helpful due to the narrow access and limited surgical spaces. For apical direct fixations, the elevation angle of the vagina is the therapeutically relevant outcome. Tried-and-tested anatomical fixation points should be preferred.Education and training in the field of urogynaecology and harmonisation with European standards (European Board & College of Obstetrics and Gynaecology) should be implemented. Skills for highly specialised mesh-based surgery and effective techniques for managing complications should be taught in the same interdisciplinary manner as diagnostic procedures such as pelvic floor sonography, which are easy to learn and use.Only an interdisciplinary urogynecological sub-specialisation can guarantee the development of required professional competences. Interdisciplinary education should be organised by the participating societies (urology, surgery and gynaecology) together., Competing Interests: Joerg Neymeyer ist Patentinhaber der gezeigten Instrumente RSD, ARSD und RTD) und erhielt in den vergangenen 3 Jahren Vortragshonorare von der Firma Serag-Wiessner. Die anderen Autoren geben an, dass kein Interessenskonflikt besteht., (© Georg Thieme Verlag KG Stuttgart · New York.)

In Europe, most of the discarded and un-wearable textiles are incinerated or landfilled. In this study, we present an enzyme-based strategy for the recovery of valuable building blocks from mixed textile waste and blends as a circular economy concept. Therefore, model and real textile waste were sequentially incubated with (1) protease for the extraction of amino acids from wool components (95% efficiency) and (2) cellulases for the recovery of glucose from cotton and rayon constituents (85% efficiency). The purity of the remaining poly(ethylene terephthalate) (PET) unaltered by the enzymatic treatments was assessed via Fourier-transformed infrared spectroscopy. Amino acids recovered from wool were characterized via elementary and molecular size analysis, while the glucose resulting from the cotton hydrolysis was successfully converted into ethanol by fermentation with Saccharomyces cerevisiae . This work demonstrated that the step-wise application of enzymes can be used for the recovery of pure building blocks (glucose) and their further reuse in fermentative processes.