Non-antibiotic strategies for the prevention of infectious complications following prostate biopsy : A Systematic Review and Meta-analysis

Acknowledgments Emma Smith from the EAU Guidelines Office assisted with the systematic review, and Robert Pickard (deceased), Newcastle upon Tyne, United Kingdom, initiated this review.Peer reviewedPostprin

Analysis of connexin 43, connexin 45 and N-cadherin in the human sertoli cell line FS1 and the human seminoma-like cell line TCam-2 in comparison with human testicular biopsies

Background: Germ cell tumors are relatively common in young men. They derive from a non-invasive precursor, called germ cell neoplasia in situ, but the exact pathogenesis is still unknown. Thus, further understanding provides the basis for diagnostics, prognostics and therapy and is therefore paramount. A recently developed cell culture model consisting of human FS1 Sertoli cells and human TCam-2 seminoma-like cells offers new opportunities for research on seminoma. Since junctional proteins within the seminiferous epithelium are involved in cell organization, differentiation and proliferation, they represent interesting candidates for investigations on intercellular adhesion and communication in context with neoplastic progression. Methods: FS1 and TCam-2 cells were characterized regarding gap-junction-related connexin 43 (Cx43) and connexin 45 (Cx45), and adherens-junction-related N-cadherin using microarray, PCR, Western blot, immunocytochemistry and immunofluorescence. Results were compared to human testicular biopsies at different stages of seminoma development via immunohistochemistry to confirm the cell lines’ representativeness. Furthermore, dye-transfer measurements were performed to investigate functional cell coupling. Results: Cx43, Cx45 and N-cadherin mRNA and protein were generally detectable in both cell lines via qualitative RT-PCR and Western blot. Immunocytochemistry and immunofluorescence revealed a mainly membrane-associated expression of N-cadherin in both cell lines, but gene expression values were higher in FS1 cells. Cx43 expression was also membrane-associated in FS1 cells but barely detectable in TCam-2 cells. Accordingly, a high gene expression value of Cx43 was measured for FS1 and a low value for TCam-2 cells. Cx45 was primary located in the cytoplasm of FS1 and TCam-2 cells and revealed similar low to medium gene expression values in both cell lines. Overall, results were comparable with corresponding biopsies. Additionally, both FS1 and TCam-2 cells showed dye diffusion into neighboring cells. Conclusion: The junctional proteins Cx43, Cx45 and N-cadherin are expressed in FS1 and TCam-2 cells at mRNA and/or protein level in different amounts and localizations, and cells of both lines are functionally coupled among each other. Concerning the expression of these junctional proteins, FS1 and TCam-2 cells are largely representative for Sertoli and seminoma cells, respectively. Thus, these results provide the basis for further coculture experiments evaluating the role of junctional proteins in context with seminoma progression

European Association of Urology Position Paper on the Prevention of Infectious Complications Following Prostate Biopsy

Funding support: This work is supported by the European Association of Urology Guidelines Office.Peer reviewedPostprin

Validation of the Spanish Acute Cystitis Symptoms Score (ACSS) in native Spanish‐speaking women of Europe and Latin America

Introduction and Objectives The Acute Cystitis Symptom Score (ACSS) is a patient self-reporting questionnaire for clinical diagnostics and patient-reported outcome (PRO), which may assess the symptoms and the effect on the quality of life in women with acute cystitis (AC). The current study aimed to create a validated Spanish version of the ACSS questionnaire. Material and Methods The process of linguistic validation of the Spanish version of the ACSS consisted of the independent forward and backward translations, revision and reconciliation, and cognitive assessment. Clinical evaluation of the study version of the ACSS was carried out in clinics in Spain and Latin America. Statistical tests included the calculation of Cronbach's α, split-half reliability, specificity, sensitivity, diagnostic odds ratio, positive and negative likelihood ratio, and area under the receiver-operating characteristic curve (AUC). Results The study was performed on 132 patients [age (mean;SD) 45.0;17.8 years] with AC and 55 controls (44.5;12.2 years). Cronbach's α of the ACSS was 0.86, and the split-half reliability was 0.82. The summary scores of the ACSS domains were significantly higher in patients than in controls, 16.0 and 2.0 (p < 0.001), respectively. The predefined cut-off point of ≥6 for a summary score of the “Typical” domain resulted in a specificity of 83.6% and a sensitivity of 99.2% for the Spanish version of the ACSS. AUC was 0.91 [0.85; 0.97]. Conclusions The validated Spanish ACSS questionnaire evaluates the symptoms and clinical outcomes of patients with AC. It can be used as a patient's self-diagnosis of AC, as a PRO measure tool, and help to rule out other pathologies in patients with voiding syndrome

Uropathogenic E. coli Induce Different Immune Response in Testicular and Peritoneal Macrophages: Implications for Testicular Immune Privilege

Infertility affects one in seven couples and ascending bacterial infections of the male genitourinary tract by Escherichia coli are an important cause of male factor infertility. Thus understanding mechanisms by which immunocompetent cells such as testicular macrophages (TM) respond to infection and how bacterial pathogens manipulate defense pathways is of importance. Whole genome expression profiling of TM and peritoneal macrophages (PM) infected with uropathogenic E. coli (UPEC) revealed major differences in regulated genes. However, a multitude of genes implicated in calcium signaling pathways was a common feature which indicated a role of calcium-dependent nuclear factor of activated T cells (NFAT) signaling. UPEC-dependent NFAT activation was confirmed in both cultured TM and in TM in an in vivo UPEC infectious rat orchitis model. Elevated expression of NFATC2-regulated anti-inflammatory cytokines was found in TM (IL-4, IL-13) and PM (IL-3, IL-4, IL-13). NFATC2 is activated by rapid influx of calcium, an activity delineated to the pore forming toxin alpha-hemolysin by bacterial mutant analysis. Alpha-hemolysin suppressed IL-6 and TNF-α cytokine release from PM and caused differential activation of MAP kinase and AP-1 signaling pathways in TM and PM leading to reciprocal expression of key pro-inflammatory cytokines in PM (IL-1α, IL-1β, IL-6 downregulated) and TM (IL-1β, IL-6 upregulated). In addition, unlike PM, LPS-treated TM were refractory to NFκB activation shown by the absence of degradation of IκBα and lack of pro-inflammatory cytokine secretion (IL-6, TNF-α). Taken together, these results suggest a mechanism to the conundrum by which TM initiate immune responses to bacteria, while maintaining testicular immune privilege with its ability to tolerate neo-autoantigens expressed on developing spermatogenic cells

Epididymitis: revelations at the convergence of clinical and basic sciences

No grant i

Validation of the American English Acute Cystitis Symptom Score

The diagnosis of acute uncomplicated cystitis (UC) is usually based on clinical symptoms. The study aims to develop and validate the American-English Acute Cystitis Symptom Score (ACSS), a self-reporting questionnaire for diagnosis and patient-reported outcome in women with acute uncomplicated cystitis (UC). After certified translation into American-English and cognitive assessment, the clinical validation of the ACSS was performed embedded in a US phase-II trial. 167 female patients with typical symptoms of UC were included in the study following US Food and Drug Administration (FDA) guidance. At Day 1 (diagnosis), the mean (SD) sum score of the six ACSS typical symptoms reached 10.60 (2.51). Of 100 patients followed-up last time on Day 5 or 6 (End-of-treatment, EoT), 91 patients showed clinical success according to the favored ACSS criteria (sum score of typical symptoms 0.98 (1.94)). There was no correlation between the severity of symptoms on Day 1 or between clinical success rate at EoT and level of bacteriuria on Day 1. The American-English ACSS showed high predictive ability and responsiveness and excellent levels of reliability and validity. It can now be recommended as the new master version in clinical and epidemiological studies, in clinical practice, or for self-diagnosis of women with symptoms of UC

Excessive unilateral proliferation of spermatogonia in a patient with non-obstructive azoospermia – adverse effect of clomiphene citrate pre-treatment?

Background!#!Clomiphene citrate has been proposed as pre-treatment for infertile men with non-obstructive, testicular azoospermia (NOA) before surgery for testicular sperm extraction (TESE), especially when serum testosterone is low.!##!Case presentation!#!Here, we report on a 33-year old azoospermic patient with a previous history of repeated 'fresh' TESE and clomiphene citrate therapy (50 mg/day over 6 months) before undergoing microscopically assisted, bilateral testicular biopsy. Comprehensive histological and immunohistochemical work-up revealed a heterogeneous spermatogenic arrest at the level of spermatogonia or primary spermatocytes, with focally preserved spermatogenesis up to elongated spermatids in the right testis. In the left testis, the majority of tubules (&amp;gt; 70%) showed no tubular lumen or regular seminiferous epithelium but a great number of spermatogonia-like cells. These cells proved to be normally differentiated spermatogonia (positive for melanoma associated antigen 4 (MAGEA4), negative for placental alkaline phosphatase (PlAP)) with increased proliferative activity (positive for proliferating cell nuclear antigen (PCNA)) and a slightly higher rate of apoptotic cells. When compared to a tissue control with normal spermatogenesis, expression of sex hormone receptors androgen receptor (AR), estrogen receptor (ER) alpha, and G-protein coupled estrogen receptor 1 (GPER1) was not altered in patient samples. Sertoli cells appeared to be mature (positive for vimentin, negative for cytokeratin 18), whereas the expression of zona occludens protein 1 (ZO-1), claudin 11, and connexin 43 was absent or dislocated in the tubules with abundance of spermatogonia.!##!Conclusion!#!This result suggests that formation of the blood-testis barrier is disturbed in affected tubules. To our knowledge this is the first observation of excessive, non-malignant proliferation of spermatogonia in a NOA patient. Although underlying molecular mechanisms remain to be elucidated, we hypothesize that the unusual pathology was triggered by the high-dose clomiphene citrate treatment preceding testicular biopsy

Reevaluation of the Acute Cystitis Symptom Score, a Self-Reporting Questionnaire. Part II. Patient-Reported Outcome Assessment

This study aimed to reevaluate the Acute Cystitis Symptom Score (ACSS). The ACSS is a self-reporting questionnaire for the clinical diagnosis of acute uncomplicated cystitis (AC) and the assessment of symptomatic changes after therapy in female patients with AC. The part II of the present study was to reevaluate the utility of the different domains of the ACSS after therapy. The applicability of these domains in assessing changes in symptoms, as a function of time, in this population was investigated. The ACSS was evaluated in 48 female patients (mean age 31.1 &plusmn; 10.6) in the Uzbek and Russian languages, who returned after therapy and filled in part B of the ACSS, which corresponds to part A with the additional &ldquo;Dynamics&rdquo; domain. Descriptive statistics were used, where suitable. The reduction of typical symptoms and quality of life assessment between first and follow-up visit correlated significantly with answers in the &ldquo;Dynamics&rdquo; domain. Success/Cure and Non-success/Failure could be clearly differentiated by the scores obtained in &ldquo;Typical&rdquo; and &ldquo;Quality of Life&rdquo; domains. The ACSS has proven to be a useful instrument to clinically diagnose AC in women. It is also a suitable instrument for patient-reported outcome measures, with applicability both in daily practice and clinical studies. Slight modifications in the &ldquo;Dynamics&rdquo; domain will even increase the applicability

Reevaluation of the Acute Cystitis Symptom Score, a Self-Reporting Questionnaire. Part I. Development, Diagnosis and Differential Diagnosis

This study aimed to reevaluate the Acute Cystitis Symptom Score (ACSS). The ACSS is a simple and standardized self-reporting questionnaire for the diagnosis of acute uncomplicated cystitis (AC) assessing typical and differential symptoms, quality of life, and possible changes after therapy in female patients with AC. This paper includes literature research, development and evaluation of the ACSS, an 18-item self-reporting questionnaire including (a) six questions about “typical” symptoms of AC, (b) four questions regarding differential diagnoses, (c) three questions on quality of life, and (d) five questions on additional conditions that may affect therapy. The ACSS was evaluated in 228 women (mean age 31.49 ± 11.71 years) in the Russian and Uzbek languages. Measurements of reliability, validity, predictive ability, and responsiveness were performed. Cronbach’s alpha for ACSS was 0.89, split-half reliability was 0.76 and 0.79 for first and second halves, and the correlation between them was 0.87. Mann-Whitney U test revealed a significant difference in scores of the “typical” symptoms between patients and controls (10.50 vs. 2.07, p &lt; 0.001). The optimal threshold score was 6 points, with a 94% sensitivity and 90% specificity to predict AC. The “typical” symptom score decreased significantly when comparing before and after therapy (10.4 and 2.5, p &lt; 0.001). The reevaluated Russian and Uzbek ACSS are accurate enough and can be recommended for clinical studies and practice for initial diagnosis and monitoring the process of the treatment of AC in women. Evaluation in German, UK English, and Hungarian languages was also performed and in other languages evaluation of the ACSS is in progres