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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

Background: Management of recurrent urinary tract infection (rUTI) is still challenging. A better understanding of the natural history of rUTI could help us reduce antibiotic use and improve antibiotic stewardship. Objective: To describe the effect of risk identification, stratification, and counseling on the natural course of the disease in women with rUTI. Design, setting, and participants: A total of 373 women affected by recurrent cystitis were enrolled in this longitudinal cohort study between December 2014 and December 2019. A systematic and standardized identification of risk factors was performed. Intervention: As intervention, risk factors were treated or removed where possible. Patients with nonremovable risk factors were included in the control group. All patients were scheduled for follow-up visits every 6 mo. Outcome measurements and statistical analysis: The main outcome measures were the rate of symptomatic recurrences and improvement in questionnaire results from baseline to the end of the follow-up period. Reduction of antibiotic usage was regarded as a secondary outcome measure. Results and Limitations: Finally, 353 women were analyzed: 196 in the study group and 157 in the control group. At the end of the follow-up period, a statistically significant reduction in the symptomatic recurrence rate was found between the two groups (0.9 ± 0.2 and 2.6 ± 0.5; p < 0.001), as well as in quality of life and anxiety according to mean questionnaire results: quality of life (0.88 ± 0.06 and 0.63 ± 0.09; p < 0.001) and Spielberger State-Trait Anxiety Inventory-Form Y (32.7 ± 9.3 and 47.5 ± 14.3; p < 0.001). The use of antibiotics was significantly lower in the study group: 4410 versus 9821 (p < 0.001). A limitation to consider is the lack of a randomized design for the active approach in the high-risk group. Conclusions: Identification, counseling, and removal of risk factors, where possible, are able to change the natural history of rUTI, by reducing the number of symptomatic episodes and antibiotic use and improving quality of life. Patient summary: In this report, we analyzed a large cohort of women affected by recurrent urinary tract infections and followed for a long time period. We found that risk factor identification and counseling may change the natural history of recurrent urinary tract infections, concluding that this approach is able to reduce the number of symptomatic episodes, reduce antibiotic usage, and improve patients’ quality of life.

Transrectal ultrasound (TRUS) parameters are not standardized, especially in men of reproductive age. Hence, the European Academy of Andrology (EAA) promoted a multicenter study to assess the TRUS characteristics of healthy-fertile men (HFM) to establish normative parameters.To report and discuss the prostate and seminal vesicles (SV) reference ranges and characteristics in HFM and their associations with clinical, seminal, biochemical parameters.188 men (35.6 ± 6.0 years) from a cohort of 248 HFM were studied, evaluating, on the same day, clinical, biochemical, seminal, TRUS parameters following Standard Operating Procedures.TRUS reference ranges and characteristics of the prostate and SV of HFM are reported herein. The mean PV was ∼25 ml. PV lower and upper limits were 15 and 35 ml, defining prostate hypotrophy and enlargement, respectively. PV was positively associated with age, waistline, current smoking (but not with T levels), seminal volume (and negatively with seminal pH), prostate inhomogeneity, macrocalcifications, calcification size and prostate arterial parameters, SV volume before and after ejaculation, deferential and epididymal size. Prostate calcifications and inhomogeneity were frequent, while midline prostatic cysts were rare and small. Ejaculatory duct abnormalities were absent. Periprostatic venous plexus size was positively associated with prostate calcifications, SV volume and arterial peak systolic velocity. Lower and upper limits of SV anterior-posterior diameter after ejaculation were 6 and 16 mm, defining SV hypotrophy or dilation, respectively. SV total volume before ejaculation and delta SV total volume (DSTV) positively correlated with ejaculate volume, and DSTV correlated positively with sperm progressive motility. SV total volume after ejaculation was associated negatively with SV ejection fraction and positively with distal ampullas size. SV US abnormalities were rare. No association between TRUS and time to pregnancy, number of children or history of miscarriage was observed.The present findings will help in better understanding male infertility pathophysiology and the meaning of specific TRUS findings.

STUDY QUESTION What is the impact of variants in the genes INSL3 (Insulin Like 3) and RXFP2 (Relaxin Family Peptide Receptor 2), respectively, on cryptorchidism and male infertility? SUMMARY ANSWER Bi-allelic loss-of-function (LoF) variants in INSL3 and RXFP2 result in bilateral cryptorchidism and male infertility, whereas heterozygous variant carriers are phenotypically unaffected. WHAT IS KNOWN ALREADY The small heterodimeric peptide INSL3 and its G protein-coupled receptor RXFP2 play a major role in the first step of the biphasic descent of the testes, and variants in the INSL3 and RXFP2 genes have long been implicated in inherited cryptorchidism. However, only one single homozygous missense variant in RXFP2 has clearly been linked to familial bilateral cryptorchidism, so the effects of bi-allelic variants in INSL3 and heterozygous variants in both genes on cryptorchidism and male infertility remain unclear. STUDY DESIGN, SIZE, DURATION Exome data of 2412 men from the MERGE (Male Reproductive Genomics) study cohort including 1902 infertile men with crypto-/azoospermia, of whom 450 men had a history of cryptorchidism, were screened for high-impact variants in INSL3 and RXFP2. PARTICIPANTS/MATERIALS, SETTING, METHODS For patients with rare, high-impact variants in INSL3 and RXFP2, detailed clinical data were collected and the testicular phenotype was determined. Genotyping of family members was performed to analyse the co-segregation of candidate variants with the condition. Immunohistochemical staining for INSL3 in patient testicular tissue and measuring serum INSL3 concentration was performed to analyse the functional impact of a homozygous loss-of-function variant in INSL3. For a homozygous missense variant in RXFP2, its impact on the protein’s cell surface expression and ability to respond to INSL3 in CRE reporter gene assay was determined. MAIN RESULTS AND THE ROLE OF CHANCE This study presents homozygous high-impact variants in INSL3 and RXFP2 and clearly correlates these to bilateral cryptorchidism. Functional impact of the identified INSL3 variant was demonstrated by absence of INSL3-specific staining in patients’ testicular Leydig cells as well as undetectable blood serum levels. The identified missense variant in RXFP2 was demonstrated to lead to reduced RXFP2 surface expression and INSL3 mediated receptor activation. LIMITATIONS, REASONS FOR CAUTION Further investigations are needed to explore a potential direct impact of bi-allelic INSL3 and RXFP2 variants on spermatogenesis. With our data, we cannot determine whether the infertility observed in our patients is a direct consequence of the disruption of a possible function of these genes on spermatogenesis or whether it occurs secondarily due to cryptorchidism. WIDER IMPLICATIONS OF THE FINDINGS In contrast to previous assumptions, this study supports an autosomal recessive inheritance of INSL3- and RXFP2-related bilateral cryptorchidism while heterozygous LoF variants in either gene can at most be regarded as a risk factor for developing cryptorchidism. Our findings have diagnostic value for patients with familial/bilateral cryptorchidism and additionally shed light on the importance of INSL3 and RXFP2 in testicular descent and fertility. STUDY FUNDING/COMPETING INTEREST(S) This study was carried out within the frame of the German Research Foundation (DFG) funded by Clinical Research Unit ‘Male Germ Cells: from Genes to Function’ (DFG, CRU326). Research at the Florey was supported by an NHMRC grant (2001027) and the Victorian Government Operational Infrastructure Support Program. A.S.B. is funded by the DFG (‘Emmy Noether Programme’ project number 464240267). The authors declare no conflict of interest. TRIAL REGISTRATION NUMBER N/A.

STUDY QUESTION Is the vertebrate protein Dead end (DND1) a causative factor for human infertility and can novel in vivo assays in zebrafish help in evaluating this? SUMMARY ANSWER Combining patient genetic data with functional in vivo assays in zebrafish reveals a possible role for DND1 in human male fertility. WHAT IS KNOWN ALREADY About 7% of the male population is affected by infertility but linking specific gene variants to the disease is challenging. The function of the DND1 protein was shown to be critical for germ cell development in several model organisms but a reliable and cost-effective method for evaluating the activity of the protein in the context of human male infertility is still missing. STUDY DESIGN, SIZE, DURATION Exome data from 1305 men included in the Male Reproductive Genomics cohort were examined in this study. A total of 1114 of the patients showed severely impaired spermatogenesis but were otherwise healthy. Eighty-five men with intact spermatogenesis were included in the study as controls. PARTICIPANTS/MATERIALS, SETTING, METHODS We screened the human exome data for rare, stop-gain, frameshift, splice site, as well as missense variants in DND1. The results were validated by Sanger sequencing. Immunohistochemical techniques and, when possible, segregation analyses were performed for patients with identified DND1 variants. The amino acid exchange in the human variant was mimicked at the corresponding site of the zebrafish protein. Using different aspects of germline development in live zebrafish embryos as biological assays, we examined the activity level of these DND1 protein variants. MAIN RESULTS AND THE ROLE OF CHANCE In human exome sequencing data, we identified four heterozygous variants in DND1 (three missense and one frameshift variant) in five unrelated patients. The function of all of the variants was examined in the zebrafish and one of those was studied in more depth in this model. We demonstrate the use of zebrafish assays as a rapid and effective biological readout for evaluating the possible impact of multiple gene variants on male fertility. This in vivo approach allowed us to assess the direct impact of the variants on germ cell function in the context of the native germline. Focusing on the DND1 gene, we find that zebrafish germ cells, expressing orthologs of DND1 variants identified in infertile men, failed to arrive correctly at the position where the gonad develops and exhibited defects in cell fate maintenance. Importantly, our analysis facilitated the evaluation of single nucleotide variants, whose impact on protein function is difficult to predict, and allowed us to distinguish variants that do not affect the protein’s activity from those that strongly reduce it and could thus potentially be the primary cause for the pathological condition. These aberrations in germline development resemble the testicular phenotype of azoospermic patients. LIMITATIONS, REASONS FOR CAUTION The pipeline we present requires access to zebrafish embryos and to basic imaging equipment. The notion that the activity of the protein in the zebrafish-based assays is relevant for the human homolog is well supported by previous knowledge. Nevertheless, the human protein may differ in some respects from its homologue in zebrafish. Thus, the assay should be considered only one of the parameters used in defining DND1 variants as causative or non-causative for infertility. WIDER IMPLICATIONS OF THE FINDINGS Using DND1 as an example, we have shown that the approach described in this study, relying on bridging between clinical findings and fundamental cell biology, can help to establish links between novel human disease candidate genes and fertility. In particular, the power of the approach we developed is manifested by the fact that it allows the identification of DND1 variants that arose de novo. The strategy presented here can be applied to different genes in other disease contexts. STUDY FUNDING/COMPETING INTEREST(S) This study was funded by the German Research Foundation, Clinical Research Unit, CRU326 ‘Male Germ Cells’. There are no competing interests. TRIAL REGISTRATION NUMBER N/A.

Chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) has a high prevalence of up to 15% and accounts for 90-95% of prostatitis diagnoses, and yet its etiopathogenesis and link to prostate cancer (PCa) are still unclear. Here, we investigated microRNAs in exosomes isolated from blood and post-prostatic-massage urine of CP/CPPS type IIIb patients and healthy men. THP-1 monocytes (human leukemia monocytic cell line) were treated with exosomes and subjected to mRNA arrays "Cancer Inflammation and Immunity Crosstalk" and "Transcription Factors." Using The Cancer Genome Atlas, the expression of CP/CPPS-associated microRNAs was analyzed in PCa and normal prostate tissue. In silico functional studies were carried out to explore the disease ontology of CP/CPPS. In CP/CPPS, urine exosomes exhibited significant upregulation of eight PCa-specific microRNAs (e.g., hsa-miR-501, hsa-miR-20a, and hsa-miR-106), whose target genes were significantly enriched for GO terms, hallmark gene sets, and pathways specific for carcinogenesis. In THP-1 monocytes, CP/CPPS-derived urine exosomes induced upregulation of PCa-associated proinflammatory genes (e.g., CCR2 and TLR2) and proto-oncogene transcription factors (e.g., MYB and JUNB). In contrast, CP/CPPS-derived blood exosomes exhibited molecular properties similar to those of healthy men. Thus, CP/CPPS exhibits molecular changes that constitute a risk for PCa and should be considered in the development of PCa biomarkers and cancer screening programs.

The COVID (coronavirus disease 2019) pandemic has shown impressively that infectious diseases can have an enormous impact on the healthcare system and beyond. In the specialty of urology, patients present in daily practice with viral infections that are associated with numerous diseases.The aim of this review is to describe viral infections relevant for urology, and in particular to emphasize vaccination prevention. A selective literature search was carried out on the subjects of "COVID and urology", "urogenital viral infections", "viral urological infections in transplant medicine", and "vaccination prevention of viral diseases".Coronaviruses have already caused two local epidemics: SARS (severe acute respiratory syndrome) epidemic and MERS (Middle East respiratory syndrome) epidemic. The fact that the SARS-CoV‑2 (SARS coronavirus 2) disease is contagious even without symptoms has essentially led to the rapid spread and global pandemic. A large number of viruses, which can also induce viremia, have been detected in the ejaculate and are thus associated with a possible urogenital infection. These include the mumps virus, Coxsackie viruses or enteroviruses, among others. It has also been shown that a Zika virus infection can also be sexually transmitted via the sperm as a carrier. Viruses therefore also play an important role in reproduction. When performing kidney transplants, urologists are often confronted with viral infections. The most effective weapon against viruses is prevention by vaccination.In terms of ethiopathogenesis, the genitourinary tract is most often affected by viruses, in the context of viremia or through reactivation due to immunosuppression. Immunomodulation and vaccination prophylaxis play a leading role in therapy.EINLEITUNG: Die COVID-19-Pandemie („coronavirus disease 2019“) hat eindrucksvoll gezeigt, dass Infektionskrankheiten enorme Auswirkungen auf das Gesundheitswesen und darüber hinaus haben können. In der Urologie spielen Viren bei spezifischen Entitäten eine Rolle, wo sich der Urologe mit Viruserkrankungen beschäftigen muss.Diese Übersichtsarbeit hat zum Ziel in der Urologie relevante Virusinfektionen zu beschreiben und insbesondere die Impfprävention hervorzuheben. Es erfolgte eine selektive Literaturrecherche zu den Themen „COVID und Urologie“, „Urogenitale Virusinfektionen“, „Virale urologische Infektionen in der Transplantationsmedizin“ sowie „Impfprävention von Viruserkrankungen“.Coronaviren sind Viren, die bereits 2‑mal lokale Epidemien verursacht haben (SARS- [„severe acute respiratory syndrome“] und MERS-Epidemie [„middle east respiratory syndrome“]). Die Tatsache, dass die SARS-CoV-2-Erkrankung („severe acute respiratory syndrome coronavirus 2“) auch ohne Symptome ansteckend ist, hat im Wesentlichen zu der raschen Ausbreitung und weltweiten Pandemie geführt. Eine Vielzahl von Viren, die auch eine Virämie induzieren können, wurde im Ejakulat nachgewiesen und wird damit mit einer etwaigen urogenitalen Infektion in Verbindung gebracht. Hierzu zählen u. a. das Mumps‑, Coxsackie-Viren oder Enteroviren. Es wurde auch gezeigt, dass auch eine Zika-Virusinfektion sexuell über die Spermien als Carrier übertragen werden kann. Somit spielen Viren auch eine wichtige Rolle in der Reproduktion. Bei der Nierentransplantation sind Urologen häufig mit viralen Infektionen konfrontiert. Die effektivste Waffe gegenüber Viren stellt die Impfprävention dar.Äthiopathogenetisch ist der Urogenitaltrakt im Rahmen einer Virämie oder über eine Reaktivierung durch eine Immunsuppression am häufigsten mitbetroffen. Therapeutisch kommt der Immunmodulation sowie der Impfprophylaxe eine führende Rolle zu.

ZusammenfassungInfektionskomplikationen nach Prostatabiopsie nehmen zu aufgrund zunehmender Antibiotikaresistenz insbesondere gegenüber Fluorchinolonen. Fluorchinolone sind als perioperative Antibiotikaprophylaxe in Deutschland durch das Bundesinstitut für Arzneimittel und Medizinprodukte (BfArM) nicht mehr zugelassen. Die Leitliniengruppe Urologische Infektionen der Europäischen Gesellschaft für Urologie (EAU) hat kürzlich eine Meta-Analyse in zwei Teilen auf der Basis randomisiert kontrollierter Studien (RCTs) veröffentlicht. Die transperineale Prostatabiopsie ist mit signifikant weniger Infektionskomplikationen assoziiert als die transrektale Biopsie und sollte deswegen bevorzugt werden. Sollte dennoch eine transrektale Biopsie durchgeführt werden, sind eine intrarektale Reinigung mit Povidon-Jod sowie eine antibiotische Prophylaxe ohne Fluorchinolone zu verwenden. Als antibiotische Prophylaxestrategien kommen die zielgerichtete Prophylaxe nach Empfindlichkeitstestung der Enddarmflora, die augmentierte Prophylaxe mit mehreren Antibiotika und die empirische Mono-Prophylaxe mit Nicht-Fluorchinolonen in Frage. Daten aus RCTs liegen hier für Aminoglykoside, 3. Generationscephalosporine und Fosfomycin trometamol vor.

Die perioperative Antibiotikaprophylaxe in der Endourologie dient der Reduktion bzw. der Vermeidung von postinterventionellen Gewebeinfektionen und komplizierten Harnwegsinfektionen. Besondere Berucksichtigung finden hierbei die Strategien des Antibiotic Stewardship mit dem Ziel, eine fortlaufende Selektion antibiotika- und multiresistenter Uropathogene sowie eine Schadigung des Mikrobioms zu vermeiden. Das individuelle Risikoprofil, die lokale Resistenzlage, das zu erwartende Erregerspektrum, die Pharmakokinetik und die Zulassung der jeweiligen Substanz sind wichtige Aspekte bei der Indikationsstellung und Auswahl der perioperativen Antibiotikaprophylaxe. Geltende Hygienevorschriften und die operative Sorgfalt eines Eingriffs sind daruber hinaus zu beachten.

Sexual health is becoming increasingly important for many HIV-positive men undergoing highly effective antiretroviral therapy (ART) but remains frequently unaddressed in routine clinical consultation.To comprehensively evaluate sexual health in male patients with HIV on stable ART over a 12-month period.The prospectively registered cohort study comprising 87 HIV-positive men on stable ART (median age: 43 years) was conducted between 2011 and 2015 at a university hospital. Patients were enrolled from the outpatient infectious disease unit and underwent an extensive andrological workup to assess parameters of sexual health (questionnaires, sex hormones, ultrasound, 2-glass urine test including semen analysis with microbiological and viral diagnostics). The study period per patient lasted 12 months.The primary endpoint was the impact of chronic HIV infection on sexual health.Although, on average, sexual health was fine at baseline, 56% of the patients reported erectile dysfunction, 28% experienced reduced libido, 5% had hypogonadism, 36% showed at least 1 atrophic testicle with a volume of10 ml, 8% suffered bacterial sexually transmitted infections, 35% had seminal inflammation, and up to 47% showed reduced sperm quality. Sexual satisfaction was linked to mental health (12-Item Short Form Health Survey questionnaire) and International Index of Erectile Function scores. During the study period, the collected parameters on sexual health were generally stable. However, 35% of patients had new sex partners (median: 5 partners), 7% had fathered a child or were planning procreation, 47% reported changed libido, 17% suffered bacterial sexually transmitted infections in the urogenital tract, 16% revealed a positive HIV viral load in blood, 11% had a positive HIV viral load in semen, and 28% were treated for andrological disorders.Sexual ill-health exists in about one third of patients. This manifests itself in sexual dysfunction, sexually transmitted infections, urogenital tract inflammation, and abnormal sperm parameters, all of which require adequate counseling and therapy.The strength of this study is its comprehensive analysis of male sexual health over a 12-month period of stable ART treatment. Limitations are a heterogeneous patient cohort and a rather small percentage of patients with a positive HIV viral load in blood or semen, which prevented multivariate risk analysis.Our study provides evidence that sexual health should be actively taken into account in the routine consultation by infectious disease specialists, and an interdisciplinary approach is desirable in the case of symptoms or signs of sexual ill-health. Pilatz A, Maresch CC, Discher T, et al. Sexual Health in HIV-Positive Men Under Stable Antiretroviral Therapy During a 12-Month Period. J Sex Med 2021;18:284-294.

Background: Scrotal color Doppler ultrasound (CDUS) still suffers from lack of standardization. Hence, the European Academy of Andrology (EAA) has promoted a multicenter study to assess the CDUS characteristics of healthy fertile men (HFM) to obtain normative parameters. Objectives: To report and discuss the scrotal organs CDUS reference ranges and characteristics in HFM and their associations with clinical, seminal, and biochemical parameters. Methods: A cohort of 248 HFM (35.3 +/- 5.9years) was studied, evaluating, on the same day, clinical, biochemical, seminal, and scrotal CDUS following Standard Operating Procedures. Results: The CDUS reference range and characteristics of the scrotal organs of HFM are reported here. CDUS showed a higher accuracy than physical examination in detecting scrotal abnormalities. Prader orchidometer (PO)- and US-measured testicular volume (TV) were closely related. The US-assessed TV with the ellipsoid formula showed the best correlation with the PO-TV. The mean TV of HFM was similar to 17 ml. The lowest reference limit for right and left testis was 12 and 11 ml, thresholds defining testicular hypotrophy. The highest reference limit for epididymal head, tail, and vas deferens was 12, 6, and 4.5 mm, respectively. Mean TV was associated positively with sperm concentration and total count and negatively with gonadotropins levels and pulse pressure. Subjects with testicular inhomogeneity or calcifications showed lower sperm vitality and concentration, respectively, than the rest of the sample. Sperm normal morphology and progressive motility were positively associated with epididymal head size/vascularization and vas deferens size, respectively. Increased epididymis and vas deferens sizes were associated with MAR test positivity. Decreased epididymal tail homogeneity/vascularization were positively associated with waistline, which was negatively associated with intratesticular vascularization. CDUS varicocele was detected in 37.2% of men and was not associated with seminal or hormonal parameters. Scrotal CDUS parameters were not associated with time to pregnancy, number of children, history of miscarriage. Conclusions: The present findings will help in better understanding male infertility pathophysiology, improving its management.

The transperineal approach is preferred to reduce prostate biopsy (PB)-related infections. Fluoroquinolones are suspended for prophylaxis of PB in the European Union; therefore, alternative antibiotics based on local resistance, or targeted prophylaxis, in conjunction with povidone-iodine rectal preparation are recommended for transrectal PB.

Acute infective epididymitis is the most common cause for scrotal pain in adults. The severe course of the disease requires immediate antimicrobial management, comprised antibiotic treatment and supportive measures. Patients with chronic indwelling catheters and developing epididymitis show a more severe clinical course compared to patients without a catheter. Although it is common clinical practice to place a catheter for the treatment of a systemic infectious condition of the genitourinary tract, there is only limited evidence of support due to the absence of clinical trials.Die akute Epididymitis ist einer der häufigsten Gründe für skrotale Schmerzen bei Erwachsenen. Schwere Verläufe mit systemischen Infektionszeichen erfordern eine stationäre Behandlung, bei der das antimikrobielle Management entscheidend ist. Die sofortige Einleitung der antibiotischen Therapie wird durch supportive Maßnahmen ergänzt. Patienten mit Katheterversorgung, die eine akute Epididymitis entwickeln, weisen einen schwereren Krankheitsverlauf auf als solche mit natürlicher Miktion. Für die häufig durchgeführte Praxis einer supportiven Katheterisierung bei Patienten mit akuter Epididymitis fehlt jegliche Evidenz aufgrund nicht vorhandener klinischer Studien.

Infektionskomplikationen nach Prostatabiopsie sind von zunehmender Relevanz und Fluorchinolone sind als perioperative Antibiotikaprophylaxe in Deutschland durch das Bundesinstitut fur Arzneimittel und Medizinprodukte (BfArM) nicht mehr zugelassen. Diese Ubersichtsarbeit soll aufzeigen, wie Infektionskomplikationen bei der Prostatabiopsie reduziert werden konnen. Die Leitliniengruppe Urologische Infektionen der Europaischen Gesellschaft fur Urologie (EAU) hat kurzlich eine Metaanalyse in zwei Teilen auf der Basis randomisiert kontrollierter Studien (RCTs) veroffentlicht, deren wichtigste Inhalte hier dargestellt werden sollen. Die transperineale Prostatabiopsie ist mit signifikant weniger Infektionskomplikationen assoziiert als die transrektale Biopsie. Sollte dennoch die transrektale Biopsie gewahlt werden, sind eine intrarektale Reinigung mit Povidon-Jod sowie eine antibiotische Prophylaxe ohne Fluorchinolone zu verwenden. Als antibiotische Prophylaxestrategien kommen die zielgerichtete Prophylaxe nach Empfindlichkeitstestung der Enddarmflora, die augmentierte Prophylaxe mit mehreren Antibiotika und die empirische Monoprophylaxe mit Nicht-Fluorchinolonen in Frage. Daten aus RCTs liegen hier fur Aminoglykoside, 3. Generationscephalosporine und Fosfomycin trometamol vor. Die transperineale Biopsie ist aufgrund signifikant niedrigerer Infektionen bevorzugt zu verwenden. Sollte die transrektale Biopsie weiterhin zum Einsatz kommen ist zu beachten, dass Fluorchinolone als Infektionsprophylaxe nicht mehr zugelassen sind.

Eine Azoospermie findet sich bei 10–15 % der Manner, die wegen eines unerfullten Kinderwunschs untersucht werden. Differenzialdiagnostisch sind die obstruktive (OA) und nichtobstruktive Azoospermie (NOA) zu unterscheiden, wobei jeweils kongenitale bzw. genetisch bedingte sowie erworbene Ursachen zugrunde liegen konnen. Am haufigsten fuhren primar den Hoden betreffende Schaden zu einer NOA, hypothalamisch-hypophysar bedingte endokrine Storungen kommen vergleichsweise selten vor. Bei OA sind neben iatrogenen Ursachen wie der Vasektomie vor allem kongenitale Fehlbildungen der ableitenden Samenwege zu berucksichtigen. Diagnosestellung und Therapieplanung erfordern eine umfassende andrologische Untersuchung; soweit keine erworbenen Ursachen einer NOA bzw. OA vorliegen, gehoren zur Abklarung auch eine gezielte genetische Diagnostik und Beratung. Haufig ist eine Einordnung des Krankheitsbilds erst anhand der histopathologischen Untersuchung von Hodenbiopsaten moglich, die auch die Identifizierung einer Keimzellneoplasie in situ erlaubt. Unter therapeutischen Aspekten kommt der Hodenhistologie der groste prognostische Stellenwert im Hinblick auf eine erfolgreiche operative Spermiengewinnung (testikulare Spermienextraktion) zu; bei 40–60 % der Patienten mit NOA lassen sich eine fokal erhaltene Spermatogenese und damit Spermien fur eine assistierte Fertilisation finden. Abgesehen von den kongenitalen, operativ nicht korrigierbaren Fehlbildungen besteht bei OA die Moglichkeit mikrochirurgisch-rekonstruktiver Verfahren. Bei der Versorgung betroffener Patienten durfen keinesfalls konservativ-medikamentos behandelbare Formen einer Azoospermie ubersehen werden; dies gilt insbesondere fur die Therapie des hypogonadotropen Hypogonadismus.

Purpose:Infectious complications following prostate biopsy are increasing and fluoroquinolone prophylaxis has recently been banned by the European Commission. In this systematic review we summarize...

Purpose Azoospermia affects 1% of men and it can be the consequence of spermatogenic maturation arrest (MA). Although the etiology of MA is likely to be of genetic origin, only 13 genes have been reported as recurrent potential causes of MA. Methods Exome sequencing in 147 selected MA patients (discovery cohort and two validation cohorts). Results We found strong evidence for five novel genes likely responsible for MA (ADAD2,TERB1,SHOC1,MSH4, andRAD21L1), for which mouse knockout (KO) models are concordant with the human phenotype. Four of them were validated in the two independent MA cohorts. In addition, nine patients carried pathogenic variants in seven previously reported genes-TEX14,DMRT1,TEX11,SYCE1,MEIOB,MEI1, andSTAG3-allowing to upgrade the clinical significance of these genes for diagnostic purposes. Our meiotic studies provide novel insight into the functional consequences of the variants, supporting their pathogenic role. Conclusion Our findings contribute substantially to the development of a pre-testicular sperm extraction (TESE) prognostic gene panel. If properly validated, the genetic diagnosis of complete MA prior to surgical interventions is clinically relevant. Wider implications include the understanding of potential genetic links between nonobstructive azoospermia (NOA) and cancer predisposition, and between NOA and premature ovarian failure.

Introduction and hypothesis The Global Prevalence Study of Infections in Urinary tract in Community Setting (GPIU.COM) includes epidemiological aspects of acute cystitis (AC) in women in Germany and Switzerland. The primary study relates to the German version of the Acute Cystitis Symptom Score (ACSS), a self-reporting questionnaire for self-diagnosis and monitoring the symptomatic course of AC in women. The current study aimed to analyze the validity and reliability of the German ACSS in German-speaking female patients with AC in Switzerland. Methods Anonymized patient data were collected and analyzed from women with AC at the first visit (diagnosis) and follow-up visits as baseline and controls, respectively. Data from 97 patients with a median age of 41 years underwent analysis. Psychometric and diagnostic characteristics of the ACSS were measured and statistically analyzed. Results Average internal consistency of the ACSS resulted in a Cronbach’s alpha (95% CI) of 0.86 (0.83; 0.89) and did not differ significantly between the Swiss and German cohorts. Diagnostic values of the ACSS for the Swiss cohort were relatively lower than for the German cohort, possible due to discrepancies between definitions of UTI in national guidelines. Conclusions The analysis showed that the German version of the ACSS is also suitable for use in the German-speaking female population of Switzerland. Minor differences in definitions of AC between German and Swiss guidelines explain the observed discrepancies in diagnostic values of the ACSS between cohorts.

The Acute Cystitis Symptom Score (ACSS) is a patient self-reporting questionnaire for the clinical diagnosis and patient-reported outcome (PRO) in women with acute uncomplicated cystitis (AC). The aim of the current study (part II) was the clinical validation of the Greek ACSS questionnaire. After linguistic validation according to internationally accepted guidelines and cognitive assessment (part I), the clinical validation was performed after ethical approval by using the Greek ACSS study version in 92 evaluable female participants including 53 patients with symptoms suspicious of AC and 39 controls. The clinical outcome using the ACSS questionnaire at different time points after the start of treatment was demonstrated as well. The age (mean±SD) of the 53 patients (44.7±17.0) and 39 controls (49.3±15.9) and their additional conditions at baseline visits, such as menstruation, premenstrual syndrome, pregnancy, menopause, diabetes mellitus, were comparable. There was, however, a significant difference (p

Purpose To evaluate and report the complications, and to analyse antimicrobial stewardship aspects following prostate biopsies (P-Bx) based on the data from a 9-year global study. Methods The primary outcome was to compare complications after P-Bx between patients of two cohorts: 2010–2014 and 2016–2019. Primary outcomes included symptoms of lower and severe/systemic urinary tract infection (LUTIS and SUTIS, respectively), and positive urine culture. Readmission to hospital after P-Bx, need for additional antimicrobial therapy, consumption of different antimicrobial agents for prophylaxis and therapy were evaluated. Students t test and chi-square test were used for comparative analyses. Results Outcome data were available for 1615 men. Fluoroquinolones-based prophylaxis rate increased from 72.0% in 2010–2014 to 78.6% in 2015–2019. Overall rates of complications increased from 6 to 11.7% including an increase in symptomatic complications from 4.7 to 10.2%, mainly due to an increase in LUTIS. Rates of patients seeking additional medical help in primary care after P-Bx increased from 7.4 to 14.4%; cases requiring post P-Bx antibiotic treatment increased from 6.1 to 9.7%, most of which received fluoroquinolones. Transperineal P-Bx was significantly associated with LUTIS. Following transrectal P-Bx, 2.8% developed febrile infections and 4.0% required hospitalisation. Two men (0.12%) died after transrectal P-Bx due to sepsis. Conclusions The rates of complications after P-Bx tended to increase in time, as well as rates of patients seeking additional medical help in the post-P-Bx period. To reduce the risk of infectious complications and to comply with the principles of antibiotic stewardship, clinicians should switch to the transperineal biopsy route.

STUDY QUESTION Does activin A contribute to testicular fibrosis under inflammatory conditions? SUMMARY ANSWER Our results show that activin A and key fibrotic proteins are increased in human testicular biopsies with leukocytic infiltrates and impaired spermatogenesis and in murine experimental autoimmune orchitis (EAO) and that activin A stimulates fibrotic responses in peritubular cells (PTCs) and NIH 3T3 fibroblasts. WHAT IS KNOWN ALREADY Fibrosis is a feature of EAO. Activin A, a regulator of fibrosis, was increased in testes of mice with EAO and its expression correlated with severity of the disease. STUDY DESIGN, SIZE, DURATION This is a cross-sectional and longitudinal study of adult mice immunized with testicular homogenate (TH) in adjuvant to induce EAO, collected at 30 (n = 6), 50 (n = 6) and 80 (n = 5) days after first immunization. Age-matched mice injected with adjuvant alone (n = 14) and untreated mice (n = 15) were included as controls. TH-immunized mice with elevated endogenous follistatin, injected with a non-replicative recombinant adeno-associated viral vector carrying a gene cassette of follistatin (rAAV-FST315; n = 3) or vector with an empty cassette (empty vector controls; n = 2) 30 days prior to the first immunization, as well as appropriate adjuvant (n = 2) and untreated (n = 2) controls, were also examined. Human testicular biopsies showing focal inflammatory lesions associated with impaired spermatogenesis (n = 7) were included. Biopsies showing intact spermatogenesis without inflammation, from obstructive azoospermia patients, served as controls (n = 7). Mouse primary PTC and NIH 3T3 fibroblasts were stimulated with activin A and follistatin 288 (FST288) to investigate the effect of activin A on the expression of fibrotic markers. Production of activin A by mouse primary Sertoli cells (SCs) was also investigated. PARTICIPANTS/MATERIALS, SETTING, METHODS Testicular RNA and protein extracts collected from mice at days 30, 50 and 80 after first immunization were used for analysis of fibrotic marker genes and proteins, respectively. Total collagen was assessed by hydroxyproline assay and fibronectin; collagen I, III and IV, α-smooth muscle actin (α-SMA) expression and phosphorylation of suppressor of mothers against decapentaplegic (SMAD) family member 2 were measured by western blot. Immunofluorescence was used to detect fibronectin. Fibronectin (Fn), αSMA (Acta2), collagen I (Col1a2), III (Col3a1) and IV (Col4a1) mRNA in PTC and NIH 3T3 cells treated with activin A and/or FST288 were measured by quantitative RT-PCR (qRT-PCR). Activin A in SC following tumour necrosis factor (TNF) or FST288 stimulation was measured by ELISA. Human testicular biopsies were analysed by qRT-PCR for PTPRC (CD45) and activin A (INHBA), hydroxyproline assay and immunofluorescence. MAIN RESULTS AND THE ROLE OF CHANCE Production of activin A by SC was stimulated by 25 and 50 ng/ml TNF (P LARGE SCALE DATA N/A. LIMITATIONS, REASONS FOR CAUTION A limited number of human testicular specimens was available for the study. Part of the study was performed in vitro, including NIH 3T3 cells as a surrogate for testicular fibroblasts. WIDER IMPLICATIONS OF THE FINDINGS Resident fibroblasts and PTC may contribute to the progression of testicular fibrosis following inflammation, and activin A is implicated as a key mediator of this process. STUDY FUNDING/COMPETING INTEREST(S) This work was supported by the National Health and Medical Research Council of Australia, the Victorian Government’s Operational Infrastructure Support Program and the International Research Training Group between Justus Liebig University (Giessen) and Monash University (Melbourne) (GRK 1871/1–2) on `Molecular pathogenesis on male reproductive disorders’ funded by the Deutsche Forschungsgemeinschaft and Monash University. The authors declare no competing financial interests.

STUDY QUESTION Can dexamethasone improve infertility-related cauda epididymidal tissue damage caused by bacterial epididymitis? SUMMARY ANSWER Dexamethasone in addition to anti-microbial treatment effectively reduces long-term deleterious epididymal tissue damage by dampening the host’s adaptive immune response. WHAT IS KNOWN ALREADY Despite effective anti-microbial treatment, ~40% of patients with epididymitis experience subsequent sub- or infertility. An epididymitis mouse model has shown that the host immune response is mainly responsible for the magnitude of epididymal tissue damage that is fundamentally causative of the subsequent fertility issues. STUDY DESIGN, SIZE, DURATION Bacterial epididymitis was induced in male mice by using uropathogenic Escherichia coli (UPEC). From Day 3 after infection onwards, mice were treated with daily doses of levofloxacin (20 mg/kg, total n = 12 mice), dexamethasone (0.5 mg/kg, total n = 9) or both in combination (total n = 11) for seven consecutive days. Control animals were left untreated, i.e. given no interventional treatment following UPEC infection (total n = 11). Half of the animals from each group were killed either at 10 or 31 days post-infection. PARTICIPANTS/MATERIALS, SETTING, METHODS A mouse model of induced bacterial epididymitis was applied to adult male C57BL/6J mice. At the respective endpoints (10 or 31 days post-infection), epididymides were collected. Effectiveness of antibiotic treatment was assessed by plating of epididymal homogenates onto lysogeny broth agar plates. Overall tissue morphology and the degree and nature of tissue damage were assessed histologically. Quantitative RT-PCR was used to assess local cytokine transcript levels. Blood was drawn and serum analysed for systemic IgG and IgM levels by ELISA. In addition, correlation analyses of clinical data and serum-analyses of IgG and IgM levels in patients with epididymitis were performed. MAIN RESULTS AND THE ROLE OF CHANCE The addition of dexamethasone to the standard anti-microbial treatment did not further worsen epididymal tissue integrity. In fact, an obviously dampened immune response and reduced tissue reaction/damage was observed at both 10 and 31 days post-infection following combined treatment. More specifically, epididymal duct continuity was preserved, enabling sperm transit. In contrast, in untreated or antibiotic-treated animals, damage of the epididymal duct and duct constrictions were observed, associated with a lack of cauda spermatozoa. In line with the bacteriostatic/bactericidal effect of levofloxacin (alone as well as in combination), local cytokine transcript levels were significantly and similarly reduced in animals treated with levofloxacin alone (P LIMITATIONS, REASONS FOR CAUTION Breeding studies to address the fertility-protecting effect of the combined treatment were not possible in the experimental animals because the vas deferens was ligated (model specific). WIDER IMPLICATIONS OF THE FINDINGS Whereas innate immunity is necessary and involved in acute bacterial clearance, adaptive immunity seems to be responsible for long-term, subclinical immunological activities that may negatively affect the pathogenesis of bacterial epididymitis even after effective bacterial eradication. These effects can be reduced in mice by the additional treatment with dexamethasone. This immunological characteristic of bacterial epididymitis shows similarities to the Jarisch–Herxheimer reaction known from other types of bacterial infection. STUDY FUNDING/COMPETING INTEREST(S) The study was supported by grants from the Deutsche Forschungsgemeinschaft, Monash University and the Medical Faculty of Justus-Liebig University to the International Research Training Group on ‘Molecular pathogenesis of male reproductive disorders’ (GRK 1871). R.W., K.L.L. and M.P.H. were supported by grants from the National Health and Medical Research Council of Australia (ID1079646, ID1081987, ID1020269 and ID1063843) and by the Victorian Government’s Operational Infrastructure Support Program. The authors have no conflicts of interest to declare. TRIAL REGISTRATION NUMBER No clinical trial involved.

Purpose To reassess the diagnostic values of the “draft” guidelines for the clinical diagnosis of acute uncomplicated cystitis (AC), recently proposed by US Food and Drug Administration (FDA) and European Medicines Agency (EMA). Methods The data of 517 female respondents (patients with acute cystitis and controls) derived from the e-USQOLAT database were analyzed and used for the validation of proposed “draft” guidelines of FDA and EMA, compared to the Acute Cystitis Symptom Score (ACSS) questionnaire. The diagnostic values of the proposals concerning signs, symptoms and their severity were assessed and compared. Results The six “typical” symptoms of the ACSS were strongly associated with the diagnosis of AC. The number of positive “typical” symptoms differed significantly between patients and controls: median 5 (IQR 4–6) vs 1 (IQR 0–3) respectively. Scored severity of “typical” symptoms also differed significantly between groups of patients and controls: median (IQR) 10 (7–13) vs 1 (0–4), respectively. The best balance between sensitivity and specificity is shown by the ACSS cut-off value of 6 scores and more of the “Typical” domain, followed by an approach proposed by FDA and EMA, justifying ACSS to be used as a diagnostic criterion for the clinical diagnosis of AC. Conclusions Not only the presence but also the severity of the symptoms is important for an accurate diagnosis of AC. The ACSS, even without urinalysis is at least as favourable as the draft diagnostic proposals by FDA and EMA. The ACSS can be recommended for epidemiological and interventional studies, and allows women to establish self-diagnosis of AC, making the ACSS also cost-effective for healthcare. Electronic supplementary material The online version of this article (10.1007/s00345-019-02761-3) contains supplementary material, which is available to authorized users.

Despite optimal treatment, urosepsis has still high morbidity and mortality rates. An updated definition and classification system for sepsis have recently been introduced. Management of urosepsis comprises four major aspects: (1) early diagnosis, (2) early empiric intravenous antimicrobial treatment, (3) identification and control of complicating factors, and (4) specific sepsis therapy. The quick sequential organ failure assessment is replacing the systemic inflammatory response syndrome scoring for rapid identification of patients with urosepsis. Patient summary: Urosepsis is a serious, life-threatening complication of infections originating from the urinary tract. As urosepsis has a very high mortality rate, it is important that is quickly spotted and that appropriate treatment is swiftly begun. Imaging of urinary tract disorders has been shown to be useful in decreasing mortality from urosepsis, and in the future microbiology techniques may also prove useful. Given the severity of urosepsis and the associated risks, large efforts need to be made to prevent high-risk infections in hospitals with appropriate prevention measures, such as the early removal of catheters used whenever possible. Urosepsis is still a serious life-threatening complication of an infection originating from the urinary tract. Early and appropriate diagnosis of urosepsis is important to allow initiation of suitable treatment without delay.