Radiological features characterising indeterminate testes masses: a systematic review and meta-analysis.

CONTEXT: The use of scrotal ultrasonography (SUS) has increased the detection rate of indeterminate testicular masses. Defining radiological characteristics that identify malignancy may reduce the number of men undergoing unnecessary radical orchidectomy. OBJECTIVE: To define which SUS or scrotal magnetic resonance imaging (MRI) characteristics can predict benign or malignant disease in pre- or post-pubertal males with indeterminate testicular masses. EVIDENCE ACQUISITION: This systematic review was conducted in accordance with Cochrane Collaboration guidance. Medline, Embase, Cochrane controlled trials and systematic reviews databases were searched from (1970 to 26 March 2021). Benign and malignant masses were classified using the reported reference test: i.e., histopathology, or 12 months progression-free radiological surveillance. Risk of bias was assessed using the Quality Assessment of Diagnostic Accuracy Studies-2 tool (QUADAS-2). EVIDENCE SYNTHESIS: A total of 32 studies were identified, including 1692 masses of which 28 studies and 1550 masses reported SUS features, four studies and 142 masses reported MRI features. Meta-analysis of different SUS (B-mode) values in post-pubertal men demonstrated that a size of ≤0.5 cm had a significantly lower odds ratio (OR) of malignancy compared to masses of >0.5 cm (P < 0.001). Comparison of masses of 0.6-1.0 cm and masses of >1.5 cm also demonstrated a significantly lower OR of malignancy (P = 0.04). There was no significant difference between masses of 0.6-1.0 and 1.1-1.5 cm. SUS in post-pubertal men also had a statistically significantly lower OR of malignancy for heterogenous masses vs homogenous masses (P = 0.04), hyperechogenic vs hypoechogenic masses (P < 0.01), normal vs increased enhancement (P < 0.01), and peripheral vs central vascularity (P < 0.01), respectively. There were limited data on pre-pubertal SUS, pre-pubertal MRI and post-pubertal MRI. CONCLUSIONS: This meta-analysis identifies radiological characteristics that have a lower OR of malignancy and may be of value in the management of the indeterminate testis mass.

The impact of low-pressure pneumoperitoneum on robotic-assisted radical cystectomy and intracorporeal ileal conduit urinary diversion: a case-control study.

PURPOSE: To evaluate the role of low intra-abdominal pressure (IAP) in improving postoperative recovery in Robotic-assisted radical cystectomy (RARC) and intracorporeal ileal conduit urinary diversion (ICUD). METHODS: A retrospective case-control study of 49 bladder cancer patients offered RARC/ICUD with standard (12 mmHg, n = 24) or low IAP (8 mmHg, n = 25). Outcomes of interest included length of procedure (LoP), estimated blood loss (EBL), blood transfusion, margin positivity rates, time to first flatus (TtFF), time to first bowel movement (TtFBM), ileus and small bowel obstruction (SBO) rates, time to safe discharge (TtSD), postoperative hospital stay (PHS) and pain levels on a postoperative day (POD) 1 and 3. Perioperative complications were recorded using the Clavien-Dindo system. RESULTS: Demographic and baseline clinical characteristics, LoP, EBL and margin positivity rates were similar between groups. No transfusions were recorded. Median (IQR) TtFF, TtFBM and TtSD were significantly longer in Group 1 vs Group 2 (4 (1) vs 2 (1), 7 (3) vs 6 (2) and 8.5 (5.75) vs 5.0 (1), respectively). PHS and rates of postoperative ileus and SBO were lower in Group 2, however not statistically significant. Severe pain was uncommon in both groups but moderate/severe pain was significantly higher in Group 1 (95.8% vs 48% on POD1 and 62.5% vs 16% on POD3). No significant intraoperative complications were recorded and ≥ Grade 3 postoperative complications at 30 and 90 days were similar. CONCLUSION: With limitations, Low-IAP RARC can be safely offered to RARC/ICUD patients and leads to faster bowel recovery, and shorter time to safe discharge compared to standard pneumoperitoneum.

What is the role of single-stage oral mucosa graft urethroplasty in the surgical management of lichen sclerosus-related stricture disease in men? A systematic review.

PURPOSE: The benefits and harms of the available types of surgical management for lichen sclerosus-related (LS) strictures remain unclear and, thus, clear and robust clinical practice recommendations cannot be given. MATERIALS AND METHODS: To assess the role of single-stage OMGU in the management of LS strictures and explore how its benefits and harms compare with the alternative management options. Medline, Embase and Cochrane controlled trial databases (CENTRAL, CDSR) were systematically searched. Randomized (RCTs) and nonrandomized studies (NRCSs) comparing single-stage OMGU with other surgical management options for LS strictures and single-arm studies on single-stage OMGU were included. Risk of bias (RoB) was assessed. RESULTS: Of the 1912 abstracts identified, 15 studies (1 NRCS and 14 single-arm studies) were included, recruiting in total 649 patients. All studies were at high RoB. In the only NRCS available, stricture-free rate (SFR) for single-stage and staged OMGU was 88% vs 60%, respectively (p = 0.05), at a mean follow-up of 66.5 months. SFR range for single-stage OMGU in single-arm studies was 65-100% (mean/median follow-up, 12-59 months). Single-stage OMGU had low complication rates and beneficial impact on LUTS and QoL. CONCLUSIONS: The present SR highlights the methodological limitations of the available literature. In the absence of adverse local tissue conditions, and taking into consideration benefit-harm balance and surgeon's skills and expertise, single-stage OMGU can be justified in patients with LS strictures.

Nonantibiotic Strategies for the Prevention of Infectious Complications following Prostate Biopsy: A Systematic Review and Meta-Analysis.

PURPOSE: We identify which nonantibiotic strategies could reduce the risk of infectious complications following prostate biopsy. MATERIALS AND METHODS: We performed a literature search on MEDLINE®, Embase® and the Cochrane Database for randomized controlled trials (inception to May 2020) assessing nonantibiotic interventions in prostate biopsy. Primary outcome was pooled infectious complications (fever, sepsis and symptomatic urinary tract infection) and secondary outcome was hospitalization. Cochrane risk of bias tool and GRADE approach were used to assess the bias and the certainty of evidence. The study protocol was registered with PROSPERO (CRD42015026354). RESULTS: A total of 90 randomized controlled trials (16,941 participants) were included in the analysis, with 83 trials being categorized into one of 10 different interventions. Transperineal biopsy was associated with significantly reduced infectious complications as compared to transrectal biopsy (RR 0.55, 95% CI 0.33-0.92, p=0.02, I2=0%, 1,330 participants, 7 studies). Rectal preparation with povidone-iodine was also shown to reduce infectious complications (RR 0.50, 95% CI 0.38-0.65, p <0.000001, I2=27%, 1,686 participants, 8 studies) as well as hospitalization (RR 0.38, 95% CI 0.21-0.69, p=0.002, I2=0%, 620 participants, 4 studies). We found no difference in infectious complications/hospitalization for 6 other interventions, ie number of biopsy cores, periprostatic nerve block, number of injections for periprostatic nerve block, needle guide type, needle type and rectal preparation with enema. In 2 interventions (needle diameter, rectal preparation with chlorhexidine) meta-analysis was not possible. Finally, 7 studies had unique interventions. The certainty of evidence was rated as low/very low for all interventions. CONCLUSIONS: Transperineal biopsy significantly reduces infectious complications compared to transrectal biopsy and should therefore be preferred. If transrectal biopsy is performed, rectal preparation with povidone-iodine is highly recommended. The other investigated nonantibiotic strategies did not significantly influence infection and hospitalization after prostate biopsy.

What influences adherence to guidance for postoperative instillation of intravesical chemotherapy to patients with bladder cancer?

OBJECTIVE: To understand the barriers and facilitators to single instillation of intravesical chemotherapy (SI-IVC) use after resection of non-muscle-invasive bladder cancer (NMIBC) in Scotland and England using a behavioural theory-informed approach. SUBJECTS AND METHODS: In a cross-sectional descriptive study of practices at seven hospitals, we investigated care pathways, policies, and interviewed 30 urology staff responsible for SI-IVC. We used the Theoretical Domains Framework (TDF) to organise our investigation and conducted deductive thematic analyses, while inductively coding emergent beliefs. RESULTS: Barriers to SI-IVC were present at different organisational levels and professional roles. In four hospitals, there was a policy to not instil SI-IVC in theatre. Six hospitals' staff reported delays in mitomycin C (MMC) ordering and/or local storage. Lack of training, skills and perceived workload affected motivation. Facilitators included access to modern instilling devices (four hospitals) and incorporating reminders in operation proforma (four hospitals). Performance targets (with audit and feedback) within a national governance framework were present in Scotland but not England. Differences in coordinated leadership, sharing best practices, and disliking being perceived as underperforming, were evident in Scotland. CONCLUSIONS: High-certainty evidence shows that SI-IVC, such as MMC, after NMIBC resection reduces recurrences. This evidence underpins international guidance. The number of eligible patients receiving SI-IVC is variable indicating suboptimal practice. Improving SI-IVC adherence requires modifications to theatre instilling policies, delivery and storage of MMC, staff training, and documentation. Centralising care, with bladder cancer expert leadership and best practices sharing with performance targets, likely led to improvements in Scotland. National quality improvement, incorporating audit and feedback, with additional implementation strategies targeted to professional role could improve adherence and patient outcomes elsewhere. This process should be controlled to clarify implementation intervention effectiveness.

Antibiotic Prophylaxis for the Prevention of Infectious Complications following Prostate Biopsy: A Systematic Review and Meta-Analysis.

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 the evidence for different antibiotic prophylaxis regimens. MATERIALS AND METHODS: We searched MEDLINE®, Embase® and Cochrane Database for randomized controlled trials (inception to October 2019) assessing antimicrobial interventions in prostate biopsy. Primary outcome was infectious complications. Exclusion criteria were simultaneous interfering interventions. GRADE (Grading of Recommendations, Assessment, Development and Evaluations) was used to assess the certainty of evidence. Protocol was registered with PROSPERO (CRD42015026354). RESULTS: Overall 59 randomized controlled trials (14,153 participants) and 7 different antimicrobial interventions were included. Antibiotic prophylaxis reduced infectious complications compared to no prophylaxis (RR 0.56, 95% CI 0.40-0.77, p=0.0005, I2=15%, participants 1,753, studies 11). A short-term prophylaxis (single shot to 3 days) was inferior to a long-term prophylaxis (1 to 7 days) with fluoroquinolone (RR 1.89, 95% CI 1.37-2.61, p=0.0001, I2=0%, participants 3,999, studies 17). Fosfomycin trometamol was an alternative to fluoroquinolone with reduced rates of infectious complications (RR 0.49, 95 CI 0.27-0.87, p=0.02, I2=54%, participants 1,239, studies 3). Empiric prophylaxis was inferior to targeted prophylaxis (RR 1.81, 95% CI 1.28-2.55, p=0.0008, I2=48%, participants 1,511, studies 6). Standard prophylaxis was inferior to augmented prophylaxis (using multiple rather than single agent) using a fixed model (RR 2.10, 95% CI 1.53-2.88, p <0.0001, I2=71%, participants 2,597, studies 9), but not using a random model (p=0.07). No difference was observed in infectious complications based on route or timing of antimicrobial prophylaxis. The certainty of evidence was rated as low/very low. CONCLUSIONS: In countries where fluoroquinolones are allowed as antibiotic prophylaxis, a minimum of a full 1-day administration as well as targeted therapy in case of fluoroquinolone resistance is recommended. In countries with a ban on fluoroquinolones, fosfomycin is a good alternative, as is augmented prophylaxis, although no established standard combination exists to date.

Perioperative antithrombotic (antiplatelet and anticoagulant) therapy in urological practice: a critical assessment and summary of the clinical practice guidelines.

PURPOSE: The perioperative management of patients who are receiving antithrombotic (antiplatelet or anticoagulant) therapy and require urologic surgery is challenging due to the inherent risk for surgical bleeding and the need to minimize thromboembolic risk. The aim of this review is to assess the quality and consistency of clinical practice guidelines (CPGs) and clinical practice recommendations (CPRs) on this topic, and to summarize the evidence and associated strength of recommendations relating to perioperative antithrombotic management. METHODS: A pragmatic search of electronic databases and guidelines websites was performed to identify relevant CPGs/CPRs. The AGREE II (Appraisal of Guidelines for REsearch and Evaluation) instrument was used to assess the methodological quality and integrity of the CPGs. RESULTS: The CPGs provided by the European Association of Urology (EAU), the American College of Chest Physicians (ACCP) and the European Society of Cardiology/European Society of Anaesthesiology (ESC/ESA), and the CPRs provided by the International Consultation on Urological Disease (ICUD)/American Urologic Association (AUA) were retrieved and reviewed. The 3 CPGs were critically assessed using the AGREE II instrument. Inconsistent recommendations were provided based on the indication for antithrombotic medication, the antiplatelet/anticoagulant agent and the type of urological procedure. Based on the AGREE II tool for CPG assessment, the EAU CPGs scored higher (83.3 points) compared to the ESC/ESA (75 points) and ACCP CPG (66.7 points). CONCLUSION: The perioperative management of antithrombotic therapy in urological patients is potentially challenging but inconsistent CPG of varying quality may create uncertainty as to best practices to minimize thromboembolic and bleeding risk.

A single dose of meropenem is superior to ciprofloxacin in preventing infections after transrectal ultrasound-guided prostate biopsies in the era of quinolone resistance.

PURPOSE: To evaluate the efficacy of meropenem single dose before transrectal prostate biopsy, instead of ciprofloxacin in the era of fluoroquinolones resistance. METHODS: This prospective study included patients with indications for prostatic biopsy from January to December 2014. Those with known resistance in fluoroquinolones or meropenem or with decreased creatinine clearance were excluded. Patients were randomized into two groups, and statistical analysis was carried out. Group A received a 3-day course of ciprofloxacin 500 bid per os starting the day before biopsy. Group B received 1 g meropenem intravenously 1 h prior to the procedure. Patients were followed up for 15 days, and those with lower urinary tract symptoms (LUTS) and fever were called for hospitalization. Urine and blood cultures were obtained. RESULTS: A total of 110 patients, 52-75 years old (mean 67.5, median 66) participated in the study, allocated in Groups A and B. After the procedure, 18 patients (32.7 %) of Group A reported macroscopic hematuria, while 10 (18.2 %) reported rectal blood loss. Nine patients (16.3 %) presented because of fever and LUTS. One of them developed septic shock and died in the ICU. Cultures revealed multi-resistant E. coli with high sensitivity to meropenem, and patients were treated accordingly. In Group B, 20 (36.3 %) patients presented with macroscopic hematuria and 9 (16.3 %) with rectal blood loss. One patient returned to hospital with LUTS and fever. Cultures revealed Klebsiella pneumoniae sensitive to colimycine. CONCLUSIONS: A single dose of meropenem prior to prostate biopsy is a safe and effective way to avoid the possible infectious complications in high-risk patients.

The impact of stapling devices use on patients with increased body mass index treated with radical cystectomy.

INTRODUCTION: The aim of this retrospective study was to evaluate the impact of stapling devices use on overweight and obese bladder cancer patients treated with radical cystectomy (RC). MATERIALS AND METHODS: Fifty-two overweight and 24 obese patients underwent open RC for muscle invasive bladder cancer. Bladder removal was performed using standard suture technique (SST) or multifire autosuture articulated vascular Endo-GIA (eG). Twenty-three overweight and 11 obese patients formed the SST arms and the remaining 29 overweight and 13 obese patients formed the eG arms. Intra and postoperative parameters and early postoperative complications (30 days) using the Clavien-Dindo classification were recorded. RESULTS: SST and eG arms of overweight and obese patients were comparable in intra and postoperative parameters. Both overweight and obese eG arms had significantly lower estimated blood loss, lower number of transfused packed red blood cells units (PRBC) and lower cystectomy intraoperative time compared with the SST ones (p < 0.05). In obese patients, staplers use led to significantly lower total length of stay compared with SST (p = 0.041). Complications rate was significantly higher in the obese group compared with the overweight group (58.33% versus 30.77%, p = 0.042). No difference in complications was found between the SST and eG arms of the overweight and obese patients. No deaths occurred. CONCLUSIONS: Staplers use in RC in overweight/obese patients is accompanied by significantly shorter intraoperative time, lower blood loss and lower number of transfused PRBC units, compared with SST. In obese patients, eG use led to shorter length of stay.

The Immune Landscape and Immunotherapeutic Strategies in Platinum-Refractory Testicular Germ Cell Tumors.

Testicular germ cell tumors (TGCTs) are cancers with very good prognosis, even in the metastatic setting, with high curative potential mainly attributed to the introduction of cisplatin-based chemotherapy. However, approximately 15% of the patients develop platinum-refractory disease and suffer multiple relapses. Therefore, there is an unmet need for novel therapeutic agents with improved efficacy and minimal long-term side effects. Recent advances in the development of immunotherapeutic agents, particularly immune checkpoint inhibitors (ICIs), have offered an opportunity to test their activity in various tumor types, including GCTs. This review aims to analyze the immune microenvironment of these tumors and present the most recently available data from studies that have tested immunotherapeutic agents against GCTs. The majority of the available knowledge derives from case reports or small cohort studies, particularly those involving ICIs of the PD-1/PD-L1 axis alone or in combination with anti-CTLA-4 monoclonal antibodies. Other immunotherapeutic targeted approaches, including antibody-drug conjugates, antibody prodrugs, vaccines, tyrosine kinase inhibitors, chimeric antigen receptor (CAR) T-cell therapy, have biological rationales and have shown preliminary activity or are currently being tested. Growing evidence on these and other approaches will assist in broadening the currently limited treatment armamentarium against platinum-refractory TGCTs.

Achieving Benchmarks for National Quality Indicators Reduces Recurrence and Progression in Non-muscle-invasive Bladder Cancer.

BACKGROUND: Noncompliance with evidence-based interventions and guidelines contributes to significant and variable recurrence and progression in patients with non-muscle-invasive bladder cancer (NMIBC). The implementation of a quality performance indicator (QPI) programme in Scotland's National Health Service (NHS) aimed to improve cancer outcomes and reduce nationwide variance. OBJECTIVE: To evaluate the effect of hospitals achieving benchmarks for two specific QPIs on time to recurrence and progression in NMIBC. DESIGN, SETTING, AND PARTICIPANTS: QPIs for bladder cancer (BC) were enforced nationally in April 2014. NHS health boards collected prospective data on all new BC patients. Prospectively recorded surveillance data were pooled from 12 collaborating centres. INTERVENTION: QPIs of interest were (1) hospitals achieving detrusor muscle (DM) sampling target at initial transurethral resection of bladder tumour (TURBT) and (2) use of single instillation of mitomycin C after TURBT (SI-MMC). OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The primary and secondary endpoints were time to recurrence and progression, respectively. Kaplan-Meier and Cox multivariable regression analyses were performed. KEY FINDINGS AND LIMITATIONS: Between April 1, 2014 and March 31, 2017, we diagnosed 3899 patients with new BC, of which 2688 were NMIBC . With a median follow up of 60.3 mo, hospitals achieving the DM sampling target had a 5.4% lower recurrence rate at 5 yr than hospitals not achieving this target (442/1136 [38.9%] vs 677/1528 [44.3%], 95% confidence interval [CI] = 1.6-9.2, p = 0.005). SI-MMC was associated with a 20.4% lower recurrence rate (634/1791 [35.4%] vs 469/840 [55.8%], 95% CI = 16.4-24.5, p < 0.001). On Cox multivariable regression, meeting the DM target and SI-MMC were associated with significant improvement in recurrence (hazard ratio [HR] 0.81, 95% CI = 0.73-0.91, p = 0.0002 and HR 0.66, 95% CI = 0.59-0.74, p < 0.004, respectively) as well as progression-free survival (HR 0.62, 95% CI = 0.45-0.84, p = 0.002 and HR 0.65, 95% CI = 0.49-0.87, p = 0.004, respectively). We did not have a national multicentre pre-QPI control. CONCLUSIONS: Within a national QPI programme, meeting targets for sampling DM and SI-MMC in the real world were independently associated with delays to recurrence and progression in NMIBC patients. PATIENT SUMMARY: Following the first 3 yr of implementing a novel quality performance indicator programme in Scotland, we evaluated compliance and outcomes in non-muscle-invasive bladder cancer. In 2688 patients followed up for 5 yr, we found that achieving targets for sampling detrusor muscle and the single instillation of mitomycin C during and after transurethral resection of bladder tumour, respectively, were associated with delays in cancer recurrence and progression.

The impact of parental bonding on sexual distress in women with type 1 diabetes mellitus.

INTRODUCTION: Psychosomatic and social issues have been found to be determinants of sexual distress in diabetic and non-diabetic populations. However, the role of parental bonding as a determinant for sexual distress has not been studied in women with type 1 diabetes mellitus (DM-1). AIM: To study the role of parental care and overprotection, in the pathogenesis of sexual distress in women with DM-1. METHODS: Seventy-seven women with uncomplicated DM-1 and 77 healthy controls were enrolled in the study. The Female Sexual Distress Scale (FSDS), the General Health Questionnaire-28, and the Parental Bonding Instrument were used to evaluate sexual distress, general health and bonding with parents, respectively. MAIN OUTCOME MEASURES: To assess the role of parental bonding as risk factor for sexual distress, in women with DM-1. RESULTS: Women with DM-1 had significantly higher FSDS scores compared with controls. Furthermore, women with DM-1 had significantly higher maternal and paternal care, and lower maternal overprotection in comparison with the healthy ones. Paternal overprotection and general health were similar in both groups (P > 0.05). Sexual distress was more frequent in women with DM-1 (31.43% vs. 8.57% of controls, P < 0.05). Diabetic women with sexual distress had lower maternal care, higher maternal overprotection and lower paternal overprotection compared to diabetics without sexual distress (P < 0.05). No difference was found in the paternal care between the two groups (P > 0.05). Moreover, sexually distressed DM-1 women had worse general health parameters in comparison with the non-sexually distressed diabetics (P < 0.05). In the DM-1 group, low maternal care and low paternal overprotection were significant risk factors for sexual distress (P < 0.05). CONCLUSIONS: Parental care and overprotection can lead to sexual distress and, therefore, to Female Sexual Dysfunction in DM-1 women. Evaluation of parental bonding is necessary in DM-1 women with distressing sexual problems.

The Impact of Enhanced Recovery after Surgery Protocol Implementation on Postoperative Pain Management in the Era of Opioid Crisis: The Postchemotherapy Open RPLND Experience.

AIM: Enhanced Recovery After Surgery (ERAS) protocols have been proven to optimize postoperative outcomes; however, misuse of opioid analgesics can still hinder postoperative recovery due to related side effects and potential complications. INTRODUCTION: To determine if the implementation of ERAS protocol in post-chemotherapy retroperitoneal lymph node dissection (PC-RPLND) patients could help with reducing postoperative pain and opioid use. METHODS: A case-control study of consecutive testicular cancer patients with indications for PCRLPND, who were offered Conventional Post-operative Management (CPM) or ERAS protocol. Outcomes of interest included Visual Analogue Scale (VAS)-assessed pain level at postoperative days 3, 7, and 30, and Morphine-Equivalent Doses (MEDs)/postoperative day. Intraoperative parameters and postoperative complications were recorded. Parametric and non-parametric tests were used for statistical analysis. RESULTS: In total, 100 opioid-naïve PC-RPLND patients were studied. CPM and ERAS groups (36 and 64 patients, respectively) had similar demographic and baseline clinical characteristics). ERAS group patients had significantly lower blood loss (p = 0.005), blood transfusion rate (p < 0.001), and duration of the procedure (p < 0.001). Post-operative complications were comparable between groups. Nausea and bowel disorders were numerically but not statistically more frequent in the CPM group. ERAS patients had shorter mean hospital stay (5.3 ± 1.4 vs. 7.4 ± 1.6 days, p < 0.001), lower daily MEDs (4.73 ± 2.63 vs. 7.04 ± 2.29, p < 0.001), and lower VAS scores on post-operative day 7 (3.89 ± 1.07 vs. 4.67 ± 1.17, p = 0.001). Post-operative pain was similar between groups on post-operative days 3 and 30. CONCLUSION: Systematic implementation of ERAS protocol after PC-RPLND improves pain management, optimizes patient recovery, and prevents over-prescription of opioid analgesics.

Is a Course of Intermittent Self-dilatation with Topical Corticosteroids Superior at Stabilising Urethral Stricture Disease in Men and Improving Functional Outcomes over a Course of Intermittent Self-dilatation Alone? A Systematic Review and Meta-analysis.

Context: Intermittent self-dilatation (ISD) is a therapeutic strategy used to stabilise a urethral stricture and postpone or avoid further treatment. Adding corticosteroids to this mode of management might further enhance its outcomes by downregulation of collagen deposition and excessive scar tissue formation. Objective: To explore whether a course of ISD with topical corticosteroids is superior at stabilising urethral stricture disease in men and improving functional outcomes over a course of ISD alone. Evidence acquisition: This systematic review and meta-analysis was undertaken by the European Association of Urology Urethral Strictures Guideline Panel according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines (CRD42021256744). The primary benefit outcome was successful stabilisation of the urethral stricture. Treatment-related complications were the primary harm outcome. Evidence synthesis: In total, 978 records were screened for eligibility, ultimately leading to five included studies, all randomised controlled trials, comprising 250 patients, of whom 124 underwent a course of ISD with corticosteroids and 126 underwent a course of ISD alone, all after direct vision internal urethrotomy (DVIU). Successful stabilisation of the stricture was achieved in 77% and 64% of patients in the group with and without corticosteroids, respectively (p = 0.04). No extra complications related to the addition of corticosteroids to the ISD regimen were reported. The risk of bias of the included studies was generally unclear to high. Conclusions: Based on the currently available data, a course of ISD with topical corticosteroids appears to be safe and superior at stabilising a urethral stricture after DVIU in the short term to a course of ISD alone. However, given the unclear to high risk of bias in the included studies, further high-quality studies are needed to fully underpin this. Patient summary: This study shows that addition of topical corticosteroids to intermittent self-dilatation after direct vision internal urethrotomy can better stabilise the stricture in the short term.

Unanswered questions in prostate cancer - findings of an international multi-stakeholder consensus by the PIONEER consortium.

PIONEER is a European network of excellence for big data in prostate cancer consisting of 37 private and public stakeholders from 9 countries across Europe. Many progresses have been done in prostate cancer management, but unanswered questions in the field still exist, and big data could help to answer these questions. The PIONEER consortium conducted a two-round modified Delphi survey aiming at building consensus between two stakeholder groups - health-care professionals and patients with prostate cancer - about the most important questions in the field of prostate cancer to be answered using big data. Respondents were asked to consider what would be the effect of answering the proposed questions on improving diagnosis and treatment outcomes for patients with prostate cancer and to score these questions on a scale of 1 (not important) to 9 (critically important). The mean percentage of participants who scored each of the proposed questions as critically important was calculated across the two stakeholder groups and used to rank the questions and identify the highest scoring questions in the critically important category. The identification of questions in prostate cancer that are important to various stakeholders will help the PIONEER consortium to provide answers to these questions to improve the clinical care of patients with prostate cancer.

First pilot study of maternal spindle transfer for the treatment of repeated in vitro fertilization failures in couples with idiopathic infertility.

OBJECTIVES: To gain insights into the technical feasibility of maternal spindle transfer (MST) applied in the context of repeated in vitro fertilization (IVF) failures for the treatment of idiopathic infertility. DESIGN: A prospective pilot study. SETTING: IVF center. PATIENT(S): Twenty-five infertile couples with multiple previous unsuccessful IVF cycles (range, 3-11), no previous pregnancy, and no history of mitochondrial DNA (mtDNA) disease participated. The study focused on women <40 years, with previous IVF attempts characterized by a pattern of low fertilization rates and/or impaired embryo development. Couples with severe male-factor infertility were not eligible. Oocyte donors with previous successful IVF outcomes were matched with patients according to standard practice. INTERVENTION(S): We performed MST by transferring metaphase II spindles from the patients' oocytes into the previously enucleated donor oocytes, followed by intracytoplasmic sperm injection, in vitro embryo culture, blastocyst biopsy, and vitrification. Only euploid blastocysts were considered for embryo transfer. MAIN OUTCOME MEASURE(S): Outcome measures included oocyte fertilization, blastocyst development, clinical pregnancy and live birth, incidence of mitochondrial carryover and potential mtDNA reversal, as well as general health of the children born. RESULT(S): Twenty-eight MST cycles produced 6 children (19 embryo transfers, 7 clinical pregnancies). Pediatric follow-up of the children, performed at intervals from birth to 12-24 months of age, revealed their development to be unremarkable. DNA fingerprinting confirmed that the nuclear DNA of MST children was inherited from both parents, without any contribution from the oocyte donor. For 5 of the children, mtDNA was derived almost exclusively (>99%) from the donor. However, 1 child, who had similarly low mtDNA carryover (0.8%) at the blastocyst stage, showed an increase in the maternal mtDNA haplotype, accounting for 30% to 60% of the total at birth. CONCLUSION(S): This pilot study provides the first insights into the feasibility of applying MST for patients with idiopathic infertility and repeated IVF failures. Reconstructed oocytes produced embryos capable of implanting, developing to term and producing apparently healthy newborns/children. However, claims concerning the efficacy of MST with respect to infertility treatment would be premature considering the limitations of this study. Importantly, mtDNA reversal was detected in one child born after MST, a finding with possible implications for mitochondrial replacement therapies. CLINICAL TRIAL REGISTRATION NUMBER: Pilot trial registry number, ISRCTN11455145. The date of registration: 20/02/2018. The date of enrolment of the first patients: 18/03/2018.

Sexual functioning and distress among premenopausal women with uncomplicated type 1 diabetes.

INTRODUCTION: Current studies indicate that women with type 1 diabetes (T1DM) have a high prevalence of sexual disorders although data on the prevalence of sexual dysfunction are limited when sexual distress is included. AIM: The frequency and the possible correlates of distressful sexual disorders in a highly selected group of type 1 diabetic women. METHODS: The sexual function, sexual distress, and general health status were assessed in 44 premenopausal women with uncomplicated T1DM and 47 healthy controls, using the Female Sexual Function Index (FSFI), the Female Sexual Distress Scale (FSDS), and the General Health Questionnaire-28 (GHQ-28). MAIN OUTCOME MEASURES: The impact of sexual distress on the frequency of female sexual dysfunction (FSD). RESULTS: The frequency of sexual disorders according to the FSFI was significantly higher in diabetic compared to control women (25% vs. 8.5%, respectively, P < 0.05). Diabetic women had significantly lower median (first to third quartile) total FSFI score compared to control group (30.55 [26.08-33.08] vs. 33.50 [30.70-34.30], P = 0.001). Desire, arousal, and satisfaction were the sexual domains significantly affected in the diabetic group. Diabetic women had significantly higher median (first to third quartile) FSDS score compared to control group (6.5 [2.3-15.8] vs. 4.0 [1.0-10.5] P = 0.043). FSD (combined pathological FSFI and FSDS scores) was present in higher proportion of diabetic women (15.9%) compared to controls (2.1%) (P = 0.020). GHQ-28 score was comparable between the groups. However, in the diabetic group, FSD was related with anxiety, depression, and low educational level. Diabetes-related factors were not associated with FSD. CONCLUSIONS: Pre-menopausal women with uncomplicated T1DM have significantly higher frequency of FSD compared to healthy controls, when the criterion of sexual distress is included. Psychosomatic and contextual factors implicated in sexual distress are correlates of FSD.