Machine Learning and External Validation of the IDENTIFY Risk Calculator for Patients with Haematuria Referred to Secondary Care for Suspected Urinary Tract Cancer.

BACKGROUND: The IDENTIFY study developed a model to predict urinary tract cancer using patient characteristics from a large multicentre, international cohort of patients referred with haematuria. In addition to calculating an individual's cancer risk, it proposes thresholds to stratify them into very-low-risk (<1%), low-risk (1-<5%), intermediate-risk (5-<20%), and high-risk (≥20%) groups. OBJECTIVE: To externally validate the IDENTIFY haematuria risk calculator and compare traditional regression with machine learning algorithms. DESIGN, SETTING, AND PARTICIPANTS: Prospective data were collected on patients referred to secondary care with new haematuria. Data were collected for patient variables included in the IDENTIFY risk calculator, cancer outcome, and TNM staging. Machine learning methods were used to evaluate whether better models than those developed with traditional regression methods existed. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The area under the receiver operating characteristic curve (AUC) for the detection of urinary tract cancer, calibration coefficient, calibration in the large (CITL), and Brier score were determined. RESULTS AND LIMITATIONS: There were 3582 patients in the validation cohort. The development and validation cohorts were well matched. The AUC of the IDENTIFY risk calculator on the validation cohort was 0.78. This improved to 0.80 on a subanalysis of urothelial cancer prevalent countries alone, with a calibration slope of 1.04, CITL of 0.24, and Brier score of 0.14. The best machine learning model was Random Forest, which achieved an AUC of 0.76 on the validation cohort. There were no cancers stratified to the very-low-risk group in the validation cohort. Most cancers were stratified to the intermediate- and high-risk groups, with more aggressive cancers in higher-risk groups. CONCLUSIONS: The IDENTIFY risk calculator performed well at predicting cancer in patients referred with haematuria on external validation. This tool can be used by urologists to better counsel patients on their cancer risks, to prioritise diagnostic resources on appropriate patients, and to avoid unnecessary invasive procedures in those with a very low risk of cancer. PATIENT SUMMARY: We previously developed a calculator that predicts patients' risk of cancer when they have blood in their urine, based on their personal characteristics. We have validated this risk calculator, by testing it on a separate group of patients to ensure that it works as expected. Most patients found to have cancer tended to be in the higher-risk groups and had more aggressive types of cancer with a higher risk. This tool can be used by clinicians to fast-track high-risk patients based on the calculator and investigate them more thoroughly.

Editorial for Special Issue: "Current and Emerging Therapies for Lower Urinary Tract Symptoms and Benign Prostatic Hyperplasia".

Lower urinary tract symptoms (LUTS) caused by benign prostatic hyperplasia (BPH) constitute a significant health concern worldwide, particularly among aging male populations [...].

The Discovery of an S-shaped Kidney in a Patient With Prostate Cancer: A Rare Finding.

Crossed fused renal ectopia (CFRE) constitutes a rare congenital anomaly of the urinary tract, typically characterized by its predominantly asymptomatic nature and frequent incidental discovery. This case report delineates the clinical profile of a 56-year-old male admitted to our Prostate Cancer Outpatient Clinic due to elevated prostate-specific antigen (PSA) levels, ultimately leading to the diagnosis of prostate cancer. The patient was asymptomatic, with no family or surgical background. Notably, a fused ectopic kidney was incidentally identified during the staging process involving abdominal computed tomography (ACT) scanning. Remarkably, no additional abnormalities of the urinary tract or renal dysfunction manifested in this specific case. The significance of this report lies in the underscored emphasis on the importance of employing precise imaging techniques and tailored management strategies for patients harboring such anatomical variations.

Experts' recommendations in laser use for the treatment of bladder cancer: a comprehensive guide by the European Section of Uro-Technology (ESUT) and Training and Research in Urological Surgery and Technology (TRUST)-Group.

PURPOSE: To identify laser settings and limits applied by experts during laser vaporization (vapBT) and laser en-bloc resection of bladder tumors (ERBT) and to identify preventive measures to reduce complications. METHODS: After a focused literature search to identify relevant questions, we conducted a survey (57 questions) which was sent to laser experts. The expert selection was based on clinical experience and scientific contribution. Participants were asked for used laser types, typical laser settings during specific scenarios, and preventive measures applied during surgery. Settings for a maximum of 2 different lasers for each scenario were possible. Responses and settings were compared among the reported laser types. RESULTS: Twenty-three of 29 (79.3%) invited experts completed the survey. Thulium fiber laser (TFL) is the most common laser (57%), followed by Holmium:Yttrium-Aluminium-Garnet (Ho:YAG) (48%), continuous wave (cw) Thulium:Yttrium-Aluminium-Garnet (Tm:YAG) (26%), and pulsed Tm:YAG (13%). Experts prefer ERBT (91.3%) to vapBT (8.7%); however, relevant limitations such as tumor size, number, and anatomical tumor location exist. Laser settings were generally comparable; however, we could find significant differences between the laser sources for lateral wall ERBT (p = 0.028) and standard ERBT (p = 0.033), with cwTm:YAG and pulsed Tm:YAG being operated in higher power modes when compared to TFL and Ho:YAG. Experts prefer long pulse modes for Ho:YAG and short pulse modes for TFL lasers. CONCLUSION: TFL seems to have replaced Ho:YAG and Tm:YAG. Most laser settings do not differ significantly among laser sources. For experts, continuous flow irrigation is the most commonly applied measure to reduce complications.

A Smart Digital Health Platform to Enable Monitoring of Quality of Life and Frailty in Older Patients with Cancer: A Mixed-Methods, Feasibility Study Protocol.

OBJECTIVES: LifeChamps is an EU Horizon 2020 project that aims to create a digital platform to enable monitoring of health-related quality of life and frailty in patients with cancer over the age of 65. Our primary objective is to assess feasibility, usability, acceptability, fidelity, adherence, and safety parameters when implementing LifeChamps in routine cancer care. Secondary objectives involve evaluating preliminary signals of efficacy and cost-effectiveness indicators. DATA SOURCES: This will be a mixed-methods exploratory project, involving four study sites in Greece, Spain, Sweden, and the United Kingdom. The quantitative component of LifeChamps (single-group, pre-post feasibility study) will integrate digital technologies, home-based motion sensors, self-administered questionnaires, and the electronic health record to (1) enable multimodal, real-world data collection, (2) provide patients with a coaching mobile app interface, and (3) equip healthcare professionals with an interactive, patient-monitoring dashboard. The qualitative component will determine end-user usability and acceptability via end-of-study surveys and interviews. CONCLUSION: The first patient was enrolled in the study in January 2023. Recruitment will be ongoing until the project finishes before the end of 2023. IMPLICATIONS FOR NURSING PRACTICE: LifeChamps provides a comprehensive digital health platform to enable continuous monitoring of frailty indicators and health-related quality of life determinants in geriatric cancer care. Real-world data collection will generate "big data" sets to enable development of predictive algorithms to enable patient risk classification, identification of patients in need for a comprehensive geriatric assessment, and subsequently personalized care.

Enucleation of the prostate as retreatment for recurrent or residual benign prostatic obstruction: a systematic review and a meta-analysis.

BACKGROUND: Anatomical endoscopic enucleation of the prostate (AEEP) is recommended for first line surgical treatment of benign prostatic obstruction (BPO) caused by moderate and large prostatic adenoma. However, its role in the retreatment setting after failed previous surgical treatment for BPO remains uncaptured. In this scope, we performed a systematic review and meta-analysis aiming to assess the safety and efficacy of AEEP in the retreatment setting. METHODS: We searched PubMed, Cochrane Library and Embase databases from inception to March 2022 for prospective or retrospective studies involving patients undergoing prostatic enucleation for recurrent or residual BPO after previous standard or minimally invasive surgical treatments for BPO. Based on data availability, we performed a meta-analysis comparing AEEP in patients with recurrent or residual BPO versus AEEP for primary BPO. PROSPERO: CRD42022308941). RESULTS: We included 15 studies in the systematic review and 10 in the meta-analysis (6553 patients, 841 with recurrent or residual BPO and 5712 with primary BPO). All included studies involved patients undergoing HoLEP or ThuLEP. In terms of Qmax, post-void residual, International Prostate Symptom Score, removed adenoma, operative time, duration of catheterization and hospital stay, as well as complications, HoLEP for recurrent or residual BPO was equally effective compared to HoLEP for primary BPO up to 1 year postoperatively. Importantly, the beneficial effect of HoLEP on the retreatment setting was observed after previous standard or minimally invasive surgical treatments for BPO. The overall strength of evidence for all outcomes was deemed very low. CONCLUSIONS: HoLEP may be safely and effectively used in experienced hands for the surgical treatment of recurrent or residual BPO in patients with large or moderate prostates following previous open, endoscopic or minimally invasive surgical treatment for BPO.

Εmerging Biomarkers in the Diagnosis and Treatment of Testicular Tumors.

Testicular germ cell tumors (TGCT) are the leading cause of cancer-related death in young males between the ages of 20-40. Surgical resection and cisplatin-based chemotherapy can achieve a cure for the majority of patients with TGCTs, with survival rates of up to 97% for patients diagnosed at an early stage. The use of serum biomarkers, such as AFP ß-HCG, and LDH, plays a significant role in both diagnosis and evaluation of response to treatment, and despite their low sensitivity and specificity levels, they are an integral part of the current tumor staging system and daily practice. Molecular biomarkers, including micro-RNAs and gene-expression profiles, are currently being developed in TGCTs and could potentially hold a prominent place in the future diagnosis, treatment selection, surveillance, and prognostication of these tumors. This review discusses how current advances in our understanding of the underlying biology of TGCTs have helped biomarker discovery, with a focus on the recognition of key molecular alterations that could serve as potential indicators of disease onset, response to systemic or/and surgical therapies, and overall clinical course.

Physical Inactivity, Metabolic Syndrome and Prostate Cancer Diagnosis: Development of a Predicting Nomogram.

Insufficient physical activity (PA) may be a shared risk factor for the development of both metabolic syndrome (MetS) and prostate cancer (PCa). To investigate this correlation and to develop a nomogram able to predict tumor diagnosis. Between 2016 and 2018, a consecutive series of men who underwent prostate biopsy at three institutions were prospectively enrolled. PA was self-assessed by patients through the Physical Activity Scale for the Elderly (PASE) questionnaire; MetS was assessed according to Adult Treatment Panel III criteria. A logistic regression analyses was used to identify predictors of PCa diagnosis and high-grade disease (defined as International Society of Uro-Pathology grade >2 tumors). A nomogram was then computed to estimate the risk of tumor diagnosis. A total of 291 patients were enrolled; 17.5% of them (n = 51) presented with MetS. PCa was diagnosed in 110 (38%) patients overall while 51 presented high-grade disease. At multivariable analysis, age (OR 1.04; 95%CI: 1.00−1.08; p = 0.048), prostate volume (PV) (OR 0.98; 95%CI: 0.79−0.99; p = 0.004), suspicious digital rectal examination (OR 2.35; 95%CI: 1.11−4.98; p = 0.02), total PSA value (OR 1.12; 95%CI: 1.05−1.2; p < 0.001), and PASE score (OR 0.99; 95%CI: 0.98−0.99; p = 0.01) were independent predictors of tumor diagnosis. The latter two also predicted high-grade PCa. MetS was not associated with PCa diagnosis and aggressiveness. The novel nomogram displayed fair discrimination for PCa diagnosis (AUC = 0.76), adequate calibration (p > 0.05) and provided a net benefit in the range of probabilities between 20% and 90%. reduced PA was associated with an increased risk of PCa diagnosis and high-grade disease. Our nomogram could improve the selection of patients scheduled for prostate biopsy at increased risk of PCa.

En bloc resection, is this the future of non-muscle invasive bladder cancer management? Presentation of our technique and brief review of the literature.

INTRODUCTION: The quality of the initial transurethral resection of bladder tumors (TURBT) plays a key role in accurate local staging thus affecting treatment decision-making and disease prognosis. TURBT is still the gold standard for non-muscle invasive bladder cancer (NMIBC). However, en bloc resection of bladder tumors (ERBT) gradually expanded as a promising alternative to TURBT, aiming to overcome certain inherent limitations of conventional resection. We hereby describe a step-by-step bipolar ERBT technique and briefly review the current trends surrounding the role of various en bloc techniques in the field. CASE PRESENTATION: We present the case of a 65-year old patient undergoing bipolar ERBT for a single, approximately 2 cm, papillary bladder mass. An experienced urologist completed the procedure within 17 min and without any intra- or postoperative complications. No conversion to TURBT was needed, and an adequate specimen for histological assessment was obtained. The patient made an uneventful recovery, and no recurrence was noted at 12-months. CONCLUSION: Our initial experience demonstrates that ERBT via bipolar current is relatively quick, safe, and reliable. Prospective comparative clinical trials will examine its efficacy, and long-term oncological superiority in managing NMIBC.

Concomitant Endoscopic Surgery for Bladder Tumors and Prostatic Obstruction: Are We Safely Hitting Two Birds with One Stone? A Systematic Review and Meta-Analysis.

BACKGROUND: Lower urinary tract symptoms (LUTS) caused by benign prostatic obstruction (BPO) and bladder tumors may co-exist, especially among elderly patients. Transurethral resection of bladder tumors (TURBT) and endoscopic surgery for benign prostatic obstruction in the same setting are avoided by many surgeons due to concerns for tumor cell seeding and recurrences in the prostatic urethra. AIM: The aim of this study was assess the effect of concomitant TURBT and endoscopic BPO surgery on oncological safety and patient quality of life via systematic review and meta-analysis. METHODS: We searched the PubMed, Cochrane Library, EMBASE, Scopus, and Clinicaltrials.gov databases and sources of grey literature published before June 2021 for relevant studies. We performed a random-effects meta-analysis of odds ratios (ORs) or weighted mean differences (WMD) to compare concomitant TURBT and BPO surgery versus TURBT alone in terms of recurrence and progression rates. Accordingly, we undertook multiple subgroups and sensitivity analyses (PROSPERO: CRD42020173363). RESULTS: Three randomized and twelve retrospective observational studies with 2421 participants were included. Across studies with good methodological quality, no statistically significant differences were demonstrated regarding overall bladder tumors recurrence rates between concomitant endoscopic BPO surgery and TURBT versus TURBT alone (OR: 0.81, 95% CI: 0.60-1.09, I2 = 42%). Similarly, no significant differences were observed in recurrences located at the bladder neck and/or prostatic urethra (OR: 1.06, 95% CI: 0.76-1.47, I2 = 0%), time to first recurrence (WMD: -0.2 months, 95% Cl: -2.2-1.8, I2 = 48%), and progression rate (OR: 1.05, 95% CI: 0.67-1.64, I2 = 0%). Subgroup analyses based on tumor grade, number of tumors, and utilization of single-instillation chemotherapy post-TURBT did not detect any significant differences in overall bladder tumor recurrence. The level of evidence was estimated as low for all outcomes. Concomitant surgery improved lower urinary tract symptoms. CONCLUSION: Concomitant endoscopic BPO surgery and TURBT are oncologically safe and improve LUTS-related quality of life.

En bloc resection of bladder tumors: challenges and unmet needs in 2022.

Non-muscle invasive bladder cancer accounts for the majority of new bladder cancer diagnoses, and endoscopic transurethral resection of bladder tumor (TURBT) represents the standard-of-care. Although a relatively safe and common procedure, TURBT is often hampered by the questionable quality of resection. The evolution of surgical techniques has brought en bloc resection of bladder tumor (ERBT) to the forefront. ERBT has emerged as an alternative to conventional TURBT, incorporating a more delicate en bloc sculpting and tumor excision, in contrast to 'piecemeal' resection by conventional TURBT. ERBT appears safe, feasible and effective with demonstrably higher rates of detrusor muscle in the pathologic specimen, all while providing better staging and obviating the need for a re-TURBT in selected patients. However, the method's adoption in the field is still limited. This review summarizes the recent evidence relevant to ERBT while further highlighting the technique's limitations and unmet needs.

Transurethral resection of bladder tumor remains the standard-of-care for non-muscle invasive bladder cancer. The procedure is the first-line diagnostic test and treatment for early-stage bladder cancer. However, the poor post-operative outcomes relevant to the surgical technique have led to constant questioning of its efficacy for years. A novel procedure, en bloc resection of bladder tumor (ERBT), has come to the forefront. This represents an attractive method that can be accomplished by a breadth of energy delivery systems. Thus far, this technique appears feasible, safe and efficient, providing excellent and precise histological specimens. Despite the recent surge in studies reporting on ERBT, well-designed, properly conducted randomized controlled trials examining the technique's long-term efficacy are still lacking and excitedly anticipated in the years to come. The present article gives an overview of current knowledge surrounding the role of ERBT, outlines the existing challenges and unmet needs, and provides future perspectives on the management of non-muscle invasive bladder cancer.

Monoclonal Antibody Therapy for the Treatment of Interstitial Cystitis.

An emerging theory regarding the potentially autoimmune nature of painful bladder syndrome/interstitial cystitis (PBS/IC) had led to several studies being conducted to assess the possible therapeutic effect of immunotherapeutic options for PBS/IC. This review presents the available evidence regarding the potential autoimmunity-based pathogenesis of PBS/IC and focuses on a main representative of the immunotherapeutic modalities for PBS/IC, aiming to summarize, evaluate, and present available data regarding the potential therapeutic role of monoclonal antibodies for PBS/IC patients. A non-systematic narrative and interpretative literature review was performed. The monoclonal antibodies included in the review were the anti-tumor necrosis factor-α (anti-TNF-α) agents adalimumab, which showed no difference compared to placebo, and certolizumab pegol, which showed statistically important differences in all outcome measures compared to placebo at the 18-week follow-up visit. Anti-nerve growth factor (anti-NGF) agents were also reviewed, including tanezumab, which showed both positive and negative efficacy results compared to placebo, and fulranumab, the study of which was discontinued owing to adverse events. In summary, monoclonal antibody therapy remains to be further researched in order for it to be proposed as a promising future treatment option for PBS/IC.

Preserving Ejaculation: A Guide Through the Landscape of Interventional and Surgical Options for Benign Prostatic Obstruction.

Surgical treatment for benign prostatic obstruction in patients wishing to preserve normal ejaculation remains a urological challenge. Standard surgical techniques are associated with high rates of postoperative ejaculatory dysfunction. Research is now concentrating on ejaculation-preserving modifications of standard surgical techniques and on alternative minimally invasive interventional techniques. Ejaculation-preserving modifications seem to be superior to standard techniques for preservation of ejaculation with comparable efficacy in terms of improvement in lower urinary tract symptoms (LUTS). Among the alternative minimally invasive interventional techniques, prostatic artery embolization and prostatic urethral lift provide high success rates for patients wishing to preserve ejaculation but are inferior to standard surgical techniques regarding improvement in LUTS. High-quality studies focusing on ejaculatory function as the primary outcome are still lacking. PATIENT SUMMARY: Benign prostate enlargement can cause obstruction of the lower urinary tract. We reviewed the evidence for techniques that preserve ejaculatory function in treatment of this condition. These ejaculation-preserving treatment techniques may have lower efficacy in improving bothersome urinary symptoms.

Very low risk T1a renal cell carcinoma presenting with pathological fracture caused by a solitary metastases to the contralateral arm.

BACKGROUND: Renal Cell Carcinomas are notorious for asynchronous metastases, atypical metastatic sites and late relapses even decades after nephrectomy. It is quite rare though for RCCs to present as metastatic, solitary and symptomatic bone lesions. Even more uncommon is a solitary bone metastasis much larger that the primary tumour caused by a low risk primary T1a RCC which would have otherwise been eligible for active surveillance. CASE PRESENTATION: An otherwise healthy 68-year-old female was seen by the orthopaedics for right shoulder and upper arm worsening pain. Imaging showed a pathological fracture caused by a 5.5 cm lytic lesion involving the coracoid process and proximal humerus. She underwent proximal humeral replacement and histology of the lesion showed metastatic RCC. Whole body CT scan revealed a primary tumour of the left kidney less than 4cm in diameter. The patient underwent laparoscopic radical nephrectomy and diagnosis of a T1a, clear cell RCC without adverse pathological features was confirmed. She has been on systematic therapy with oral TKIs since and is free from recurrence at 12-months follow up. CONCLUSIONS: Even T1a RCCs without adverse pathological features can give rise to distant metastases following unpredictable patterns of spread thereby questioning the safety of active surveillance in healthy and fit patients.

Management of local recurrence after radical nephrectomy: surgical removal with or without systemic treatment is still the gold standard. Results from a multicenter international cohort.

OBJECTIVE: To evaluate the survival outcomes of patients with local recurrence after radical nephrectomy (RN) and to test the effect of surgery, as monotherapy or in combination with systemic treatment, on cancer-specific mortality (CSM). METHODS: Patients with local recurrence after RN were abstracted from an international dataset. The primary outcome was CSM. Cox's proportional hazard models tested the main predictors of CSM. Kaplan-Meier method estimates the 3-year survival rates. RESULTS: Overall, 96 patients were included. Of these, 44 (45.8%) were metastatic at the time of recurrence. The median time to recurrence after RN was 14.5 months. The 3-year cancer-specific survival rates after local recurrence were 92.3% (± 7.4%) for those who were treated with surgery and systemic therapy, 63.2% (± 13.2%) for those who only underwent surgery, 22.7% (± 0.9%) for those who only received systemic therapy and 20.5% (± 10.4%) for those who received no treatment (p < 0.001). Receiving only medical treatment (HR: 5.40, 95% CI 2.06-14.15, p = 0.001) or no treatment (HR: 5.63, 95% CI 2.21-14.92, p = 0.001) were both independently associated with higher CSM rates, even after multivariable adjustment. Following surgical treatment of local recurrence 8 (16.0%) patients reported complications, and 2/8 were graded as Clavien-Dindo ≥ 3. CONCLUSIONS: Surgical treatment of local recurrence after RN, when feasible, should be offered to patients. Moreover, its association with a systemic treatment seems to warrantee adjunctive advantages in terms of survival, even in the presence of metastases.

Corrigendum to: Can Medical Therapy Fix Sexual Dysfunction after Major Pelvic and Prostate Surgery and does it Work for Kidney Stones? Chemotherapy before Cystectomy, New Schemes for which Patients?

Due to an editorial oversight, we would like to apologize for an error that occurred in the both print and online version of an editorial entitled "Can Medical Therapy Fix Sexual Dysfunction after Major Pelvic and Prostate Surgery and does it Work for Kidney Stones? Chemotherapy before Cystectomy, New Schemes for which Patients?. It was published without the co-authors' names in the journal "Current Drug Targets" 2021; 22(1): 2 [1]. The original editorial can be found online at https://doi.org/10.2174/138945012201201231123209 REFERENCE [1] Petros S, Ioannis M, Ioannis V, Luca C, Can medical therapy fix sexual dysfunction after major pelvic and prostate surgery and does it work for kidney stones? chemotherapy before cystectomy, new schemes for which patients? Curr Drug Targets 2021; 22(1): 1.

Amyloidosis of the Urinary Bladder: A Systematic Review and a Proposed Management Algorithm.

OBJECTIVE: To propose an algorithm for the management of bladder amyloidosis based on a systematic review of the literature, given that the bladder is the second most commonly affected organ of the urinary tract in the course of systemic or localized amyloidosis. METHODS: We searched PubMed, Cochrane Library and Scopus databases utilizing PRISMA methodology from inception to November 30, 2020 (PROSPERO: CRD42020207855). RESULTS: We included 76 studies with 184 patients (9 case series and 67 case reports). Presenting symptoms of bladder amyloidosis comprised of hematuria, irritative or obstructive urinary symptoms, and cystitis-like symptoms. The diagnosis of amyloidosis was established by histologic examination of specimens retrieved during transurethral resection of bladder lesions. Complete endoscopic resection, the cornerstone of management of localized disease, was feasible in 89.1% cases. The included patients were followed up for a mean of 54 months, within which 65 patients (35.3%) recurred. The time to first amyloidosis recurrence was 20 months (range: 1-168). Additionally, 16 individuals presented with concomitant bladder amyloidosis and bladder cancer, while 4 developed bladder malignancy during follow-up. Due to the frequent and early recurrences of patients with bladder amyloidosis, a check-up cystoscopy at 3, 12, and 24 months' after initial resection is recommended. Recurrences should be managed with transurethral resection, while intravesical instillations of dimethyl sulfoxide (DMSO) and cystectomy should be reserved for refractory cases. CONCLUSION: We propose a management algorithm for bladder amyloidosis based on the available evidence for this rare benign entity that mimics bladder cancer.

Sexual Dysfunction in Women With End-Stage Renal Disease: A Systematic Review and Meta-Analysis.

BACKGROUND: In women with end-stage renal disease (ESRD), female sexual dysfunction (SD) remains underestimated. AIM: To explore the prevalence, correlates, diagnostic approach and treatment modalities of sexual symptoms in females with ESRD. METHODS: We performed a systematic review and meta-analysis to estimate both the prevalence of SD and the pooled Female Sexual Function Index (FSFI) scores in ESRD females. Similarly, for studies reporting the FSFI score before and after renal transplantation (RT), we estimated the effect of RT on sexual function. Further assessment of heterogeneity was conducted via subgroup and sensitivity analyses, cumulative meta-analysis and univariate meta-regression of important correlates. Records were identified through searching PubMed, Cochrane Library and Scopus databases as well as sources of grey literature until November 2020 (PROSPERO ID: CRD42020215178). OUTCOMES: We included 47 studies with 61 patient group entries and 3490 ESRD female individuals (median age: 45.2 years, ΙQR: 40.4-50.6). RESULTS: The SD prevalence in all females with ESRD was 74% (95%CI: 67%-80%, I2 = 92%) and the FSFI total score 16.1 points (95%CI: 14.3-17.8, I2 = 98%). The female SD prevalence was 63% (95%CI: 43%-81%, I2 = 92%) in renal transplant recipients, 80% (95%CI: 72%-87%, I2 = 91%) in hemodialysis patients and 67% (95%CI: 46%-84%, I2 = 90%) in peritoneal dialysis patients. The total FSFI score improved by 7.5 points (95%CI: 3.9-11.1, I2 = 92%) after RT. Older age and menopause were associated with higher SD prevalence. CLINICAL TRANSLATION: Female SD is highly prevalent in all ESRD women, but renal transplant recipients reported improved sexual function. STRENGTHS & LIMITATIONS: We provide the first study about SD in females and assessed the role of RT on sexual function. Contrary, none of the included studies evaluated the concomitant presence of distress with SD. The levels of heterogeneity were substantially high for all outcomes and we could not adjust for further correlates, which might have affected our measures. CONCLUSIONS: Sexual symptoms negatively affect the quality of life and warrants appropriate clinical attention, as they are an underdetermined and undertreated clinical entity in females with ESRD. Studies on treatment modalities of female SD in patients with ESRD are mandatory, as currently no relevant studies or clinical recommendations exist. Pyrgidis N, Mykoniatis I, Tishukov M, et al. Sexual Dysfunction in Women With End-Stage Renal Disease: A Systematic Review and Meta-Analysis. Sex Med Rev 2021;18:936-945.

Assessment of Combination Therapies vs Monotherapy for Erectile Dysfunction: A Systematic Review and Meta-analysis.

Importance: Combining 2 first-line treatments for erectile dysfunction (ED) or initiating other modalities in addition to a first-line therapy may produce beneficial outcomes. Objective: To assess whether different ED combination therapies were associated with improved outcomes compared with first-line ED monotherapy in various subgroups of patients with ED. Data Sources: Studies were identified through a systematic search in MEDLINE, Cochrane Library, and Scopus from inception of these databases to October 10, 2020. Study Selection: Randomized clinical trials or prospective interventional studies of the outcomes of combination therapy vs recommended monotherapy in men with ED were identified. Only comparative human studies, which evaluated the change from baseline of self-reported erectile function using validated questionnaires, that were published in any language were included. Data Extraction and Synthesis: Data extraction and synthesis were performed according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) reporting guideline. Main Outcomes and Measures: A meta-analysis was conducted that included randomized clinical trials that compared outcomes of combination therapy with phosphodiesterase type 5 (PDE5) inhibitors plus another agent vs PDE5 inhibitor monotherapy. Separate analyses were performed for the mean International Index of Erectile Function (IIEF) score change from baseline and the number of adverse events (AEs) by different treatment modalities and subgroups of patients. Results: A total of 44 studies included 3853 men with a mean (SD) age of 55.8 (11.9) years. Combination therapy compared with monotherapy was associated with a mean IIEF score improvement of 1.76 points (95% CI, 1.27-2.24; I2 = 77%; 95% PI, -0.56 to 4.08). Adding daily tadalafil, low-intensity shockwave therapy, vacuum erectile device, folic acid, metformin hydrochloride, or angiotensin-converting enzyme inhibitors was associated with a significant IIEF score improvement, but each measure was based on only 1 study. Specifically, the weighted mean difference (WMD) in IIEF score was 1.70 (95% CI, 0.79-2.61) for the addition of daily tadalafil, 3.50 (95% CI, 0.22-6.78) for the addition of low-intensity shockwave therapy, 8.40 (95% CI, 4.90-11.90) for the addition of a vacuum erectile device, 3.46 (95% CI, 2.16-4.76) for the addition of folic acid, 4.90 (95% CI, 2.82-6.98) for the addition of metformin hydrochloride and 2.07 (95% CI, 1.37-2.77) for the addition of angiotensin-converting enzyme inhibitors. The addition of α-blockers to PDE5 inhibitors was not associated with improvement in IIEF score (WMD, 0.80; 95% CI, -0.06 to 1.65; I2 = 72%). Compared with monotherapy, combination therapy was associated with improved IIEF score in patients with hypogonadism (WMD, 1.61; 95% CI, 0.99-2.23; I2 = 0%), monotherapy-resistant ED (WMD, 4.38; 95% CI, 2.37-6.40; I2 = 52%), or prostatectomy-induced ED (WMD, 5.47; 95% CI, 3.11-7.83; I2 = 53%). The treatment-related AEs did not differ between combination therapy and monotherapy (odds ratio, 1.10; 95% CI, 0.66-1.85; I2 = 78%). Despite multiple subgroup and sensitivity analyses, the levels of heterogeneity remained high. Conclusions and Relevance: This study found that combination therapy of PDE5 inhibitors and antioxidants was associated with improved ED without increasing the AEs. Treatment with PDE5 inhibitors and daily tadalafil, shockwaves, or a vacuum device was associated with additional improvement, but this result was based on limited data. These findings suggest that combination therapy is safe, associated with improved outcomes, and should be considered as a first-line therapy for refractory, complex, or difficult-to-treat cases of ED.