Can nutraceuticals counteract the detrimental effects of the environment on male fertility? A parallel systematic review and expert opinion.

INTRODUCTION: Male fertility relies on a complex physiology that may be negatively influenced by lifestyle, diet, and environment. The beneficial effect of nutraceuticals on male fertility is a debated claim. The aim of this study was to assess if the positive effect of nutraceuticals can counteract the negative effects of the environment on male fertility. EVIDENCE ACQUISITION: PubMed®/MEDLINE®, Embase and Cochrane Database were searched (September-October 2023), along with crosschecking of references and search for ongoing studies of the effects of the environment and nutraceuticals on male fertility, in accordance with the guidelines of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). EVIDENCE SYNTHESIS: Several environmental factors such as microplastic and other endocrine-disrupting chemicals and climate changes may affect the sperm quality in terms of reduction of sperm count number, mobility and altered morphology and thereby reduce male fertility. On the other hand, new evidence demonstrates that a balanced diet rich in antioxidants and essential nutrients, together with minimized exposure to environmental toxins, may improve male fertility and reproductive health. Several nutraceutical compounds proved a protective role against negative environmental effects on male fertility. CONCLUSIONS: Available evidence confirms that the environment may negatively impact male fertility, and this impact is estimated to rise in the forthcoming years. On the other hand, new data indicate that nutraceuticals may have a protective role against the negative impact of environmental factors on male fertility. The need for future studies to monitor and explore these aspects of men's health cannot be underestimated.

Proficiency score as a predictor of early trifecta achievement during the learning curve of robot-assisted radical prostatectomy for high-risk prostate cancer: Results of a multicentric series.

Background: Recently, an innovative tool called "proficiency score" was introduced to assess the learning curve for robot-assisted radical prostatectomy (RARP). However, the initial study only focused on patients with low-risk prostate cancer for whom pelvic lymph node dissection (PLND) was not required. To address this issue, we aimed to validate proficiency scores of a contemporary multicenter cohort of patients with high-risk prostate cancer treated with RARP plus extended PLND by trainee surgeons. Material and methods: Between 2010 and 2020, 4 Italian institutional prostate-cancer datasets were merged and queried for "RARP" and "high-risk prostate cancer." High-risk prostate cancer was defined according to the most recent European Association of Urology guidelines as follows: prostate-specific antigen >20 ng/mL, International Society of Urological Pathology ≥4, and/or clinical stage (cT) ≥ 2c on preoperative imaging. The selected cohort (n = 144) included clinical cases performed by trainee surgeons (n = 4) after completing their RARP learning curve (50 procedures for low-risk prostate cancer). The outcome of interest, the proficiency score, was defined as the coexistence of all the following criteria: a comparable operation time to the interquartile range of the mentor surgeon at each center, absence of any significant perioperative complications Clavien-Dindo Grade 3-5, no perioperative blood transfusions, and negative surgical margins. A logistic binary regression model was built to identify the predictors of 1-year trifecta achievement in the trainee cohort. For all statistical analyses, a 2-sided p < 0.05 was considered significant. Results: A proficiency score was achieved in 42.3% patients. At univariable level, proficiency score was associated with 1-year trifecta achievement (odds ratio, 8.77; 95% confidence interval, 2.42-31.7; p = 0.001). After multivariable adjustments for age, nerve-sparing, and surgical technique, the proficiency score independently predicted 1-year trifecta achievement (odds ratio, 9.58; 95% confidence interval, 1.83-50.1; p = 0.007). Conclusions: Our findings support the use of proficiency scores in patients and require extended PLND in addition to RARP.

Antibiotic-sparing Strategies for Prevention of Recurrent Urinary Tract Infection.

Non-antimicrobial prophylactic options for recurrent urinary tract infections (rUTIs) can be personalized for each patient. A combination of different non-antibiotic strategies may provide the optimal strategy for reducing rUTIs. Management of rUTIs remains challenging for urologists and distressing for patients.

Systematic Review and Meta-Analysis Provide no Guidance on Management of Asymptomatic Bacteriuria within the First Year after Kidney Transplantation.

(1) Background: Urinary tract infections (UTIs) are among the most frequent complications in kidney transplant (KT) recipients. Asymptomatic bacteriuria (ASB) may be a risk factor for UTIs and graft rejection. We aimed to evaluate available evidence regarding the benefit of screening and treatment of ASB within the first year after KT. (2) Evidence acquisition: A systematic literature search was conducted in MEDLINE, the Cochrane Library CENTRAL and Embase. Inclusion criteria were manuscripts in English addressing the management of ASB after KT. The PICO questions concerned Patients (adults receiving a KT), Intervention (screening, diagnosis and treatment of ASB), Control (screening and no antibiotic treatment) and Outcome (UTIs, sepsis, kidney failure and death). (3) Evidence synthesis: The systematic review identified 151 studies, and 16 full-text articles were evaluated. Seven were excluded because they did not evaluate the effect of treatment of ASB. There was no evidence for a higher incidence of lower UTIs, acute pyelonephritis, graft loss, or mortality in patients not treated with antibiotics for ASB. Analysis of comparative non-randomized and observational studies did not provide supplementary evidence to guide clinical recommendations. We believe this lack of evidence is due to confounding risk factors that are not being considered in the stratification of study patients.

European Association of Urology Guidelines on Urological Infections: Summary of the 2024 Guidelines.

BACKGROUND AND OBJECTIVE: Urological infections significantly impact the wellbeing and quality of life of individuals owing to their widespread occurrence and diverse clinical manifestations. The objective of the guidelines panel was to provide evidence-based guidance on the diagnosis, treatment, and prevention of urinary tract infections (UTIs) and male accessory-gland infections, while addressing crucial public health aspects related to infection control and antimicrobial stewardship. METHODS: For the 2024 guidelines on urological infections, new and relevant evidence was identified, collated, and appraised via a structured assessment of the literature. Databases searched included Medline, EMBASE, and the Cochrane Libraries. Recommendations within the guidelines were developed by the panel to prioritise clinically important care decisions. The strength of each recommendation was determined according to a balance between desirable and undesirable consequences of alternative management strategies, the quality of the evidence (including the certainty of estimates), and the nature and variability of patient values and preferences. KEY FINDINGS AND LIMITATIONS: Key recommendations emphasise the importance of a thorough medical history and physical examination for patients with urological infections. The guidelines stress the role of antimicrobial stewardship to combat the rising threat of antimicrobial resistance, providing recommendations for antibiotic selection, dosing, and duration on the basis of the latest evidence. CONCLUSIONS AND CLINICAL IMPLICATIONS: This overview of the 2024 EAU guidelines offers valuable insights into managing urological infections and are designed for effective integration into clinical practice. PATIENT SUMMARY: The European Association of Urology has issued an updated guideline on urological infections. The guidelines provide recommendations for diagnosis, treatment, and prevention, with a particular focus on minimising antibiotic use because of the increasing global threat of antimicrobial resistance.

Therapeutic strategies for uncomplicated cystitis in women.

Uncomplicated cystitis is affecting many women of all ages and has a great impact on the quality of life, especially in women suffering from recurrent, uncomplicated cystitis. By far the most frequent uropathogen, E. coli, may have acquired increasing resistance against a variety of oral antibiotics, which may differ between countries and regions. Therefore, local resistance data are important to be considered. On the other hand, non-antibiotic therapy has also become an option which should be discussed and offered to the patient. In patients suffering from recurrent uncomplicated cystitis, individual risk factors and possible behavioral changes should first be taken into account. Non-antimicrobial prophylactic strategies shown to be successful in well-designed clinical studies are the next options. Long term antibiotic prophylaxis, however, should only be considered as a last option. For some of those patients self-diagnosis and self-treatment may be suitable, e.g. by using a recognized questionnaire.

Icarifil® in Association with Daily Use of Tadalafil (5 mg) versus Standard Tadalafil Daily Dose (5 mg) or Alone: Results from a Controlled, Randomized Clinical Trial.

Background: The management of erectile dysfunction (ED) shows several grey zones and new treatments are required to reduce the percentage of patients discontinuing treatment. Here, we aim to evaluate the role of a natural mixture named Icarifil® (L-Citrulline, L-Carnitine, Eruca vesicaria, Panax ginseng, Tribulus terrestris, Turnera diffusa, Taurine, Vitamin E, Zinc) in the management of patients with ED. Methods: From September 2022 to March 2023, all patients attending 3 urological institutions due to ED were randomized to receive the following for 3 months: Icarifil® 1 sachet every 24 h (Group 1) or Icarifil® 1 sachet + tadalafil 5 mg 1 tablet every 24 h (Group 2) or tadalafil 5 mg 1 tablet daily (Group 3). All patients underwent urologic visits and dedicated questionnaires (IIEF-5, SEP-2, SEP-3) at enrollment and at the follow-up evaluation (3 months). Patient-Reported Outcomes (PROs) at the follow-up evaluation were used. The primary endpoint was the difference in the questionnaires at the follow-up visit compared to the one at enrollment among the study groups. Results: In the per-protocol analysis, 52 patients in Group 1, 55 in Group 2 and 57 in Group 3 were analyzed. At the follow-up evaluation, IIEF-5 scores improved in all the 3 groups between enrollment and the follow-up evaluation, but a statistically significant difference was reported between Group 2 (+7.4) and Group 1 (+4.1) or Group 3 (+5.1), (p < 0.001; p < 0.001). Moreover, 47 patients (94.0%) in Group 2 showed an improvement in the SEP questionnaires, when compared with the baseline, while 29 in Group 1 (56.9%) and 42 in Group 3 (82.3%) showed a statistically significant difference (p = 0.004; p = 0.003) among the groups. The PRO analysis reported better efficacy and patient satisfaction in Group 2 when compared with Group 1 or Group 3. Conclusions: In conclusion, Icarifil® is able to improve penile erectile function in mild-moderate ED and significantly improve the clinical efficacy of daily used tadalafil 5 mg. Icarifil® could represent an interesting alternative treatment in patients experiencing adverse effects or with contraindications for chronic treatment with PDE5-is.

The diagnostic yield of the Meares & Stamey test can be significantly improved by symptom-based patient selection and the experience of the test performer.

BACKGROUND: Even if Meares-Stamey 4-glass (M&S) test is regarded a decisive tool for diagnosing prostatitis its use is only rarely performed in everyday clinical practice. Here, we analyze if the diagnostic yield of the M&S test could be improved by a pre-test categorization of patients due to undergo a M&S test. METHODS: All clinical and microbiological data of patients who underwent M&S test in two urological centers from January 2004 to December 2021 were analyzed in this retrospective cohort study. One center has a dedicated staff member for the study of prostatitis (Cohort I), while the other center is a general urological unit (Cohort II). All patients were divided into 3 groups on the basis of the assembled data: patients with symptoms related to prostatitis only (Group I), patients with symptoms related to both prostatitis and BPH (Group II), patients with symptoms related to BPH only (Group III). The rates of positive microbiological results in each group were compared. RESULTS: In the whole period, 9347 patients were analyzed and categorized as follows: Group I, 1884; Group II, 5151; Group III, 2312. Three-thousand and eight-hundred twenty-three patients showed positive culture results (40.9%). The most common isolated species was Escherichia coli (49.7%), followed by Enteroccus spp. (31.8%). The rates of positive M&S tests in the different symptom groups were: Group I, 1532 (81.4%); Group II, 1494 (29.0%); Group III, 797 (34.4%). The overall rate of positive M&S tests in each urology center showed that the center with a staff member who is dedicated to prostatitis studies (Cohort I) had a significantly higher rate of positive M&S tests than the general urological department (Cohort II) (64.3% vs 31.4%; p < 0.001). CONCLUSIONS: Symptom-based patient selection and dedicated staff members will increase the diagnostic yield of the M&S test and reduce the number of unnecessary tests.

Phytotherapy Might Have a Role in Reducing Unnecessary Prostate Biopsies: Results from an Exploratory, Randomized Controlled Trial of Two Different Phytotherapeutic Agents.

BACKGROUND: We aimed to evaluate the impact of two different phytotherapeutic agents on decision making regarding prostate biopsy for patients with higher-than-normal prostate-specific antigen (PSA) levels. METHODS: From June 2022 to May 2023, all patients attending two urological institutions due to higher-than-normal PSA levels were randomized to receive either oral capsules of Curcuma Longa, Boswellia, Pinus pinaster and Urtica dioica (Group A) or Serenoa Repens 320 mg (Group B) for 3 months. At the follow-up visit after 3 months, all patients underwent PSA tests and multiparametric magnetic resonance imaging (mpMRI). RESULTS: In the per-protocol analysis, data from 66 patients in Group A and 76 in Group B were analyzed. Fifty patients in Group A (75.7%) showed a significant reduction in total PSA compared to forty-nine in Group B (64.4%) (p < 0.001). Twenty-eight patients had PI-RADS III or higher in mpMRI: twelve in Group A and fourteen in Group B. Twenty-three patients (34.8%) in Group A and fifty-nine (77.6%) in Group B (p < 0.001) underwent prostate biopsy based on the mpMRI findings and PSA values. Three patients in Group A showed a significant reduction in total PSA values while having positive mpMRI findings (6%) compared with nine in Group B (19.5%) (p < 0.001). On the contrary, 7 patients in Group A did not show significant reduction in total PSA values and had negative mpMRI findings (43%) compared to 22 in Group B (81.4%) (p < 0.001). CONCLUSIONS: In conclusion, a three-month course of a combination of Curcuma Longa, Boswellia, Pinus pinaster and Urtica dioica seems to be an interesting tool to avoid unnecessary prostate biopsies among men with higher-than-normal PSA levels.

The Subcutaneous Administration of Beta-Lactams: A Case Report and Literary Review-To Do Small Things in a Great Way.

The subcutaneous (s.c.) route is a commonly used method for delivering various drugs, although its application in the administration of antibiotics is relatively uncommon. In this case, we report a successful treatment of nosocomial pneumonia using piperacillin/tazobactam via continuous subcutaneous administration. Furthermore, this article provides an overview of the current literature regarding the s.c. administration of beta-lactam antibiotics. Based on our analysis, we identified only 15 studies that described the s.c. use of beta-lactam antibiotics in human subjects. Among these studies, cephalosporins were the most extensively investigated antibiotic class, with 10 available studies. According to the study findings, all three antibiotic classes (cephalosporins, penicillins, and carbapenems) demonstrated a similar pharmacokinetic profile when administered via the subcutaneous route. The subcutaneous route appears to be associated with a lower peak serum concentration (Cmax) but a comparable minimum blood concentration (Cmin) and an extended half-life (t1/2) when compared to conventional routes of antibiotic administration. Further research is necessary to determine whether subcutaneously administered beta-lactam antibiotics in human subjects achieve pharmacodynamic targets and demonstrate clinical efficacy.

Correction: Kostev, K.; Cai, T. Cystitis and Utipro® Plus: Real-World Evidence. Healthcare 2023, 11, 2564.

In the original publication [...].

Genitourinary Tuberculosis: A Brief Manual for Urologists on Diagnosis and Treatment from the European Association of Urology Urological Infections Panel.

Although tuberculosis (TB) ranks among the most frequent infectious diseases worldwide, one of its extrapulmonary (EP) manifestations, genitourinary (GU) TB, is often underestimated by urologists, particularly in areas such as Europe where TB is not endemic. The aim of this review is to give urologists a concise overview of GUTB as a supplement to the more comprehensive European Association of Urology 2023 update on urological infections guidelines. EPTB can develop in 16% of TB cases. GUTB accounts for 4.6% of EPTB and is often asymptomatic or nonspecific, so it can be confused with other urogenital diseases. GUTB can be highly destructive, leading to failure of urogenital organs. Diagnosis is via microbiological, molecular, and histological testing for urine, genital secretions, or genitourinary tissue, supported by imaging. A 6-mo combinational medical regimen is the first-line treatment for GUTB. However, surgical interventions are also frequently required for the treatment of GUTB complications. Therefore, it is important to keep GUTB in mind for differential diagnosis. PATIENT SUMMARY: We reviewed scientific studies on the occurrence, diagnosis, and treatment of tuberculosis in the genitourinary tract. Our aim is to raise awareness among urologists from countries where this disease does not occur frequently, as urogenital tuberculosis can occur without any symptoms or with unspecific symptoms that can be confused with other diseases.

Antimicrobial Prophylaxis in Robot-Assisted Laparoscopic Radical Prostatectomy: A Systematic Review.

It remains unclear whether antibiotic prophylaxis (AP) should be recommended or discouraged in robot-assisted laparoscopic radical prostatectomy (RALP) for prostate cancer (PCa). The development of microbial resistance and side effects are risks of antibiotic use. This systematic review (SR) investigates the evidence base for AP in RALP. A systematic literature search was conducted until 12 January 2023, using Embase, MEDLINE, Cochrane CENTRAL, Cochrane CDSR (via Ovid) and CINAHL for studies reporting the effect of AP on postoperative infectious complications in RALP. Of 436 screened publications, 8 studies comprising 6378 RALP procedures met the inclusion criteria. There was no evidence of a difference in the rate and severity of infective complications within 30 days after RALP surgery between different AP protocols. No studies omitted AP. For patients who received AP, the overall occurrence of postoperative infectious complications varied between 0.6% and 6.6%. The reported urinary tract infection (UTI) rates varied from 0.16% (4/2500) to 8.9% (15/169). Wound infections were reported in 0.46% (4/865) to 1.12% (1/89). Sepsis/bacteraemia and hyperpyrexia were registered in 0.1% (1/1084) and 1.6% (5/317), respectively. Infected lymphoceles (iLC) rates were 0.9% (3 of 317) in a RALP cohort that included 88.6% pelvic lymph node dissections (PLND), and 3% (26 of 865) in a RALP cohort where all patients underwent PLND. Our findings underscore that AP is being administered in RALP procedures without scientifically proven evidence. Prospective studies that apply consistent and uniform criteria for measuring infectious complications and antibiotic-related side effects are needed to ensure the comparability of results and guidance on AP in RALP.

Validation of the Italian version of the Peyronie's Disease Questionnaire (PDQ).

Peyronie's disease (PD) is a connective tissue disorder characterized by the formation of fibrous plaques in the tunica albuginea of the penis which can result in pain, deformity and erectile dysfunction (ED). The Peyronie's Disease Questionnaire (PDQ) assesses the severity of symptoms, including pain, penile curvature and ED, as well as the impact on sexual function, emotional well-being, and overall quality of life of PD patients. Previous studies validated the PDQ in languages other than English and confirmed its test-retest reliability and clinical utility. Despite this, in many countries the unavailability of an adequate PDQ validation in native language hampers its use in clinical practice. In the present non-interventional, observational study we aimed at validating the Italian version of the PDQ (PDQ-I). Between January 2019 and November 2021, 79 PD patients from 6 Italian high-volume centers were administrated the PDQ-I in two separated office visits distanced by a period of 6 months. Intraclass correlation coefficients (ICCs) were used to evaluate the association between the three PDQ scale scores at visit 1 and 2. Paired t-tests were used to evaluate significant score changes between the 2 visits. Cronbach's alpha was used to assess internal consistency reliability. PDQ-I demonstrated an excellent test-retest reliability in the Italian population (ICC 0.78-0.92) as well as a strong internal consistency, with all three scale scores showing a Cronbach's alpha coefficient above 0.70. PDQ-I proved to be a useful tool which allows to reliably evaluate Italian PD patients' quality of life in both everyday andrological practice and clinical research. External validation of our results is pending.

The Use of Vacuum Devices as Adjuvant Therapy before and after Penile Curvature Surgery in Patients Affected by La Peyronie's Disease: Results from a Comparative Study.

BACKGROUND: Peyronie's disease (PD) represents a challenging urological disease, due to not optimal post-operative surgical outcomes. We aim to retrospectively evaluate if vacuum erection device (VED) treatment before penile curvature surgery is able to improve post-operative surgical outcomes. METHODS: All enrolled patients were assigned to the following groups: (a) the treatment group: VED treatment (three times per week) starting 3 months before surgery and (three times per week) one month after surgery; and (b) the control group: VED treatment (three times per week) one month after surgery. Follow-up urologic visits were scheduled for 3 and 6 months after surgery, and the two groups were compared. RESULTS: A total of 38 patients were enrolled (median age 67 years, 57-74, IQR): 20 in the treatment group and 18 in the control group. At the follow-up visits, the two groups were different in terms of IIEF-5 (26 vs. 24; p = 0.02), "yes" to SEP2 and 3 (85% vs. 55%; p < 0.001, 85% vs. 50%; p < 0.001, respectively), and PDQ (-16 vs. -11; p = 0.03). Complete correction of penile curvature was achieved in 36 patients (94.7%). In the treatment group, no hourglass deformity was reported, whereas one patient reported a mild hourglass deformity in the control group. In the treatment group, we obtained a longer total penile length (median +1.5 cm). The overall satisfaction rate was 98% in the treatment group and 96% in the control group. CONCLUSIONS: The VED treatment before penile curvature surgery in patients affected by PD was able to improve surgical outcomes.

Penile revascularization using the descending branch of the lateral circumflex femoral artery: An alternative vascular graft.

INTRODUCTION AND RELEVANCE: Microsurgical revascularization stands as the preferred method for addressing erectile dysfunction (ED) resulting from traumatic penile arterial insufficiency. Traditional microarterial bypass surgery (MABS) techniques have typically relied on utilizing the inferior epigastric artery (IEA) as the graft vessel. However, issues such as endothelial dysfunction in the vessel and alterations in abdominal tissue can negatively impact surgical outcomes. MABS using the descending branch of the lateral circumflex artery of the femur (DLCFA) should be proposed as a surgical option for penile arterial revascularization. CASE PRESENTATION: A 29-year-old who experienced ED after a pelvic bone fracture with hypogastric vascular injury was referred to our center. Preoperatory penile Doppler ultrasound (PDU) examination documented the presence of arterial insufficiency. Selective hypogastric angiography pointed out the interruption of arterial blood flow at the level of the distal right internal pudendal artery. CASE DISCUSSION: Access to the dorsal penile artery was gained through an infrapubic incision, the DLCFA pedicle was isolated through an incision along the anterolateral right thigh. After its transposition, the arterial bundle was anastomosed to the dorsal penile artery in an end-to-end fashion. Intraoperative PDU has been used to verify the patency of the anastomosis. At 6 months follow-up, optimal flow parameters on PDU were persistently registered, and the patient had consistent clinical improvement on the IIEF-5 score. CONCLUSION: DLCFA grafting for penile revascularization is a suitable therapeutic option in traumatic ED due to its size and accessibility. Further experience is necessary to compare clinical outcomes among different revascularization techniques.

Cystitis and Utipro® Plus: Real-World Evidence.

BACKGROUND: The emergence of drug resistance in the etiological agents of uncomplicated urinary tract infections (UTIs) emphasizes the need to shift the paradigm towards alternative therapeutic strategies. The objective of the present study was to evaluate the use of a medical device containing xyloglucan, hibiscus, and propolis for reducing UTI symptomatic episodes, antibiotic prescription, and days of sick leave. MATERIALS AND METHODS: It used retrospective, cross-sectional study data provided by office-based physicians from Germany (Disease Analyzer, IQVIA database), including those on 3586 patients with a diagnosis of UTI treated with Utipro® Plus (Noventure, Barcelona, Spain) from January 2015 to December 2020. RESULTS: The majority of patients were women (94.2%) and had a mean age (standard deviation, SD) of 57.7 years (19.0). Within 12 months after the prescription and compared to the 12 months before, it was observed that there was a reduction in the proportion of patients with at least one UTI diagnosis (from 79.4% to 36.4%, p < 0.001), in antibiotic prescriptions (from 33.5% to 22.1%, p < 0.001), and in the proportion of patients with at least one day of sick leave (from 4.1% to 2.7%). CONCLUSIONS: The use of Utipro® Plus is able to decrease UTI recurrence and can lead to the reduction of antibiotic prescriptions and disease burden in individuals affected by uncomplicated cystitis.

Diagnostic concordance between traditional and digital workflows. A study on 1427 prostate biopsies.

Objective: To evaluate intra-observer diagnostic reproducibility using traditional slides (TS) versus whole slide images (WSI). Methods: TS and WSI of 1427 prostatic biopsies (107 consecutive patients) were evaluated by a single pathologist. Agreement between readings was evaluated with Gwet's Agreement coefficient (AC) and Landis and Koch benchmark scale. Results: The positive/negative agreement between the readings was almost perfect (AC1= 0.962; 95% CI[0.949,0.974]), with method independent distribution of discrepancies. Among positive biopsies, 212 had identical Gleason score (GS) on TS and WSI and discordant GS in 69 cases (AC2 = 0.932; 95% CI[0.907, 0.956]). Concordant negative and positive patient classification was observed in 39 and 64 cases, respectively; two cases were assigned to the positive group on TS and 2 on WSI configuring an almost perfect agreement (AC1=0.929; 95% C1[0.860, 0.998]). ISUP Grade group (ISUP GG) agreement was evaluated in the 60 concordantly positive cases: in 45 cases it was identical on TS and WSI; in 10 biopsies the discrepancy implied a modification of the assigned ISUP GG of ≤ 1 class and in 5 the discrepancy implied a modification of 2 classes. Gwet's agreement coefficient was (95% CI [0.834, 0.962]), i.e.: almost perfect agreement. Conclusions: Our data show almost perfect agreement between digital and traditional diagnostic activity in a routine setting, confirming that digital pathology can be safely introduced into routine workflows.