Polycystic ovary syndrome (PCOS) is a common endocrinopathy affecting women of reproductive age, characterized by oligo- or anovulation, hyperandrogenism, and polycystic ovarian morphology. Beyond its reproductive manifestations, PCOS is increasingly recognized as a complex endocrine–metabolic disorder frequently associated with impaired carbohydrate metabolism and insulin resistance, often independent of body mass. Despite extensive research, the molecular mechanisms underlying insulin resistance across metabolic and reproductive tissues in PCOS remain incompletely characterized. This scoping review aimed to systematically map molecular disturbances in insulin signaling and carbohydrate metabolism in PCOS, explore associations between tissue-specific mechanisms, and identify key gaps in the current evidence. We included peer-reviewed original studies published in English between January 2018 and May 2025, retrieved from PubMed, Embase, and Web of Science, that investigated molecular or cellular pathways related to insulin resistance or glucose metabolism in PCOS. The available evidence predominantly addressed granulosa cells and ovarian tissue, with additional data from endometrium, liver, adipose tissue, skeletal muscle, pancreatic beta-cells, and systemic regulatory pathways. Recurrent mechanisms underlying insulin resistance in PCOS included post-receptor defects in IRS/PI3K/AKT and MAPK signaling, impaired GLUT4 expression and trafficking, mitochondrial and glycolytic dysfunction, chronic low-grade inflammation, androgen receptor–mediated metabolic reprogramming, circadian rhythm disruption, and epigenetic or environmental modulators. Evidence from human studies remains limited, with many proposed molecular mechanisms being supported predominantly by rodent or cell line models. To translate this knowledge to clinical and therapeutic application, additional high-quality longitudinal human research with comprehensive multi-omics is necessary to validate key mechanisms in ovarian and metabolic tissues, especially those involving IRS/PI3K/AKT signaling, GLUT4 regulation, inflammation, and androgen-driven metabolic dysfunction.

Background: Upper tract urothelial carcinoma (UTUC) is a rare malignancy representing approximately 5–10% of all urothelial cancers. Key risk factors include smoking, chemical exposures, selected metabolic conditions, and hereditary cancer syndromes. This narrative review summarises current knowledge on UTUC molecular pathogenesis, major risk determinants, and contemporary therapeutic strategies. Methods: This study was conducted as a narrative review with a structured literature search. PubMed, Web of Science, Embase, and Scopus were searched using predefined combinations of UTUC-related terms covering molecular pathogenesis, carcinogenic risk factors, and treatment strategies. The review was prepared according to SANRA principles to improve transparency and consistency; however, no formal systematic review methodology or meta-analysis was performed. Results: Available genomic studies indicate that UTUC has a molecular profile distinct from urothelial bladder carcinoma (UBC), with recurrent alterations involving FGFR3, HRAS, KMT2D, CDKN2A, KRAS, MYC, and BRIP1. Smoking, aristolochic acid exposure, Lynch syndrome, and possibly early-onset urolithiasis contribute to carcinogenesis through distinct but incompletely understood mechanisms. Surgical treatment remains the standard of care for high-risk localised disease, whereas perioperative chemotherapy, immunotherapy, and targeted agents are expanding treatment options, particularly in advanced disease. A substantial proportion of the therapeutic evidence, however, is derived from broader urothelial carcinoma populations rather than UTUC-specific studies. Conclusions: UTUC is biologically heterogeneous and shaped by both molecular alterations and environmental exposures. Although substantial progress has been made, important gaps remain in understanding UTUC-specific carcinogenic mechanisms and in defining evidence-based personalised treatment strategies. Better integration of molecular, environmental, and clinical data is needed to improve risk stratification and treatment selection.

Background: It is estimated that approximately 20–30% of women suffer from recurrent urinary tract infections (rUTIs). The disease is primarily bacterial, especially Escherichia coli, making antibiotics the standard treatment. Increasing antibiotic resistance of uropathogens reduces treatment effectiveness. Therefore, non-antibiotic approaches are increasingly being investigated for the management of rUTIs. This narrative review provides a comprehensive overview of currently available and emerging methods of treatment and prevention of rUTIs in women. Methods: This paper employs a narrative review with a structured literature search and synthesizes data from three major databases, including PubMed, Web of Science, and Scopus. The review was conducted in accordance with the Scale for the Assessment of Narrative Review Articles (SANRA) checklist. Scientific articles were searched using the following keywords: ‘recurrent urinary tract infections in women’, ‘antibiotic prophylaxis’, ‘immunoprophylaxis’, ‘urinary microbiome’. Results: Observational evidence has reported an association between continuous antibiotic prophylaxis and severe outcomes, including pyelonephritis and septicemia; however, these findings are susceptible to confounding by indication and should not be interpreted as evidence of a causal relationship. Clinical studies suggest that immunomodulatory approaches, such as OM-89 bacterial lysate, next-generation polybacterial mucosal vaccines (e.g., MV140), and oral immunostimulants, have potential to reduce the frequency of rUTI recurrences in women, although the strength and certainty of evidence vary between interventions. Bacteriophage therapy is an emerging and exploratory targeted approach supported by early clinical and experimental evidence, but its efficacy for preventing recurrent uncomplicated UTIs remains uncertain, though rapid development of phage resistance remains a potential limitation. Prophylactic strategies, including Lactobacillus-based probiotics, low-dose estriol, and microbiota transplantation, have shown preliminary or variable results, with limited evidence for rUTI prevention. In particular, findings on vaginal dysbiosis and microbiota modulation should not be interpreted as a direct evidence of rUTI prevention. Conclusions: While antibiotic therapy remains essential, continuous prophylaxis may contribute to antimicrobial resistance and disrupt microbial balance. Therefore, novel therapeutic strategies are still being studied. Several non-antibiotic strategies, including immunoprophylaxis and microbiome modulation, represent potential preventive approaches, whereas bacteriophage therapy and vaginal microbiota transplantation remain exploratory and require further clinical validation. Their preventive efficacy against rUTIs remains unestablished. Moreover, antimicrobial peptides (AMPs), nanotechnology, molecularly targeted therapies, and precision medicine strategies are being investigated. Plant-based therapies may provide benefit, but their clinical efficacy remains to be established. Overall, further clinical studies are needed to confirm the preventive efficacy of these emerging approaches.

Cancer is a major cause of morbidity worldwide. Prostate cancer (PCa) is one of the most commonly diagnosed malignancies in men and is clinically heterogeneous, highlighting the need for additional biomarkers that may improve risk stratification. Lipoprotein(a) [Lp(a)] is a genetically determined and increasingly available biomarker, but its relationship with PCa remains uncertain. This systematic review aimed to synthesize observational, genetic, and Mendelian randomization evidence on the associations of circulating Lp(a), LPA-related genetic variants, and genetically predicted Lp(a) with prostate cancer incidence, mortality, and clinicopathological features, and to assess the potential clinical implications of the available evidence. We conducted this review in accordance with PRISMA guidelines. PubMed, Scopus, and Web of Science databases were searched from inception to May 2026. Eligible studies were original, peer-reviewed studies in English that assessed circulating Lp(a), LPA-related genetic variants, or genetically predicted Lp(a) in relation to prostate cancer incidence, mortality, or clinicopathological features. Certainty of evidence was assessed using GRADE. Due to heterogeneity in study designs, exposure assessments, endpoints, and effect measures, results were synthesized narratively; no meta-analysis was performed. The search identified 489 records. After duplicate removal, 253 records were screened, 15 full-text reports were assessed, and 12 studies were included. These comprised prospective cohort or biobank-observational studies, observational studies, one genetic cohort study, and Mendelian randomization studies. Studies of circulating Lp(a) showed inconsistent findings for prostate cancer incidence and mortality. One cohort reported a positive association in a categorical analysis, whereas other studies found no association or a non-significant inverse association. The genetic cohort study found no robust association between LPAL2–LPA variants and prostate cancer incidence after correction for multiple testing. Mendelian randomization findings were mixed. Although several analyses yielded directionally positive or statistically significant estimates, several primary analyses were null or borderline, and estimates varied across methods and datasets. Overall, the Mendelian randomization evidence was of low certainty and does not establish a causal association between genetically predicted Lp(a) and PCa risk. Evidence for clinicopathological features was limited and inconsistent. Certainty of evidence was low for Mendelian randomization studies and very low for circulating Lp(a), genetic cohort evidence, and clinicopathological outcomes. Current evidence regarding Lp(a), LPA genetic variants, and genetically predicted Lp(a) in PCa remains heterogeneous and clinically inconclusive. Although some studies reported positive associations, the overall evidence linking Lp(a) to prostate cancer is inconsistent and of low certainty, and does not currently support a clear association.

Introduction: Clinical staging based on digital rectal examination is imprecise, leading to pathological upstaging in patients with prostate cancer (PCa). Accurate preoperative assessment remains a challenge despite the use of multiparametric magnetic resonance imaging (mpMRI) and fusion-guided biopsy. This study aims to identify key predictors of upstaging in preoperative patients. Materials and Methods: A retrospective analysis of 924 patients who underwent radical prostatectomy between July 2012 and January 2025 was performed. Variables included prostate-specific antigen, prostate volume, biopsy type, MRI, body mass index and age. Upstaging was defined as ≥pT3 in patients staged clinically as cT1–2. Optimal cut-offs for continuous variables were defined statistically. Multivariable logistic regression was applied to identify independent predictors of upstaging and minor staging upgrading (MSU)—defined as any upward shift in the pathological T stage relative to the clinical T stage. Model performance was evaluated using the area under the Receiver Operating Characteristic (ROC) curve (AUC). Results: Upstaging occurred in 31.9% and MSU in 50.6% of patients. The mean age was 65 years. Cut-off values for PSA density (PSAD) were 0.29 for upstaging and 0.28 for MSU. In the full-cohort model (AUC = 0.628), PSAD (odds ratio (OR) = 2.55), age (OR = 1.04), and hypertension (HT) (OR = 1.47) were associated with upstaging. In PIRADS-based models, PIRADS 5 and PSAD predicted both upstaging (OR = 1.62 and 6.10, respectively; AUC = 0.664) and MSU (OR = 1.75 and 4.67, respectively; AUC = 0.659). MSU was also associated with HT and a lack of fusion biopsy (AUC = 0.622). Conclusions: PSAD and PIRADS 5 lesions are strong determinants of pathological upstaging and MSU in PCa. These factors should be considered in preoperative risk stratification to improve staging accuracy. Despite advances in imaging and biopsy techniques, upstaging remains a common phenomenon, underlining the need for further refinement of diagnostic protocols.

Robot-assisted radical prostatectomy (RARP) requires a balance between complete cancer excision and preservation of urinary continence and erectile function. Because the preservation of neurovascular bundles adjacent to the prostate surface contributes to postoperative functional recovery, intraoperative margin assessment and surgeon-guidance technologies may help refine resection and support individualized nerve-sparing decision-making. Neurovascular structure-adjacent frozen-section examination remains the most studied and clinically established method, with evidence supporting reduced positive surgical margins and broader nerve preservation, but its use is limited by cost, workflow complexity, and pathology infrastructure. Fluorescence confocal microscopy is promising but remains limited by short and apical margins; its improved accuracy for longer margins raises concerns about its reliability for routine intraoperative margin assessment. Other optical, spectroscopic, and prostate-specific membrane antigen-targeted molecular margin assessment techniques have demonstrated inconsistent diagnostic performance, with particularly low sensitivity for assessment approaches remain investigational, whereas intraoperative ultrasound, three-dimensional and augmented-reality models, fluorescence guidance, and image-enhancement systems should be viewed as surgical guidance tools rather than direct margin-assessment methods. Intraoperative technologies may improve surgical decision-making during RARP, but prospective multicenter studies with standardized oncological and functional endpoints are needed before broader adoption.