ABSTRACT
The process-of-male reproduction is intricate, and various medical conditions-have the potential to disrupt spermatogenesis. Moreover, infertility in males can serve as an indicator of-potential future health issue. Numerous conditions with systemic implications have been identified, encompassing genetic factors (such as Klinefelter Syndrome), obesity, psychological stress, environmental factors, and others. Consequently, infertility assessment-presents an opportunity for comprehensive health counseling, extending-beyond discussions about reproductive goals. Furthermore, male infertility has been suggested as a harbinger of future health problems, as poor semen quality and a diagnosis of-male infertility are associated with an increased risk of hypogonadism, cardiometabolic disorders, cancer, and even mortality. This review explores the existing-literature on the relationship between systemic illnesses and male fertility, impacting both clinical-outcomes and semen parameters. The majority of the literature analyzed, which compared gonadal function with genetic, chronic, infectious or tumoral diseases, confirm the association between overall male health and infertility.
Subject(s)
Infertility, Male , Male , Humans , Infertility, Male/physiopathology , Spermatogenesis/physiology , Semen Analysis/methods , Hypogonadism/physiopathology , Men's Health , AnimalsABSTRACT
BACKGROUND: There is a strong clinical need to fill the gap of identifying clinically significant prostate cancer (csPCa) in men with prostate-specific antigen (PSA) gray zone values. Promising, but not definitive results have been obtained using PSA derivatives such as prostate health index (PHI) and PHI density (PHID) and the percentage (-2)proPSA/free PSA (%p2PSA/fPSA). Thus, this study aimed to compare the diagnostic value of PHI, PHID, %proPSA/fPSA, and (-2)proPSA/freePSA density (-2pPSA/fPSAD) for csPCa in the patients with PSA within 2-10 ng/mL. METHODS: Serum samples and clinicopathological features were prospectively collected from 142 patients who underwent robot-assisted radical prostatectomy between September 2021 and December 2023. According to the inclusion criteria, the patients with total PSA within 2 and 10 ng/mL and negative or suspicious digital rectal examination were enrolled. We used two different classifications for csPCa: 1) patients with Gleason score (GS) ≥ 7(4 + 3) and 2) patients with GS ≥ 7(3 + 4). The receiver operating characteristic curves and the area under the curve (AUC) values were used to assess the diagnostic performance. RESULTS: Of the 142 men included, 116 (82%) patients were diagnosed with csPCa as GS ≥ 3 + 4 and 107 (75%) defined as csPCa as GS ≥ 7(4 + 3), respectively. We found that p2PSA/fPSA, p2PSA/fPSAD, PHI, and PHID were significantly higher in csPCa classified as GS ≥ 7(3 + 4) as well as GS ≥ 7(4 + 3), with p-values 0.027, 0.054, 0.0016, and 0.0027, respectively. AUCs of the analyzed variables were higher when used to predict csPCa as GS ≥ 6 compared to csPCa as GS ≥7(4 + 3), with an AUC equal, respectively, to 0.679 (95% CI: 0.571-0.786), 0.685 (95% CI: 0.571-0.799), 0.737 (95% CI: 0.639-0.836), and 0.736 (95% CI: 0.630-0.841) in the first subgroup and with an AUC equal, respectively, to 0.653 (95% CI: 0.552-0.754), 0.665 (95% CI: 0.560-0.770), 0.668 (95% CI: 0.568-0.769), and 0.670 (95% CI: 0.567-0.773) in the second, respectively. Both PHID and p2PSA/fPSAD allowed improvement in the diagnostic accuracy with respect to PHI and p2PSA/fPSA ratio, however the differences were not statistically significant (p = 0.409, 0.180 for csPCa as G ≥ Gleason grade (GG) 2 and 0.558 and 0.087 for csPCa as G ≥ GG3, respectively). We found that PHI, PHID, p2PSA/fPSA ratio, and p2PSA/fPSAD showed higher sensitivity, specificity, and positive predictive value when used to predict csPCa as GG ≥ 2, whereas negative predictive value of all four parameters was higher when used to predict GG ≥ 3. CONCLUSIONS: In men with a PSA level between 2 and 10 ng/mL, PHI and PHID, p2PSA/fPSA, and p2PSA/fPSAD showed good diagnostic performance for postoperative csPCa. However, PHID and p2PSA/fPSAD had a small advantage over PHI which needs to be further investigated for the reduction of unnecessary surgical interventions. This finding suggests that it could be a promising biomarker for making the treatment-decision strategy.
Subject(s)
Prostate-Specific Antigen , Prostatectomy , Prostatic Neoplasms , Humans , Male , Prostatic Neoplasms/blood , Prostatic Neoplasms/surgery , Prostatic Neoplasms/pathology , Prostatic Neoplasms/diagnosis , Prostate-Specific Antigen/blood , Middle Aged , Aged , Prospective Studies , Prostate/pathology , Prostate/surgeryABSTRACT
Renal cell carcinoma (RCC) remains a formidable diagnostic challenge, especially in the context of small renal masses. The quest for non-invasive screening tools and biomarkers has steered research towards liquid biopsy, focusing on microRNAs (miRNAs), exosomes, and circulating tumor cells (CTCs). MiRNAs, small non-coding RNAs, exhibit notable dysregulation in RCC, offering promising avenues for diagnosis and prognosis. Studies underscore their potential across various biofluids, including plasma, serum, and urine, for RCC detection and subtype characterization. Encouraging miRNA signatures show correlations with overall survival, indicative of their future relevance in RCC management. Exosomes, with their diverse molecular cargo, including miRNAs, emerge as enticing biomarkers, while CTCs, emanating from primary tumors into the bloodstream, provide valuable insights into cancer progression. Despite these advancements, clinical translation necessitates further validation and standardization, encompassing larger-scale studies and robust evidence generation. Currently lacking approved diagnostic assays for renal cancer, the potential future applications of liquid biopsy in follow-up care, treatment selection, and outcome prediction in RCC patients are profound. This review aims to discuss and highlight recent advancements in liquid biopsy for RCC, exploring their strengths and weaknesses in the comprehensive management of this disease.
Subject(s)
Carcinoma, Renal Cell , Kidney Neoplasms , MicroRNAs , Humans , Carcinoma, Renal Cell/diagnosis , Carcinoma, Renal Cell/genetics , Precision Medicine , Kidney Neoplasms/diagnosis , Kidney Neoplasms/genetics , MicroRNAs/genetics , Liquid Biopsy , BiomarkersABSTRACT
This review focuses on ablative techniques for small renal masses (SRMs), including radiofrequency ablation (RFA), cryoablation (CA), microwave ablation (MWA), and irreversible electroporation (IRE), and discusses recurrence management. Through an extensive literature review, we outline the procedures, outcomes, and follow-up strategies associated with each ablative method. The review provides a detailed examination of these techniques-RFA, CA, MWA, and IRE-elucidating their respective outcomes. Recurrence rates vary among them, with RFA and CA showing comparable rates, MWA demonstrating favorable short-term results, and IRE exhibiting promise in experimental stages. For managing recurrences, various strategies are considered, including active surveillance, re-ablation, or salvage surgery. Surveillance is preferred post-RFA and post-CA, due to slow SRM growth, while re-ablation, particularly with RFA and CA, is deemed feasible without additional complications. Salvage surgery emerges as a viable option for larger or resistant tumors. While ablative techniques offer short-term results comparable to surgery, further research is essential to understand their long-term effects fully. Decisions concerning recurrence management should consider individual and tumor-specific factors. Imaging, notably contrast-enhanced ultrasounds, plays a pivotal role in assessing treatment success, emphasizing the necessity of a multidisciplinary approach for optimal outcomes. The lack of randomized trials highlights the need for further research.
ABSTRACT
Fragile X syndrome (FXS) is a genetic disorder characterized by mutation in the FMR1 gene, leading to the absence or reduced levels of fragile X Messenger Ribonucleoprotein 1 (FMRP). This results in neurodevelopmental deficits, including autistic spectrum conditions. On the other hand, Fragile X-associated tremor/ataxia syndrome (FXTAS) is a distinct disorder caused by the premutation in the FMR1 gene. FXTAS is associated with elevated levels of FMR1 mRNA, leading to neurodegenerative manifestations such as tremors and ataxia.Mounting evidence suggests a link between both syndromes and mitochondrial dysfunction (MDF). In this minireview, we critically examine the intricate relationship between FXS, FXTAS, and MDF, focusing on potential therapeutic avenues to counteract or mitigate their adverse effects. Specifically, we explore the role of mitochondrial cofactors and antioxidants, with a particular emphasis on alpha-lipoic acid (ALA), carnitine (CARN) and Coenzyme Q10 (CoQ10). Findings from this review will contribute to a deeper understanding of these disorders and foster novel therapeutic strategies to enhance patient outcomes.