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Urinary tract infections (UTIs) are the second most frequent type of infection observed in clinical practice. Gram-negative Enterobacteriaceae are common pathogens in UTIs. Excessive antibiotic use in humans and animals, poor infection control, and increased global travel have accelerated the spread of multidrug-resistant strains (MDR). Carbapenem antibiotics are commonly considered the last line of defense against MDR Gram-negative bacteria; however, their efficacy is now threatened by the increasing prevalence of carbapenem-resistant Enterobacteriaceae (CRE). This comprehensive review aims to explore the biological mechanisms underlying carbapenem resistance and to present a focus on therapeutic alternatives currently available for complicated UTIs (cUTIs). A comprehensive bibliographic search was conducted on the PubMed/MEDLINE, Scopus, and Web of Science databases in December 2023. The best evidence on the topic was selected, described, and discussed. Analyzed with particular interest were the clinical trials pivotal to the introduction of new pharmacological treatments in the management of complicated cUTIs. Additional suitable articles were collected by manually cross-referencing the bibliography of previously selected papers. This overview provides a current and comprehensive examination of the treatment options available for CRE infections, offering a valuable resource for understanding this constantly evolving public health challenge.

Background and Objectives : Despite advancements in the diagnosis and treatment of testicular germ cell tumours (TGTCs), challenges persist in identifying reliable biomarkers for early detection and precise disease management. This narrative review addresses the role of microRNAs (miRNAs) as potential diagnostic tools and therapeutic targets in the treatment of TGCTs. Materials and Methods : Three databases (PubMed ® , Web of Science™, and Scopus ® ) were queried for studies investigating the utility of miRNA as diagnostic tools, assessing their prognostic significance, and evaluating their potential to guide TGCT treatment. Different combinations of the following keywords were used, according to a free-text protocol: "miRNA", "non-coding RNA", "small RNA", "Testicular Cancer", "seminomatous testicular germ cell", "non-seminomatous testicular germ cell". Results : The potential of miRNAs as possible biomarkers for a non-invasive diagnosis of TGCT is appealing. Their integration into the diagnostic pathway for TGCT patients holds the potential to enhance the discriminative power of conventional serum tumour markers (STMs) and could expedite early diagnosis, given that miRNA overexpression was observed in 50% of GCNIS cases. Among miRNAs, miR-371a-3p stands out with the most promising evidence, suggesting its relevance in the primary diagnosis of TGCT, particularly when conventional STMs offer limited value. Indeed, it demonstrated high specificity (90-99%) and sensitivity (84-89%), with good positive predictive value (97.2%) and negative predictive value (82.7%). Furthermore, a direct relationship between miRNA concentration, disease burden, and treatment response exists, regardless of disease stages. The initial evidence of miRNA decrease in response to surgical treatment and systemic chemotherapy has been further supported by more recent results suggesting the potential utility of this tool not only in evaluating treatment response but also in monitoring residual disease and predicting disease relapse. Conclusions : MiRNAs could represent a reliable tool for accurate diagnosis and disease monitoring in the treatment of TGCT, providing more precise tools for early detection and treatment stratification. Nevertheless, well-designed clinical trials and comprehensive long-term data are needed to ensure their translation into effective clinical tools.

In the past decades, several treatments have been proposed for the management of metastatic renal cell carcinoma (mRCC). Among these, cytoreductive nephrectomy (CN) represents a controversial and open issue in the era of targeted therapy and novel immunotherapy with immune checkpoint inhibitors. Two important studies, CARMENA and SURTIME, analyzed therapy with sunitinib with or without CN, and immediate CN followed by sunitinib versus a deferred CN after three cycles of sunitinib, respectively. CARMENA showed the non-inferiority of sunitinib alone versus sunitinib plus CN, whereas SURTIME showed no difference in progression-free survival (PFS), but a better median OS among patients with deferred CN. Therefore, more prospective clinical trials and appropriate patient identification are necessary to support CN in this new scenario. This review provides a snapshot of the current evidence for CN in mRCC, discusses the management strategies, and offers perspectives on the direction of future research.

Background and Objectives : Multiparametric magnetic resonance imaging (mpMRI) of the prostate and prostate-specific membrane antigen positron emission tomography (PSMA PET) are some examples of how the advancement of imaging techniques have revolutionized the diagnosis, staging, and consequently management of patients with prostate cancer (PCa). Although with less striking results, novel radiological modalities have also been proposed for bladder cancer (BCa) in recent years. Micro-ultrasound (MUS) is an imaging examination characterized by high real-time spatial resolution, recently introduced in the urological field. This article aimed to describe the current evidence regarding the application of MUS for the diagnosis and staging of PCa and BCa. Materials and Methods : We designed a narrative review. A comprehensive search in the MEDLINE, Scopus, and Cochrane Library databases was performed. Articles in English-language and published until July 2022 were deemed eligible. Retrospective and prospective primary clinical studies, as well as meta-analyses, were included. Results : MUS-guided prostate biopsy showed high sensitivity (0.91, 95% CI, 0.79-0.97) in the diagnosis of clinically significant PCa (csPCa). It was associated with a higher detection rate of csPCa than a systematic biopsy (1.18, 95% CI 0.83-1.68). No significant difference was found between MUS and mpMRI-guided biopsy in the total detection of PCa ( p = 0.89) and in the detection of Grade Groups ≥ 2 ( p = 0.92). The use of MUS to distinguish between non-muscle-invasive and muscle-invasive BCa was described, highlighting an up-staging with MUS only in a minority of cases (28.6%). Conclusions : Promising findings have emerged regarding the feasibility and accuracy of MUS in the diagnosis and staging of PCa and BCa. However, the available evidence is limited and should be considered preliminary.

Background and objective: Fibrinogen and albumin are two proteins widely used, singularly and in combination, in cancer patients as biomarkers of nutritional status, inflammation and disease prognosis. The aim of our study was to investigate the preoperative fibrinogen-to-albumin ratio (FAR) as a preoperative predictor of malignancy as well as advanced grade in patients with bladder cancer. Materials and Methods: A retrospective analysis of patients who underwent TURBT at our institution between 2017 and 2021 was conducted. FAR was obtained from preoperative venous blood samples performed within 30 days from scheduled surgery and was analyzed in relation to histopathological reports, as was the presence of malignancy. Statistical analysis was performed using a Kruskal−Wallis Test, and univariate and multivariate logistic regression analysis, assuming p < 0.05 to be statistically significant. Results: A total of 510 patients were included in the study (81% male, 19% female), with a mean age of 71.66 ± 11.64 years. The mean FAR was significantly higher in patients with low-grade and high-grade bladder cancer, with values of 80.71 ± 23.15 and 84.93 ± 29.96, respectively, compared to patients without cancer (75.50 ± 24.81) (p = 0.006). Univariate regression analysis reported FAR to be irrelevant when considered as a continuous variable (OR = 1.013, 95% CI = 1.004−1.022; p = 0.004), while when considered as a categorical variable, utilizing a cut-off set at 76, OR was 2.062 (95% CI = 1.378−3.084; p < 0.0001). Nevertheless, the data were not confirmed in the multivariate analysis. Conclusions: Elevated preoperative FAR is a potential predictor of malignancy as well as advanced grade in patients with bladder cancer. Further data are required to suggest a promising role of the fibrinogen-to-albumin ratio as a diagnostic biomarker for bladder tumors.

Intravesical chemotherapy may cause chemical cystitis and related lower urinary tract symptoms (LUTS). The aims of this study were to evaluate the efficacy and safety of an oral preparation of hyaluronic acid (HA), chondroitin sulfate (CS), curcumin, and quercetin (Ialuril® Soft Gels) to reduce the severity of LUTS in patients with a history of bladder cancer (BCa) undergoing intravesical chemotherapy. We designed a monocentric, randomized, double-blind, placebo-controlled pilot trial. Patients referred to our institute between November 2016 and March 2018 were enrolled. All subjects had non-muscle-invasive BCa and received intravesical chemotherapy with mitomycin C (MMC). Patients were randomized 1:1 in two groups (intervention vs. control). All subjects underwent oral administration (Ialuril® Soft Gels or placebo) starting one week before the first weekly instillation and ending 30 days after the last one, subsequently starting one week before each monthly instillation and ending 14 days after it. International prostate symptom score (IPSS) and 0-100 visual analogue scale (VAS) were used to assess the efficacy of the treatment. Adverse events were also described. Patients were evaluated at baseline and after 1, 4, 7, and 13 months of intravesical chemotherapy. A total of 34 patients were enrolled. The median IPSS score was significantly lower in the intervention group compared to the control group at 4 (13 vs. 17 points; p = 0.038), 7 (10 vs. 18 points; p < 0.001), and 13 (10 vs. 17 points; p = 0.002) months. The median VAS score was significantly lower in the intervention group compared to the control group at 7 (22 vs. 37 points; p = 0.021) and 13 (20 vs. 35 points; p = 0.024) months. No AE specifically related to supplement or placebo was recorded. Oral formulation of HA, CS, quercetin, and curcumin could be an effective and safe supportive therapy against chemical cystitis in patients receiving intravesical chemotherapy for BCa.

The aim of our study was to compare compressed sensing (CS) time-of-flight (TOF) magnetic resonance angiography (MRA) with parallel imaging (PI) TOF MRA in the evaluation of patients with intracranial aneurysms treated with coil embolization or stent-assisted coiling. We enrolled 22 patients who underwent follow-up imaging after intracranial aneurysm coil embolization. All patients underwent both PI TOF and CS TOF MRA during the same examination. Image evaluation aimed to compare the performance of CS to PI TOF MRA in determining the degree of aneurysm occlusion, as well as the depiction of parent vessel and vessels adjacent to the aneurysm dome. The reference standard for the evaluation of aneurysm occlusion was PI TOF MRA. The inter-modality agreement between CS and PI TOF MRA in the evaluation of aneurysm occlusion was almost perfect (κ  =  0.98, p  <  0.001) and the overall inter-rater agreement was substantial (κ  =  0.70, p  <  0.001). The visualization of aneurysm parent vessel in CS TOF images compared with PI TOF images was evaluated to be better in 11.4%, equal in 86.4%, and worse in 2.3%. CS TOF MRA, with almost 70% scan time reduction with respect to PI TOF MRA, yields comparable results for assessing the occlusion status of coiled intracranial aneurysms. Short scan times increase patient comfort, reduce the risk of motion artifacts, and increase patient throughput, with a resulting reduction in costs. CS TOF MRA may therefore be a potential replacement for PI TOF MRA as a first-line follow-up examination in patients with intracranial aneurysms treated with coil embolization.

Bartter (BS) and Gitelman (GS) syndrome are autosomal recessive inherited tubulopathies, whose clinical diagnosis can be challenging, due to rarity and phenotypic overlap. Genotype-phenotype correlations have important implications in defining kidney and global outcomes. The aim of our study was to assess the diagnostic rate of whole-exome sequencing (WES) coupled with a bioinformatic analysis of copy number variations in a population of 63 patients with BS and GS from a single institution, and to explore genotype-phenotype correlations. We obtained a diagnostic yield of 86% (54/63 patients), allowing disease reclassification in about 14% of patients. Although some clinical and laboratory features were more commonly reported in patients with BS or GS, a significant overlap does exist, and age at onset, preterm birth, gestational age and nephro-calcinosis are frequently misleading. Finally, chronic kidney disease (CKD) occurs in about 30% of patients with BS or GS, suggesting that the long-term prognosis can be unfavorable. In our cohort the features associated with CKD were lower gestational age at birth and a molecular diagnosis of BS, especially BS type 1. The results of our study demonstrate that WES is useful in dealing with the phenotypic heterogeneity of these disorders, improving differential diagnosis and genotype-phenotype correlation.

The management of patients with oligometastatic urothelial carcinoma (UC) represents an evolving field in uro-oncology, and the role of metastasis-directed therapies, including metastasectomy and metastasis-directed radiation therapy (MDRT), is gaining increasing attention. Herein, we summarize available evidence about the role of MDRT with consolidative intent in oligometastatic UC patients. A systematic review was performed in December 2021. Six studies involving 158 patients were identified. Most patients ( n = 120, 90.2%) had a history of bladder cancer and the most frequent sites of metastases were lymph nodes ( n = 61, 52.1%) followed by the lungs ( n = 34, 29%). Overall, 144 metastases were treated with MDRT. Median follow-up ranged from 17.2 to 25 months. Local control rates ranged from 57% to 100%. Median Overall Survival (OS) ranged from 14.9 to 51.0 months and median progression-free survival ranged from 2.9 to 10.1 months. Rates of OS at one and two years ranged from 78.9% to 96% and from 26% to 63%, respectively. Treatment-related toxicity was recorded in few patients and in most cases a low-grade toxicity was evident. MDRT with consolidative intent represents a potential treatment option for selected patients with oligometastatic UC.

Testosterone is the most important hormone in male health. Aging is characterized by testosterone deficiency due to decreasing testosterone levels associated with low testicular production, genetic factors, adiposity, and illness. Low testosterone levels in men are associated with sexual dysfunction (low sexual desire, erectile dysfunction), reduced skeletal muscle mass and strength, decreased bone mineral density, increased cardiovascular risk and alterations of the glycometabolic profile. Testosterone replacement therapy (TRT) shows several therapeutic effects while maintaining a good safety profile in hypogonadal men. TRT restores normal levels of serum testosterone in men, increasing libido and energy level and producing beneficial effects on bone density, strength and muscle as well as yielding cardioprotective effects. Nevertheless, TRT could be contraindicated in men with untreated prostate cancer, although poor findings are reported in the literature. In addition, different potential side effects, such as polycythemia, cardiac events and obstructive sleep apnea, should be monitored. The aim of our review is to provide an updated background regarding the pros and cons of TRT, evaluating its role and its clinical applicability in different domains.

Steroid-resistant nephrotic syndrome (SRNS) is a clinical picture defined by the lack of response to standard steroid treatment, frequently progressing toward end-stage kidney disease. The genetic basis of SRNS has been thoroughly explored since the end of the 1990s and especially with the advent of next-generation sequencing. Genetic forms represent about 30% of cases of SRNS. However, recent evidence supports the hypothesis that "phenocopies" could account for a non-negligible fraction of SRNS patients who are currently classified as non-genetic, paving the way for a more comprehensive understanding of the genetic background of the disease. The identification of phenocopies is mandatory in order to provide patients with appropriate clinical management and to inform therapy. Extended genetic testing including phenocopy genes, coupled with reverse phenotyping, is recommended for all young patients with SRNS to avoid unnecessary and potentially harmful diagnostic procedures and treatment, and for the reclassification of the disease. The aim of this work is to review the main steps of the evolution of genetic testing in SRNS, demonstrating how a paradigm shifting from "forward" to "reverse" genetics could significantly improve the identification of the molecular mechanisms of the disease, as well as the overall clinical management of affected patients.

Noninvasive tools for diagnosis or prediction of acute kidney allograft rejection have been extensively investigated in recent years. Biochemical and molecular analyses of blood and urine provide a liquid biopsy that could offer new possibilities for rejection prevention, monitoring, and therefore, treatment. Nevertheless, these tools are not yet available for routine use in clinical practice. In this systematic review, MEDLINE was searched for articles assessing urinary biomarkers for diagnosis or prediction of kidney allograft acute rejection published in the last five years (from January 1, 2015 to May 31, 2020). This review follows the Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA) guidelines. Articles providing targeted or unbiased urine sample analysis for the diagnosis or prediction of both acute cellular and antibody-mediated kidney allograft rejection were included, analyzed, and graded for methodological quality with a particular focus on study design and diagnostic test accuracy measures. Urinary C-X-C motif chemokine ligands were the most promising and frequently studied biomarkers. The combination of precise diagnostic reference in training sets with accurate validation in real-life cohorts provided the most relevant results and exciting groundwork for future studies.

Increasing evidence has demonstrated the bidirectional link between acute kidney injury (AKI) and chronic kidney disease (CKD) such that, in the clinical setting, the new concept of a unified syndrome has been proposed. The pathophysiological reasons, along with the cellular and molecular mechanisms, behind the ability of a single, acute, apparently self-limiting event to drive chronic kidney disease progression are yet to be explained. This acute injury could promote progression to chronic disease through different pathways involving the endothelium, the inflammatory response and the development of fibrosis. The interplay among endothelial cells, macrophages and other immune cells, pericytes and fibroblasts often converge in the tubular epithelial cells that play a central role. Recent evidence has strengthened this concept by demonstrating that injured tubules respond to acute tubular necrosis through two main mechanisms: The polyploidization of tubular cells and the proliferation of a small population of self-renewing renal progenitors. This alternative pathophysiological interpretation could better characterize functional recovery after AKI.