Unlocking Precision Medicine: Liquid Biopsy Advancements in Renal Cancer Detection and Monitoring.

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.

Which inflammatory marker, between systemic immune-inflammation index and neutrophil to eosinophil ratio, is associated with Peyronie's disease and are there any implications for a better understanding of its mechanisms?

BACKGROUND: Peyronie's disease affects up to 9% of men and is often accompanied by pain and/or erectile dysfunction. It is characterized by an inflammatory process that is the grassroots of the subsequent fibrosis stage. There is an unmet need to evaluate its onset and progression. Among the newly proposed biomarkers of inflammation, authors developed a novel systemic immune-inflammation index (SII) based on lymphocyte, neutrophil, and platelet counts. Similarly, a recent study reported that a neutrophil-to-eosinophil ratio (NER) represents systemic inflammation. RESULTS: A 49-patient group with Peyronie's disease as confronted with 50 well-matched for age and BMI controls. As laboratory evaluation of inflammation, SII, NER and the eosinophil to neutrophil ratio (ENR) were studied. As a likely risk factor for the presence of Peyronie's disease, a higher prevalence of hypercholesterolemia, hyperglycemia and hypertension was discovered in the patients compared to controls. A significant difference was found in the median values of the NER between the two selected groups, i.e., 32.5 versus 17.3 (p = 0.0021). As expected, also ENR was significantly different. The receiver operating characteristic curves for SII, ENR and NER were 0.55, 0.32 and 0.67, respectively, highlighting the best performance of NER. The cut-off for NER was 12.1, according to the Youden test. CONCLUSIONS: According to our results, any evaluation of circulating eosinophil, evaluated as NER, beyond being a signature of immuno-inflammatory response, help assess tissue homeostasis, since eosinophils are now considered multifunctional leukocytes and give a picture of the inflammatory process and repair process belonging to Peyronie's disease.

RéSUMé: CONTEXTE: La maladie de La Peyronie touche jusqu'à 9% des hommes et s'accompagne souvent de douleurs et/ou de dysfonction érectile. Elle se caractérise par un processus inflammatoire qui est. à la base de l'étape de fibrose ultérieure. Il existe un besoin non satisfait d'en évaluer son apparition et sa progression. Parmi les biomarqueurs de l'inflammation nouvellement proposés, les auteurs ont développé un nouvel indice d'inflammation immunitaire systémique (SII) basé sur le nombre de lymphocytes, de neutrophiles et de plaquettes. De même, une étude récente a rapporté qu'un rapport neutrophiles/éosinophiles (NER) représente une inflammation systémique. RéSULTATS: Un groupe de 49 patients atteints de la maladie de La Peyronie a été confronté à 50 témoins étroitement appariés sur l'âge et l'IMC. Dans le cadre de l'évaluation de l'inflammation au laboratoire, le SII, le NER et le rapport éosinophiles/neutrophiles (ENR) ont été étudiés. En tant que facteur de risque probable de la présence de la maladie de La Peyronie, une prévalence plus élevée d'hypercholestérolémie, d'hyperglycémie et d'hypertension a été découverte chez les patients par rapport aux témoins. Une différence significative a été constatée pour les valeurs médianes du NER entre les deux groupes sélectionnés, c'est-à-dire 32,5 contre 17,3 (p = 0,0021). Comme on pouvait s'y attendre, le ERN était également significativement différent. Les courbes caractéristiques de fonctionnement du récepteur pour le SII, l'ENR et le NER étaient respectivement de 0,55, 0,32 et 0,67, ce qui met en évidence les meilleures performances du NER. Le seuil pour le NER était de 12,1 (test de Youden). CONCLUSIONS: D'après nos résultats, toute évaluation de l'éosinophilie circulante, sous la forme NER, au-delà d'être une signature de la réponse immuno-inflammatoire, permet d'évaluer l'homéostasie tissulaire, puisque les éosinophiles sont maintenant considérés comme étant des leucocytes multifonctionnels, et donne une image du processus inflammatoire et du processus de réparation appartenant à la maladie de La Peyronie. MOTS-CLéS: Maladie de La Peyronie Rapport Neutrophiles/Eosinophiles Rapport Eosinophiles/Neutrophiles Indice d'Inflammation immunitaire systémique Réponse Immuno-inflammatoire.

Novel Key Ingredients in Urinary Tract Health-The Role of D-mannose, Chondroitin Sulphate, Hyaluronic Acid, and N-acetylcysteine in Urinary Tract Infections (Uroial PLUS®).

Urinary tract infections represent a common and significant health concern worldwide. The high rate of recurrence and the increasing antibiotic resistance of uropathogens are further worsening the current scenario. Nevertheless, novel key ingredients such as D-mannose, chondroitin sulphate, hyaluronic acid, and N-acetylcysteine could represent an important alternative or adjuvant to the prevention and treatment strategies of urinary tract infections. Several studies have indeed evaluated the efficacy and the potential use of these compounds in urinary tract health. In this review, we aimed to summarize the characteristics, the role, and the application of the previously reported compounds, alone and in combination, in urinary tract health, focusing on their potential role in urinary tract infections.

Comparing cardiovascular adverse events in cancer patients: A meta-analysis of combination therapy with angiogenesis inhibitors and immune checkpoint inhibitors versus angiogenesis inhibitors alone.

Anti-VEGF (vascular endothelial growth factor) agents were associated with increased risk of several cardiovascular events, while one meta-analysis did not show any significantly increased risk of cardiotoxicity associated with the use of immune checkpoint inhibitors (ICIs). This meta-analysis of randomized-controlled trials (RCTs) was designed to compare cardiovascular toxicity of anti-VEGF agents plus ICI vs anti-VEGF agents without ICIs. A systematic search of the literature was conducted to include all full papers reporting about phase II and III randomized controlled trials (RCTs) conducted in patients with solid malignancies randomized to an anti-VEGF agent plus an ICI vs. an anti-VEGF agent without an ICI. Overall incidences of cardiovascular events were compared between these two treatment groups estimating the corresponding odds ratios. This analysis suggests that ICIs may increase the risk of cardiovascular toxicities associated with anti-VEGF therapies. Further research, including real world studies, is warranted.

The Efficacy of Flogofilm® in the Treatment of Chronic Bacterial Prostatitis as an Adjuvant to Antibiotic Therapy: A Randomized Prospective Trial.

INTRODUCTION: Bacterial prostatitis (BP) is a common prostatic infection characterized by a bimodal distribution in young and older men, with a prevalence between 5-10% among all cases of prostatitis and a high impact on quality of life. Although the management of bacterial prostatitis involves the use of appropriate spectrum antibiotics, which represent the first choice of treatment, a multimodal approach encompassing antibiotics and nutraceutical products in order to improve the efficacy of chosen antimicrobial regimen is often required. OBJECTIVE: To evaluate the efficacy of Flogofilm® in association with fluoroquinolones in patients with chronic bacterial prostatitis (CBP). METHODS: Patients diagnosed with prostatitis (positivity to Meares-Stamey Test and symptoms duration > 3 months) at the University of Naples "Federico II", Italy, from July 2021 to December 2021, were included in this study. All patients underwent bacterial cultures and trans-rectal ultrasounds. Patients were randomized into two groups (A and B) receiving antibiotic alone or an association of antibiotics plus Flogofilm® tablets containing Flogomicina® for one month, respectively. The NIH-CPSI and IPSS questionnaires were administered at baseline, four weeks, twelve and twenty-four weeks. RESULTS: A total of 96 (Group A = 47, Group B = 49) patients concluded the study protocol. The mean age was comparable, with a mean age of 34.62 ± 9.04 years for Group A and 35.29 ± 10.32 years for Group B (p = 0.755), and IPSS at the baseline was 8.28 ± 6.33 and 9.88 ± 6.89 (p = 0.256), respectively, while NIH-CPSI at baseline was 21.70 ± 4.38 and 21.67 ± 6.06 (p = 0.959), respectively. At 1, 3 and 6 months, the IPSS score was 6.45 ± 4.8 versus 4.31 ± 4.35 (p = 0.020), 5.32 ± 4.63 versus 3.20 ± 3.05 (p = 0.042) and 4.91 ± 4.47 versus 2.63 ± 3.28 (p = 0.005) for Groups A and B, respectively. Similarly, the NIH-CPSI total score at 1, 3 and 6 months was 16.15 ± 3.31 versus 13.10 ± 5.03 (p < 0.0001), 13.47 ± 3.07 versus 9.65 ± 4.23 (p < 0.0001) and 9.83 ± 2.53 versus 5.51 ± 2.84 (p < 0.0001), respectively. CONCLUSIONS: Flogofilm®, associated with fluoroquinolones, demonstrate a significant improvement in pain, urinary symptoms and quality of life in patients affected by chronic bacterial prostatitis in both IPSS and NIH-CPSI scores compared with fluoroquinolones alone.

A Novel Low-Cost Uroflowmetry for Patient Telemonitoring.

Uroflowmetry (UF) is a crucial guideline-recommended tool for men with benign prostatic obstruction (BPO). Moreover, UF is a helpful decision-making tool for the management of patients with lower urinary tract symptoms (LUTS) and benign prostatic hyperplasia (BPH). In the last few years, telemedicine and telehealth have increased exponentially as cost-effective treatment options for both patients and physicians. Telemedicine and telehealth have been well positioned during the COVID-19 pandemic to prevent healthcare system overload and to ensure adequate management of patients through screening, diagnosis, and follow-up at home. In the present manuscript, the main characteristics and performance of a novel and low-cost device for home-based UF have been analyzed. The simple weight-transducer method has been applied to perform UF. An inexpensive load cell connected to a 24 bit analogic digital converter (ADC) sends data to a cloud server via SIM card or home Wi-Fi. Data are processed and shown in graphics with both volume and flow rate as a function of time, allowing for measurement of average flow rate, maximum flow rate, voided volume, and voiding time. A numerical algorithm allows for filtering of the dynamic effect due to the urine gravity acceleration and for removing the funnel to simplify the home measurement procedure. Through an online platform, the physician can see and compare each UF data. The device's reliability has been validated in a first laboratory setting and showed excellent performance. This approach based on domiciliary tests and an online platform can revolutionize the urologic clinic landscape by offering a constant patient cost-effective follow-up, eliminating the time wasted waiting in the office setting.

The Impact of Meat Intake on Bladder Cancer Incidence: Is It Really a Relevant Risk?

Bladder cancer (BC) represents the second most common genitourinary malignancy. The major risk factors for BC include age, gender, smoking, occupational exposure, and infections. The BC etiology and pathogenesis have not been fully defined yet. Since catabolites are excreted through the urinary tract, the diet may play a pivotal role in bladder carcinogenesis. Meat, conventionally classified as "red", "white" or "processed", represents a significant risk factor for chronic diseases like cardiovascular disease, obesity, type 2 diabetes, and cancer. In particular, red and processed meat consumption seems to increase the risk of BC onset. The most accepted mechanism proposed for explaining the correlation between meat intake and BC involves the generation of carcinogens, such as heterocyclic amines and polycyclic aromatic hydrocarbons by high-temperature cooking. This evidence claims the consumption limitation of meat. We reviewed the current literature on potential biological mechanisms underlying the impact of meat (red, white, and processed) intake on the increased risk of BC development and progression. Toward this purpose, we performed an online search on PubMed using the term "bladder cancer" in combination with "meat", "red meat", "white meat" or "processed meat". Although some studies did not report any association between BC and meat intake, several reports highlighted a positive correlation between red or processed meat intake, especially salami, pastrami, corned beef and bacon, and BC risk. We speculate that a reduction or rather a weighting of the consumption of red and processed meat can reduce the risk of developing BC. Obviously, this remark claims future indications regarding food education (type of meat to be preferred, quantity of red meat to be eaten and how to cook it) to reduce the risk of developing BC. Further well-designed prospective studies are needed to corroborate these findings.

Preoperative monocyte-to-lymphocyte ratio as a potential predictor of bladder cancer.

OBJECTIVES: The aim of this study was to investigate the role of preoperative Monocyte-to-Lymphocyte ratio (MLR) as a potential predictor of bladder cancer (BC). METHODS: Clinical data of patients who underwent TURBT at our institution between 2017 and 2021 were collected and retrospectively analysed. MLR was obtained from preoperative blood analyses performed within 1 month from hospital admission. The association of MLR with different clinic-pathological features obtained from histological reports was further analysed. Statistical analysis was performed using the Kruskal Wallis test for non-parametric variables, assuming p<0.05 as statistically significant. RESULTS: 510 patients were included in the study (81% males, 19% females), with a mean age of 71.66 ± 11.64 years. Mean MLR was higher in patients with any-type bladder cancer, reporting an MLR of 0.41 ± 0.11 compared to 0.38 ± 0.43 in patients without bladder cancer (p=0.043). In the subsequent comparison among low-grade and high-grade bladder cancer, MLR did not report statistically significant differences, with 0.29 ± 0.12 for low-grade BC and 0.51 ± 0.81 for high-grade BC (p=0.085). CONCLUSIONS: Our findings reported elevated preoperative MLR should be considered a potential biomarker predicting malignancy for bladder tumours. Furthermore, research are necessary to assess its role in discerning low-grade from high-grade patients.

Liquid Biopsy in Prostate Cancer Management-Current Challenges and Future Perspectives.

Although appreciable attempts in screening and diagnostic approaches have been achieved, prostate cancer (PCa) remains a widespread malignancy, representing the second leading cause of cancer-related death in men. Drugs currently used in PCa therapy initially show a potent anti-tumor effect, but frequently induce resistance and PCa progresses toward metastatic castration-resistant forms (mCRPC), virtually incurable. Liquid biopsy has emerged as an attractive and promising strategy complementary to invasive tissue biopsy to guide PCa diagnosis and treatment. Liquid biopsy shows the ability to represent the tumor microenvironment, allow comprehensive information and follow-up the progression of the tumor, enabling the development of different treatment strategies as well as permitting the monitoring of therapy response. Liquid biopsy, indeed, is endowed with a significant potential to modify PCa management. Several blood biomarkers could be analyzed for diagnostic, prognostic and predictive purposes, including circulating tumor cells (CTCs), extracellular vesicles (EVs), circulating tumor DNA (ctDNA) and RNA (ctRNA). In addition, several other body fluids may be adopted (i.e., urine, sperm, etc.) beyond blood. This review dissects recent advancements and future perspectives of liquid biopsies, highlighting their strength and weaknesses in PCa management.

Immune Checkpoint Inhibitors as a Neoadjuvant/Adjuvant Treatment of Muscle-Invasive Bladder Cancer: A Systematic Review.

Bladder cancer is the ninth most common cancer worldwide. Over 75% of non-muscle invasive cancer patients require conservative local treatment, while the remaining 25% of patients undergo radical cystectomy or radiotherapy. Immune checkpoint inhibitors represent a novel class of immunotherapy drugs that restore natural antitumoral immune activity via the blockage of inhibitory receptors and ligands expressed on antigen-presenting cells, T lymphocytes and tumour cells. The use of immune checkpoint inhibitors in bladder cancer has been expanded from the neoadjuvant setting, i.e., after radical cystectomy, to the adjuvant setting, i.e., before the operative time or chemotherapy, in order to improve the overall survival and to reduce the morbidity and mortality of both the disease and its treatment. However, some patients do not respond to checkpoint inhibitors. As result, the capability for identifying patients that are eligible for this immunotherapy represent one of the efforts of ongoing studies. The aim of this systematic review is to summarize the most recent evidence regarding the use of immune checkpoint inhibitors, in a neoadjuvant and adjuvant setting, in the treatment of muscle-invasive bladder cancer.

N-palmitoyl-D-glucosamine, a Natural Monosaccharide-Based Glycolipid, Inhibits TLR4 and Prevents LPS-Induced Inflammation and Neuropathic Pain in Mice.

Toll-like receptors (TLRs) are key receptors through which infectious and non-infectious challenges act with consequent activation of the inflammatory cascade that plays a critical function in various acute and chronic diseases, behaving as amplification and chronicization factors of the inflammatory response. Previous studies have shown that synthetic analogues of lipid A based on glucosamine with few chains of unsaturated and saturated fatty acids, bind MD-2 and inhibit TLR4 receptors. These synthetic compounds showed antagonistic activity against TLR4 activation in vitro by LPS, but little or no activity in vivo. This study aimed to show the potential use of N-palmitoyl-D-glucosamine (PGA), a bacterial molecule with structural similarity to the lipid A component of LPS, which could be useful for preventing LPS-induced tissue damage or even peripheral neuropathies. Molecular docking and molecular dynamics simulations showed that PGA stably binds MD-2 with a MD-2/(PGA)3 stoichiometry. Treatment with PGA resulted in the following effects: (i) it prevented the NF-kB activation in LPS stimulated RAW264.7 cells; (ii) it decreased LPS-induced keratitis and corneal pro-inflammatory cytokines, whilst increasing anti-inflammatory cytokines; (iii) it normalized LPS-induced miR-20a-5p and miR-106a-5p upregulation and increased miR-27a-3p levels in the inflamed corneas; (iv) it decreased allodynia in peripheral neuropathy induced by oxaliplatin or formalin, but not following spared nerve injury of the sciatic nerve (SNI); (v) it prevented the formalin- or oxaliplatin-induced myelino-axonal degeneration of sciatic nerve. SIGNIFICANCE STATEMENT We report that PGA acts as a TLR4 antagonist and this may be the basis of its potent anti-inflammatory activity. Being unique because of its potency and stability, as compared to other similar congeners, PGA can represent a tool for the optimization of new TLR4 modulating drugs directed against the cytokine storm and the chronization of inflammation.