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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.

To test for rates of inpatient palliative care (IPC) in metastatic testicular cancer patients receiving critical care therapy (CCT). Within the Nationwide Inpatient Sample (NIS) database (2008–2019), we tabulated IPC rates in metastatic testicular cancer patients receiving CCT, namely invasive mechanical ventilation (IMV), percutaneous endoscopic gastrostomy tube (PEG), dialysis for acute kidney failure (AKF), total parenteral nutrition (TPN) or tracheostomy. Univariable and multivariable logistic regression models addressing IPC were fitted. Of 420 metastatic testicular cancer patients undergoing CCT, 70 (17%) received IPC. Between 2008 and 2019, the rates of IPC among metastatic testicular cancer patients undergoing CCT increased from 5 to 19%, with the highest rate of 30% in 2018 (EAPC: + 9.5%; 95% CI + 4.7 to + 15.2%; p = 0.005). IPC patients were older (35 vs. 31 years, p = 0.01), more frequently had do not resuscitate (DNR) status (34 vs. 4%, p < 0.001), more frequently exhibited brain metastases (29 vs. 17%, p = 0.03), were more frequently treated with IMV (76 vs. 53%, p < 0.001) and exhibited higher rate of inpatient mortality (74 vs. 29%, p < 0.001). In multivariable analyses, DNR status (OR 10.23, p < 0.001) and African American race/ethnicity (OR 4.69, p = 0.003) were identified as independent predictors of higher IPC use. We observed a significant increase in rates of IPC use in metastatic testicular cancer patients receiving CCT, rising from 5 to 19% between 2008 and 2019. However, this rates remain lower compared to metastatic lung cancer patients, indicating the need for further awareness among clinicians treating metastatic testicular cancer. The increase in IPC rates for metastatic testicular cancer patients receiving CCT indicates a need for ongoing education and awareness among healthcare providers. This could enhance the integration of IPC in the treatment of advanced cancer, potentially improving quality of life and care outcomes for survivors.

Background and Objectives: To describe the predictors of cribriform variant status and perineural invasion (PNI) in robot-assisted radical prostatectomy (RARP) histology. To define the rates of upgrading between biopsy specimens and final histology and their possible predictive factors in prostate cancer (PCa) patients undergoing RARP. Material and Methods: Within our institutional database, 265 PCa patients who underwent prostate biopsies and consecutive RARP at our center were enrolled (2018–2022). In the overall population, two independent multivariable logistic regression models (LRMs) predicting the presence of PNI or cribriform variant status at RARP were performed. In low- and intermediate-risk PCa patients according to D’Amico risk classification, three independent multivariable LRMs were fitted to predict upgrading. Results: Of all, 30.9% were low-risk, 18.9% were intermediate-risk and 50.2% were high-risk PCa patients. In the overall population, the rates of the cribriform variant and PNI at RARP were 55.8% and 71.1%, respectively. After multivariable LRMs predicting PNI, total tumor length in biopsy cores (>24 mm [OR: 2.37, p-value = 0.03], relative to <24 mm) was an independent predictor. After multivariable LRMs predicting cribriform variant status, PIRADS (3 [OR:15.37], 4 [OR: 13.57] or 5 [OR: 16.51] relative to PIRADS 2, all p = 0.01) and total tumor length in biopsy cores (>24 mm [OR: 2.47, p = 0.01], relative to <24 mm) were independent predicting factors. In low- and intermediate-risk PCa patients, the rate of upgrading was 74.4% and 78.0%, respectively. After multivariable LRMs predicting upgrading, PIRADS (PIRADS 3 [OR: 7.01], 4 [OR: 16.98] or 5 [OR: 20.96] relative to PIRADS 2, all p = 0.01) was an independent predicting factor. Conclusions: RARP represents a tailored and risk-adapted treatment strategy for PCa patients. The indication of RP progressively migrates to high-risk PCa after a pre-operative assessment. Specifically, the PIRADS score at mpMRI should guide the decision-making process of urologists for PCa patients.

[FeFe]-hydrogenases reversibly catalyse molecular hydrogen evolution by reduction of two protons. Proton supply to the catalytic site (H-cluster) is essential for enzymatic activity. Cysteine 298 is a highly conserved residue in all [FeFe]-hydrogenases; moreover C298 is structurally very close to the H-cluster and it is important for hydrogenase activity. Here, the function of C298 in catalysis was investigated in detail by means of site saturation mutagenesis, simultaneously studying the effect of C298 replacement with all other 19 amino acids and selecting for mutants with high retained activity. We demonstrated that efficient enzymatic turnover was maintained only when C298 was replaced by aspartic acid, despite the structural diversity between the two residues. Purified CaHydA C298D does not show any significant structural difference in terms of secondary structure and iron incorporation, demonstrating that the mutation does not affect the overall protein fold. C298D retains the hydrogen evolution activity with a decrease of k(cat) only by 2-fold at pH 8.0 and it caused a shift of the optimum pH from 8.0 to 7.0. Moreover, the oxygen inactivation rate was not affected demonstrating that the mutation does not influence O(2) diffusion to the active site or its reactivity with the H-cluster. Our results clearly demonstrate that, in order to maintain the catalytic efficiency and the high turnover number typical of [FeFe] hydrogenases, the highly conserved C298 can be replaced only by another ionisable residue with similar steric hindrance, giving evidence of its involvement in the catalytic function of [FeFe]-hydrogenases in agreement with an essential role in proton transfer to the active site.

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.

In recent years, vaccines and immunotherapy have become two of the most promising and effective tools in the fight against a wide range of diseases, from the common cold to cancer [...].In recent years, vaccines and immunotherapy have become two of the most promising and effective tools in the fight against a wide range of diseases, from the common cold to cancer [...].

Background/Objective: The grade of recommendation for renal cell carcinoma (RCC) salvage treatment options is weak. The aim of the current study is to summarize available evidence about the surgical, oncological, and functional outcomes of salvage renal options after previous treatments for RCC. Methods: A systematic search (PROSPERO: CRD42024618629) was performed according to the PRISMA statement. A pooled analysis was performed to quantify the effect size (ES) for an overall postoperative Clavien–Dindo (CD) grade ≥ III and postoperative and intraoperative complications for either partial or radical nephrectomy (PN or RN) subgroups. Results: Overall, 11 studies involving 331 patients were included in the final analysis. The median age ranged from 44 to 75 years. Primary treatments for RCC included 267 (80.6%) PNs, 40 (12.0%) radiofrequency ablations (RFAs), 23 (6.9%) cryotherapies, and 1 (0.3%) stereotactic radiotherapy. Overall, the median time of local recurrence for RCC patients was from 25 to 99 months for PNs, 13 months for RFA and cryotherapy, and 6 months for stereotactic radiotherapy. The overall pooled analysis was associated with an ES of 0.28 for overall postoperative complications and of 0.11 for CD ≥ III postoperative complications (all p < 0.001). Within subgroup analyses, RN was invariably associated with less complications (the ES ranged from 0.05 to 0.17). Conclusions: The profile of oncological safety as well as the morbidity and mortality of salvage treatment options for RCC may justify considering such procedures in a salvage setting.

The Prostate Imaging Reporting and Data System (PI-RADS) classification is based on a scale of values from 1 to 5. The value is assigned according to the probability that a finding is a malignant tumor (prostate carcinoma) and is calculated by evaluating the signal behavior in morphological, diffusion, and post-contrastographic sequences. A PI-RADS score of 3 is recognized as the equivocal likelihood of clinically significant prostate cancer, making its diagnosis very challenging. While PI-RADS values of 4 and 5 make biopsy necessary, it is very hard to establish whether to perform a biopsy or not in patients with a PI-RADS score 3. In recent years, machine learning algorithms have been proposed for a wide range of applications in medical fields, thanks to their ability to extract hidden information and to learn from a set of data without previous specific programming. In this paper, we evaluate machine learning approaches in detecting prostate cancer in patients with PI-RADS score 3 lesions via considering clinical-radiological characteristics. A total of 109 patients were included in this study. We collected data on body mass index (BMI), location of suspicious PI-RADS 3 lesions, serum prostate-specific antigen (PSA) level, prostate volume, PSA density, and histopathology results. The implemented classifiers exploit a patient’s clinical and radiological information to generate a probability of malignancy that could help the physicians in diagnostic decisions, including the need for a biopsy.

Bladder cancer (BCa) is an endocrine-related tumour and the activation of androgen signalling pathways may promote bladder tumorigenesis. We summarized the available preclinical and clinical evidence on the implications of the manipulation of androgen signalling pathways on the outcomes of BCa therapies. A systematic review was performed in December 2020. We included papers that met the following criteria: original preclinical and clinical research; evaluating the impact of androgen signalling modulation on the outcomes of BCa therapies. Six preclinical and eight clinical studies were identified. The preclinical evidence demonstrates that the modulation of androgen receptor-related pathways has the potential to interfere with the activity of the Bacillus Calmette Guerin, doxorubicin, cisplatin, gemcitabine, and radiotherapy. The relative risk of BCa recurrence after transurethral resection of the bladder tumour (TURBT) is significantly lower in patients undergoing therapy with 5 alpha reductase inhibitors (5-ARIs) or androgen deprivation therapy (ADT) (Relative risk: 0.50, 95% CI: 0.30–0.82; p = 0.006). Subgroup analysis in patients receiving 5-ARIs revealed a relative risk of BCa recurrence of 0.46 (95% CI: 0.22–0.95; p = 0.040). A significant negative association between the ratio of T1 BCa patients in treated/control groups and the relative risk of BCa recurrence was observed. Therapy with 5-ARIs may represent a potential strategy aimed at reducing BCa recurrence rate, mainly in patients with low stage disease. Further studies are needed to confirm these preliminary data.

Background and Objective: Blood loss represents a long-standing concern of radical prostatectomy (RP). This study aimed to assess how red line cell values changed following robot-assisted radical prostatectomy (RARP) for prostate cancer (PCa). Materials and Methods: The blood panels of 453 consecutive PCa patients undergoing RARP at a single tertiary academic referral center, from September 2020 to April 2022, were reviewed. Data from 363 patients with the blood panel available for the following timeframe: within seven days before surgery, six hours after surgery, and the first three postoperative days, were analyzed. Specifically, hemoglobin (Hb, g/dL), red blood cells (RBCs, ×106/μL), and hematocrit (HCT, %) trends were collected. Results: Considering the Hb trend, the median values in the preoperative day, postoperative day (POD) 2, and POD 3 are 14.7 (interquartile range (IQR) = 13.9–15.4), 12.1 (IQR = 11.2–12.9), and 12.2 (IQR = 11.2–13.1), respectively. The ∆ between preoperative day and POD 2 is 2.5 (IQR = 1.8–3.2) (p < 0.001). Considering the RBCs trend, the median values in the preoperative day, POD 2, and POD 3 are 4.9 (IQR = 4.7–5.3), 4.1 (IQR = 3.8–4.4), and 4.1 (IQR = 3.8–4.5), respectively. The ∆ between preoperative day and POD 2 is 0.9 (IQR = 0.6–1.1) (p < 0.001). Considering the HCT trend, the median values in the preoperative day, POD 2, and POD 3 are 44.4 (IQR = 41.7–46.6), 36.4 (IQR = 33.8–38.9), and 36.1 (IQR = 33.5–38.7), respectively. The ∆ between preoperative day and POD 2 is 7.8 (IQR = 5.2–10.5) (p < 0.001). Conclusions: Overall, patients undergoing RARP experience a significant, but clinically limited, decline in red line cell values between the preoperative time and the second day post-surgery. These observations are important to provide physicians with knowledge of the expected postoperative course and, thus, to improve the quality of patient care.