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STING is a molecule involved in immune reactions against double-stranded DNA fragments, released in infective and neoplastic diseases, whose role in the interactions between immune and neoplastic cells in clear cell renal cell carcinoma has not been studied yet. We investigated the immunohistochemical expression of STING in a series of 146 clear-cell renal cell carcinomas and correlated it with the main pathological prognostic factors. Furthermore, tumoral inflammatory infiltrate was evaluated and studied for the subpopulations of lymphocytes. Expression of STING was observed in 36% (53/146) of the samples, more frequently in high-grade (G3–G4) tumors (48%,43/90) and recurrent/metastatic ones (75%, 24/32) than in low grade (G1–G2) and indolent neoplasms (16%, 9/55). STING staining correlated with parameters of aggressive behavior, including coagulative granular necrosis (p = 0.001), stage (p < 0.001), and development of metastases (p < 0.001). Among prognostic parameters, STING immune expression reached an independent statistical significance (p = 0.029) in multivariable analysis, along with the stage and the presence of coagulative granular necrosis. About tumor immune-environment, no significant statistical association has been demonstrated between tumor-infiltrating lymphocytes and STING. Our results provide novel insights regarding the role of STING in aggressive clear cell renal cell carcinomas, suggesting its adoption as a prognostic marker and a potentially targetable molecule for specific immunotherapies.

Objective: to evaluate predictors and the prognostic impact of favorable vs. unfavorable tumor upgrading among low-risk prostate cancer (LR PCa) patients treated with robot-assisted radical prostatectomy (RARP). Methods: From January 2013 to October 2020, LR PCa patients treated with RARP at our institution were identified. Unfavorable tumor upgrading was defined as the presence of an International Society of Urological Pathology (ISUP) grade group at final pathology > 2. Disease relapse was coded as biochemical recurrence and/or local recurrence and/or presence of distant metastases. Regression analyses tested the association between clinical and pathological features and the risk of unfavorable tumor upgrading and disease relapse. Results: Of the 237 total LR PCa patients, 60 (25.3%) harbored unfavorable tumor upgrading. Disease relapse occurred in 20 (8.4%) patients. Unfavorable upgrading represented an independent predictor of disease relapse, even after adjustment for other clinical and pathological variables. Conversely, favorable tumor upgrading did not show any statistically significant association with PCa relapse. Unfavorable tumor upgrading was associated with tumors being larger (OR: 1.03; p = 0.031), tumors extending beyond the gland (OR: 8.54, p < 0.001), age (OR: 1.07, p = 0.009), and PSA density (PSAD) ≥ 0.15 ng/mL/cc (OR: 1.07, p = 0.009). Conclusions: LR PCa patients with unfavorable upgrading at final pathology were more likely to be older, to have PSAD ≥ 0.15 ng/mL/cc, and to experience disease relapse. Unfavorable tumor upgrading is an issue to consider when counseling these patients to avoid delayed treatments, which may impair cancer-specific survival.

Recent technological advances in molecular biology have led to great progress in the knowledge of structure and function of cells and their main constituents. In this setting, ‘omics’ is standing out in order to significantly improve the understanding of etiopathogenetic mechanisms of disease and contribute to the development of new biochemical diagnostics and therapeutic tools. ‘Omics’ indicates the scientific branches investigating every aspect of cell’s biology, including structures, functions and dynamics pathways. The main ‘omics’ are genomics, epigenomics, proteomics, transcriptomics, metabolomics and radiomics. Their diffusion, success and proliferation, addressed to many research fields, has led to many important acquisitions, even in Urology. Aim of this narrative review is to define the state of art of ‘omics’ application in Urology, describing the most recent and relevant findings, in both oncological and non-oncological diseases, focusing the attention on urinary tract infectious, interstitial cystitis, urolithiasis, prostate cancer, bladder cancer and renal cell carcinoma. In Urology the majority of ‘omics’ applications regard the pathogenesis and diagnosis of the investigated diseases. In future, its role should be implemented in order to develop specific predictors and tailored treatments.

The aim of this study was to describe the frequency, major symptoms, and characteristics of colonic polyps in a cohort of children. A retrospective chart review of patients aged ≤ 18 years who were diagnosed with colonic polyp(s) from 2006 to 2019 in a tertiary hospital was included. Data collected included demographics, clinical presentation, interval of time between the onset of symptoms and the endoscopic diagnosis of colonic polyps, family history, characteristics of the polyp, and associated lesions. Over the study period, 35 Caucasian children were diagnosed with juvenile colonic polyps. Twenty-three patients (65.7%) were males. Lower gastrointestinal bleeding of a mean duration of 5.3 ± 4.9 months was the presenting symptom in nearly all cases (n = 34, 97%), and it was isolated in 17 patients. Clinical presentation did not significantly vary according to the age or the location or size of the polyp (p = 0.262, p = 1.000, and p = 0.149, respectively). The polyps were mainly located in the left colon (n = 29, 83%). Right colonic polyps were significantly larger than left colonic polyps (p = 0.037).Conclusion: Lower gastrointestinal bleeding represents the most common presentation of colonic polyps in children. Right-sided colonic polyps occur and may be even larger than left-sided ones. A total colonoscopy is therefore mandatory for all cases of suspected colonic polyps. This study represents a real-life contribution, and it can help improve the management strategies of this condition in childhood. What is Known: • Colonic polyps are quite common in children. • The majority of pediatric colonic polyps are solitary, benign, and located in the left colon. What is New: • Right-sided colonic polyps occur and may be even larger than left-sided ones. • A total colonoscopy is mandatory for all cases of suspected colonic polyps.

Since before the COVID-19 pandemic, hospital-acquired infections (HAIs) represented a global healthcare crisis. Few studies suggested that COVID-19-related basic hygiene measures (BHM) could lower HAIs rates, reaching inconclusive results. The aim of this study was to investigate the hypothetical benefit on HAIs rate of COVID-19-enhanced BHM systematic introduction after major elective urological surgery.Since the pandemic began, our hospital has implemented BHM to limit the spread of COVID-19. We compared patients operated in the pre-COVID-19 era (no-BHM period) with those operated after the pandemic started (BHM period). Outcomes were the incidence of HAIs and postoperative complications, and the length of hospital stay (LOS). Two balanced groups were generated by propensity score 1:1 matching.Of 1053 major urological interventions, 604 were performed in the no-BHM period, and 449 in the BHM period. After matched analysis, the comparison groups consisted of 310 patients each. Of 107 recorded HAIs, 43 occurred during the BHM period (13.9%), and 64 during the no-BHM period (20.7%), with a statistically significant difference in multivariable analysis (OR 0.5 [95% CI 0.3-0.8], P=0.004). Postoperative complications rate was significantly lower in the BHM period than in the no-BHM period (29.0% versus 36.5%, OR 0.6 [95% CI 0.4-0.9], P=0.01). The LOS differed significantly between BHM and no-BHM periods: a median of 5 (5-8) days versus 6 (5-8), respectively (P0.001).The risk of infections, postoperative complications, and prolonged LOS after major urological surgery was significantly reduced with the systematic introduction of COVID-19-related BHM, their application could, therefore, be prolonged with lasting benefits.

Altitude exposure affects hormonal homeostasis, but the adaptation of different populations is still not finely defined. This study aims to compare the mid-term effects of combining physical activity and altitude hypoxia on hormonal profiles in foreign trekkers coming from Italy versus indigenous Nepalese porters during a Himalayan trek. Participants (6 Italians and 6 Nepalese) completed a 300 km distance in 19 days of an accumulated altitude difference of 16,000 m, with an average daily walk of 6 h. The effect of high altitude on hormonal pathways was assessed by collecting blood samples the day before the expedition and the day after its completion. Foreign trekkers had an additional follow-up sample collected after 10 days. The findings revealed a different adaptation of thyroidal and gonadal axes to mid-term strenuous physical activity combined with high-altitude hypobaric hypoxia. The thyroid function shifted to the protective mechanism of low free triiodothyronine (FT3), whereas the gonadal axis was suppressed. The Italian trekkers and Nepalese porters had lower total testosterone and 17-β-estradiol levels after the expedition. At the follow-up, the Italians had increased testosterone values. Prolactin secretion decreased in the Italians but increased in the Nepalese. We conclude that exposure to high-altitude affects the hormonal axes. The effect seems notably pronounced for the hypothalamus-pituitary gonadal axis, suppressed after high-altitude exposure.

Altitude exposure affects hormonal homeostasis, but the adaptation of different populations is still not finely defined. This study aims to compare the mid-term effects of combining physical activity and altitude hypoxia on hormonal profiles in foreign trekkers coming from Italy versus indigenous Nepalese porters during a Himalayan trek. Participants (6 Italians and 6 Nepalese) completed a 300 km distance in 19 days of an accumulated altitude difference of 16,000 m, with an average daily walk of 6 h. The effect of high altitude on hormonal pathways was assessed by collecting blood samples the day before the expedition and the day after its completion. Foreign trekkers had an additional follow-up sample collected after 10 days. The findings revealed a different adaptation of thyroidal and gonadal axes to mid-term strenuous physical activity combined with high-altitude hypobaric hypoxia. The thyroid function shifted to the protective mechanism of low free triiodothyronine (FT3), whereas the gonadal axis was suppressed. The Italian trekkers and Nepalese porters had lower total testosterone and 17-β-estradiol levels after the expedition. At the follow-up, the Italians had increased testosterone values. Prolactin secretion decreased in the Italians but increased in the Nepalese. We conclude that exposure to high-altitude affects the hormonal axes. The effect seems notably pronounced for the hypothalamus-pituitary gonadal axis, suppressed after high-altitude exposure.

The Divertor Tokamak Test facility (DTT) is the new tokamak whose construction is starting in Frascati (Italy), with the main aim of testing different divertor magnetic configurations and technologies in view of DEMO. In the present design, the DTT heating mix includes one Negative Neutral Beam Injector (NBI), with a power injected in the plasma of 10 MW and a beam energy of 500 keV. The NBI conceptual design is under development and includes solutions already adopted for ITER (RF-driven ion source, gas neutralizer, electrostatic Residual Ion Dump), but with some simplifications to reduce costs and complexity deemed feasible for DTT. In particular, the beam source is air-insulated and fed by the gas-insulated Transmission Line through gas-air bushings. This paper presents the status of the conceptual design of the main power supplies of the DTT NBI. The main ratings are collected from physics requirements and NBI design. On this basis, the reference technical solutions are selected, considering the experience gained at the ITER Neutral Beam Test Facility in Padova (Italy), the specific design of the DTT NBI and the layout constraints of the DTT Site. For the Acceleration Grid Power Supply, besides the ITER-like design, an innovative approach based on the Modular Multilevel Converter technology, never adopted in this application, is considered; pros and cons of the two solutions are evaluated.

The multidisciplinary treatment with targeted alpha therapy, as the treatment with Radium 223, plays an important role in the management of patients with castration resistance prostate cancer and metastatic bone disease. The AUA approved the Ra223 as the second line of treatment of castration resistance prostate cancer in patients with bone metastases, in the absence of visceral metastases. Currently the EMA authorizes the use of Ra223 at a dose of 55 kBq / kg for a total of 6 administrations in patients with CRPC, but the dose of Ra223 needs to be made on an individual patient basis taking into consideration the potential clinical benefits and risk. We have outlined a new methodology, which can be executed in all departments of nuclear medicine in collaboration with health-related physics at no cost. Our methodology allows a correct evaluation of the doses of Radium 223 to be administered and of the number of cycles to be performed, to increase the therapeutic efficacy. We can avoid overtreatment or undertreatment of patients ensuring a perfect fit between patients and Ra223 treatment. The multidisciplinary approach between nuclear physician, oncologist and health related physics is crucial throughout the treatment process to improve QoL in patients at risk.

Radium 223 dichloride (Ra223) is a novel first in class alpha emitting radiopharmaceutical that has been approved for the treatment of castration resistance prostate cancer with bone metastases. Radium 223 was demonstrated to improve overall survival and symptoms in patients with CRPC in ALSYMPCA trial. In our institution, a patient with breast cancer affected by osteolytic metastases was treated with off-label use of Ra223, after obtaining informed consent. Were administered six treatments of Ra223. The patient did not develop skeletal related events (SREs; i.e., radiation to bone, pathological fracture, spinal cord compression, surgery to bone), the major complications of bone metastases, up to now. Radium 223 has improved patient survival and it has eliminated bone pain whilst keeping hematological toxicity to a minimum. It is, to our knowledge, the first example of complete recovery of bone metastatic disease treated with Ra223, published to data. We have shown that Radium223 dichloride can be safely administered in hormone refractory bone metastases from breast cancer; Radium 223 may play a critical role in the management of breast cancer.

Aliment Pharmacol Ther 2011; 33: 697–706 Summary Background Accuracy of intraepithelial lymphocytes counts for diagnosing mild enteropathy coeliac disease in absence of villous atrophy can be limited by inappropriate controls included in the studies. Aim To determine the diagnostic accuracy of intraepithelial lymphocytes counts utilising controls lacking HLA coeliac disease-associated alleles. Methods Intraepithelial lymphocytes counting at villus tip and per 100 enterocytes was performed at haematoxylin and eosin (H&E) and CD3-stainings in: 29 cases (21 with potential coeliac disease and 8 affected by latent coeliac disease) representing the patient population and 14 noncoeliac controls lacking HLA-DQ2/DQ8 alleles. Results Threshold (mean + 2 s.d.) of duodenal intraepithelial lymphocytes at villus tip and per 100 enterocytes in noncoeliac controls was respectively: 3.5 and 18 at H&E, 3.2 and 17 following CD3-staining. Considering the whole patient population, the sensitivity of tip intraepithelial lymphocytes in detecting mild enteropathy coeliac disease was 90% (95% CI = 72.6–97.8) both at H&E and CD3-stainings. The sensitivity of intraepithelial lymphocytes per 100 enterocytes was 93% (95% CI = 77.2–99.2) both at H&E and CD3-staining. Specificity of both intraepithelial lymphocytes counts was 100% (95% CI = 76.8–100). Using a threshold of 25 intraepithelial lymphocytes per 100 enterocytes could miss 59% of cases at H&E and 48% following CD3-staining. Conclusions Intraepithelial lymphocytes counts are diagnostic feasible tools to detect mild enteropathy coeliac disease. Threshold of duodenal intraepithelial lymphocytes may be lower than currently accepted.