Electrophysiological Impact of SARS-CoV-2 Envelope Protein in U251 Human Glioblastoma Cells: Possible Implications in Gliomagenesis?

SARS-CoV-2 is the causative agent of the COVID-19 pandemic, the acute respiratory disease which, so far, has led to over 7 million deaths. There are several symptoms associated with SARS-CoV-2 infections which include neurological and psychiatric disorders, at least in the case of pre-Omicron variants. SARS-CoV-2 infection can also promote the onset of glioblastoma in patients without prior malignancies. In this study, we focused on the Envelope protein codified by the virus genome, which acts as viroporin and that is reported to be central for virus propagation. In particular, we characterized the electrophysiological profile of E-protein transfected U251 and HEK293 cells through the patch-clamp technique and FURA-2 measurements. Specifically, we observed an increase in the voltage-dependent (Kv) and calcium-dependent (KCa) potassium currents in HEK293 and U251 cell lines, respectively. Interestingly, in both cellular models, we observed a depolarization of the mitochondrial membrane potential in accordance with an alteration of U251 cell growth. We, therefore, investigated the transcriptional effect of E protein on the signaling pathways and found several gene alterations associated with apoptosis, cytokines and WNT pathways. The electrophysiological and transcriptional changes observed after E protein expression could explain the impact of SARS-CoV-2 infection on gliomagenesis.

Ventral Onlay Buccal Mucosa Graft Urethroplasty for Female Urethral Stricture: Medium-term Results in a Single Surgeon Experience.

OBJECTIVE: To describe our own approach using buccal mucosal grafting and to assess the outcome of this approach. MATERIALS AND METHODS: A total of 42 patients underwent ventral onlay BMG by a single surgeon between 2017 and 2022. A longitudinal incision along the length of the urethra was made through the anterior vaginal wall and the periurethral fascia was incised to create 2 flaps. This ventral urethrotomy ran from the meatus into the proximal healthy urethra above the level of the stricture. A buccal mucosal graft was harvested and sutured to the margins of the urethral mucosa itself and the flaps of periurethral fascia. The vaginal wall was then closed. RESULTS: The mean age of the patients was 53.6 ± 12.8 years. There were no perioperative or postoperative complications. At a mean follow-up of 38.1 months, 41 patients (98%) were stricture-free. Peak flow rate improved from a mean of 7.7 ± 3.2 mL/s preoperatively to 25.9 ± 5.9 mL/s postoperatively. No patient developed incontinence. One patient developed a recurrent urethral stricture which was treated by redo urethroplasty. CONCLUSION: The surgical technique applied has proved efficiency. The ventral BMG preserves the urethral sphincter and so avoids postoperative incontinence. The use of periurethral fascia represents a good vascular and mechanical support for the graft.

Is early continence recovery related to the length of spared urethra? A prospective multicenter study comparing preoperative MRI and histologic specimen measurements after robotic radical prostatectomy.

BACKGROUND: Urinary incontinence (UI) is a common complication after radical prostatectomy, significantly affecting patients' quality of life. This study aimed to correlate the length of preserved urethra in robotic radical prostatectomy (RALP) patients with short-term urinary continence rates within 90 days post-surgery. METHODS: A prospective multicentric study enrolled 190 prostate adenocarcinoma patients undergoing RALP. Using preoperative magnetic resonance imaging (mpMRI), urethral length was measured from the external urethral sphincter to the bladder neck. After surgery, histological measurements of the removed urethra were compared to the preoperative mpMRI data. Patients were categorized into two groups at the three-month follow-up based on urinary continence assessed through Urodynamic Study (UDS): Group A (94 patients without UI) and Group B (96 patients with UI). RESULTS: Results revealed a significant difference in mean UI recovery time (Group A: 12.35 days, SD: 3.09 vs. Group B: 93.86 days, SD: 34.8, p < 0.0001). A ROC curve identified a 16.5% cut-off value (p < 0.000, sensitivity 87.5%, specificity 91.8%). Both groups showed a significant negative correlation between preserved urethral percentage and UI recovery time (Group A: r -0.655, p < 0.0001; Group B: r -0.340, p: 0.017). Group A had an average of 21.52% preserved urethra, while Group B had 13.86% (p < 0.0001). At one-year follow-up, 93.2% overall patients reported urinary continence without pads. CONCLUSIONS: This study emphasizes the positive correlation between preserved urethra percentage in RALP and early urinary continence recovery, highlighting its surgical significance.

Multiparametric Prostate MRI Accuracy of Prostate Imaging Reporting and Data System (v2.1) Scores 4 and 5: The Influence of Image Quality According to the Prostate Imaging Quality Score.

Purpose: The accuracy of multiparametric magnetic resonance imaging (mpMRI) heavily relies on image quality, as evidenced by the evolution of the prostate imaging quality (PI-QUAL) scoring system for the evaluation of clinically significant prostate cancer (csPC). This study aims to evaluate the impact of PI-QUAL scores in detecting csPC within PI-RADS 4 and 5 lesions. Methods: We retrospectively selected from our database all mpMRI performed from January 2019 to March 2022. Inclusion criteria were as follows: (1) mpMRI acquired in our institution according to the technical requirements from the PI-RADS (v2.1) guidelines; (2) single lesion scored as PI-RADS (v2.1) 4 or 5; (3) MRI-TBx performed in our institution; (4) complete histology report; and (5) complete clinical record. Results: A total of 257 male patients, mean age 70.42 ± 7.6 years, with a single PI-RADS 4 or 5 lesion undergoing MRI-targeted biopsy, were retrospectively studied. Of these, 61.5% were PI-RADS 4, and 38.5% were PI-RADS 5, with 84% confirming neoplastic cells. In high-quality image lesions (PI-QUAL ≥ 4), all PI-RADS 5 lesions were accurately identified as positive at the final histological examination (100% of CDR). For PI-RADS 4 lesions, 37 (23%) were negative, resulting in a cancer detection rate of 77% (95% CI: 67.51-84.83). Conclusions: The accuracy of mpMRI, independently of the PI-RADS score, progressively decreased according to the decreasing PI-QUAL score. These findings emphasize the crucial role of the PI-QUAL scoring system in evaluating PI-RADS 4 and 5 lesions, influencing mpMRI accuracy.

Fluorescence Confocal Microscopy in Urological Malignancies: Current Applications and Future Perspectives.

Fluorescence confocal microscopy (FCM) represents a novel diagnostic technique able to provide real-time histological images from non-fixed specimens. As a consequence of its recent developments, FCM is gaining growing popularity in urological practice. Nevertheless, evidence is still sparse, and, at the moment, its applications are heterogeneous. We performed a narrative review of the current literature on this topic. Papers were selected from the Pubmed, Embase, and Medline archives. We focused on FCM applications in prostate cancer (PCa), urothelial carcinoma (UC), and renal cell carcinoma (RCC). Articles investigating both office and intraoperative settings were included. The review of the literature showed that FCM displays promising accuracy as compared to conventional histopathology. These results represent significant steps along the path of FCM's formal validation as an innovative ready-to-use diagnostic support in urological practice. Instant access to a reliable histological evaluation may indeed significantly influence physicians' decision-making process. In this regard, FCM addresses this still unmet clinical need and introduces intriguing perspectives into future diagnostic pathways. Further studies are required to thoroughly assess the whole potential of this technique.