Persistence of circulating CD169+monocytes and HLA-DR downregulation underline the immune response impairment in PASC individuals: the potential contribution of different COVID-19 pandemic waves.

The use of CD169 as a marker of viral infection has been widely discussed in the context of COVID-19, and in particular, its crucial role in the early detection of SARS-CoV-2 infection and its association with the severity and clinical outcome of COVID-19 were demonstrated. COVID-19 patients show relevant systemic alteration and immunological dysfunction that persists in individuals with post-acute sequelae of SARS-CoV-2 infection (PASC). It is critical to implement the characterization of the disease, focusing also on the possible impact of the different COVID-19 waves and the consequent effects found after infection. On this basis, we evaluated by flow cytometry the expression of CD169 and HLA-DR on monocytes from COVID-19 patients and PASC individuals to better elucidate their involvement in immunological dysfunction, also evaluating the possible impact of different pandemic waves. The results confirm CD169 RMFI is a good marker of viral infection. Moreover, COVID-19 patients and PASC individuals showed high percentage of CD169+ monocytes, but low percentage of HLA-DR+ monocytes and the alteration of systemic inflammatory indices. We have also observed alterations of CD169 and HLA-DR expression and indices of inflammation upon different COVID-19 waves. The persistence of specific myeloid subpopulations suggests a role of CD169+ monocytes and HLA-DR in COVID-19 disease and chronic post-infection inflammation, opening new opportunities to evaluate the impact of specific pandemic waves on the immune response impairment and systemic alterations with the perspective to provide new tools to monitoring new variants and diseases associated to emerging respiratory viruses.

Preliminary Evidence of the Differential Expression of Human Endogenous Retroviruses in Kawasaki Disease and SARS-CoV-2-Associated Multisystem Inflammatory Syndrome in Children.

Multisystem inflammatory syndrome in children (MIS-C) is a postinfectious sequela of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), with some clinical features overlapping with Kawasaki disease (KD). Our research group and others have highlighted that the spike protein of SARS-CoV-2 can trigger the activation of human endogenous retroviruses (HERVs), which in turn induces inflammatory and immune reactions, suggesting HERVs as contributing factors in COVID-19 immunopathology. With the aim to identify new factors involved in the processes underlying KD and MIS-C, we analysed the transcriptional levels of HERVs, HERV-related genes, and immune mediators in children during the acute and subacute phases compared with COVID-19 paediatric patients and healthy controls. The results showed higher levels of HERV-W, HERV-K, Syn-1, and ASCT-1/2 in KD, MIS-C, and COV patients, while higher levels of Syn-2 and MFSD2A were found only in MIS-C patients. Moreover, KD and MIS-C shared the dysregulation of several inflammatory and regulatory cytokines. Interestingly, in MIS-C patients, negative correlations have been found between HERV-W and IL-10 and between Syn-2 and IL-10, while positive correlations have been found between HERV-K and IL-10. In addition, HERV-W expression positively correlated with the C-reactive protein. This pilot study supports the role of HERVs in inflammatory diseases, suggesting their interplay with the immune system in this setting. The elevated expression of Syn-2 and MFSD2A seems to be a distinctive trait of MIS-C patients, allowing to distinguish them from KD ones. The understanding of pathological mechanisms can lead to the best available treatment for these two diseases, limiting complications and serious outcomes.

Attachment and resilience as mediators or moderators in the relationship between trauma and psychotic-like experiences.

BACKGROUND: A large body of evidence has established a tight relation between traumatic experiences (TEs) and psychotic-like experiences (PLEs). Nevertheless, more comprehensive models involving multiple interactions of serial or parallel mediations and moderations still need to be elucidated. Among the many potential mediators or moderators, insecure attachment and resilience play a key role in the association of stress with PLEs. Hence, we aim to explore the complex pathways that lead from different types of TEs to PLEs, involving attachment and resilience modeled as mediators or moderators. METHODS: One thousand ten high school students completed the International Trauma Exposure Measure (ITEM), the 11-item Resilience Scale for Adults (RSA-11), the 16-item Prodromal Questionnaire (iPQ-16), and the Relationship Questionnaire (RQ). A path analysis was conducted to assess mediation and moderation. RESULTS: The final model showed that the impact of childhood TEs on PLEs was mediated by a pathway through anxious-insecure attachment styles (i.e., fearful and preoccupied, respectively, 8.75 % and 8.53 % of the total effect) and personal resilience resources. Conversely, the avoidant-insecure attachment was associated with lower interpersonal resilience (b = 0.14 [0.08, 0.20]), which in turn moderated the impact of recent TEs on PLEs (interaction term b = 0.34 [0.21, 0.47]). CONCLUSIONS: Our model examines a complex model that includes factors buffering the effect of traumatic experiences on PLEs. Our results highlight the importance of insecure-anxious attachment to personal resilience resources and of insecure-avoidant attachment to interpersonal resilience as potential targets for clinical practice.

Expression profile of HERVs and inflammatory mediators detected in nasal mucosa as a predictive biomarker of COVID-19 severity.

Introduction: Our research group and others demonstrated the implication of the human endogenous retroviruses (HERVs) in SARS-CoV-2 infection and their association with disease progression, suggesting HERVs as contributing factors in COVID-19 immunopathology. To identify early predictive biomarkers of the COVID-19 severity, we analyzed the expression of HERVs and inflammatory mediators in SARS-CoV-2-positive and -negative nasopharyngeal/oropharyngeal swabs with respect to biochemical parameters and clinical outcome. Methods: Residuals of swab samples (20 SARS-CoV-2-negative and 43 SARS-CoV-2-positive) were collected during the first wave of the pandemic and expression levels of HERVs and inflammatory mediators were analyzed by qRT-Real time PCR. Results: The results obtained show that infection with SARS-CoV-2 resulted in a general increase in the expression of HERVs and mediators of the immune response. In particular, SARS-CoV-2 infection is associated with increased expression of HERV-K and HERV-W, IL-1ß, IL-6, IL-17, TNF-α, MCP-1, INF-γ, TLR-3, and TLR-7, while lower levels of IL-10, IFN-α, IFN-ß, and TLR-4 were found in individuals who underwent hospitalization. Moreover, higher expression of HERV-W, IL-1ß, IL-6, IFN-α, and IFN-ß reflected the respiratory outcome of patients during hospitalization. Interestingly, a machine learning model was able to classify hospitalized vs not hospitalized patients with good accuracy based on the expression levels of HERV-K, HERV-W, IL-6, TNF-a, TLR-3, TLR-7, and the N gene of SARS-CoV-2. These latest biomarkers also correlated with parameters of coagulation and inflammation. Discussion: Overall, the present results suggest HERVs as contributing elements in COVID-19 and early genomic biomarkers to predict COVID-19 severity and disease outcome.

ZNF750: A Novel Prognostic Biomarker in Metastatic Prostate Cancer.

Prostate cancer is the most frequently diagnosed cancer and the fifth leading cause of cancer death among men in 2020. The clinical decision making for prostate cancer patients is based on the stratification of the patients according to both clinical and pathological parameters such as Gleason score and prostate-specific antigen levels. However, these tools still do not adequately predict patient outcome. The aim of this study was to investigate whether ZNF750 could have a role in better stratifying patients, identifying those with a higher risk of metastasis and with the poorest prognosis. The data reported here revealed that ZNF750 protein levels are reduced in human prostate cancer samples, and this reduction is even higher in metastatic samples. Interestingly, nuclear positivity is significantly reduced in patients with metastatic prostate cancer, regardless of both Gleason score and grade group. More importantly, the bioinformatics analysis indicates that ZNF750 expression is positively correlated with better prognosis. Overall, our findings suggest that nuclear expression of ZNF750 may be a reliable prognostic biomarker for metastatic prostate cancer, which lays the foundation for the development of new biological therapies.

Ejaculatory function following transperineal laser ablation vs TURP for benign prostatic obstruction: a randomized trial.

OBJECTIVES: To evaluate the reliability of transperineal interstitial laser ablation of the prostate (TPLA) in preserving antegrade ejaculation compared to transurethral resection of the prostate (TURP). PATIENTS AND METHODS: In this single-centre, prospective, randomized, open-label study, consecutive patients with indication for surgical treatment for benign prostatic obstruction (BPO) were enrolled between January 2020 and September 2021 (NCT04781049). Patients were randomized to one of two treatment arms: Group A: TPLA (experimental group) and Group B: TURP (reference standard group). The primary endpoint was change in ejaculatory function (assessed by the Male Sexual Health Questionnaire - Ejaculatory function domain [EJ-MSHQ]) at 1 month after surgery. Secondary endpoints included comparison of visual analogue scale (VAS) scores, changes in sexual function (assessed using the five-item International Index of Erectile Function [IIEF-5]), change in International Prostate Symptom Score [IPSS], change in quality of life score, and maximum urinary flow rate [Qmax ] improvement at 1-6 months, as appropriate. RESULTS: Fifty-one patients (26 TPLA vs 25 TURP) were analysed. No differences in the perception of pain assessed by VAS and no differences in IIEF-5 score were found between the groups. The distribution of ejaculatory function assessed by the EJ-MSHQ remained unmodified after TPLA (P = 0.2), while a median 30% decrease in EJ-MSHQ score was observed after TURP (P = 0.01). Absence of antegrade ejaculation was reported in one patient in the TPLA group (vs 18 patients in the TURP group). A statistically significant difference between the treatment groups was found in terms of postoperative Qmax (TPLA vs TURP: 15.2 [interquartile range 13.5-18.3] mL/s vs 26.0 [interquartile range 22.0-48.0] mL/s; P < 0.001). Both treatments significantly improved Qmax , with a mean 23.9 mL/s improvement after TURP (95% confidence interval [CI] 17.1-30.7) vs 6.0 mL/s after TPLA (95% CI 5.0-7.0), and IPSS, with a mean decrease of 11.6 (95% CI 9.7-13.5) vs 5.8 after TPLA (95% CI.2-9.6) with respect to baseline. CONCLUSION: In our study, TPLA preserved ejaculatory function in 96% of cases in addition to providing significant relief from BPO.

Modulation of human endogenous retroviruses and cytokines expression in peripheral blood mononuclear cells from autistic children and their parents.

BACKGROUND: Putative pathogenic effects mediated by human endogenous retroviruses (HERVs) in neurological and psychiatric disorders in humans have been extensively described. HERVs may alter the development of the brain by means of several mechanisms, including modulation of gene expression, alteration of DNA stability, and activation of immune system. We recently demonstrated that autistic children and their mothers share high expression levels of some HERVs and cytokines in peripheral blood mononuclear cells (PBMCs) ex vivo, suggesting a close mother-child association in Autism Spectrum Disorder (ASD). RESULTS: In the present study, PBMCs from autistic children and their parents were exposed to stimulating factors (Interleukin-2/Phytohaemagglutinin) or drugs, as Valproic acid and Efavirenz. The results show that HERVs and cytokines expression can be modulated in vitro by different stimuli in PBMCs from autistic children and their mothers, while no significant changes were found in PBMCs ASD fathers or in controls individuals. In particular, in vitro exposure to interleukin-2/Phytohaemagglutinin or valproic acid induces the expression of several HERVs and cytokines while Efavirenz inhibits them. CONCLUSION: Herein we show that autistic children and their mothers share an intrinsic responsiveness to in vitro microenvironmental changes in expressing HERVs and pro-inflammatory cytokines. Remarkably, the antiretroviral drug Efavirenz restores the expression of specific HERV families to values similar to those of the controls, also reducing the expression of proinflammatory cytokines but keeping the regulatory ones high. Our findings open new perspectives to study the role of HERVs in the biological mechanisms underlying Autism.

Randomized Clinical Trial Comparing On-clamp Versus Off-clamp Laparoscopic Partial Nephrectomy for Small Renal Masses (CLOCK II Laparoscopic Study): A Intention-to-treat Analysis of Perioperative Outcomes.

Background: Recent randomized trials (RCTs) in the field of robotic partial nephrectomy (PN) showed no significant differences in perioperative outcomes between the off- and on-clamp approaches. Objective: To compare the perioperative outcomes of on- versus off-clamp pure laparoscopic PN (LPN). Design setting and participants: A multi-institutional analysis of the on- versus off-clamp approach during LPN in the setting of an RCT (CLOCK II trial; ClinicalTrials.gov NCT02287987) was performed. Intervention: Off- versus on-clamp LPN. Outcome measurements and statistical analysis: Baseline patient and tumor variables, and peri- and postoperative data were collected. Randomized allocation with a 1:1 ratio was assigned. Surgical strategy for managing the renal pedicle was dictated by the study protocol. In the off-clamp arm, the renal artery had to remain unclamped for the duration of the whole procedure. Reporting the intention-to-treat analysis is the purpose of the study. Results and limitations: The study recruited 249 patients. Of them, 123 and 126 were randomized and allocated into the on- and off-clamp treatment groups, respectively. Treatment groups were comparable at baseline after randomization with respect to patients' demographics, comorbidities, renal function, and tumor size and complexity. A univariable analysis found no differences in the perioperative outcomes between the groups, including median (interquartile range) estimated blood loss (150 [100-200] vs 150 [100-250] ml, p = 0.2), grade ≥2 complication rate as classified according to the Clavien-Dindo system (5.7% vs 4.8%, p = 0.6), and positive surgical margin rate (8.2% vs 3.5% for the on- vs off-clamp group, p = 0.1). No differences were found in terms of the 1st (81.3 [66.7-94.3] vs 85.3 [71.0-97.7] ml/min, p = 0.2) and 5th postoperative days estimated glomerular filtration rate (83.3 [70.5-93.7] vs 83.4 [68.6-139.3] ml/min, p = 0.2). A multivariable analysis found each +1 increase in RENAL score corresponded to an increase in the protection from the occurrence of complications (odds ratio [OR] 0.72, 95% confidence interval [CI] 0.54-0.97, p = 0.034), while each +1 cm increase in tumor size corresponded to an increase in the risk of blood transfusion (OR 1.39, 95% CI 1.14-1.70, p = 0.001). Conclusions: In the setting of an RCT, no differences were found in the perioperative and early functional outcomes between on- and off-clamp LPN. Patient summary: In this study, we investigated, by means of a randomized trial, whether avoiding the clamping of renal artery during laparoscopic resection of renal mass is able to translate into benefits. We found no differences in terms of safety, efficacy, and renal function from the standard approach, which includes arterial clamping.

Differential Expression of Endogenous Retroviruses and Inflammatory Mediators in Female and Male Offspring in a Mouse Model of Maternal Immune Activation.

Maternal infections during pregnancy and the consequent maternal immune activation (MIA) are the major risk factors for autism spectrum disorder (ASD). Epidemiological evidence is corroborated by the preclinical models in which MIA leads to ASD-like behavioral abnormalities and altered neuroinflammatory profiles, with an increase in pro-inflammatory cytokines and microglial markers. In addition to neuroinflammatory response, an abnormal expression of endogenous retroviruses (ERVs) has been identified in neurodevelopmental disorders and have been found to correlate with disease severity. Our aim was to evaluate the transcriptional profile of several ERV families, ERV-related genes, and inflammatory mediators (by RT real-time PCR) in mouse offspring of both sexes, prenatally exposed to polyinosinic:polycytidylic acid (Poly I:C), a synthetic double-stranded RNA molecule targeting TLR-3 that mimics viral maternal infection during pregnancy. We found that prenatal exposure to Poly I:C deregulated the expression of some ERVs and ERV-related genes both in the prefrontal cortex (PFC) and hippocampus, while no changes were detected in the blood. Interestingly, sex-related differences in the expression levels of some ERVs, ERV-related genes, and inflammatory mediators that were higher in females than in males emerged only in PFC. Our findings support the tissue specificity of ERV and ERV-related transcriptional profiles in MIA mice.

Urethral and bladder neck stenosis after thulium laser enucleation of the prostate: Analysis of risk factors in a series of 1003 patients.

We assessed the incidence and risks factors of bladder neck and urethral stenosis after Thulium laser enucleation of the prostate. Patients who underwent surgery at two centres were retrospectively reviewed (December 2014-June 2020). Exclusion criteria: previous urethral/prostatic surgery, pelvic irradiation, prostate cancer, neurogenic bladder, history of bladder neck and urethral stenosis, concomitant transurethral surgery, active urinary tract infection. Significant variables at univariate analysis (p < 0.05) were included in a multivariate logistic regression analysis to establish their association with bladder neck/urethral stenosis. One thousand and three patients were included. Median age was 69.0 (63.0-75.0) years. Median prostate volume was 65.0 (46.3-82.0) ml. Median follow-up was 31 (25-75) months. Thirty patients (2.99%) developed bladder neck stenosis [median time after surgery: 15 (11-17.75) months], 50 patients (4.98%) urethral stenosis [median time after surgery: 9 (7-11) months]. Men with bladder neck and urethral stenosis had significantly smaller prostate volume (median volume 43.5 ml vs. 66.0 ml, p = 0.008, and 52.0 ml vs. 66.0 ml, p = 0.009, respectively). At multivariable analysis, short surgical time predicted for bladder neck stenosis (OR 0.973; 95% CI 0.957-0.994, p = 0.002), and re-catheterization (OR 3.956; 95% CI 1.867-8.382, p < 0.001) for urethral stenosis, whereas prostate volume was significantly associated with a lower incidence of US (OR 0.984, 95% CI 0.972-0.998, p = 0.03).

Thulium laser enucleation of prostate versus laparoscopic trans-vesical simple prostatectomy in the treatment of large benign prostatic hyperplasia: head-to-head comparison

ABSTRACT Objectives: To compare thulium laser enucleation of prostate (ThuLEP) versus laparoscopic trans-vesical simple prostatectomy (LSP) in the treatment of benign prostatic hyperplasia (BPH). Materials and Methods: Data of patients who underwent surgery for "large" BPH (>80mL) at three Institutions were collected and analyzed. Two institutions performed ThuLEP only; the third institution performed LSP only. Preoperative (indwelling catheter status, prostate volume (PVol), hemoglobin (Hb), Qmax, post-voiding residual volume (PVR), IPSS, QoL, IIEF-5) and perioperative data (operative time, enucleated adenoma, catheterization time, length of stay, Hb-drop, complications) were compared. Functional (Qmax, PVR, %ΔQmax) and patient-reported outcomes (IPSS, QoL, IIEF-5, %ΔIPSS, %ΔQoL) were compared at last follow-up. Results: 80 and 115 patients underwent LSP and ThuLEP, respectively. At baseline, median PVol was 130 versus 120mL, p <0.001; Qmax 9.6 vs. 7.1mL/s, p=0.005; IPSS 21 versus 25, p <0.001. Groups were comparable in terms of intraoperative complications (1 during LSP vs. 3 during ThuLEP) and transfusions (1 per group). Differences in terms of operative time (156 vs. 92 minutes, p <0.001), Hb-drop (-2.5 vs. −0.9g/dL, p <0.001), catheterization time (5 vs. 2 days, p <0.001) and postoperative complications (13.8% vs. 0, p <0.001) favored ThuLEP. At median follow-up of 40 months after LSP versus 30 after ThuLEP (p <0.001), Qmax improved by 226% vs. 205% (p=0.5), IPSS decreased by 88% versus 85% (p=0.9), QoL decreased by 80% with IIEF-5 remaining almost unmodified for both the approaches. Conclusions: Our analysis showed that LSP and ThuLEP are comparable in relieving from BPO and improving the patient-reported outcomes. Invasiveness of LSP is more significant.

The efficacy of a suppository based on Phenolmicin P3 and Bosexil (Mictalase®) in control of irritative symptoms in patients undergoing thulium laser enucleation of prostate: a single-center, randomized, controlled, open label, phase III study.

BACKGROUND: Several studies described post-operative irritative symptoms after laser enucleation of prostate, sometimes associated with urge incontinence, probably linked to laser-induced prostatic capsule irritation, and potential for lower urinary tract infections We aimed to evaluate the efficacy of a suppository based on Phenolmicin P3 and Bosexil (Mictalase®) in control of irritative symptoms in patients undergoing thulium laser enucleation of prostate (ThuLEP). METHODS: In this single-center, prospective, randomized, open label, phase-III study, patients with indication to ThuLEP were enrolled (Dec2019-Feb2021-Institutional ethics committee STS CE Lazio approval no.1/N-726-ClinicalTrials.gov NCT05130918). The report conformed to CONSORT 2010 guidelines. Eligible patients were 1:1 randomized. Randomization defined Group A: patients who were administered Mictalase® suppositories twice a day for 5 days, then once a day for other 10 days; Group B: patients who did not receive Mictalase® ("controls"). Study endpoints were evaluated at 15 and 30 days postoperation. Primary endpoint included evaluation of effects of the suppository on irritative symptoms by administering IPSS + QoL questionnaire. Secondary endpoint included evaluation of effects on urinary tract infections by performance of urinalysis with urine culture. RESULTS: 111 patients were randomized: 56 in Group A received Mictalase®. Baseline and perioperative data were comparable. At 15-days, no significant differences were found in terms of IPSS + QoL scores and urinalysis parameters. A significant difference in the rate of positive urine cultures favored Group A (p = 0.04). At 30-days follow-up, significant differences were found in median IPSS score (6 [IQR 3-11] versus 10 [5-13], Group A vs B, respectively, p = 0.02). Urinalysis parameters and rate of positive urine cultures were not significantly different. CONCLUSIONS: The present randomized trial investigated the efficacy of Mictalase® in control of irritative symptoms and prevention of lower urinary tract infections in patients undergoing ThuLEP. IPSS improvement 30-days postoperation was more pronounced in patients who received Mictalase®. Lower rate of positive urine culture favored Mictalase® group 15-days postoperatively. TRIAL REGISTRATION: The clinical trial has been registered on ClinicalTrials.gov on November 23rd, 2021-Registration number NCT05130918.

Thulium laser enucleation of prostate versus laparoscopic trans-vesical simple prostatectomy in the treatment of large benign prostatic hyperplasia: head-to-head comparison.

OBJECTIVES: To compare thulium laser enucleation of prostate (ThuLEP) versus laparoscopic trans-vesical simple prostatectomy (LSP) in the treatment of benign prostatic hyperplasia (BPH). MATERIALS AND METHODS: Data of patients who underwent surgery for "large" BPH (>80mL) at three Institutions were collected and analyzed. Two institutions performed ThuLEP only; the third institution performed LSP only. Preoperative (indwelling catheter status, prostate volume (PVol), hemoglobin (Hb), Qmax, post-voiding residual volume (PVR), IPSS, QoL, IIEF-5) and perioperative data (operative time, enucleated adenoma, catheterization time, length of stay, Hb-drop, complications) were compared. Functional (Qmax, PVR, %ΔQmax) and patient-reported outcomes (IPSS, QoL, IIEF-5, %ΔIPSS, %ΔQoL) were compared at last follow-up. RESULTS: 80 and 115 patients underwent LSP and ThuLEP, respectively. At baseline, median PVol was 130 versus 120mL, p <0.001; Qmax 9.6 vs. 7.1mL/s, p=0.005; IPSS 21 versus 25, p <0.001. Groups were comparable in terms of intraoperative complications (1 during LSP vs. 3 during ThuLEP) and transfusions (1 per group). Differences in terms of operative time (156 vs. 92 minutes, p <0.001), Hb-drop (-2.5 vs. -0.9g/dL, p <0.001), catheterization time (5 vs. 2 days, p <0.001) and postoperative complications (13.8% vs. 0, p <0.001) favored ThuLEP. At median follow-up of 40 months after LSP versus 30 after ThuLEP (p <0.001), Qmax improved by 226% vs. 205% (p=0.5), IPSS decreased by 88% versus 85% (p=0.9), QoL decreased by 80% with IIEF-5 remaining almost unmodified for both the approaches. CONCLUSIONS: Our analysis showed that LSP and ThuLEP are comparable in relieving from BPO and improving the patient-reported outcomes. Invasiveness of LSP is more significant.

The microbiological profile of patients with Fournier's gangrene: A retrospective multi-institutional cohort study.

OBJECTIVES: To evaluate the role of the microbiological profile and of disease-related factors in the management of patients affected with Fournier's gangrene (FG). PATIENTS AND METHODS: Data regarding patients admitted for FG at nine Italian Hospitals (March 2007-June 2018) were collected. Patients were stratified according to the number of microorganisms documented: Group A - one microorganism; Group B - two microorganisms; Group C - more than three microorganisms. Baseline blood tests, dedicated scoring systems, predisposing risk factors, disease's features, management and post-operative course were analyzed. UpSet technique for visualizing set intersections in a matrix layout and Cuzick's nonparametric test for trend across ordered groups were used. RESULTS: Eighty-one patients were available for the analysis: 18 included in Group A, 32 in Group B, 31 in Group C. The most common microorganism isolated was Escherichia coli. In Group B-C, Escherichia coli was often associated to Enterococcus faecalis, Pseudomonas aeruginosa, and Klebsiella pneumoniae. Statistically significant positive association was highlighted among the number of pathogens (Group A vs B vs C) and serum C-reactive Protein (p < 0.001), procalcitonin (p = 0.02) and creatinine (p = 0.03). Scoring systems were associated with the number of microorganisms detected (p < 0.02). A significant association between the number of microorganisms and the use of VAC therapy and need of a fecal diversion was found (p < 0.02). The number of microorganisms was positively associated with the length of stay (LOS) (p = 0.02). Ten weeks after initial debridement, wound closure was achieved in 11 (91.7%), 22 (84.6%) and 20 (80%) patients in Group A, B, and C, respectively, with no differences in overall survival. CONCLUSION: Polymicrobial infections in FG are positively associated with inflammatory scores, the need for fecal diversion and the LOS. This results may help the counseling and the clinical management of this rare niche of patients.

Robotic Off-Clamp Simple Enucleation Single-Layer Renorrhaphy Partial Nephrectomy (ROSS): Surgical Insights after an Initial Experience.

Robotic technology allows the beginner surgeon to approach minimally-invasive partial nephrectomy (PN) avoiding the otherwise long learning curve of pure laparoscopy. The present video-article reported the surgical technique and the outcomes of the first 11 cases performed by a young surgeon starting with the experience of robotic PN. Transperitoneal robotic PN, with an off-clamp approach, a simple enucleation technique, and a single-layer medullar renorrhaphy was performed uneventfully in all cases but one, with comparable outcomes to the available literature. With the present experience, we are trying to give the reader a different point of view of the current knowledge. In our series, off-clamp robotic PN was not chosen while looking for a better functional outcome, but rather as a "forced" choice within the specific "in training" setting the interventions were performed in. We underline how the off-clamp approach was the way to cut out the potential for vascular complications derived from the application/removal of the clamp itself on the renal artery. Indeed, when Scanlan bulldogs are not available, one of the limits of robotic PN is that the first surgeon is not autonomous in placing/removing the clamp. We found that tumour enucleation resection technique had the perfect synergistic effect in maximizing the perioperative vision, and thus the safety, notwithstanding the clampless approach.

Is thulium laser vapoenucleation of the prostate equally safe and effective in elderly patients? A propensity score matched analysis of early perioperative and functional outcomes.

PURPOSE: To evaluate if thulium laser vapoenucleation of the prostate (ThuVEP) is equally safe and effective in a selected cohort of elderly patients when compared to "younger" patients. MATERIALS AND METHODS: We performed a retrospective analysis of consecutive patients who underwent ThuVEP between September 2018 and February 2020. After application of the inclusion/exclusion criteria, patients were stratified according to the 75 years-old cut-off point suggested by the WHO. Group A included patients ≤75 years-old; Group B included patients >75 years-old. Preoperative assessment included urological consultation, prostate specific antigen (PSA), International Prostate Symptom Score (IPSS) and quality of life index, transrectal ultrasound to estimate prostate volume (PVol), and uroflowmetry to assess preoperative Qmax, Qave and post-void residual volume (PVR). Perioperative and postoperative data were analyzed during 3-month follow-up. RESULTS: After propensity-score analysis, 51 versus 51 patients were 1:1 matched according to PVol, PSA, Qmax, IPSS and QoL. Patients were comparable at baseline excluding age (65 (IQR 59-70) versus 79 (IQR 77-82) years, Group A versus B, respectively, P-value <.001). No differences were found in terms of hemoglobin drop, complications rate, catheterization time and length of hospital stay. Group A (younger) patients had more significant improvement in 30-days absolute Qmax, Qave and ΔQmax. At 90-days follow-up, the differences between the groups disappeared. Within the 90-days follow-up, no significant differences were found in the readmission rate, with no need of reinterventions. CONCLUSIONS: In our hands, even in elderly patients affected by BPH, ThuVEP appears to be a safe and effective treatment option.

Global mapping of cancers: The Cancer Genome Atlas and beyond.

Cancer genomes have been explored from the early 2000s through massive exome sequencing efforts, leading to the publication of The Cancer Genome Atlas in 2013. Sequencing techniques have been developed alongside this project and have allowed scientists to bypass the limitation of costs for whole-genome sequencing (WGS) of single specimens by developing more accurate and extensive cancer sequencing projects, such as deep sequencing of whole genomes and transcriptomic analysis. The Pan-Cancer Analysis of Whole Genomes recently published WGS data from more than 2600 human cancers together with almost 1200 related transcriptomes. The application of WGS on a large database allowed, for the first time in history, a global analysis of features such as molecular signatures, large structural variations and noncoding regions of the genome, as well as the evaluation of RNA alterations in the absence of underlying DNA mutations. The vast amount of data generated still needs to be thoroughly deciphered, and the advent of machine-learning approaches will be the next step towards the generation of personalized approaches for cancer medicine. The present manuscript wants to give a broad perspective on some of the biological evidence derived from the largest sequencing attempts on human cancers so far, discussing advantages and limitations of this approach and its power in the era of machine learning.

Robot-assisted re-do sacrohysteropexy after anterior abdominal wall hysteropexy.

INTRODUCTION AND HYPOTHESIS: We report the case of a 49-year-old woman who came to our institution complaining of bowel constipation and bladder outlet obstruction due to the recurrence of a pelvic prolapse after anterior abdominal wall hysteropexy performed 1 year before. METHODS: The patient was counseled to undergo robot-assisted re-do sacrohysteropexy performed using the da Vinci Xi surgical system. The step-by-step technique used for the herein reported clinical case of robot-assisted re-do sacrohysteropexy is shown in the accompanying video. RESULTS: Operative time was 120 min. There was virtually no blood loss. No intraoperative complications occurred. Use of analgesic drugs was stopped on the 1st postoperative day. The patient was mobilized on postoperative day 2. The catheter was removed on the 3rd postoperative day, and the patient got back to spontaneous micturition with no post-voiding residual. On the same day, the patient was discharged. At 3-month follow-up, the patient was well with neither bowel nor bladder symptoms. Uroflowmetry was normal. CONCLUSION: We demonstrated the feasibility of robot-assisted re-do sacrohysteropexy. In the surgical technique herein reported, we showed how we were able to partially re-use a previously implanted mesh together with a new one to ensure fixation of a multi-compartment pelvic organ prolapse.