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Intensive therapies of delayed cerebral ischemia (DCI) following aneurysmal subarachnoid hemorrhage (aSAH) have still controversial and unproven benefit. We aimed to compare the overall efficacy of two different center-driven strategies for the treatment of DCI respectively with and without vasospasm angioplasty. Two hundred consecutive patients with aSAH were enrolled in each of two northern European centers. In an interventional center, vasospasm angioplasty was indicated as first line rather than rescue treatment of DCI using distal percutaneous balloon angioplasty technique combined with intravenous milrinone. In non-interventional center, induced hypertension was the only intensive therapy of DCI. Radiological DCI (new cerebral infarcts not visible on immediate post-treatment imaging), death at 1 month, and favorable outcome at 6 months (modified Rankin scale score ≤ 2) were retrospectively analyzed by independent observers and compared between two centers before and after propensity score (PS) matching for baseline characteristics. Baseline characteristics only differed between centers for age and rate of smokers and patients with chronic high blood pressure. In the interventional center, vasospasm angioplasty was performed in 38% of patients with median time from bleeding of 8 days (Q1 = 6.5;Q3 = 10). There was no significant difference of incidence of radiological DCI (9% vs.14%, P = 0.11), death (8% vs. 9%, P = 0.4), and favorable outcome 74% vs. 72% (P = 0.4) between interventional and non-interventional centers before and after PS matching. Our results suggest either that there is no benefit, or might be minimal, of one between two different center-driven strategies for intensive treatment of DCI. Despite potential lack of power or unknown confounders in our study, these results question the use of such intensive therapies in daily practice without further optimization and validation.

Background The Silk Vista Baby (SVB) flow diverter (FDS) is the only FDS deliverable via a 0.017 inch microcatheter and is specifically designed for the distal vasculature. We sought to evaluate the safety and efficacy of the SVB. Materials and Methods We performed a retrospective review to identify SVB cases at 4 tertiary neurosurgical centres within the U.K. Clinical, procedural, angiographic and follow-up data were collected. Results We identified 60 patients (35 female, 58%) of average age 54 ± 10.5 (range 30–72) with 61 aneurysms, 50 (81.9%) located in the anterior circulation. The majority of the aneurysms treated were unruptured (46, 75.4%) and saccular (46, 75.4%). Dome size was 6.2 ± 6.2 mm (range 1–36mm) and parent vessel diameter was 2.3 ± 0.4 mm (range 1.2-3.3 mm). An average number of 1.07 devices were implanted. Coils or other devices were implanted in 14 aneurysms (23.3%). At last angiographic follow-up (n = 55), 7.5 ± 4.2 months post-procedure, 32 aneurysms (57.1%) were graded as RRC I, 7 (12.5%) RRC II, and 17 RRC III (30.4%). Clinical complications, excluding death, were seen in 4 patients (6.8%) including 1 delayed aneurysm rupture and 3 symptomatic ischaemic events. Only one patient had permanent morbidity (mRS 1). 3 patients died during follow-up (5.1%); 2 deaths were related to the aneurysms (3.4%) – one ruptured dissecting MCA aneurysm, and one giant partially thrombosed posterior circulation aneurysm. 93% of patients were mRS ≤ 2 at last follow-up. Conclusion The SVB has high rates of technical success and an acceptable safety profile. Distal aneurysms may occlude slower due to relative oversizing of the devices.

Antiplatelet therapies are commonly used in neurointerventional procedures. However, specific guidelines for their use in these settings is lacking and it can often be difficult to balance the potential risks and benefits of these medications. Considering the continued growth and adoption of neurointerventional procedures, it is crucial to understand the properties of these agents in order to use them safely. Large-scale clinical trials are still needed to clarify many of these aspects for this emerging field. However, the existing literature already provides insight into which antiplatelet drugs are of benefit to the neurointerventionalist as well as their associated risks of ischemic and hemorrhagic complications. Hence, this review focuses on the applications of GPIIb/IIIA inhibitors to neurointerventional procedures.

The use of antiplatelets is widespread in clinical practice. However, for neurointerventional procedures, protocols for antiplatelet use are scarce and practice varies between individuals and institutions. This is further complicated by the quantity of antiplatelet agents which differ in route of administration, dosage, onset of action, efficacy and ischemic and hemorrhagic complications. Clarifying the individual characteristics for each antiplatelet agent, and their associated risks, will increasingly become relevant as the practice of mechanical thrombectomy, stenting, coiling and flow diversion procedures grows. The aim of this review is to summarize the existing literature for the use of P2Y12 inhibitors in neurointerventional procedures, examine the quality of the evidence, and highlight areas in need of further research.

Hypoxia-induced miR-210 is a crucial component of the tissue response to ischemia, stimulating angiogenesis and improving tissue regeneration. Previous analysis of miR-210 impact on the transcriptome in a mouse model of hindlimb ischemia showed that miR-210 regulated not only vascular regeneration functions, but also inflammation. To investigate this event, doxycycline-inducible miR-210 transgenic mice (Tg-210) and anti-miR-210 LNA-oligonucleotides were used. It was found that global miR-210 expression decreased inflammatory cells density and macrophages accumulation in the ischemic tissue. To dissect the underpinning cell mechanisms, Tg-210 mice were used in bone marrow (BM) transplantation experiments and chimeric mice underwent hindlimb ischemia. MiR-210 overexpression in the ischemic tissue was sufficient to increase capillary density and tissue repair, and to reduce inflammation in the presence of Wt-BM infiltrating cells. Conversely, when Tg-210-BM cells migrated in a Wt ischemic tissue, dysfunctional angiogenesis, inflammation, and impaired tissue repair, accompanied by fibrosis were observed. The fibrotic regions were positive for α-SMA, Vimentin, and Collagen V fibrotic markers and for phospho-Smad3, highlighting the activation of TGF-β1 pathway. Identification of Tg-210 cells by in situ hybridization showed that BM-derived cells contributed directly to fibrotic areas, where macrophages co-expressing fibrotic markers were observed. Cell cultures of Tg-210 BM-derived macrophages exhibited a pro-fibrotic phenotype and were enriched with myofibroblast-like cells, which expressed canonical fibrosis markers. Interestingly, inhibitors of TGF-β type-1-receptor completely abrogated this pro-fibrotic phenotype. In conclusion, a context-dependent regulation by miR-210 of the inflammatory response was identified. miR-210 expression in infiltrating macrophages is associated to improved angiogenesis and tissue repair when the ischemic recipient tissue also expresses high levels of miR-210. Conversely, when infiltrating an ischemic tissue with mismatched miR-210 levels, macrophages expressing high miR-210 levels display a pro-fibrotic phenotype, leading to impaired tissue repair, fibrosis, and dysfunctional angiogenesis. ispartof: CELL DEATH & DISEASE vol:12 issue:5 ispartof: location:England status: published

The intestinal epithelial barrier (IEB) is one of the largest interfaces between the environment and the internal milieu of the body. It is essential to limit the passage of harmful antigens and microorganisms and, on the other side, to assure the absorption of nutrients and water. The maintenance of this delicate equilibrium is tightly regulated as it is essential for human homeostasis. Luminal solutes and ions can pass across the IEBviatwo main routes: the transcellular pathway or the paracellular pathway. Tight junctions (TJs) are a multi-protein complex responsible for the regulation of paracellular permeability. TJs control the passage of antigens through the IEB and have a key role in maintaining barrier integrity. Several factors, including cytokines, gut microbiota, and dietary components are known to regulate intestinal TJs. Gut microbiota participates in several human functions including the modulation of epithelial cells and immune system through the release of several metabolites, such as short-chain fatty acids (SCFAs). Mediators released by immune cells can induce epithelial cell damage and TJs dysfunction. The subsequent disruption of the IEB allows the passage of antigens into the mucosa leading to further inflammation. Growing evidence indicates that dysbiosis, immune activation, and IEB dysfunction have a role in several diseases, including irritable bowel syndrome (IBS), inflammatory bowel disease (IBD), and gluten-related conditions. Here we summarize the interplay between the IEB and gut microbiota and mucosal immune system and their involvement in IBS, IBD, and gluten-related disorders.

ObjectiveNon-coeliac gluten sensitivity (NCGS) is characterised by intestinal and extraintestinal symptoms related to the ingestion of gluten-containing foods, in the absence of coeliac disease (CD) and wheat allergy. No biomarkers are available to diagnose NCGS and the gold standard double-blind placebo-controlled gluten challenge is clinically impractical. The aim of our work was to investigate the role of serum zonulin as a diagnostic biomarker of NCGS and to develop a diagnostic algorithm.DesignIn a multicentre study, we enrolled 86 patients with either self-reported or double-blind confirmed NCGS, 59 patients with diarrhoea-predominant IBS (IBS-D), 15 patients with CD and 25 asymptomatic controls (AC). Zonulin serum levels were assessed and the associated diagnostic power calculated. Clinical and symptomatic data were recorded. The effect of diet on zonulin levels was evaluated in a subgroup of patients with NCGS.ResultsCompared with ACs, the NCGS, irrespective of modality of diagnosis, and patients with CD had significantly increased levels of zonulin, as did both NCGS and patients with CD compared with participants with IBS-D. Self-reported NCGS showed increased zonulin levels compared with double-blind confirmed and not-confirmed NCGS. Six-month wheat avoidance significantly reduced zonulin levels only in HLA-DQ2/8-positive participants with NCGS. The diagnostic accuracy of zonulin levels in distinguishing NCGS from IBS-D was 81%. After exclusion of CD, a diagnostic algorithm combining zonulin levels, symptoms and gender improved the accuracy to 89%.ConclusionZonulin can be considered a diagnostic biomarker in NCGS and combined with demographic and clinical data differentiates NCGS from IBS-D with high accuracy. Wheat withdrawal was associated with a reduction in zonulin levels only in NCGS carrying HLA genotype.

Background: Diversion after radical cystectomy (RC) is crucial when considering elderly subjects. Data on the quality of life (QoL) impact with different diversions is scarce. This study aims to compare complications and QoL in patients aged > 75 y.o., who underwent minimally invasive (MI) RC with Bricker intracorporeal urinary derivation and single stoma ureterocutaneostomy. Methods: We conducted a retrospective analysis of elderly patients who underwent MIRC and intracorporeal diversion. The 78 subjects were divided into two groups: group A, ileal conduit, and group B, single stoma ureterocutaneostomy. We evaluated the bowel’s recovery time and complications rate. We investigated QoL 3 and 6 months after surgery using the Stoma-QoL questionnaire. Results: Mean age was 77.2 in group A and 82.4 in group B. The mean ASA score and Charlson Comorbidity index were comparable between the two groups. Rates of complications were 57.6% and 37.4% in groups A and B, respectively. The mean postoperative Stoma-QoL score 3 months after surgery was 52.2 and 52.4 in groups A and B, respectively. At 6 months of follow-up the Stoma QoL mean score was 63.4, showing homogeneity between the groups. Conclusion: MIRC with single stoma ureterocutaneostomy represents an alternative to ileal conduit, with comparable QoL and ostomy management 6 months after surgery, reporting fewer complications.

Gluten-free diets are increasingly chosen in the Western world, even in the absence of a diagnosis of celiac disease. Around 10% of people worldwide self-report gluten-related complaints, including intestinal and extra-intestinal symptoms. In most cases, these subjects would be labeled as patients suffering from irritable bowel syndrome (IBS) who place themselves on a gluten-free diet even in the absence of celiac disease. In some instances, patients report a clear benefit by avoiding gluten from their diet and/or symptom worsening upon gluten reintroduction. This clinical entity has been termed non-celiac gluten sensitivity (NCGS). The symptoms referred by these patients are both intestinal and extra-intestinal, suggesting that similarly to functional gastrointestinal disorders, NCGS is a disorder of gut–brain interaction. It remains unclear if gluten is the only wheat component involved in NCGS. The mechanisms underlying symptom generation in NCGS remain to be fully clarified, although in the past few years, the research has significantly moved forward with new data linking NCGS to changes in gut motility, permeability and innate immunity. The diagnosis is largely based on the self-reported reaction to gluten by the patient, as there are no available biomarkers, and confirmatory double-blind challenge protocols are unfeasible in daily clinical practice. Some studies suggest that a small proportion of patients with IBS have an intolerance to gluten. However, the benefits of gluten-free or low-gluten diets in non-celiac disease-related conditions are limited, and the long-term consequences of this practice may include nutritional and gut microbiota unbalance. Here, we summarize the role of gluten in the clinical features, pathophysiology, and management of NCGS and disorders of gut–brain interaction.

INTRODUCTION AND OBJECTIVE:Ureteral injuries are well-known complications of abdominal surgery. The aim of the study is to evaluate the safety and feasibility of Allium ureteral prosthesis in patie...

INTRODUCTION AND OBJECTIVE:There has been a significant development of minimally invasive surgical techniques (MISTs) for the treatment of BPH. Prostatic artery embolization (PAE) is one of the mos...

Redox homeostasis plays a pivotal role in vascular cell function and its imbalance has a causal role in a variety of vascular diseases. Accordingly, the response of mammalian cells to redox cues requires precise transcriptional and post-transcriptional modulation of gene expression patterns. Recent Advances: Mounting evidence shows that nonprotein-coding RNAs (ncRNAs) are important for the functional regulation of most, if not all, cellular processes and tissues. Not surprisingly, a prominent role of ncRNAs has been identified also in the vascular system response to oxidative stress.The highly heterogeneous family of ncRNAs has been divided into several groups. In this article we focus on two classes of regulatory ncRNAs: microRNAs and long ncRNAs (lncRNAs). Although knowledge in many circumstances, and especially for lncRNAs, is still fragmentary, ncRNAs are clinically interesting because of their diagnostic and therapeutic potential. We outline ncRNAs that are regulated by oxidative stress as well as ncRNAs that modulate reactive oxygen species production and scavenging. More importantly, we describe the role of these ncRNAs in vascular physiopathology and specifically in disease conditions wherein oxidative stress plays a crucial role, such as hypoxia and ischemia, ischemia reperfusion, inflammation, diabetes mellitus, and atherosclerosis.The therapeutic potential of ncRNAs in vascular diseases and in redox homeostasis is discussed.

Background: The T1 substaging of bladder cancer (BCa) potentially impacts disease progression. The objective of the study was to compare the prognostic accuracy of two substaging systems on the recurrence and progression of primary pathologic T1 (pT1) BCa and to test a nomogram based on pT1 substaging for predicting recurrence-free survival (RFS) and progression-free survival (PFS).Methods: The medical records of 204 patients affected by pT1 BCa were retrospectively reviewed. Substaging was defined according to the depth of lamina propria invasion in T1a−c and the extension of the lamina propria invasion to T1-microinvasive (T1m) or T1-extensive (T1e). Uni- and multivariable Cox regression models evaluated the independent variables correlated with recurrence and progression. The predictive accuracies of the two substaging systems were compared by Harrell's C index. Multivariate Cox regression models for the RFS and PFS were also depicted by a nomogram.Results: The 5-year RFS was 47.5% with a significant difference between T1c and T1a (p = 0.02) and between T1e and T1m (p < 0.001). The 5-year PFS was 75.9% with a significant difference between T1c and T1a (p = 0.011) and between T1e and T1m (p < 0.001). Model T1m−e showed a higher predictive power than T1a−c for predicting RFS and PFS. In the univariate and multivariate model subcategory T1e, the diameter, location, and number of tumors were confirmed as factors influencing recurrence and progression after adjusting for the other variables. The nomogram incorporating the T1m−e model showed a satisfactory agreement between model predictions at 5 years and actual observations.Conclusions: Substaging is significantly associated with RFS and PFS for patients affected by T1 BCa and should be included in innovative prognostic nomograms.

Hypoxia-induced miR-210 is a crucial component of the tissue response to ischemia, stimulating angiogenesis and improving tissue regeneration. Previous analysis of miR-210 impact on the transcriptome in a mouse model of hindlimb ischemia showed that miR-210 regulated not only vascular regeneration functions, but also inflammation. To investigate this event, doxycycline-inducible miR-210 transgenic mice (Tg-210) and anti-miR-210 LNA-oligonucleotides were used. It was found that global miR-210 expression decreased inflammatory cells density and macrophages accumulation in the ischemic tissue. To dissect the underpinning cell mechanisms, Tg-210 mice were used in bone marrow (BM) transplantation experiments and chimeric mice underwent hindlimb ischemia. MiR-210 overexpression in the ischemic tissue was sufficient to increase capillary density and tissue repair, and to reduce inflammation in the presence of Wt-BM infiltrating cells. Conversely, when Tg-210-BM cells migrated in a Wt ischemic tissue, dysfunctional angiogenesis, inflammation, and impaired tissue repair, accompanied by fibrosis were observed. The fibrotic regions were positive for α-SMA, Vimentin, and Collagen V fibrotic markers and for phospho-Smad3, highlighting the activation of TGF-β1 pathway. Identification of Tg-210 cells by in situ hybridization showed that BM-derived cells contributed directly to fibrotic areas, where macrophages co-expressing fibrotic markers were observed. Cell cultures of Tg-210 BM-derived macrophages exhibited a pro-fibrotic phenotype and were enriched with myofibroblast-like cells, which expressed canonical fibrosis markers. Interestingly, inhibitors of TGF-β type-1-receptor completely abrogated this pro-fibrotic phenotype. In conclusion, a context-dependent regulation by miR-210 of the inflammatory response was identified. miR-210 expression in infiltrating macrophages is associated to improved angiogenesis and tissue repair when the ischemic recipient tissue also expresses high levels of miR-210. Conversely, when infiltrating an ischemic tissue with mismatched miR-210 levels, macrophages expressing high miR-210 levels display a pro-fibrotic phenotype, leading to impaired tissue repair, fibrosis, and dysfunctional angiogenesis.

Critical limb ischemia is the most serious form of peripheral artery disease, characterized by severe functional consequences, difficult clinical management and reduced life expectancy. The goal of this study was to investigate the miR-210 role in the neo-angiogenic response after acute limb ischemia. Complementary approaches were used in a mouse model of hindlimb ischemia: miR-210 loss-of-function was obtained by administration of LNA-oligonucleotides anti-miR-210, for miR-210 gain-of-function, a doxycycline-inducible miR-210 transgenic mouse was used. We tested miR-210 ability to stimulate vascular regeneration following ischemia. We found that miR-210 was necessary and sufficient to stimulate blood perfusion recovery, as well as arteriolar and capillary density increase, in the ischemic muscle. To clarify the molecular events underpinning miR-210 pro-angiogenic action, the transcriptomic changes in ischemic muscles upon miR-210 blocking were analyzed. We found that miR-210 impacted the transcriptome significantly, regulating pathways and functions linked to vascular regeneration. In agreement with a pro-angiogenic role, miR-210 also improved cardiac function and left ventricular remodeling after myocardial infarction. Moreover, miR-210 blocking decreased capillary density in a Matrigel plug assay, indicating that miR-210 is necessary for angiogenesis independently of ischemia. Collectively, these data indicate that miR-210 plays a pivotal role in promoting vascular regeneration.

Introduction We previously demonstrated in mouse models of peripheral and heart ischemia that miR-210 is necessary and sufficient to stimulate blood perfusion recovery, as well as arteriolar and capillary density increase following ischemic damage. Aim To clarify the role of inflammatory cells in miR-210-induced angiogenesis. Methods and results In a mouse model of acute limb ischemia, miR-210 loss-of-function was obtained by administration of complementary anti-miR-210 LNA oligonucleotides (anti-210), while doxycycline-inducible miR-210 transgenic mice (Tg210) were used for gain-of-function experiments. Transcriptomic and gene ontology analysis in ischemic gastrocnemius muscles upon miR-210 blocking displayed an enrichment of categories related not only to angiogenesis, but also to inflammation, suggesting that miR-210 decrease prompted a pro-inflammatory and anti-regenerative response. Accordingly, immunofluorescence staining of ischemic muscles of anti-210 treated mice, showed an increased presence of granulocytes (Scr = 28±7, anti-210 = 108±17 cells/mm2, p Conclusions Collectively, these data show that a miR-210 enriched milieu was sufficient to improve angiogenesis after ischemia. Moreover, a context-dependent regulation by miR-210 of the inflammatory response and of fibrosis were identified. Funding Acknowledgement Type of funding source: Public hospital(s). Main funding source(s): Italian Ministry of health: Ricerca Corrente and 5X1000

Papillary renal cell carcinoma (PRCC) is a rare cancer and is the second most frequent histologic type among all renal cell carcinoma, accounting for up to 15%. A 72-year-old man underwent a right radical nephrectomy 7 years ago with final histopathology diagnosis of type 1 PRCC with negative surgical margins. Five years after surgery, computed tomography scan imaging showed the presence of multiple masses suspicious for node recurrences disease localized in the renal lodge, in the inter-aorto-caval space, at the iliac vessels bifurcation and right common iliac vessels. Patient underwent a robotic retroperitoneal lymphadenectomy. The histopathological examination confirmed the recurrence of type I papillary renal cancer in all the specimens. No further recurrences have been observed at 24-month follow-up after surgery. This report is the first describing a robot-assisted minimally invasive surgical excision for type I papillary renal cancer nodal and renal fossa recurrences.

AIMS Shear wave elastosonography (SWE) is a non-invasive ultrasound imaging modality used to assess the mechanical properties of tissues such as rigidity and elasticity. In this prospective study, we investigated the effect of laparoscopic varicocelectomy on the elasticity, degree of fibrosis and function of the testes through SWE and we evaluated the correlation with semen parameters and histology findings. METHODS Male patients with monolateral left varicocele and progressive alteration of the semen quality were enrolled prospectively. Patients were evaluated before varicocelectomy, 3 and 6 months after surgery with semen analysis, ecocolordoppler US and SWE. In all patients, a left testicular biopsy was performed at the time of varicocelectomy and it was repeated after 6 months in 55% of patients in order to investigate the histological findings and to correlate with SWE results. RESULTS The study was conducted on 82 patients. SWE showed a statistically significant difference between left and right testicles. Three months after surgery the mean left testicular volume increased, mean left SWE features decreased, and sperm count increased (P values

Background Obtaining detrusor muscle (DM) in transurethral resection of bladder tumor (TURBt) specimen is considered a surrogate marker of resection quality. However, evidence was principally investigated in high-risk tumors. Therefore, DM sampling for low-grade (LG) urothelial carcinoma (UC) remains poorly investigated and certainly requires further investigation. Objective To assess whether the absence of DM in TURBt specimen has a negative impact on recurrence-free survival (RFS) in patients with a Ta LG UC. Design, setting, and participants A multicenter TURBt database was queried for “LG, Ta, UC of the bladder.” All patients treated between 1996 and 2018 with tumor grade assessed according to both 1973 World Health Organization and 2004 WHO/International Society of Urological Pathology grading classifications and with a minimum follow-up of 1 yr were included. Patients with a previous history of high-grade UC, upper urinary tract UC, or bladder tumor differentiations other than UC were excluded. Intervention TURBt. Outcome measurements and statistical analysis Baseline demographic, clinical, and pathologic data were analyzed. The European Organization for Research and Treatment of Cancer (EORTC) risk group was recorded. Kaplan-Meier analysis was performed to assess the predictive role of clinical and pathologic data for RFS. Univariable and multivariable Cox regression analyses were performed to identify the predictors of recurrence. Results and limitations Overall, 521 patients were included. At Kaplan-Meier analysis, the low-risk cohort displayed significantly higher RFS than the intermediate-risk cohort (1-yr RFS 87% vs 79%; log-rank p = 0.007). At univariable Cox regression analysis, only gender, multiple tumors, tumor diameter ≥3 cm, and EORTC risk group were significant predictors of recurrence. Absence of DM had no impact on RFS. Multivariable Cox regression analysis confirmed gender and EORTC risk group as independent predictors of recurrence. Conclusions Absence of DM in TURBt specimen has negligible role in RFS of patients with Ta LG tumors of the bladder. Patient summary In this study, we assessed the role that detrusor muscle (DM) in transurethral resection of bladder tumor specimen has in recurrence-free survival, in patients with a Ta low-grade urothelial carcinoma of the bladder. Absence of DM has no impact on tumor recurrence; therefore, it does not require additional attention.

BackgroundWhile anatomic features associated with the risk of posterior communicating artery (PcoA) occlusion after embolization of aneurysms of the PcoA segment of the internal carotid artery (ICA) are well known, the link between perforator origin and perforator infarction has only been reported following neurosurgical clipping. The aim of this study was to determine the origin of anterior thalamic perforators and correlate it with risk of perforator infarction after embolization of PcoA segment aneurysms.MethodsOne-hundred-and-ninety consecutive patients treated for PcoA segment aneurysms between 2017 and 2019 were included. PcoA and anterior thalamic perforator origin anatomy was assessed with computed tomography (CT) angiography, digital subtracted angiography, and high-resolution three-dimensional rotational cone-beam CT angiography (CBCT-A) by two independent interventional neuroradiologists. The presence of perforator infarction after embolization was ascertained from the patient’s notes and follow-up imaging.ResultsCBCT-A was superior in demonstrating the origin of perforators (PConclusionsOur study suggests that anterior thalamic perforators may arise from aneurysm wall when there is no PcoA. Anatomic association between PcoA agenesis and perforator arising from ICA could underlie such findings, and careful consideration is essential before aneurysm repair to anticipate the risk of thalamic infarction in such cases.

Post-prostatectomy urinary incontinence is an adverse event leading to significant distress. Our aim was to evaluate immediate urinary continence (UC) recovery in a single-surgeon prospective randomized comparative study between the traditional robot-assisted laparoscopic radical prostatectomy (TR-RALP) and the Retzius-sparing RALP (RS-RALP), for the treatment of the clinically localized prostate cancer (PCa). 102 consecutive PCa patients were prospectively randomized to TR-RALP (57) or RS-RALP (45). Postoperative continence was defined as patient-reported absence of leakage or use of 0 pads/day. The immediate continence rate and 95% confidence interval (CI 95%) were calculated for each treatment. Univariable and multivariate logistic regressions were used to assess predictors of immediate continence following RALP. Continence rates from 1 to 6 months were calculated by Kaplan–Meier curves; log-rank test was used for the curve comparison. Two analyses were performed, considering a per-protocol (PP) population regarding all randomized patients that received nerve-sparing RALP and an Intention-To-Treat (ITT) population regarding all randomized patients that received RALP. In the PP analysis, the rates of immediate continence were 12/40 (30%) (CI 95% 17–47%) for the TR-RALP and 20/39 (51.3%) (CI 95% 35–68%) for the RS-RALP (p = 0.05). In the ITT analysis, the corresponding rates were 12/57 (21%) (CI 95% 11–34%) for the TR-RALP and 23/45 (51%) (CI 95% 36–66%) for the RS-RALP (p = 0.001). Median time to continence was 21 days for the TR-RALP and 1 day for RS-RALP, respectively (p = 0.02). The relative Kaplan–Meier curves regarding continence resulted statistically different when compared with the log rank test (p = 0.02). In the multivariate analysis, lower age and the Retzius-sparing approach were significantly associated to earlier continence recovery. The Retzius-sparing approach significantly reduces time to continence following RALP. Further studies are required to confirm the reproducibility of our results and investigate the role of the RS-RALP as an additional “protective” factor for postoperative continence in the elderly population.

Myotonic dystrophy type 1 (DM1) is a multi-systemic disorder caused by abnormally expanded stretches of CTG DNA triplets in the DMPK gene, leading to mutated-transcript RNA-toxicity. MicroRNAs (miRNAs) are short non-coding RNAs that, after maturation, are loaded onto the RISC effector complex that destabilizes target mRNAs and represses their translation. In DM1 muscle biopsies not only the expression, but also the intracellular localization of specific miRNAs is disrupted, leading to the dysregulation of the relevant mRNA targets. To investigate the functional alterations of the miRNA/target interactions in DM1, we analyzed by RNA-sequencing the RISC-associated RNAs in skeletal muscle biopsies derived from DM1 patients and matched controls. The mRNAs found deregulated in DM1 biopsies were involved in pathways and functions relevant for the disease, such as energetic metabolism, calcium signaling, muscle contraction and p53-dependent apoptosis. Bioinformatic analysis of the miRNA/mRNA interactions based on the RISC enrichment profiles, identified 24 miRNA/mRNA correlations. Following validation in 21 independent samples, we focused on the couple miR-29c/ASB2 because of the role of miR-29c in fibrosis (a feature of late-stage DM1 patients) and of ASB2 in the regulation of muscle mass. Luciferase reporter assay confirmed the direct interaction between miR-29c and ASB2. Moreover, decreased miR-29c and increased ASB2 levels were verified also in immortalized myogenic cells and primary fibroblasts, derived from biopsies of DM1 patients and controls. CRISPR/Cas9-mediated deletion of CTG expansions rescued normal miR-29c and ASB2 levels, indicating a direct link between the mutant repeats and the miRNA/target expression. In conclusion, functionally relevant miRNA/mRNA interactions were identified in skeletal muscles of DM1 patients, highlighting the dysfunction of miR-29c and ASB2.

INTRODUCTION AND OBJECTIVES:Several nomograms have been developed to predict prostate cancer upgrading however very little artificial intelligence (AI) tools are available for this purpose. Aim of ...

Background: Colonic diverticulosis is a common condition in industrialized countries. Up to 25% of patients with diverticula develop symptoms, a condition termed symptomatic uncomplicated diverticular disease (SUDD). The aim of the present study was to characterize neuroimmune interactions and nerve fiber plasticity in the colonic mucosa of patients with diverticula. Methods: Controls, patients with diverticulosis and with SUDD were enrolled in the study. Mucosal biopsies were obtained close to diverticula (diverticular region) and in a normal mucosa (distant site), corresponding to sigmoid and descending colon in the controls. Quantitative immunohistochemistry was used to assess mast cells, T cells, macrophages, nerve fibers, and neuronal outgrowth (growth-associated protein 43, GAP43+fibers). Key Results: No difference emerged in mast cells and T cells among the three groups. Macrophages were increased in patients with SUDD and diverticulosis as compared to controls. Nerve fibers were enhanced in patients with SUDD and diverticulosis in comparison with controls in the diverticular region. GAP43+fibers were increased only in patients with SUDD as compared to controls and to patients with diverticulosis in the diverticular region. In patients with SUDD, GAP43 density was increased in the diverticular region compared to distant site. Macrophages close to GAP43+ fibers were increased in the diverticular region of patients with SUDD. Significant correlations were found between GAP43+ fibers and immune cells. Conclusions and Inferences: Patients with diverticula are characterized by increased macrophage counts, while nerve fiber sprouting is increased only in the diverticular region of patients with SUDD suggesting a role in symptom generation.

Aim of the study Among minimally invasive procedures for treating benign prostate hyperplasia (BPH) prostate artery embolisation (PAE) is described as safe and effective. Aim of this study is to report our results, focusing on sexual outcomes (erectile and ejaculatory functions sparing) of PAE in patients suffering from bladder outlet obstruction (BOO) secondary to BPH. Methods We prospectively enrolled and submitted to PAE subjects suffering from BOO secondary to BPH. All patients were not suitable for surgery or declined invasive approaches. All subjects were preoperatively and postoperatively (3, 6, 12 and 18 months after) evaluated by urinary flowmetry, post voiding residual volume, prostate volume, serum PSA levels, International Index of Erectile Function, International Prostate Symptom Score and QoL scores. Results PAE was performed in 147 patients (mean age 72.5 y.o.). PAE was technically successful in all patients. The procedure lasted a mean time of 94.3 minutes, with a mean fluoroscopic time of 42.5 minutes. Twelve months follow-up data were available for all patients, while 126 patients (85%) completed the 18 months follow up. At 12 months follow up, the mean IPSS and QoL scores significantly decreased, and all the objective parameters (mean Qmax, PVR and prostate volume) reported a significant improvement. A total of 130 patients (88.5%) at 12 months reported the antegrade ejaculation preserved, and a slight not significant improvement of IIEF scores. The 18 months after PAE outcomes confirmed the significant improvement of all the variables evaluated (even for PSA values and IIEF scores). No major complications occurred. Conclusions Our results evidence prostate artery embolisation as highly feasible and safe procedure with interesting outcomes. In particular, in our study PAE reported promising results in preserving antegrade ejaculation and erectile function. Our data are in line with the literature, confirming how PAE reduces obstructive symptoms in BPH patients not suitable or refusing standard surgical approaches.

Background About 75% of urothelial bladder cancers are non-muscle invasive (NMIBC), and limited to mucosa (Ta or CIS) or sub-mucosa (T1). An increase of androgen expression and androgen receptors has a positive effect on oncogenic expression. We aimed to evaluate whether 5-alpha reductase inhibitors (5-ARI) have a role in NMIBC. Methods We retrospectively evaluated the clinical and pathological data of 423 patients with NMIBC who underwent transurethral bladder resection. We analysed the number of resections, number of total recurrences, time of recurrences, and histopathology details. The population was classified into two groups: treated and untreated with 5-ARIs. The enrolled patients were in treatment with 5ARIs for symptomatic prostatic hyperplasia for at least 12 months. Mean follow-up time was 30.43 months. Results Patients treated with 5-ARIs had a lower rate of recurrence (14%) than the untreated group (37%). There was a significant difference in the mean number of recurrences between the untreated and the treated group (p value: 0.006). Furthermore, the treated group showed a significantly greater number of low than high grade tumours, compared to the untreated group (p value ≤ 0.05). There was a significant decrease in the number of muscle invasive tumours in treated patients (p value = 0.032). The recurrence- free survival rate of patients treated with 5-ARIs was significantly higher (p value: 0.0001). Conclusions Long-term treatment with 5- ARIs might reduce the risk of bladder tumour recurrence, extension of lesions and increase the recurrence-free survival rate. A long-term, randomized prospective study could definitively assess the possible role of these drugs.

INTRODUCTION AND OBJECTIVES:Recent evidence suggested the importance of preoperative patients' quality of life on post-operative functional and oncological outcomes. The aim of our study was to eva...

INTRODUCTION AND OBJECTIVES:Cholesterol is the main lipid component of the sperm cell that is essential for sperm membrane fluidity, capacitation, and acrosomal reaction. The main objective of the ...

INTRODUCTION AND OBJECTIVES:The Briganti nomogram, since its publication, has been widely adopted worldwide to predict the risk lymph node invasion in patients undergoing radical prostatectomy. How...

INTRODUCTION AND OBJECTIVES:The aim of the study was to evaluate the long-term (48 months follow-up)outcomes of pelvic floor muscle (PFM) rehabilitation in males suffering from lifelong premature e...

INTRODUCTION AND OBJECTIVES:About 75% of urothelial carcinoma of the bladder are non-invasive (non muscle-invasive bladder cancer, NMIBC), therefore limited to mucosa (Ta or CIS) or sub-mucous (T1)...

Circular RNAs (circRNAs) constitute a recently re-discovered class of non-coding RNAs functioning as sponges for miRNAs and proteins, affecting RNA splicing and regulating transcription. CircRNAs are generated by &ldquo, back-splicing&rdquo, which is the linking covalently of 3&prime, and 5&prime, ends of exons. Thus, circRNA levels might be deregulated in conditions associated with altered RNA-splicing. Significantly, growing evidence indicates their role in human diseases. Specifically, myotonic dystrophy type 1 (DM1) is a multisystemic disorder caused by expanded CTG repeats in the DMPK gene which results in abnormal mRNA-splicing. In this investigation, circRNAs expressed in DM1 skeletal muscles were identified by analyzing RNA-sequencing data-sets followed by qPCR validation. In muscle biopsies, out of nine tested, four transcripts showed an increased circular fraction: CDYL, HIPK3, RTN4_03, and ZNF609. Their circular fraction values correlated with skeletal muscle strength and with splicing biomarkers of disease severity, and displayed higher values in more severely affected patients. Moreover, Receiver-Operating-Characteristics curves of these four circRNAs discriminated DM1 patients from controls. The identified circRNAs were also detectable in peripheral-blood-mononuclear-cells (PBMCs) and the plasma of DM1 patients, but they were not regulated significantly. Finally, increased circular fractions of RTN4_03 and ZNF609 were also observed in differentiated myogenic cell lines derived from DM1 patients. In conclusion, this pilot study identified circRNA dysregulation in DM1 patients.

Background Intestinal permeability is altered in a subgroup of irritable bowel syndrome (IBS) patients and may contribute to symptom development. The aim of this study was to evaluate the in vitro effect of the probiotic Escherichia coli Nissle 1917 (EcN) on Caco-2 permeability alterations induced by mediators released by IBS mucosal biopsies compared to asymptomatic controls (AC). Methods Caco-2 cells were used as an in vitro model of intestinal permeability. Seven AC and 28 well-phenotyped IBS (9 IBS-D, 8 IBS-C, and 11 IBS-M) patients were enrolled. Mucosal mediators spontaneously released (SUP) by IBS and AC biopsies were collected. Two concentrations of EcN (108 and 106 ) were applied to Caco-2 with or without SUP or SLIGRL (a protease-activated receptor-2 activating peptide), tumor necrosis factor-α, and interferon-γ. Paracellular permeability was assessed by evaluating the flow of sulfonic-acid conjugated to fluorescein through Caco-2 monolayer. Key results EcN 108 significantly reinforced Caco-2 monolayer compared to cells incubated with medium alone. IBS SUP induced a significant increase in paracellular permeability compared to AC SUP, independently of IBS bowel habit. EcN 108 induced a significant recovery of permeability rate compared to IBS SUP. Permeability increase induced by IBS SUP significantly correlated with severity and frequency of abdominal pain and abdominal distension. The co-incubation of EcN and IBS SUP abolished the above significant correlations. Conclusions and inferences EcN reinforces the integrity of Caco-2 monolayer and reverts the increase of permeability induced by mediators released by IBS biopsies. Future studies should investigate EcN therapeutic potentials in IBS.

The aim of this study is to investigate the change in quality of life (QoL) and sexual function in women treated for pure stress urinary incontinence (SUI) using tension-free transobturator suburethral tape (TVT-O) and single-incision sling (SIS) procedures.From December 2013 to January 2015, a total of 48 female patients with pure SUI and normotonic urethra were consecutively enrolled and randomized into two treatment groups: TVT-O versus SIS. Both groups were homogeneous in the preoperative evaluation of age, body mass index, comorbidities, and pregnancies. Exclusion criteria included urge urinary incontinence, neurogenic bladder, previous surgery for incontinence, and mental or neurological disorders. The female sexual function and QoL were assessed preoperatively and postoperatively (3-12 months follow-up), using the Female Sexual Function Index (FSFI) and the International Consultation on Incontinence Questionnaire.A total of 42 patients completed both the questionnaires (21 patients in the TVT-O group and 21 patients in the SIS group, whereas 6 patients were lost to follow-up). Of the 19/21 (90.4%) of patients who successfully underwent the SIS procedure, 17 (80.9%) reported a complete resolution of SUI, whereas 2 (9.5%) reported an improvement in urinary incontinence at follow-up. In the TVT-O group, 18/21 (85.7%) of patients reported complete recovery, whereas 4.1% patients reported an improvement in the incontinence. The FSFI score increased significantly in both the SIS groups (from 23:51 ± 3.78 to 27.42 ± 3.34; p 0.001) and TVT-O group (from 23.96 ± 5:56 to 28.09 ± 3.62) with no statistically significant differences between the two treatment groups.In our study, both slings showed a high rate of continence without any major complications. The sexual function also improved sharply in all the six FSFI domains, with no statistically significant difference between the two treatment groups.