Indocyanine green-marked fluorescence-guided off-clamp versus intraoperative ultrasound-guided on-clamp robotic partial nephrectomy: Outcomes on surgical procedure.

Objectives: To compare surgical and functional outcomes between off-clamp robot-assisted partial nephrectomy with indocyanine-green tumour marking through preliminary superselective embolization and on-clamp robot-assisted partial nephrectomy with intraoperative ultrasound identification of the renal mass. Material and methods: One hundred and forty patients with a single renal mass underwent indocyanine-green fluorescence-guided off-clamp robot-assisted partial nephrectomy with preoperative superselective embolization (Group A, 70 patients) versus intraoperative ultrasound-guided on-clamp robot-assisted partial nephrectomy without embolization (Group B, 70 patients). We assessed operative time, intraoperative blood loss, complications, length of stay, renal function, need for ancillary procedures and blood transfusions. Results: Mean tumour size was 24 versus 25 mm in Group A versus Group B (p = 0.19). Mean operative time was 86.5 versus 121.8 min (p = 0.02), mean blood loss was 72.8 versus 214.2 mL (p = 0.02), and mean haemoglobin drop on postoperative day 1 was 1.1 versus 2.6 g/dL (p = 0.04) in Group A versus Group B. One-month creatinine, hospital stay and enucleated tumour volume were comparable. Ten postoperative complications occurred in Group A (13.3%) and 11 in Group B (15.3%). Following superselective embolization, no patients required blood transfusions versus two patients in Group B. Postoperative selective renal embolization was needed in one case per group. Conclusions: Preoperative superselective embolization of a renal mass with indocyanine-green before off-clamp robot-assisted partial nephrectomy significantly reduces operative time and intraoperative blood loss compared to on-clamp intraoperative ultrasound-guided robot-assisted partial nephrectomy. A longer follow-up is needed to establish the effect on renal function.

Pathological report and prognostic meaning of Bosniak IV cysts: results from a contemporary cohort.

Introduction: Surgery is the recommended treatment for Bosniak IV renal cysts. We performed a retrospective analysis of Bosniak IV lesions surgically removed to increase evidence on their prognostic meaning. Material and methods: Patients with a Bosniak IV cyst were considered. A contrast-enhanced computed tomography (CT) scan or magnetic resonance imaging (MRI) detected a solid component with contrast enhancement. In no case a percutaneous biopsy was performed. A radical (9, 21.4%) or partial (33, 78.6%) nephrectomy was performed with laparoscopic (14, 33.3%) or robot-assisted (28, 66.7%) approach. Analysis of the final pathology was performed, and recurrence rate was assessed. Results: 42 patients were included. Median lesion size was 54.7 mm (IQR 20.0-81.2). A solid tumour was detected in 40 patients (95.2%), whereas in 2 cases (4.8%) a benign cyst without neoplastic component was diagnosed. Final pathology revealed a low-grade clear cell renal cell carcinoma (ccRCC) in 16 cases (38.0%), a multilocular cystic renal neoplasm of low malignant potential in 6 cases (14.3%), a low-grade papillary RCC (pRCC) type I in 4 cases (9.5%), a clear cell papillary RCC (ccpRCC) in 10 cases (23.8%) and an oncocytoma in 2 cases (4.8%). A high-grade ccRCC was detected in 2 cases (4.8%), whereas no patients had a pRCC type II. In all cases surgical margins were negative. Median follow-up was 24 months and no recurrence occurred. Conclusions: Our results increase evidence on the favourable pathology and good prognosis of Bosniak IV renal cysts, supporting the role of surgery as a definitive treatment and suggesting the need for a low-intensity follow-up.

Three-Dimensional Customized Imaging Reconstruction for Urological Surgery: Diffusion and Role in Real-Life Practice from an International Survey.

Despite the arising interest in three-dimensional (3D) reconstruction models from 2D imaging, their diffusion and perception among urologists have been scarcely explored. The aim of the study is to report the results of an international survey investigating the use of such tools among urologists of different backgrounds and origins. Beyond demographics, the survey explored the degree to which 3D models are perceived to improve surgical outcomes, the procedures mostly making use of them, the settings in which those tools are mostly applied, the surgical steps benefiting from 3D reconstructions and future perspectives of improvement. One hundred responders fully completed the survey. All levels of expertise were allowed; more than half (53%) were first surgeons, and 59% had already completed their training. Their main application was partial nephrectomy (85%), followed by radical nephrectomy and radical prostatectomy. Three-dimensional models are mostly used for preoperative planning (75%), intraoperative consultation and tailoring. More than half recognized that 3D models may highly improve surgical outcomes. Despite their recognized usefulness, 77% of responders use 3D models in less than 25% of their major operations due to costs or the extra time taken to perform the reconstruction. Technical improvements and a higher availability of the 3D models will further increase their role in surgical and clinical daily practice.

Downregulation of Circulating Hsa-miR-200c-3p Correlates with Dyslipidemia in Patients with Stable Coronary Artery Disease.

Coronary heart disease (CHD), one of the leading causes of disability and death worldwide, is a multifactorial disease whose early diagnosis is demanding. Thus, biomarkers predicting the occurrence of this pathology are of great importance from a clinical and therapeutic standpoint. By means of a pilot study on peripheral blood cells (PBMCs) of subjects with no coronary lesions (CTR; n = 2) and patients with stable CAD (CAD; n = 2), we revealed 61 differentially methylated regions (DMRs) (18 promoter regions, 24 genes and 19 CpG islands) and 14.997 differentially methylated single CpG sites (DMCs) in CAD patients. MiRNA-seq results displayed a peculiar miRNAs profile in CAD patients with 18 upregulated and 32 downregulated miRNAs (FC ≥ ±1.5, p ≤ 0.05). An integrated analysis of genome-wide DNA methylation and miRNA-seq results indicated a significant downregulation of hsa-miR-200c-3p (FCCAD = −2.97, p ≤ 0.05) associated to the hypermethylation of two sites (genomic coordinates: chr12:7073122-7073122 and chr12:7072599-7072599) located intragenic to the miR-200c/141 genomic locus (encoding hsa-miR-200c-3p) (p-value = 0.009) in CAD patients. We extended the hsa-miR-200c-3p expression study in a larger cohort (CAD = 72, CTR = 24), confirming its reduced expression level in CAD patients (FCCAD = −2; p = 0.02). However, when we analyzed the methylation status of the two CpG sites in the same cohort, we failed to identify significant differences. A ROC curve analysis showed good performance of hsa-miR-200c-3p expression level (AUC = 0.65; p = 0.02) in distinguishing CAD from CTR. Moreover, we found a significant positive correlation between hsa-miR-200c-3p expression and creatinine clearance (R2 = 0.212, p < 0.005, Pearson r = 0.461) in CAD patients. Finally, a phenotypic correlation performed in the CAD group revealed lower hsa-miR-200c-3p expression levels in CAD patients affected by dyslipidemia (+DLP, n = 58) (p < 0.01). These results indicate hsa-miR-200c-3p as potential epi-biomarker for the diagnosis and clinical progression of CAD and highlight the importance of deeper studies on the expression of this miRNA to understand its functional role in coronary artery disease development.

Treatment of ureteral stones with LithoEVO device and Vapor Tunnel tool.

BACKGROUND: Vapor Tunnel (VT) technology is the result of a pulse modulation during holmium laser emission which reduces stone retropulsion. We present the outcomes of this tool in the treatment of ureteral stones. METHODS: Two hundred ten patients with a ureteral stone were randomly assigned to holmium laser lithotripsy with (group A) or without (group B) the VT technology. The 35 W LithoEVO laser generator (Quanta System, Samarate, Varese, Italy) was used. We compared operative time, dusting time, delivered energy, retreatment rate due to stone push-up, ureteral lesions, and stone-free rate (SFR) and postoperative strictures at 1 month. We also compared outcomes according to stone position. RESULTS: VT technology was associated with significantly lower mean operative time (25.7 vs. 37.2 min), dusting time (9.7 vs. 15.3 min), delivered energy (7.7 vs. 19.9 KJ). In group B 9 patients (8.5%) were retreated due to stone push-up (P=0.01) for a proximal or middle stone, 6 (5.7%) postoperative strictures occurred (P=0.03) and a higher ureteral lesion rate was observed (7.6% vs 35.2%, P=0.04). 1-month SFR was comparable (93.4% vs. 88.6%, P=0.11). Postoperative complication rate was higher in group B (P=0.05). Without VT technology, ureteral lesions and strictures rates were significantly higher independently from stone position. CONCLUSIONS: The VT technology is associated with significantly lower operative and dusting time independently from stone position, due to a reduced retropulsion, which makes treatment quicker and easier. It also avoids stone push-up especially for proximal and middle stones and reduces ureteral lesions, postoperative complications, and ureteral strictures.

"Bordeaux Neobladder": First Evaluation of the Urodynamic Outcomes.

Background: The intracorporeal orthotopic modified-Y "Bordeaux" neobladder (iYNB) was first described in 2016. No urodynamic evaluation of this neobladder has yet been performed. Objective: To present the urodynamic features of the iYNB and incontinence-specific health-related quality of life (HRQoL) outcomes. Design setting and participants: We prospectively assessed 26 patients operated between September 2018 and November 2020. Surgical procedure: Robotic radical cystectomy for malignant disease of the bladder and iYNB, performed by a single surgeon, were used. Measurements: Three months after surgery and in November 2021, consenting patients underwent clinical evaluation and multichannel urodynamic study (UDS). The incontinence quality of life (I-QoL) questionnaire was used to evaluate HRQoL. Continence was classified into day- and nighttime, and clinically defined as the use of zero pads. A descriptive statistical analysis was performed. Results and limitations: The mean age at surgery was 65.4 yr. The mean follow-up period was 27 mo (12-38). The mean time for the neobladder reconstruction was 192 min (110-340). The mean maximum capacity was 431 cm3 (range 200-553). The mean postvoid residual was 101.6 ml (0-310), and the rate of clean intermittent catheterization was 17.6%. With the exception of a significant reduction in the volume of the first sensation of bladder fullness, no other statistically significant changes in the UDS parameters of both the storage and the voiding phase were observed over time. Day- and nighttime continence rates were 58.8% and 23.5%, respectively. The mean postoperative I-QoL score was 103.3 (89-110). Limitations include the small number of patients and short follow-up. Conclusions: The UDS evaluation of iYNB demonstrates that both the volumetric and the pressure characteristics are acceptable and may enhance quality of life. Prospective studies with larger numbers of patients and longer follow-up are needed to further evaluate the iYNB. Patient summary: The "Bordeaux" neobladder provides acceptable urodynamic outcomes. It is associated with high levels of health-related quality of life and good rates of continence in patients.

Thulium: YAG vs continuous-wave thulium fiber laser enucleation of the prostate: do potential advantages of thulium fiber lasers translate into relevant clinical differences?

PURPOSE: To compare endoscopic enucleation of the prostate using a thulium: yttrium-aluminum-garnet (Tm:YAG) laser and a super-pulsed thulium fiber laser set in continuous-wave (CW) mode, and to evaluate whether theoretical advantages of thulium fiber lasers, related to their shorter wavelength, translate into relevant clinical differences. METHODS: In total, 110 patients suffering from lower urinary tract symptoms (LUTS) due to benign prostatic hyperplasia were randomized to undergo either thulium:YAG laser enucleation of the prostate (ThuLEP) or CW thulium fiber laser enucleation of the prostate (CW-ThuFLEP). Intraoperative and postoperative variables and complications were compared. Micturition improvement was assessed at 3-month follow-up using the International Prostate Symptom Score (IPSS), post-void residual urine (PVR) and maximum flow rate (Qmax). Erectile function was evaluated using the International Index of Erectile Function-5 (IIEF-5). RESULTS: No significant differences between the ThuLEP and CW-ThuFLEP groups were found in terms of operative time (70.69 vs 72.41 min), enucleation time (50.23 vs 53.33 min), enucleated tissue weight (40.2 vs 41.9 g), enucleation efficiency (0.80 vs 0.79 g/min), catheterization time (2.45 vs 2.57 days), hospital stay (2.82 vs 2.95 days) and hemoglobin drop (1.05 vs 1.27 g/dl). At 3-month follow-up, no significant differences were found in IPSS (5.09 vs 5.81), Qmax (26.51 vs 27.13 ml/s), PVR (25.22 vs 23.81 ml) and IIEF-5 (14.01 vs 14.54). CONCLUSION: ThuLEP and CW-ThuFLEP were equivalent in relieving patients from LUTS and improving micturition. Theoretical advantages of the TFL, such as shallower penetration depth and improved vaporization capacity, did not translate into relevant perioperative outcomes or clinical differences.

Expression analysis of miRNA hsa-let7b-5p in naso-oropharyngeal swabs of COVID-19 patients supports its role in regulating ACE2 and DPP4 receptors.

Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) is the novel coronavirus responsible for worldwide coronavirus disease (COVID-19). We previously observed that Angiotensin-converting enzyme 2 (ACE2) and Dipeptidyl peptidase-4 (DPP4) are significantly overexpressed in naso-oropharyngeal swabs (NPS) of COVID-19 patients, suggesting their putative functional role in the disease progression. ACE2 and DPP4 overexpression in COVID-19 patients may be associated to epigenetic mechanism, such as miRNA differential expression. We investigated if hsa-let7b-5p, reported to target both ACE2 and DPP4 transcripts, could be involved in the regulation of these genes. We verified that the inhibition and overexpression of hsa-let7b-5p matched to a modulation of both ACE2 and DPP4 levels. Then, we observed a statistically significant downregulation (FC = -1.5; p < 0.05) of hsa-let7b-5p in the same COVID-19 and control samples of our previous study. This is the first study that shows hsa-let7b-5p low expression in naso-oropharyngeal swabs of COVID-19 patients and demonstrates a functional role of this miR in regulating ACE2 and DPP4 levels. These data suggest the involvement of hsa-let7b-5p in the regulation of genes necessary for SARS-CoV-2 infections and its putative role as a therapeutic target for COVID-19.

A comparison among RIRS and MiniPerc for renal stones between 10 and 20 mm using thulium fiber laser (Fiber Dust): a randomized controlled trial.

PURPOSE: We performed a prospective randomized comparison among Retrograde IntraRenal Surgery (RIRS) and MiniPerc (MP) for stones between 10 and 20 mm to evaluate outcomes with the same laser device: Fiber Dust. METHODS: Patients with a single renal stone between 10 and 20 mm were randomized to RIRS (Group A) versus MP (Group B). Exclusion criteria were age < 18 or > 75, presence of acute infection, coagulation impairments, cardiovascular or pulmonary comorbidities. In both groups, the Fiber Dust laser was used. A CT scan after 3 months was performed. A negative CT scan or asymptomatic patients with stone fragments < 3 mm and a negative urinary culture were the criteria to assess the stone-free status. A statistical analysis was carried out to assess success, complication and retreatment rates and need for auxiliary treatments. RESULTS: Between January 2021 and January 2022, 186 patients were enrolled (90 in Group A and 96 in Group B). Mean stone size was 15.8 mm and 14.9 mm in Group A and B, respectively (p = 0.23). The overall stone-free rate (SFR) was 73.3% for Group A and 84.4% for Group B. A higher SFR was reached for upper calyceal stones in Group A (90.4%) lower calyceal stones in Group B (91.6%). Retreatment rate (p = 0.31) and auxiliary procedure rate (p = 0.18) were comparable. Complication rate was 5.5% and 5.2% for Groups A and B, respectively. CONCLUSIONS: RIRS and MP are both effective to obtain a postoperative SFR with Fiber Dust. According to the stone position one treatment is superior to the other one.

Hsa-miR223-3p circulating level is upregulated in Friedreich's ataxia and inversely associated with HCLS1 associated protein X-1, HAX-1.

Frataxin (FXN) deficiency is responsible for Friedreich's ataxia (FRDA) in which, besides the characteristic features of spinocerebellar ataxia, two thirds of patients develop hypertrophic cardiomyopathy that often progresses to heart failure and premature death. Different mechanisms might underlie FRDA pathogenesis. Among them, the role of miRNAs deserves investigations. We carried out an miRNA PCR-array analysis of plasma samples of early-, intermediate- and late-onset FRDA groups, defining a set of 30 differentially expressed miRNAs. Hsa-miR223-3p is the only miRNA shared between the three patient groups and appears upregulated in all of them. The up-regulation of hsa-miR223-3p was further validated in all enrolled patients (n = 37, Fc = +2.3; P < 0.0001). Using a receiver operating characteristic curve analysis, we quantified the predictive value of circulating hsa-miR223-3p for FRDA, obtaining an area under the ROC curve value of 0.835 (P < 0.0001) for all patients. Interestingly, we found a significant positive correlation between hsa-miR223-3p expression and cardiac parameters in typical FRDA patients (onset < 25 years). Moreover, a significant negative correlation between hsa-miR223-3p expression and HAX-1 (HCLS1-associated protein X-1) at mRNA and protein level was observed in all FRDA patients. In silico analyses suggested HAX-1 as a target gene of hsa-miR223-3p. Accordingly, we report that HAX-1 is negatively regulated by hsa-miR223-3p in cardiomyocytes (AC16) and neurons (SH-SY5Y), which are critically affected cell types in FRDA. This study describes for the first time the association between hsa-miR223-3p and HAX-1 expression in FRDA, thus supporting a potential role of this microRNA as non-invasive epigenetic biomarker for FRDA.

Initial Experience and Evaluation of a Nomogram for Outcome Prediction in Management of Medium-sized (1-2 cm) Kidney Stones.

BACKGROUND: The gold standard treatment for solitary medium-sized (1-2 cm) renal stones is not defined by recent guidelines, since management modalities including shockwave lithotripsy (SWL), retrograde intrarenal surgery (RIRS), and percutaneous nephrolithotomy (PNL) are recommended. Improved ability to predict patient outcomes would aid in patients' counseling and decision-making. OBJECTIVE: To develop a nomogram predicting treatment failure, based on preoperative clinical variables, to be used in the preplanning setting. DESIGN, SETTING, AND PARTICIPANTS: We recruited 2605 patients from 14 centers and carried out a multicenter retrospective analysis of 699 SWL, 1290 RIRS, and 616 PN L procedures performed as first-line treatment for 1-2-cm kidney stones. The variables evaluated included age, gender, previous renal surgery, body mass index, stone size, location, stone density, skin-to-stone distance, presence of urinary tract infections (UTIs), and hydronephrosis. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Multivariate logistic regression was fitted to predict treatment failure, defined as the presence of residual fragments >4 mm. A nomogram was developed based on the coefficients of the logit function. RESULTS AND LIMITATIONS: A total of 2431 (93.3%) patients were stone free; 174 (6.7%) treatment failures were recorded and considered the event to be predicted. On univariate analysis, type of procedure, preoperative hydronephrosis, stone density, stone location, and laterality turned out to be statistically significant. Skin-to-stone distance, UTIs, and previous renal surgery were predictors of failure on multivariate analysis. Each variable was given a score based on statistical relevance. The main limitation of the current study is its retrospective nature. CONCLUSIONS: This nomogram provides a prediction of treatment failure and need of reintervention for medium-sized kidney stones. External validation is needed to determine its reproducibility and validity. PATIENT SUMMARY: We developed a preoperative model of treatment outcomes for 1-2-cm kidney stones. Its application may assist urologists to counsel patients with regard to stone management modality.

Two RECK Splice Variants (Long and Short) Are Differentially Expressed in Patients with Stable and Unstable Coronary Artery Disease: A Pilot Study.

Primary prevention is crucial for coronary heart disease (CAD) and the identification of new reliable biomarkers might help risk stratification or predict adverse coronary events. Alternative splicing (AS) is a less investigated genetic factors implicated in CAD etiology. We performed an RNA-seq study on PBMCs from CAD patients and control subjects (CTR) and observed 113 differentially regulated AS events (24 up and 89 downregulated) in 86 genes. The RECK (Reversion-inducing-cysteine-rich protein with Kazal motifs) gene was further analyzed in a larger case study (24 CTR subjects, 72 CAD and 32 AMI patients) for its Splicing-Index FC (FC = -2.64; p = 0.0217), the AS event involving an exon (exon 18), and its role in vascular inflammation and remodeling. We observed a significant downregulation of Long RECK splice variant (containing exon 18) in PBMCs of AMI compared to CTR subjects (FC = -3.3; p < 0.005). Interestingly, the Short RECK splice variant (lacking exon 18) was under-expressed in AMI compared to both CTR (FC = -4.5; p < 0.0001) and CAD patients (FC = -4.2; p < 0.0001). A ROC curve, constructed combining Long and Short RECK expression data, shows an AUC = 0.81 (p < 0.001) to distinguish AMI from stable CAD patients. A significant negative correlation between Long RECK and triglycerides in CTR group and a positive correlation in the AMI group was found. The combined evaluation of Long and Short RECK expression levels is a potential genomic biomarker for the discrimination of AMI from CAD patients. Our results underline the relevance of deeper studies on the expression of these two splice variants to elucidate their functional role in CAD development and progression.

Case Report: An Atypical Form of Familial Partial Lipodystrophy Type 2 Due to Mutation in the Rod Domain of Lamin A/C.

Purpose: Familial partial lipodystrophy type 2 (FPLD2) patients generally develop a wide variety of severe metabolic complications. However, they are not usually affected by primary cardiomyopathy and conduction system disturbances, although a few cases of FPLD2 and cardiomyopathy have been reported in the literature. These were all due to amino-terminal heterozygous lamin A/C mutations, which are considered as new forms of overlapping syndromes. Methods and Results: Here we report the identification of a female patient with FPLD2 due to a heterozygous missense variant c.604G>A in the exon 3 of the LMNA gene, leading to amino acid substitution (p.Glu202Lys) in the central alpha-helical rod domain of lamin A/C with a high propensity to form coiled-coil dimers. The patient's cardiac evaluations that followed the genetic diagnosis revealed cardiac rhythm disturbances which were promptly treated pharmacologically. Conclusions: This report supports the idea that there are "atypical forms" of FPLD2 with cardiomyopathy, especially when a pathogenic variant affects the lamin A/C head or alpha-helical rod domain. It also highlights how increased understanding of the genotype-phenotype correlation could help clinicians to schedule personalized monitoring of the lipodystrophic patient, in order to prevent uncommon but possible devastating manifestations, including arrhythmias and sudden death.

Frataxin deficiency in Friedreich's ataxia is associated with reduced levels of HAX-1, a regulator of cardiomyocyte death and survival.

Frataxin deficiency, responsible for Friedreich's ataxia (FRDA), is crucial for cell survival since it critically affects viability of neurons, pancreatic beta cells and cardiomyocytes. In FRDA, the heart is frequently affected with typical manifestation of hypertrophic cardiomyopathy, which can progress to heart failure and cause premature death. A microarray analysis performed on FRDA patient's lymphoblastoid cells stably reconstituted with frataxin, indicated HS-1-associated protein X-1 (HAX-1) as the most significantly upregulated transcript (FC = +2, P < 0.0006). quantitative Reverse Transcription-Polymerase Chain Reaction (qRT-PCR) and western blot analysis performed on (I) HEK293 stably transfected with empty vector compared to wild-type frataxin and (II) lymphoblasts from FRDA patients show that low frataxin mRNA and protein expression correspond to reduced levels of HAX-1. Frataxin overexpression and silencing were also performed in the AC16 human cardiomyocyte cell line. HAX-1 protein levels are indeed regulated through frataxin modulation. Moreover, correlation between frataxin and HAX-1 was further evaluated in peripheral blood mononuclear cells (PBMCs) from FRDA patients and from non-related healthy controls. A regression model for frataxin which included HAX-1, group membership and group* HAX-1 interaction revealed that frataxin and HAX-1 are associated both at mRNA and protein levels. Additionally, a linked expression of FXN, HAX-1 and antioxidant defence proteins MnSOD and Nrf2 was observed both in PBMCs and AC16 cardiomyocytes. Our results suggest that HAX-1 could be considered as a potential biomarker of cardiac disease in FRDA and the evaluation of its expression might provide insights into its pathogenesis as well as improving risk stratification strategies.

Drug-Induced Urolithiasis in Pediatric Patients.

Drug-induced nephrolithiasis is a rare condition in children. The involved drugs may be divided into two different categories according to the mechanism involved in calculi formation. The first one includes poorly soluble drugs that favor the crystallization and calculi formation. The second category includes drugs that enhance calculi formation through their metabolic effects. The diagnosis of these specific calculi depends on a detailed medical history, associated comorbidities and the patient's history of drug consumption. There are several risk factors associated with drug-induced stones, such as high dose of consumed drugs and long duration of treatment. Moreover, there are some specific risk factors, including urinary pH and the amount of fluid consumed by children. There are limited data regarding pediatric lithogenic drugs, and hence, our aim was to perform a comprehensive review of the literature to summarize these drugs and identify the possible mechanisms involved in calculi formation and discuss the management and preventive measures for these calculi.

MiR-423 is differentially expressed in patients with stable and unstable coronary artery disease: A pilot study.

Coronary artery disease (CAD) and acute myocardial infarction (AMI) are the leading causes of death worldwide. Since only a subset of CAD patients develops myocardial infarction, it is likely that unique factors predispose to AMI. Circulating microRNAs represent diagnostic powerful biomarkers for detection of heart injuries and patients' risk stratification. Using an array-based approach, the expression of 84 circulating miRNAs was analyzed in plasma of pooled stable CAD patients (CAD; n = 5) and unstable CAD patients (AMI_T0; n = 5) enrolled within 24 hours from an AMI event. The array experiments showed 27 miRNAs differentially expressed with a two-fold up- or down-regulation (10 up- and 17 down-regulated miRNAs). Among them, miR-423-5p dis-regulation was confirmed in a larger case study (n = 99). Circulating miR-423-5p resulted to be significantly down-regulated within 24 hours from the AMI event (FC = -2, p≤0.05). Interestingly, miR-423-5p expression resulted to be increased (FC = +2; p≤0.005) in a subgroup of the same AMI patients (AMI_T1; n = 11) analyzed after 6 months from the acute event. We extended miR-423-5p expression study on PBMCs (peripheral blood mononuclear cells), confirming also in this tissue its up-regulation at 6 months post-AMI. Receiver operating characteristic analyses (ROC) were performed to detect the power of miR-423-5p to discriminate stable and unstable CAD. In plasma, miR-423-5p expression accurately distinguishes stable and unstable CAD patients (AUC = 0.7143, p≤0.005). Interestingly, the highest discriminatory value (AUC = 0.8529 p≤0.0005) was identified in blood cells, where miR-423-5p expression is able to differentiate unstable CAD patients during an acute event (AMI_T0) from those at six months post-AMI (AMI_T1). Furthermore, cellular miR-423-5p may discriminate also stable CAD patients from unstable CAD patients after six months post-AMI (AUC = 0.7355 p≤0.05). The results of this pilot-study suggest that miR-423-5p expression level both in plasma and blood cells, could represent a new promising biomarker for risk stratification of CAD patients.

Pro-oncogenic action of LOX-1 and its splice variant LOX-1Δ4 in breast cancer phenotypes.

The identification of new predictive biomarkers and therapeutic target for tailored therapy in breast cancer onset and progression is an interesting challenge. OLR-1 gene encodes the cell membrane receptor LOX-1 (lectin-like oxidized low-density lipoprotein receptor). We have recently identified a novel alternative OLR-1 isoform, LOX-1Δ4, whose expression and functions are still not clarified. In the present paper, we demonstrated that LOX-1 is overexpressed in 70% of human breast cancer (n = 47) and positively correlated to the tumor stage and grade (p < 0.01). Observations on LOX-1 and its splice variant Δ4 pointed out a different expression pattern correlated to breast cancer phenotypes. Overexpressing LOX-1 and LOX-1Δ4 in vitro, we obtained a strong enhancement of proliferative rate and a downregulation of cell death-related proteins. In addition, we observed a strong modulation of histone H4 acetylation and Ku70, the limiting factor of DNA double-strand breaks repair machinery implied in apoptosis inhibition and drug resistance acquisition. Moreover, LOX-1Δ4 overexpression is able to increase proliferation in a non-tumorigenic epithelial cell line, MCF12-F, acting as an oncogene. Altogether, these results suggest that LOX-1 may acts as a molecular link among metabolism, inflammation and cancer, indicating its potential role as biomarker and new molecular target, representing an attractive and concrete opportunity to improve current strategies for breast cancer tailored therapy.

Effect of puboprostatic ligament reconstruction on continence recovery after robot-assisted laparoscopic prostatectomy: our initial experience.

BACKGROUND: Prostate cancer represents a serious health problem worldwide. Radical prostatectomy is the gold standard for management of localized prostate cancer. Urinary incontinence is among the most common complications affecting robot-assisted laparoscopic prostatectomy (RALP) patients' postoperative quality of life. Several surgical modifications were introduced to overcome this problem including the puboprostatic ligament reconstruction. In this study, we discuss our technique of anterior reconstruction of the puboprostatic ligament during RALP and its effect on the continence outcome postoperatively. METHODS: In this retrospective study, the data of 95 consecutive patients were analyzed and the patients were divided in two groups; the control group "group A" (47 patients) and the anterior reconstruction group "group B" (48 patients). The primary endpoint of this study was to compare both groups as regards the postoperative continence rates. RESULTS: Complete continence (no pads) rates were reported at time of catheter removal (T0), 1 month (T1), 4 months (T4), 6 months (T6) and 12 months (T12) postoperatively. Moreover, the social continence (0-1 security pad) was reported at 12 months postoperatively. Complete continence was significantly different between both groups at T0 and T6 (P=0.022, and P=0.035 respectively). The social continence was not significantly different between both groups (85.1% vs. 89.6% in group A vs. group B). CONCLUSIONS: Despite anterior reconstruction of the puboprostatic ligament showed no significant effect on the overall continence, it showed earlier return to continence up to 6 months, which supports the theory that anterior puboprostatic reconstruction may provide better immediate continence and shorten the time to continence for RALP patients. However, most of the published literature showed better continence rates with the total anatomical reconstruction (combined anterior and posterior). Therefore, we started to offer patients in our center total anatomical reconstruction during RALP.

Assembly and Functional Analysis of an S/MAR Based Episome with the Cystic Fibrosis Transmembrane Conductance Regulator Gene.

Improving the efficacy of gene therapy vectors is still an important goal toward the development of safe and efficient gene therapy treatments. S/MAR (scaffold/matrix attached region)-based vectors are maintained extra-chromosomally in numerous cell types, which is similar to viral-based vectors. Additionally, when established as an episome, they show a very high mitotic stability. In the present study we tested the idea that addition of an S/MAR element to a CFTR (cystic fibrosis transmembrane conductance regulator) expression vector, may allow the establishment of a CFTR episome in bronchial epithelial cells. Starting from the observation that the S/MAR vector pEPI-EGFP (enhanced green fluorescence protein) is maintained as an episome in human bronchial epithelial cells, we assembled the CFTR vector pBQ-S/MAR. This vector, transfected in bronchial epithelial cells with mutated CFTR, supported long term wt CFTR expression and activity, which in turn positively impacted on the assembly of tight junctions in polarized epithelial cells. Additionally, the recovery of intact pBQ-S/MAR, but not the parental vector lacking the S/MAR element, from transfected cells after extensive proliferation, strongly suggested that pBQ-S/MAR was established as an episome. These results add a new element, the S/MAR, that can be considered to improve the persistence and safety of gene therapy vectors for cystic fibrosis pulmonary disease.

Training in urological robotic surgery. Future perspectives / Formación en cirugía urológica robótica. Perspectivas futuras

As robotics are becoming more integrated into the medical field, robotic training is becoming more crucial in order to overcome the lack of experienced robotic surgeons. However, there are several obstacles facing the development of robotic training programs like the high cost of training and the increased operative time during the initial period of the learning curve, which, in turn increase the operative cost. Robotic-assisted laparoscopic prostatectomy is the most commonly performed robotic surgery. Moreover, robotic surgery is becoming more popular among urologic oncologists and pediatric urologists. The need for a standardized end validated robotic training curriculum was growing along with the increased number of urologic centers and institutes adopting the robotic technology. Robotic training includes proctorship, mentorship or fellowship, telementoring, simulators and video training. In this chapter, we are going to discuss the different training methods, how to evaluate robotic skills, the available robotic training curriculum, and the future perspectives (AU)

A medida que la robótica va integrándose más en el campo de la medicina, el entrenamiento en robótica se está volviendo más crucial para superar la falta de cirujanos robóticos experimentados. Sin embargo, hay varios obstáculos a los que se enfrenta el desarrollo de programas de formación en robótica, como el alto coste de la formación y el aumento del tiempo operatorio durante el periodo inicial de la curva de aprendizaje, lo cual incrementa el coste de la operación. La prostatectomía laparoscópica asistida por robot es la cirugía robótica realizada con mayor frecuencia. Además, la cirugía robótica se está volviendo más popular entre oncourólogos y urólogos pediátricos. La necesidad de un curriculum de formación en robótica estandarizado y validado fue creciendo con el aumento del número de centros urológicos e institutos que adoptaban la tecnología robótica. La formación en robótica incluye monitorización, tutorización o fellowships, teletutela, simuladores y video entrenamiento. En este capítulo vamos a discutir los diferentes métodos de aprendizaje, cómo evaluar las habilidades roboticas, el curriculum en robotica disponible y las perspectivas futuras (AU)