InCliniGene enables high-throughput and comprehensive in vivo clonal tracking toward clinical genomics data integration.

High-throughput clonal tracking in patients under hematopoietic stem cell gene therapy with integrating vector is instrumental in assessing bio-safety and efficacy. Monitoring the fate of millions of transplanted clones and their progeny across differentiation and proliferation over time leverages the identification of the vector integration sites, used as surrogates of clonal identity. Although γ-tracking retroviral insertion sites (γ-TRIS) is the state-of-the-art algorithm for clonal identification, the computational drawbacks in the tracking algorithm, based on a combinatorial all-versus-all strategy, limit its use in clinical studies with several thousands of samples per patient. We developed the first clonal tracking graph database, InCliniGene (https://github.com/calabrialab/InCliniGene), that imports the output files of γ-TRIS and generates the graph of clones (nodes) connected by arches if two nodes share common genomic features as defined by the γ-TRIS rules. Embedding both clonal data and their connections in the graph, InCliniGene can track all clones longitudinally over samples through data queries that fully explore the graph. This approach resulted in being highly accurate and scalable. We validated InCliniGene using an in vitro dataset, specifically designed to mimic clinical cases, and tested the accuracy and precision. InCliniGene allows extensive use of γ-TRIS in large gene therapy clinical applications and naturally realizes the full data integration of molecular and genomics data, clinical and treatment measurements and genomic annotations. Further extensions of InCliniGene with data federation and with application programming interface will support data mining toward precision, personalized and predictive medicine in gene therapy. Database URL:  https://github.com/calabrialab/InCliniGene.

On the Origins of Phenotypic Parallelism in Benthic and Limnetic Stickleback.

Rapid evolution of similar phenotypes in similar environments, giving rise to in situ parallel adaptation, is an important hallmark of ecological speciation. However, what appears to be in situ adaptation can also arise by dispersal of divergent lineages from elsewhere. We test whether two contrasting phenotypes repeatedly evolved in parallel, or have a single origin, in an archetypal example of ecological adaptive radiation: benthic-limnetic three-spined stickleback (Gasterosteus aculeatus) across species pair and solitary lakes in British Columbia. We identify two genomic clusters across freshwater populations, which differ in benthic-limnetic divergent phenotypic traits and separate benthic from limnetic individuals in species pair lakes. Phylogenetic reconstruction and niche evolution modeling both suggest a single evolutionary origin for each of these clusters. We detected strong phylogenetic signal in benthic-limnetic divergent traits, suggesting that they are ancestrally retained. Accounting for ancestral state retention, we identify local adaptation of body armor due to the presence of an intraguild predator, the sculpin (Cottus asper), and environmental effects of lake depth and pH on body size. Taken together, our results imply a predominant role for retention of ancestral characteristics in driving trait distribution, with further selection imposed on some traits by environmental factors.

Automatic Passenger Counting on the Edge via Unsupervised Clustering.

We present a device- and network-based solution for automatic passnger counting that operates on the edge in real time. The proposed solution consists of a low-cost WiFi scanner device equipped with custom algorithms for dealing with MAC address randomization. Our low-cost scanner is able to capture and analyze 802.11 probe requests emitted by passengers' devices such as laptops, smartphones, and tablets. The device is configured with a Python data-processing pipeline that combines data coming from different types of sensors and processes them on the fly. For the analysis task, we have devised a lightweight version of the DBSCAN algorithm. Our software artifact is designed in a modular way in order to accommodate possible extensions of the pipeline, e.g., either additional filters or data sources. Furthermore, we exploit multi-threading and multi-processing for speeding up the entire computation. The proposed solution has been tested with different types of mobile devices, obtaining promising experimental results. In this paper, we present the key ingredients of our edge computing solution.

Long-term, basin-scale salinity impacts from desalination in the Arabian/Persian Gulf.

The nations on the shoreline of the Arabian/Persian Gulf are the world's largest users of desalination technologies, which are essential to meet their freshwater needs. Desalinated freshwater production is projected to rapidly increase in future decades. Thus, concerns have been raised that desalination activities may result in non-negligible long-term, basin-wide increases of salinity, which would have widespread detrimental effects on the Gulf marine ecosystems, with ripple effects on fisheries, as well as impacting the desalination activities themselves. We find that current yearly desalinated freshwater production amounts to about 2% of the net yearly evaporation from the Gulf. Projections to 2050 bring this value to 8%, leading to the possibility that, later in the second half of the century, desalinated freshwater production may exceed 10% of net evaporation, an amount which is comparable to interannual fluctuations in net evaporation. With the help of a model we examine several climatological scenarios, and we find that, under IPCC's SSP5-8.5 worst-case scenarios, end-of-century increases in air temperature may result in salinity increases comparable or larger to those produced by desalination activities. The same scenario suggests a reduced evaporation and an increased precipitation, which would have a mitigating effect. Finally we find that, owing to a strong overturning circulation, high-salinity waters are quickly flushed through the Strait of Hormuz. Thus, even in the worst-case scenarios, basin-scale salinity increases are unlikely to exceed 1 psu, and, under less extreme hypothesis, will likely remain well below 0.5 psu, levels that have negligible environmental implications at the basin-wide scale.

Robotic-assisted, laparoscopic, and open radical cystectomy: surgical data of 1400 patients from The Italian Radical Cystectomy Registry on intraoperative outcomes.

Introduction: The Italian Radical Cystectomy Registry (Registro Italiano Cistectomie - RIC) aimed to analyse outcomes of a multicenter series of patients treated with radical cystectomy (RC) for bladder cancer. Material and methods: An observational, prospective, multicenter, cohort study was performed to collect data from RC and urinary diversion via open (ORC), laparoscopic (LRC), or robotic-assisted (RARC) techniques performed in 28 Italian Urological Departments. The enrolment was planned from January 2017 to June 2020 (goal: 1000 patients), with a total of 1425 patients included. Chi-square and t-tests were used for categorical and continuous variables. All tests were 2-sided, with a significance level set at p <0.05. Results: Overall median operative-time was longer in RARCs (390 minutes, IQR 335-465) than ORCs (250, 217-309) and LRCs (292, 228-350) (p <0.001). Lymph node dissection (LND) was performed more frequently in RARCs (97.1%) and LRCs (93.5%) than ORCs (85.6%) (p <0.001), with extended-LND performed 2-fold more frequently in RARCs (61.6%) (p <0.001). The neobladder rate was significantly higher (more than one-half) in RARCs. The median estimated blood loss (EBL) rate was lower in RARCs (250 ml, 165-400) than LRCs (330, 200-600) and ORCs (400, 250-600) (p <0.001), with intraoperative blood transfusion rates of 11.4%, 21.7% and 35.6%, respectively (p <0.001). The conversion to open rate was slightly higher in RARCs (6.8%) than LRCs (4.3%). Intraoperative complications occurred in 1.3% of cases without statistically significant differences among the approaches. Conclusions: Data from the RIC confirmed the need to collect as much data as possible in a multicenter manner. RARCs proves to be feasible with perioperative complication rates that do not differ from the other approaches.

Robot-Assisted, Laparoscopic, and Open Radical Cystectomy: Pre-Operative Data of 1400 Patients From The Italian Radical Cystectomy Registry.

Introduction: The Italian Radical Cystectomy Registry (RIC) is an observational prospective study aiming to understand clinical variables and patient characteristics associated with short- and long-term outcomes among bladder cancer (BC) patients undergoing radical cystectomy (RC). Moreover, it compares the effectiveness of three RC techniques - open, robotic, and laparoscopic. Methods: From 2017 to 2020, 1400 patients were enrolled at one of the 28 centers across Italy. Patient characteristics, as well as preoperative, postoperative, and follow-up (3, 6, 12, and 24 months) clinical variables and outcomes were collected. Results: Preoperatively, it was found that patients undergoing robotic procedures were younger (p<.001) and more likely to have undergone preoperative neoadjuvant chemotherapy (p<.001) and BCG instillation (p<.001). Hypertension was the most common comorbidity among all patients (55%), and overall, patients undergoing open and laparoscopic RC had a higher Charlson Comorbidities Index (CCI) compared to robotic RC (p<.001). Finally, laparoscopic patients had a lower G-stage classification (p=.003) and open patients had a higher ASA score (p<.001). Conclusion: The present study summarizes the characteristic of patients included in the RIC. Future results will provide invaluable information about outcomes among BC patients undergoing RC. This will inform physicians about the best techniques and course of care based on patient clinical factors and characteristics.

Long-term outcomes of Holmium laser enucleation of prostate and predictive model for symptom recurrence.

INTRODUCTION AND OBJECTIVES: Holmium laser enucleation of prostate (HoLEP) represents one of the most studied surgical techniques for benign prostatic hyperplasia (BPH). Its efficacy in symptom relief has been widely depicted. However, few evidence is available regarding the possible predictors of symptom recurrence. We aimed to evaluate long-term outcomes, symptom recurrence rate, and predictors in patients that underwent HoLEP. MATERIALS AND METHODS: We retrospectively analyzed data from patients that consecutively underwent HoLEP for BPH from 2012 to 2015 at two tertiary referral centers. Functional outcomes were evaluated by uroflowmetry parameters and International Prostate Symptom Score (IPSS) questionnaire administration at follow-up visits at 12, 24, and 60 months. The primary outcome was the symptomatic patients' rate presenting lower urinary tract symptoms (LUTS) after 60 months from surgery, defined as in case of one or more of the following: IPSS more than 7, post voidal residue (PVR) more than 20 ml, need for medical therapy for LUTS or redo surgery for bladder outlet obstruction. Multivariable logistic regression analyses evaluated predictors for being symptomatic at follow-up. Covariates consisted of: preoperative peak flow rate (PFR), PVR, and IPSS, prostate volume, age (all as continuous), and surgical technique. RESULTS: A total of 567 patients were available for our analyses. Median prostate volume was 80cc, with a median PFR of 8 ml/s and median PVR of 100cc. One hundred and twenty-five (22%) patients were found to be symptomatic at follow-up. Redo surgery was needed for 25 (4.4%) patients. After adjusting for possible confounders, an increase in preoperative PVR (odds ratio [OR] 1.005) and IPSS (OR 1.12) resulted as independent predictors for symptom recurrence (all p < 0.001). CONCLUSIONS: HoLEP can provide durable symptom relief regardless of the chosen technique. Patients with an important preoperative symptom burden or a high PVR should be carefully counseled on the risk of symptom recurrence.

Perioperative Outcomes of Holmium Laser Enucleation of the Prostate: A Systematic Review.

INTRODUCTION: The aim of the study was to systematically review the literature and describe perioperative complications of holmium laser enucleation of the prostate (HoLEP), including the Clavien-Dindo classification of surgical complications. METHODS: All English language publications on HoLEP were evaluated. We followed the PRISMA (Preferred Reporting Items for Systematic Review and Meta-Analyses) guidelines to evaluate PubMed®, Scopus®, and Web of Science™ databases from January 1, 1998, to June 1, 2020. RESULTS: Fifty-seven studies were included, for a total of 10,371 procedures. We distinguished between intra-, peri-, and postoperative complications. Overall, the rate of complications is 0-7%. Intraoperative complications include incomplete morcellation (2.3%), capsular perforation (2.2%), bladder (2.4%), and ureteric orifice (0.4%) injuries. Perioperative complications include postoperative urinary retention (0.2%), hematuria and clot retention (2.6%), and cystoscopy for clot evacuation (0.7%). Postoperative complications include dysuria (7.5%), stress (4.0%), urge (1.8%), transient (7%) and permanent (1.3%) urinary incontinence, urethral stricture (2%) and bladder neck contracture (1%). CONCLUSIONS: HoLEP is a safe procedure, with a satisfactory low complication rate. The most common reported perioperative complications are not severe (Clavien-Dindo classification grades 1-2). Further randomized studies are certainly warranted to fully determine the predictor of surgical complications in order to prevent them and improve this technique.

Short Time Delay Between Previous Prostate Biopsy for Prostate Cancer Assessment and Holmium Laser Enucleation of the Prostate Correlates with Worse Perioperative Outcomes.

BACKGROUND: No data are available regarding the impact of time between a previous transrectal prostate biopsy (PB) and holmium laser enucleation of the prostate (HoLEP) on perioperative outcomes. OBJECTIVE: To evaluate the impact of time from PB to HoLEP on perioperative outcomes. DESIGN, SETTING, AND PARTICIPANTS: A total of 172 consecutive patients treated with HoLEP within 12 mo of a single previous transrectal PB at two tertiary centers were included. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Patients were stratified into two groups according to the median time from PB to HoLEP (namely, ≤6 and >6 mo). The primary outcome was intraoperative complications. Multivariate logistic regressions were used to identify the predictors of intraoperative complications. Linear regressions were used to test the association between the time from PB to HoLEP and intraoperative complications, enucleation efficiency, and enucleation time. RESULTS AND LIMITATIONS: In total, 93 (54%) and 79 (46%) patients had PB ≤ 6 and >6 mo before HoLEP, respectively. Patients in PB ≤ 6 mo group experienced higher rates of intraoperative complications than those in PB > 6 mo group (14% vs 2.6%, p = 0.04). At multivariable analysis, time between PB and HoLEP was an independent predictor of intraoperative complications (odds ratio: 0.74; 95% confidence interval: 0.6-0.9; p = 0.006). Finally, the risk of intraoperative complications reduced by 1.5%, efficiency of enucleation increased by 4.1%, and enucleation time reduced by 1.7 min for each month passed from PB to HoLEP (all p ≤ 0.006). Selection of patients with only one previous PB represents the main limitation. CONCLUSIONS: The time from PB to HoLEP of ≤6 mo is associated with a higher risk of intraoperative complications, lower enucleation efficacy, and longer enucleation time. PATIENT SUMMARY: Patients with a prostate biopsy (PB) ≤6 mo before holmium laser enucleation of the prostate (HoLEP) had significantly worse outcomes than those with a PB > 6 mo before HoLEP.

T-L technique for HoLEP: perioperative outcomes of a large single-centre series.

INTRODUCTION: The aim of this article was to describe, step-by-step, an original technique (T-L technique) in a single centre series of patients who underwent holmium laser enucleation of the prostate (HoLEP) for symptomatic benign prostatic hyperplasia and analyze perioperative outcomes. MATERIAL AND METHODS: We retrospectively analyzed data of 567 patients who underwent HoLEP. The T-L technique consists of a series of incisions used as landmarks, performed at the beginning of the procedure before enucleation. Two T-shape incisions are performed at the level of bladder neck (at the 5-7 and 12 o'clock positions); two L-shape incisions are performed at the level of verumontanum, bilaterally, to mark the apex and to limit the sphincter. Another T-shape incision is performed on the bladder neck at the 12 o'clock position posterior to the level of verumontanum. RESULTS: The median operative time (OT) was 80 minutes (IQR 64-105); 50 minutes (IQR 35-70) and 15 minutes (IQR 10-20) for enucleation and the morcellation phase, respectively. Conversion to transurethral resection of the prostate (TURP) was necessary in 3/567 (0.6%) patients. Intraoperative complications occurred in 3.4% of cases, capsule perforation occurred in 12/567 (2%) of cases, while bladder perforation during morcellation occurred in 8/567 (1.4%) of cases. Postoperative complications were observed in 20/567 (3.5%) of patients. Specifically, grade 1-2 occurred in 19/567 (3.3%) and grade 3 was recorded in 1/567 (0.2%). CONCLUSIONS: The T-L technique for HoLEP is safe and reproducible with a low rate of perioperative complications. The positioning of some landmarks before enucleation allows for the better orientation during enucleation and could be very useful in case of large prostates.

The combination of waterjet ablation (Aquabeam®) and holmium laser power for treatment of symptomatic benign prostatic hyperplasia: early functional results.

INTRODUCTION: The aim of this study was to assess the short-term functional outcomes and the efficacy of hemostasis performed with holmium laser performed following prostatic hydroablation with the Aquabeam® system. MATERIAL AND METHODS: Between June 2019 and July 2020, 53 consecutive patients underwent Aquabeam® with our modified hemostasis approach with holmium laser. The following standard preoperative assessments were retrospectively recorded: prostate volume; International Prostate Symptom Score (IPSS) and Quality of Life (IPSS-QoL); uroflowmetry including Qmax and post void residual volume (PVR). RESULTS: Fifty-three patients consecutively underwent aquablation and holmium laser hemostasis. Median age at surgery, median prostate-specific antigen (PSA) and median prostate volume were 62 years (IQR: 57-66), 2.95 ng/ml (IQR: 1.6-4.8) and 55 ml (IQR: 43-65), respectively.Median operative time was 60 minutes (IQR: 40-80). Median catheterization time and length of hospital stay were 2 days (IQR: 1-3) for both parameters. The median hemoglobin decrease between the preoperative values and those assessed on the second day was equal to 1.25 g/dl (IQR: 0.7-1.85).Continence rate was 100% at catheter removal. Thirty-six patients (72%) reported anterograde ejaculation preservation. IPSS (6, 3-21) and Qmax (19, 9-26) changed dramatically between baseline and 3 months follow-up. CONCLUSIONS: The combination of Aquabeam® and holmium laser energy for hemostasis is a safe, reproducible technique to relieve moderate lower urinary tract symptoms (LUTS) in men with benign prostatic hyperplasia (BPH) while preserving ejaculation in younger and sexually active individuals. The short-term results showed a lower rate of complications; the encouraging functional results confirm that this can be a valid surgical approach for treatment of BPH.

Advantages of using graph databases to explore chromatin conformation capture experiments.

BACKGROUND: High-throughput sequencing Chromosome Conformation Capture (Hi-C) allows the study of DNA interactions and 3D chromosome folding at the genome-wide scale. Usually, these data are represented as matrices describing the binary contacts among the different chromosome regions. On the other hand, a graph-based representation can be advantageous to describe the complex topology achieved by the DNA in the nucleus of eukaryotic cells. METHODS: Here we discuss the use of a graph database for storing and analysing data achieved by performing Hi-C experiments. The main issue is the size of the produced data and, working with a graph-based representation, the consequent necessity of adequately managing a large number of edges (contacts) connecting nodes (genes), which represents the sources of information. For this, currently available graph visualisation tools and libraries fall short with Hi-C data. The use of graph databases, instead, supports both the analysis and the visualisation of the spatial pattern present in Hi-C data, in particular for comparing different experiments or for re-mapping omics data in a space-aware context efficiently. In particular, the possibility of describing graphs through statistical indicators and, even more, the capability of correlating them through statistical distributions allows highlighting similarities and differences among different Hi-C experiments, in different cell conditions or different cell types. RESULTS: These concepts have been implemented in NeoHiC, an open-source and user-friendly web application for the progressive visualisation and analysis of Hi-C networks based on the use of the Neo4j graph database (version 3.5). CONCLUSION: With the accumulation of more experiments, the tool will provide invaluable support to compare neighbours of genes across experiments and conditions, helping in highlighting changes in functional domains and identifying new co-organised genomic compartments.

The Clinical Efficacy of Nitrofurantoin for Treating Uncomplicated Urinary Tract Infection in Adults: A Systematic Review of Randomized Control Trials.

OBJECTIVE: To provide an updated systematic review of randomized control trials (RCTs) to investigate the clinical and microbiological efficacy of nitrofurantoin compared to other antibiotics or placebo for treatment of uncomplicated urinary tract infections (uUTI). A secondary aim is to assess whether nitrofurantoin use is associated with increased side effects compared to other treatment regimens. SUMMARY: The review was performed according to PRISMA guidelines. We searched 4 databases for articles published from database inception to May 6, 2020: (1) PubMed electronic database of the National Library of Medicine, (2) Web of Science, (3) Embase, and (4) Cochrane Library. Nine RCTs were selected for the review. RCTs were a mixture of double-blind, single-blind, and open-label trials. The most common comparators were trimethoprim-sulfamethoxazole and fosfomycin tromethamine. Overall study quality was poor with a high risk of bias. The clinical cure rates in nitrofurantoin ranged from 51 to 94% depending on the length of follow-up, and bacteriological cure rates ranged from 61 to 92%. Overall the evidence suggests that nitrofurantoin is at least comparable with other uUTI treatments in terms of efficacy. Patients taking nitrofurantoin reported fewer side effects than other drugs and the most commonly reported were gastrointestinal and central nervous system symptoms. Key Messages: Evidence on the clinical and bacteriological efficacy of nitrofurantoin is sparse, with a lack of new data, and hampered by high risk of bias. Although no firm conclusions can be made on the current base of evidence, the studies generally suggest that nitrofurantoin is at least comparable to other common uUTI treatments in terms of clinical and bacteriological cure. More robust research with well-designed double-blinded RCTs is needed.

Protocol of the Italian Radical Cystectomy Registry (RIC): a non-randomized, 24-month, multicenter study comparing robotic-assisted, laparoscopic, and open surgery for radical cystectomy in bladder cancer.

BACKGROUND: Bladder cancer is the ninth most common type of cancer worldwide. In the past, radical cystectomy via open surgery has been considered the gold-standard treatment for muscle invasive bladder cancer. However, in recent years there has been a progressive increase in the use of robot-assisted laparoscopic radical cystectomy. The aim of the current project is to investigate the surgical, oncological, and functional outcomes of patients with bladder cancer who undergo radical cystectomy comparing three different surgical techniques (robotic-assisted, laparoscopic, and open surgery). Pre-, peri- and post-operative factors will be examined, and participants will be followed for a period of up to 24 months to identify risks of mortality, oncological outcomes, hospital readmission, sexual performance, and continence. METHODS: We describe a protocol for an observational, prospective, multicenter, cohort study to assess patients affected by bladder neoplasms undergoing radical cystectomy and urinary diversion. The Italian Radical Cystectomy Registry is an electronic registry to prospectively collect the data of patients undergoing radical cystectomy conducted with any technique (open, laparoscopic, robotic-assisted). Twenty-eight urology departments across Italy will provide data for the study, with the recruitment phase between 1st January 2017-31st October 2020. Information is collected from the patients at the moment of surgical intervention and during follow-up (3, 6, 12, and 24 months after radical cystectomy). Peri-operative variables include surgery time, type of urinary diversion, conversion to open surgery, bleeding, nerve sparing and lymphadenectomy. Follow-up data collection includes histological information (e.g., post-op staging, grading, and tumor histology), short- and long-term outcomes (e.g., mortality, post-op complications, hospital readmission, sexual potency, continence etc). DISCUSSION: The current protocol aims to contribute additional data to the field concerning the short- and long-term outcomes of three different radical cystectomy surgical techniques for patients with bladder cancer, including open, laparoscopic, and robot-assisted. This is a comparative-effectiveness trial that takes into account a complex range of factors and decision making by both physicians and patients that affect their choice of surgical technique. TRIAL REGISTRATION: ClinicalTrials.gov , NCT04228198 . Registered 14th January 2020- Retrospectively registered.

Prognostic performance of magnetic resonance imaging-guided biopsy in defining prostate cancer anterior lesions.

PURPOSE: Diagnosis of anterior prostate cancer (PCa) can be quite challenging, often leading to delay in treatment. mpMRI-guided biopsy (GB) has been introduced aiming to increase the number of diagnoses of clinically significant PCa with fewer cores. The aim of our study is to compare pathological findings of prostate biopsy, In-bore or Fusion technique, with histopathological evaluation of radical prostatectomy. METHODS: We prospectively collected data from 90 consecutive patients who underwent either In-bore or Fusion biopsy following the detection of an index suspicious lesion at mpMRI in the anterior part of the prostatic gland. Bioptical pathological findings were compared with pathological findings reported after robot-assisted radical prostatectomy. RESULTS: Patients who underwent In-bore GB had a higher rate of previous negative prostate biopsies (19% vs 44%, p = 0.02). Median number of bioptic cores taken (13 vs 2) and number of positive cores (3 vs 2) were significantly superior in the Fusion group compared to the In-bore group (p < 0.001 and p = 0.002, respectively), whilst clinical International Society of Urological Pathology (ISUP) grade was homogeneous within groups. The concordance between anterior lesions detected at biopsy and those reported in the histopathological finding of radical prostatectomy was very high, without statistically significant difference between groups. CONCLUSION: Both Fusion and In-bore GB are accurate in detecting anterior PCa, with enhanced precision detecting clinically significant tumours, as evidenced by pathologic examinations which confirmed the presence of index anterior PCa in > 50% of patients overall. Additional sextant biopsy is still required, especially among biopsy-näive patients, to avoid missing clinically significant PCa.

The role of magnetic resonance imaging-guided biopsy for diagnosis of prostate cancer; comparison between FUSION and "IN-BORE" approaches.

BACKGROUND: The aim of the present study is to evaluate the difference in terms of feasibility and detection rate of two magnetic resonance imaging (MRI) guided biopsy approaches (MRI fusion versus "in-bore" MRI) in a single tertiary center. METHODS: We retrospectively identified 297 patients with suspected prostate cancer who underwent MRI based target prostate biopsy (FUSION or "in-bore" approaches) between January 2016 and January 2018 in a single tertiary center. RESULTS: Lesion site (peripheral vs. central) and localization (anterior vs. posterior) were equally comparable among two groups, but maximum diameter of multiparametric-MRI Index lesion was slightly superior in the in-bore MRI-GB group (14 vs. 12 mm, P=0.002). Mean random biopsy cores taken were 11.2±2.1, with 1.3±2 positive cores in FUSION-GB group. Mean number of targeted biopsy cores taken was significantly superior in the FUSION-GB group as compared to the in-bore MRI-GB group (2.6±0.7 vs.1.7±1, P<0.001), whereas mean number of positive targeted biopsy cores was comparable between two groups (1±1.3 vs.1±0.9, P=0.1). 70 (45.5%) and 75 (52.8%) patients had positive targeted bioptic cores at pathologic examination among FUSION-GB and in-bore MRI-GB groups, respectively (P=0.2). Bioptical ISUP grade was also comparable among two groups (P=0.2) in multivariate analysis PI-RADS Score (OR=3.04 and OR=8.32 for PI-RADS 4 and 5, respectively) and PSA density (OR=2.69) were identified as independent predictors of positive targeted cores at histological examination (P<0.001 and P=0.01, respectively). CONCLUSIONS: In-bore MRI-GB approaches represent a promising technique that may offer some advantages compared to standard systematic FUSION-GB despite higher costs of in bore-procedure. Our experience, although not showing a clear advantage between the FUSION technique and the "in-bore" technique, resulted safe and feasible and represents a viable procedure for the diagnosis and characterization of prostate especially in a subgroup of patient with clinically significant disease. Further investigations are needed in order to identify the best approach for MRI-GB.

The dramatic COVID 19 outbreak in Italy is responsible of a huge drop of urological surgical activity: a multicenter observational study.

OBJECTIVE: To describe the trend in surgical volume in urology in Italy during the coronavirus disease 2019 (COVID-19) outbreak, as a result of the abrupt reorganisation of the Italian national health system to augment care provision to symptomatic patients with COVID-19. METHODS: A total of 33 urological units with physicians affiliated to the AGILE consortium (Italian Group for Advanced Laparo-Endoscopic Surgery; www.agilegroup.it) were surveyed. Urologists were asked to report the amount of surgical elective procedures week-by-week, from the beginning of the emergency to the following month. RESULTS: The 33 hospitals involved in the study account overall for 22 945 beds and are distributed in 13/20 Italian regions. Before the outbreak, the involved urology units performed overall 1213 procedures/week, half of which were oncological. A month later, the number of surgeries had declined by 78%. Lombardy, the first region with positive COVID-19 cases, experienced a 94% reduction. The decrease in oncological and non-oncological surgical activity was 35.9% and 89%, respectively. The trend of the decline showed a delay of roughly 2 weeks for the other regions. CONCLUSION: Italy, a country with a high fatality rate from COVID-19, experienced a sudden decline in surgical activity. This decline was inversely related to the increase in COVID-19 care, with potential harm particularly in the oncological field. The Italian experience may be helpful for future surgical pre-planning in other countries not so drastically affected by the disease to date.

Intercontinental genomic parallelism in multiple three-spined stickleback adaptive radiations.

Parallelism, the evolution of similar traits in populations diversifying in similar conditions, provides strong evidence of adaptation by natural selection. Many studies of parallelism focus on comparisons of different ecotypes or contrasting environments, defined a priori, which could upwardly bias the apparent prevalence of parallelism. Here, we estimated genomic parallelism associated with components of environmental and phenotypic variation at an intercontinental scale across four freshwater adaptive radiations (Alaska, British Columbia, Iceland and Scotland) of the three-spined stickleback (Gasterosteus aculeatus). We combined large-scale biological sampling and phenotyping with restriction site associated DNA sequencing (RAD-Seq) data from 73 freshwater lake populations and four marine ones (1,380 fish) to associate genome-wide allele frequencies with continuous distributions of environmental and phenotypic variation. Our three main findings demonstrate that (1) quantitative variation in phenotypes and environments can predict genomic parallelism; (2) genomic parallelism at the early stages of adaptive radiations, even at large geographic scales, is founded on standing variation; and (3) similar environments are a better predictor of genome-wide parallelism than similar phenotypes. Overall, this study validates the importance and predictive power of major phenotypic and environmental factors likely to influence the emergence of common patterns of genomic divergence, providing a clearer picture than analyses of dichotomous phenotypes and environments.

Adding systematic biopsy to magnetic resonance ultrasound fusion targeted biopsy of the prostate in men with previous negative biopsy or enrolled in active surveillance programs: A prospective single center, randomized study.

Magnetic resonance imaging (MRI) targeted biopsy (TBx) of the prostate demonstrated to improve detection rate (DR) of clinically significant prostate cancer (csPCa) in biopsy-naive patients achieving strong level of evidence. Nevertheless, the csPCa yield for TBx alone versus TBx plus systematic biopsy (SBx) after accounting for overlapping of SBx cores with TBx cores, in prior-negative or active surveillance (AS) patients has not been well established.The objective of the study was to investigate benefits in terms of detection rate and pathological stratification of prostate cancer (PCa) using contextual SBx during MRI-TBx.Patients previously submitted to negative-SBx (cohort A) and those enrolled in an AS program (cohort B) who showed at least 1 suspicious area with a PIRADSv2 score ≥ 3 were prospectively and randomly assigned to only TBx strategy versus TBx plus SBx strategy. SBx locations could not encompass the TBx sites, so that the results of each type of biopsy were independent and did not overlap.A total of 312 patients were included in the 2 cohorts (cohort A: 213 cases; cohort B: 99 cases). No significant differences were found in terms of overall PCa-DR (77.6% vs 69.6% respectively; P = .36) and csPCa-DR (48.2% vs 60.9 respectively; P = .12). The MRI-TBx alone cohort showed higher csPCa/PCa ratio (87.5% vs 62.2%; P = .03). The MRI-TBx plus SBx group subanalysis showed significantly higher csPCa-DR obtained at the MRI-TBx cores when compared with the SBx cores (43.7% vs 24.1%, respectively; P = .01). Independently to age, prostatic-specific antigen and prostate imaging-reporting and data system score, either in rebiopsy (OR 0.43, 0.21-0.97) or AS (OR 0.46, 0.32-0.89) setting, SBx cores were negatively associated with the csPCa-DR when combined to TBx cores.MRI-TBx should be considered the elective method to perform prostate biopsy in patients with previous negative SBx and those considered for an AS program. Adding SBx samples to MRI-TBx did not improve detection rate of csPCa.