Robot-Assisted Radical Prostatectomy Performed with the Novel Hugo™ RAS System: A Systematic Review and Pooled Analysis of Surgical, Oncological, and Functional Outcomes.

Background/Objectives: to assess surgical, oncological, and functional outcomes of robot-assisted radical prostatectomy (RARP) performed using the novel Hugo™ RAS system. Methods: A systematic review was conducted following the PRISMA guidelines, using PubMed, Web of Science, Scopus, and Embase databases. Eligible papers included studies involving adult males undergoing RARP with the Hugo™ RAS platform, with at least ten patients analyzed. The pooled analysis was performed using a random-effect model. Results: Quantitative analysis was conducted on 12 studies including 579 patients. The pooled median docking time, console time, and operative time were 11 min (95% CI 7.95-14.50; I2 = 98.4%, ten studies), 142 min (95% CI 119.74-164.68; I2 = 96.5%, seven studies), and 176 min (95% CI 148.33-203.76; I2 = 96.3%, seven studies), respectively. The pooled median estimated blood loss was 223 mL (95% CI 166.75-280.17; I2 = 96.5%, eleven studies). The pooled median length of hospital stay and time to catheter removal were 2.8 days (95% CI 1.67-3.89; I2 = 100%, ten studies) and 8.3 days (95% CI 5.53-11.09; I2 = 100%, eight studies), respectively. The pooled rate of postoperative CD ≥ 2 complications was 4.1% (95% CI 1-8.5; I2 = 63.6%, eleven studies). The pooled rate of positive surgical margins and undetectable postoperative PSA were 20% (95% CI 12.6-28.5; I2 = 71.5%, nine studies) and 94.2% (95% CI 87.7-98.6; I2 = 48.9%, three studies), respectively. At three months, a pooled rate of social continence of 81.9% (95% CI 73.8-88.9; I2 = 66.7%, seven studies) was found. Erectile function at six months was 31% in one study. Conclusions: despite the preliminary nature of the evidence, this systematic review and pooled analysis underscores the feasibility, safety, and reproducibility of the Hugo™ RAS system in the context of RARP.

Robot-Assisted Radical Prostatectomy Performed with the Novel Surgical Robotic Platform Hugo™ RAS: Monocentric First Series of 132 Cases Reporting Surgical, and Early Functional and Oncological Outcomes at a Tertiary Referral Robotic Center.

BACKGROUND: Robotic-assisted surgery is the gold standard for performing radical prostatectomy (RARP), with new robotic devices such as HugoTM RAS gaining prominence worldwide. OBJECTIVE: We report the surgical, perioperative, and early postoperative outcomes of RARP using HugoTM RAS. DESIGN, SETTING, AND PARTICIPANTS: Between April 2022 and October 2023, we performed 132 procedures using the Montsouris technique with a four-robotic-arm configuration in patients with biopsy-proven prostate cancer (PCa). OUTCOME MEASURES: We collected intraoperative and perioperative data during hospitalization, along with follow-up data at predefined postoperative intervals of 3 and 6 months. RESULTS AND LIMITATIONS: Lymphadenectomy was performed in 25 procedures, with a bilateral nerve-sparing technique in 33 and a monolateral nerve-sparing technique in 33 cases. The mean total surgery time was 242 (±57) min, the mean console time was 124 (±48) min, and the mean docking time was 10 (±2) min. We identified 17 system errors related to robotic arm failures, 9 robotic instrument breakdowns, and 8 significant conflicts between robotic arms. One post-operative complication was classified as Clavien-Dindo 3b. None of the adverse events, whether singular or combined, increased the operative time. Positive margins (pR1) were found in 54 (40.9%) histological specimens, 37 (28.0%) of which were clinically significant. At 3 and 6 months post-surgery, the PSA levels were undetectable in 94.6% and 92.1% of patients, respectively. Social urinary continence was regained in 86% after 6 months. Limitations of our study include its observational monocentric case-series design and the short follow-up data for functional and oncological outcomes. CONCLUSIONS: Our initial experience highlights the reliability of the HugoTM RAS system in performing RARP. Additionally, we also list problems and solutions found in our daily work.

Elderly and bladder cancer: The role of radical cystectomy and orthotopic urinary diversion.

The incidence of bladder cancer (BC) depends on advancing age and other risk factors, significantly impacting on surgical, functional and oncological outcomes. Radical cystectomy (RC) with urinary diversion is the gold standard therapy for muscle invasive bladder cancer; however, it remains a complex surgery and requires careful analysis of risk factors in order to potentially decrease post-surgical complication rates. Age in surgery is a limiting factor that can modify surgical and oncological outcomes, and is correlated with a high rate of post-dimssion hospital readmissions. The reconstruction of the bladder with the intestine represents a crucial point of radical cystectomy and the urinary derivation (UD) is at the center of many debates. A non-continent UD seems to be the best choice in elderly patients (>75 years old), while orthotopic neobladder (ON) is poorly practiced. We reviewed the literature to identify studies reporting outcomes, complications, patient- selection criteria, and quality-of-life data on elderly patients, who underwent ON following radical cystectomy. Reviewing the literature there is no clear evidence on the use of age as an exclusion criterion. Certainly, the elderly patient with multiple comorbidities is not eligible for ON, preferring other UD or rescue therapies. A careful preoperative selection of elderly patients could greatly improve clinical, surgical and oncological outcomes, giving the chance to selected patients to receive an ON.

Efficacy of transurethral botulinum toxin A injections for bladder outlet obstruction: A systematic review and meta-analysis.

INTRODUCTION: Botulinum toxin A (BoNT-A) injections in the prostate gland have been used as a minimally invasive option for treating bladder outlet obstruction (BOO). However, the efficacy of transurethral BoNT-A injections for BOO is not well established in the literature. The aim of this study is to collect evidence on the efficacy of transurethral BoNT-A injections for the treatment of BOO. MATERIALS AND METHODS: This systematic review and meta-analyses was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) statement. A systematic literature search was performed till December 2022. The study population consisted of adult patients diagnosed with BOO, who underwent transurethral injections of BoNT-A for the treatment of BOO. EVIDENCE SYNTHESIS: Out of 883 records, we identified seven studies enrolling 232 participants, of which only one nonrandomized controlled trial was found. Four prospective studies and two retrospective studies. Three studies included patients with lower urinary tract symptoms (LUTS) and benign prostatic hyperplasia (BPH) and were included in the meta-analysis. Three studies included patients with urethral sphincter hyperactivity. One study included patients with primary bladder neck disease (PBND). All studies showed significant improvements from baseline in maximum urinary flow rate (Qmax), International Prostate Symptom Score (IPSS), and postvoid residual (PVR) at 3 and 6 months. The adverse events were mild in all studies. Hematuria, UTI, and urinary retention were reported across all studies. CONCLUSION: In conclusion, transurethral BoNT-A injections have been shown to improve LUTS, QoL, and urodynamic parameters of individuals with BOO at 3 and 6 months after injections, and no serious adverse effects have been reported. However, data on the long-term benefits of this treatment are scarce, and more prospective, randomized studies with larger samples examining various injection techniques, dosages, and extended follow-up of recurrent injections are needed.

Etiology, presentation and management of urinary tract infections in multiple sclerosis patients: A review of the current literature.

Urinary tract infections (UTIs) present a formidable challenge in the care of individuals affected by multiple sclerosis (MS). Lower urinary tract dysfunction is a prevalent issue among MS patients, predisposing them to an elevated risk of UTIs. When left untreated, UTIs can further exacerbate the already compromised quality of life in individuals with MS. The diagnosis and management of UTIs in MS patients necessitate a careful clinical evaluation. The objective of this review is to delineate preventive strategies and current and developing therapeutic approaches for preventing and treating UTIs associated with urinary dysfunction, catheterization, and upper urinary tract infections in patients with MS. Effectively addressing UTIs and urinary tract dysfunction in individuals with multiple sclerosis calls for a comprehensive, interdisciplinary approach.

Prevalence and Antimicrobial Resistance Patterns of Hospital Acquired Infections through the COVID-19 Pandemic: Real-Word Data from a Tertiary Urological Centre.

BACKGROUND: Antimicrobial resistance (AMR) remains a significant public health concern, closely linked to antibiotic overuse. During the COVID-19 pandemic, broad-spectrum antibiotics were frequently administered, potentially exacerbating AMR. This study aimed to assess AMR patterns in our urology department before and after the pandemic. METHODS: The study encompassed patients admitted to our urology department from January 2016 to December 2022, with confirmed urinary tract infection, bloodstream infection, or wound infection based on positive culture results. Descriptive statistics, including mean, frequency, and percentage, summarized the data. Trends were analyzed using the Joinpoint Regression program. RESULTS: A total of 506 patients were included. Escherichia coli and Klebsiella pneumoniae displayed resistance rates of 65% and 62% to ciprofloxacin, respectively. K. pneumoniae showed resistance rates of 41% to piperacillin tazobactam and 3rd generation cephalosporins (3GC). Carbapenem resistance was observed in 38% of K. pneumoniae isolates. Additionally, 26% of E. coli, 26% of K. pneumoniae, and 59% of Proteus mirabilis isolates were ESBL-positive. Among gram+, 72% of Staphylococcus aureus isolates were MRSA, and 23% of Enterococcus faecium isolates were VRE. Trends in antimicrobial susceptibility patterns over the 7-year study period revealed a statistically significant decrease in E. coli resistance to amoxicillin-clavulanic acid (APC: -5.85; C.I. 95% p < 0.05) and a statistically significant increase in K. pneumoniae resistance to 3GC (APC: 9.93; CI (-19.9-14.4 95% p < 0.05). There were no statistically significant differences in AMR incidence pre- and post-COVID-19. CONCLUSION: The COVID-19 pandemic did not appear to influence the AMR incidence in our urology department. However, the overall prevalence of AMR and MDROs in our department remains high compared to European AMR.

What can the metaverse do for urology?

Everyone talks about the metaverse but few know what it really is. Augmented reality, virtual reality, internet of things (IoT), 5G, blockchain: these are just some of the technologies underlying the structure of the metaverse, a sort of parallel dimension in which the physical and virtual worlds merge together enabling users to interact by emerging technologies in order to enhance their actions and decisions. The healthcare scientific community is already looking at the metaverse as a new research frontier, a tool to improve medical knowledge and patient care. We reviewed the metaverse applications and services, looking for those that could best be developed in the urological field. Urology, due to its technological nature, is a privileged laboratory for experimenting and exploiting the applications of the metaverse both inside and outside the operating room. The revolution of the metaverse is already happening, which is why it is necessary that urologists face it as protagonists in order to lead it in the right direction.

A survey on preferences, attitudes, and perspectives of Italian urology trainees: implications of the novel national residency matching program.

BACKGROUND: Since 2014, a new residency program selection process has been established with a national examination. The aim of this study was to assess characteristics, career goals, and practice preferences of current Italian urology residents. METHODS: A web-based survey of 25 items performed from May 2021 to September 2021 was sent to 585 Italian urology residents. Descriptive analyses were conducted to describe the surveys' domains: demographics characteristics, studies, plans for fellowship training, interest in the urology field, and career expectations. RESULTS: Four hundred and one residents completed the online survey (response rate 68.5%). Most residents were male (70.3%), with a median of 29 (IQR 28-31) years. Urology was the first chosen School in 325 (81.0%) cases, and 174 (43.4%) trainees have chosen to remain in the same University. Uro-oncology was the main field, and endourology the main subspeciality of interest, respectively. More than 40.0% of residents expressed a good level of satisfaction for the training urological course. 232 (57.2%) residents were strongly interested in seeking a hospital career, followed by private career (43.4%) and academic career (20%). CONCLUSIONS: After the introduction of the novel national residency matching program the Italian Urology trainees showed a good satisfaction level. Further improvements of the Italian residency programs should be focused on the training network within and outside the main School of Urology.

Classification and management of sexual dysfunctions in multiple sclerosis patients: A review of current literature.

Multiple sclerosis (MS) is the most frequent neurological disease in young adults, with the greatest incidence between age of 30 and 35 years. Sexual dysfunctions (SDs) are frequent, but are often underestimated in patients with MS, and can have a significantly high impact on patient's quality of life. Aim of this review is to summarize sexual dysfunctions in male and female MS patients and to illustrate current and emerging therapeutic options for treatment.

Transalbugineal Artificial Urinary Sphincter: A Refined Implantation Technique to Improve Surgical Outcomes.

The artificial urinary sphincter (AUS) implantation is an effective treatment of post-prostatectomy urinary incontinence (PPI). Still, it may result in troublesome complications such as intraoperative urethral lesion and postoperative erosion. Based on the multilayered structure of the tunica albuginea of the corpora cavernosa, we evaluated an alternative transalbugineal surgical technique of AUS cuff placement with the aim to decrease perioperative morbidity while preserving the integrity of the corpora cavernosa. A retrospective study was conducted in a tertiary referral center from September 2012 to October 2021, including 47 consecutive patients undergoing AUS (AMS800®) transalbugineal implantation. At a median (IQR) follow-up of 60 (24-84) months, no intraoperative urethral injury and only one noniatrogenic erosion occurred. The actuarial 12 mo and 5 yr overall erosion-free rates were 95.74% (95% CI: 84.04-98.92) and 91.76% (95% CI: 75.23-97.43), respectively. In preoperatively potent patients, the IIEF-5 score remained unchanged. The social continence (0-1 pads per day) rate was 82.98% (CI 95%: 68.83-91.10) at 12 mos and 76.81% (CI 95%: 60.56-87.04) at 5 yrs follow-up. Our technically refined approach to AUS implantation may help to avoid intraoperative urethral lesions and lower the risk of subsequent erosion without compromising sexual function in potent patients. Prospective and adequately powered studies are necessary to achieve more compelling evidence.

Value of transrectal color Doppler ultrasound of the common penile arteries in the diagnosis of arteriogenic erectile dysfunction: A pilot study.

BACKGROUND: Penile duplex Doppler ultrasound in combination with intra-cavernous injection of vasoactive agents (PDDU-ICI) is the most accepted tool for diagnosis of arteriogenic erectile dysfunction (AED), but is invasive, time consuming and at risk of side effects. OBJECTIVES: The purpose of this pilot study is to evaluate the potential of transrectal color Doppler ultrasound (TR-CDU) of the common penile arteries as a non-invasive method for the diagnosis of AED. MATERIALS AND METHODS: A consecutive series of 61 men consulting for erectile dysfunction (ED) and 20 controls underwent TR-CDU examination, aged from 40 to 80 years. Sonographic parameters were correlated with the International Index of Erectile Function, short form (IIEF-5). Sensitivity and specificity were calculated and the areas under the receiver operating characteristic curves (AUC) were compared to evaluate the diagnostic performance. RESULTS: Receiver operating characteristic curve analysis showed no significant results for IIEF-5 score ⩾21 in relation to the Doppler parameters. However, we found a good diagnostic performance for patients with ED grading from moderate to severe at IIEF-5. In this cohort, we found that mean peak systolic velocity >15.8 cm/s predicted IIEF-5 ⩾17 (AUC = 0.73, p = 0.002) with 61.5% sensitivity and 85.7% specificity. Mean end diastolic velocity >1.46 cm/s predicted IIEF-5 ⩾17 (AUC = 0.68, p = 0.02) with 80.7% sensitivity and 52.4% specificity. Mean resistance index ⩽0.72 predicted IIEF-5 ⩾17 (AUC = 0.71, p = 0.004) with 46.2% sensitivity and 95.2% specificity. Mean pulsatility index ⩽1.41 predicted IIEF-5 ⩾17 (AUC = 0.75, p = 0.0005) with 48.5% sensitivity and 95.14% specificity. CONCLUSIONS: TR-CDU proved to be a feasible and non-invasive procedure, easily repeatable and not time consuming, overcoming the limits of PDDU-ICI. Diagnostic accuracy seems to be promising in discriminating patients with normal erectile function or mild dysfunction from those with moderate to severe ED. However, these findings need to be verified in future controlled randomized clinical trials.

Solvent effects on catechol's binding affinity: investigating the role of the intra-molecular hydrogen bond through a multi-level computational approach.

The subtle interplay between the inter-molecular interactions established by catechol with the surrounding solvent and the intra-molecular hydrogen bond (HB) characterizing its conformational dynamics is investigated through a multi-level computational approach. First, quantum mechanical (QM) calculations are employed to accurately characterize both large portions of the catechol's potential energy surface and the interaction energy with neighboring solvent molecules. The acquired information is thereafter exploited to develop a QM derived force-field (QMD-FF), in turn employed in molecular dynamics (MD) simulations based on classical mechanics. The reliability of the QMD-FF is further validated through a comparison with the outcomes of ab initio molecular dynamics, also purposely carried out in this work. In agreement with recent experimental findings, the MD results reveal remarkable differences in the conformational behavior of isolated and solvated catechol, as well as among the investigated solvents, namely water, acetonitrile or cyclohexane. The rather strong intramolecular HB, settled between the vicinal phenolic groups and maintained in the gas phase, loses stability when catechol is solvated in polar solvents, and is definitively lost in protic solvents such as water. In fact, the internal energy increase associated with the rotation of one hydroxyl group and the breaking of the internal HB is well compensated by the intermolecular HB network available when both phenolic hydrogens point toward the surrounding solvent. In such a case, catechol is stabilized in a chelating conformation, which in turn could be very effective in water removal and surface anchoring. Besides unraveling the role of the different contributors that govern catechol's conformational dynamics, the QMD-FF developed in this work could be in future employed to model larger catechol containing molecules, due to its accuracy to reliably model both internal flexibility and solvent effects, while exploiting MD computational benefits to include more complex players as for instance surfaces, ions or biomolecules.

The new surgical robotic platform HUGOTM RAS: System description and docking settings for robot-assisted radical prostatectomy.

BACKGROUND: To date, robotic surgery in urology is well established all over the world. The newest platform on the market is the HUGO™ RAS system, developed by Medtronic. In this paper we provide a brief description of the system and describe our system set-up and surgical approach with this new platform in our initial experience of robotic radical prostatectomy (RARP) series. MATERIALS AND METHODS: After an official training, seven consecutive patients affected by localized prostate cancer underwent RARP with HUGOTM RAS system at our Institution. A description of our surgical approach and docking setup is provided. Docking and console times were reported for all precedures together with main suggestions to facilitate the use of this new system at the beginning of the experience. RESULTS: Our operating room setup has shown to be safe, effective, and easy replicable. During our series, operative times appeared to be easy reproducible and comparable to those obtained with daVinci system. No major system faults and conflicts between robotic arms were observed after the first procedure. CONCLUSIONS: Our surgical approach and system configuration for performing RARP with the new HUGO™ RAS system appears to be safe, efficient and easy reproducible.

Chasing unphysical TD-DFT excited states in transition metal complexes with a simple diagnostic tool.

Transition Metal Complexes (TMCs) are known for the rich variety of their excited states showing different nature and degrees of locality. Describing the energies of these excited states with the same degree of accuracy is still problematic when using time-dependent density functional theory in conjunction with the most current density functional approximations. In particular, the presence of unphysically low lying excited states possessing a relevant Charge Transfer (CT) character may significantly affect the spectra computed at such a level of theory and, more relevantly, the interpretation of their photophysical behavior. In this work, we propose an improved version of the MAC index, recently proposed by the authors and collaborators, as a simple and computationally inexpensive diagnostic tool that can be used for the detection and correction of the unphysically predicted low lying excited states. The analysis, performed on five prototype TMCs, shows that spurious and ghost states can appear in a wide spectral range and that it is difficult to detect them only on the basis of their CT extent. Indeed, both delocalization of the excited state and CT extent are criteria that must be combined, as in the MAC index, to detect unphysical states.

Multiparametric magnetic resonance imaging of the prostate: Lights and shadows.

Prostate cancer is the second most commonly diagnosed cancer in man. Since the first MRI was performed, enormous progress has been made in diagnosis, treatment, and follow up of PCa, mainly due to multiparametric prostatic MRI (mpMRI). Although mpMRI has become the best imaging tool for identifying PCa, some limitations still exist. Prostate imaging with mpMRI is, to date, the best way to locate suspicious lesions to trigger prostate biopsy, plan active surveillance, or definitive treatment. In case of relapse, mpMRI can help detect local disease and provide specific management. It is well known that there is a subset of patients in whom mpMRI fails to depict csPCa. These missed significant cancers demand great attention. Prostate mpMRI quality depends on several factors related to equipment (including equipment vendor, magnet field and gradient strength, coil set used, software and hardware levels, sequence parameter choices), patient (medications, body habitus, motion, metal implants, rectal gas), and most importantly the radiologic interpretation of images (learning curve effects, subjectivity of observations, interobserver variations, and reporting styles). Inter-reader variability represents a huge current limitation of this method. Therefore, mpMRI remains the best imaging tool available to detect PCa, guiding diagnosis, treatment, and follow up while inter-reader variability represents the best limitation. Radiomics can help identifying imaging biomarkers to help radiologist in detecting significant PCa, reducing examination times, and costs.

Rate of clinically significant prostate cancer on repeat saturation biopsy after a diagnosis of atypical small acinar proliferation.

BACKGROUND: Atypical small acinar proliferation (ASAP) occurs in approximately 5% of prostate biopsies. Approximately 30%-40% of these patients may develop prostate cancer (PCa) within a 5-year period, often not clinically significant. Current guidelines recommend a repeat biopsy within 3-6 months after the initial diagnosis, but it seem not to be the best strategy. METHODS: Objectives-evaluating the natural history of ASAP, stratifying the risk of csPCa after ASAP, identifying predictive factors of PCa after atypical diagnosis. Materials and methods-retrospective single-institutional study on patients undergoing prostate biopsy for suspicious PCa (2005-2016). We evaluated the incidence of overall PCa, intermediate-high risk of PCa and csPCa in case of ASAP, according to D'Amico classification and Epstein modified criteria. RESULTS: Out of 4.567 patients undergoing prostate biopsy, ASAP was detected in 2.6% of cases. All patients with ASAP underwent repeat saturation biopsy within 6 months and PCa was diagnosed in 34.5%. According to D'Amico classification, 26%, 5.9%, and 2.5% had low, intermediate, and high-risk disease, respectively. According modified Epstein criteria, the incidence of csPCa was 12.6%. LRT showed that the overall probability to develop PCa doubled when PSA density (PSAD) moved from values lower than 0.13 ng/ml/cc to class 0.13-0.30 ng/ml/cc, and it tripled when PSAD was higher than 0.30 ng/ml/cc. CONCLUSIONS: The rate of csPCa in patients with an initial diagnosis of ASAP who had repeat biopsy was 12.6%. The overall PCa rate was 34.5%. Among patient undergoing RP, an upgrading from ncsPCa to csPCa was reported in 35% of cases. PSAD is the only predictive factor directly associated to the risk of developing PCa on repeat biopsy. These findings suggest that immediate repeat biopsy remains the correct strategy in absence of novel predictor factors and non-invasive diagnostic evaluations.

Automated parameterization of quantum-mechanically derived force-fields including explicit sigma holes: A pathway to energetic and structural features of halogen bonds in gas and condensed phase.

In classical molecular dynamics, general purpose atomistic force-fields (FFs) often deliver inaccurate results when dealing with halogen bonds (XBs), notwithstanding their crucial role in many fields of science, ranging from material design to drug development. Given the large dimensions of the systems of interest, it would be therefore desirable to increase the FF accuracy maintaining the simplicity of the standard Lennard-Jones (LJ) plus point charge description to avoid an excessive computational cost. A simple yet effective strategy consists in introducing a number of virtual sites able to mimic the so-called "explicit σ-hole." In this work, we present an automated FF parameterization strategy based on a global optimization of both LJ and charge parameters with respect to accurate quantum mechanical data, purposely computed for the system under investigation. As a test case, we report on two homologue series, characterized either by weak or strong XBs, namely, the di-halogenated methanes and the mono-, di-, and tri-substituted acetonitriles, taking into consideration Cl, Br, and I substituents. The resulting quantum mechanically derived FFs are validated for each compound in the gas and in the condensed phase by comparing them to general purpose and specific FFs without virtual sites and to highly accurate reference quantum mechanical data. The results strongly support the adoption of the specific FFs with virtual sites, which overcome the other investigated models in representing both gas phase energetics and the structural patterns of the liquid phase structure related to the presence of XBs.

General Density-Based Index to Analyze Charge Transfer Phenomena: From Models to Butterfly Molecules.

We present a new formula and implementation for a descriptor enabling quantification of the electron-hole distance associated with a charge transfer of an optical transition, on the basis of the knowledge of the densities of the electronic ground and excited states. This index is able to define a charge-transfer length even for systems that would be otherwise difficult to treat, like symmetric molecules, while maintaining a very low computational cost and the possibility to be coupled to any method providing ground and excited state electron densities. After a benchmark of its performance on a series of push-pull molecules, the index has been applied to a set of large symmetric luminophores, the so-called "butterfly molecules", showing promising applications in optoelectronics, to highlight its potential use in the design of new compounds.

Following the evolution of excited states along photochemical reaction pathways.

Analyzing the behavior of potential energy surfaces (PESs) of diabatic excited states (ESs) becomes of crucial importance for a complete understanding of complex photochemical reactions. Since the definition of a compact representation for the transition density matrix, the use of the natural transition orbitals (NTOs) has become a routine practice in time-dependent density functional theory calculations. Their popularity has remarkably grown due to its simple orbital description of electronic excitations. Indeed, very recently, we have presented a new formalism used for the optimization of ESs by tracking the state of interest computing the NTO's overlap between consecutive steps of the procedure. In this new contribution, we generalize the use of this NTO's overlap-based state-tracking formalism for the analysis of all the desired diabatic states along any chemical reaction pathway. Determining the PES of the different diabatic states has been automatized by developing an extension of our recently presented algorithm, the so-called SDNTO: "Steepest Descent minimization using NTOs." This automatized overlap-based procedure allows an agile and convenient analysis of the evolution of the ESs avoiding the intrinsic ambiguity of visualizing orbitals or comparing physical observables. The analysis of two photochemical reactions of the same nature with different PES landscapes perfectly illustrates the utility of this new tool.

Circulating tumor cells as prognostic biological marker in different stages prostate cancer and the effect of different therapeutic approaches on their expression.

BACKGROUND: Circulating tumor cells (CTCs) represent a prerequisite for the formation of metastases. The aim of the study was to identify the role of CTCs as a biological marker of aggressiveness of prostate cancer and verify the expression of molecular markers predictive of response to different therapeutic approaches. METHODS: Prospective, single-arm, non-randomized trial. Twenty-four patients with prostate cancer were enrolled into two groups: group 1 (N.=11) with localized prostate cancer treated with radical prostatectomy; group 2 (N.=13) with metastatic disease. We performed, dosage of blood PSA and testosterone, detection of EGFR, PSMA, PSA and Androgen Receptor (AR) expression on CTC during pre-treatment and follow-up at 1, 3, 9 and 18 months. RESULTS: A total of 65 blood samples were evaluated. In group 1, pre-treatment sampling was negative for the expression of markers on CTC in 90% of the patients while group 2 pre-treatment sampling was positive for the expression of at least one biomarker in seven of 13 patients (54%). After treatment, four patients in group 2 experienced a reduced expression of the markers on CTC, however, in one case there was a new increase of PSA and PSMA at 3 months. One patient had a positivity of AR at 3 months. CONCLUSIONS: The expression of PSA, PSMA, EGFR and AR on CTCs appears to be absent in the pre-treatment samplings in cases of localized prostate cancer. The same markers are hyper-expressed before treatment mostly in metastatic prostate cancer and can relate with early biochemical relapse.