Ten-year functional and oncological outcomes of a prospective randomized controlled trial comparing laparoscopic versus robot-assisted radical prostatectomy.

BACKGROUND: Among prostate cancer (PCa) treatment options, mini-invasive surgical approaches have gained a wide diffusion in the last decades. The aim of this study was to present oncological, functional, and quality of life data after 10 years of follow-up of a prospective randomized controlled trial (RCT) (ISRCTN11552140) comparing robot-assisted radical prostatectomy (RARP) versus laparoscopic radical prostatectomy (LRP) for the treatment of PCa. METHODS: Patients with localized PCa were randomized to undergo LRP or RARP between January 2010 and January 2011. Functional (continence and potency) and oncological (prostate-specific antigen, biochemical recurrence [BCR] and BCR-free survival [BCRFS]) variables were evaluated. BCRFS curves were estimated by the Kaplan-Meier method and compared using the log-rank test. Machine learning partial least square-discriminant analysis (PLS-DA) was used to identify the variables characterizing more the patients who underwent RARP or LRP. RESULTS: Seventy-five of the originally enrolled 120 patients remained on follow-up for 10 years; 40 (53%) underwent RARP and 35 (47%) LRP. Continence and potency recovery rates did not show significant differences (p = 0.068 and p = 0.56, respectively), despite a Δ12% for continence and Δ8% for potency in favor of the robotic approach. However, the quality of continence (in terms of International Consultation on Incontinence Questionnaire-Short Form [ICIQ-SF] score) and erection (in terms of International Index of Erectile Function-5 [IIEF-5] score) was significantly better after 10 years in the robotic group (p = 0.02 and p < 0.001). PLS-DA revealed that LRP was characterized by the worst functional-related outcomes analyzing the entire follow-up period. Four (10%) and six (17%) patients experienced BCR in RARP and LRP groups, respectively (p = 0.36), with an overall 10-year BCR-free survival of 88% and 78% (p = 0.16). CONCLUSIONS: Comparable continence and potency rates were observed between RARP and LRP after a 10-year follow-up. However, the RARP group exhibited superior totally dry rate and erection quality. No difference in terms of oncological outcomes was found.

Iron Overload in Brain: Transport Mismatches, Microbleeding Events, and How Nanochelating Therapies May Counteract Their Effects.

Iron overload in many brain regions is a common feature of aging and most neurodegenerative diseases. In this review, the causes, mechanisms, mathematical models, and possible therapies are summarized. Indeed, physiological and pathological conditions can be investigated using compartmental models mimicking iron trafficking across the blood-brain barrier and the Cerebrospinal Fluid-Brain exchange membranes located in the choroid plexus. In silico models can investigate the alteration of iron homeostasis and simulate iron concentration in the brain environment, as well as the effects of intracerebral iron chelation, determining potential doses and timing to recover the physiological state. Novel formulations of non-toxic nanovectors with chelating capacity are already tested in organotypic brain models and could be available to move from in silico to in vivo experiments.

Uterine smooth muscle tumors: a multicenter, retrospective, comparative study of clinical and ultrasound features.

OBJECTIVE: To evaluate a wide range of clinical and ultrasound characteristics of different uterine smooth muscle tumors to identify features capable of discriminating between these types. METHODS: This was a retrospective, multicenter study that included 285 patients diagnosed with uterine smooth muscle tumors (50 leiomyosarcomas, 35 smooth muscle tumors of uncertain malignant potential, and 200 leiomyomas). The patients were divided into three groups based on the histological type of their tumors, and the groups were compared according to the variables collected. RESULTS: Leiomyosarcomas were more common in older and post-menopausal women. Compared with leiomyomas, smooth muscle tumors of uncertain malignant potential and leiomyosarcomas had similar ultrasound features such as absence of normal myometrium, multilocular appearance, hyper-echogenicity in case of uniform echogenicity, absence of posterior shadows, echogenic areas, and hyperechoic rim. Leiomyosarcomas were larger, had more cystic areas, and were associated with a higher prevalence of pelvic free fluid. Smooth muscle tumors of uncertain malignant potential were characterized by a higher frequency of International Federation of Gynecology and Obstetrics (FIGO) type 6-7, the absence of internal shadows, and, in the case of cystic area, the presence of a regular internal wall. Tumor outline varied among the three histological types. A color score of 1 was typical of leiomyoma, a color score 2 was mainly observed in leiomyomas and smooth muscle tumors of uncertain malignant potential, a color score 3 did not differ among the tumors, while a color of score 4 was related to leiomyosarcomas. When combining color scores 3 and 4, leiomyosarcomas and smooth muscle tumors of uncertain malignant potential showed a high percentage of both circumferential and intra-lesional vascularization. A cooked appearance was not statistically different among the tumors. CONCLUSIONS: Based on our findings, specific ultrasonographic features as well as age and menopausal status are associated with different uterine smooth muscle tumor types. Integration of these data can help the pre-operative assessment of these lesions for proper management.

Iron Deposition in Brain: Does Aging Matter?

The alteration of iron homeostasis related to the aging process is responsible for increased iron levels, potentially leading to oxidative cellular damage. Iron is modulated in the Central Nervous System in a very sensitive manner and an abnormal accumulation of iron in the brain has been proposed as a biomarker of neurodegeneration. However, contrasting results have been presented regarding brain iron accumulation and the potential link with other factors during aging and neurodegeneration. Such uncertainties partly depend on the fact that different techniques can be used to estimate the distribution of iron in the brain, e.g., indirect (e.g., MRI) or direct (post-mortem estimation) approaches. Furthermore, recent evidence suggests that the propensity of brain cells to accumulate excessive iron as a function of aging largely depends on their anatomical location. This review aims to collect the available data on the association between iron concentration in the brain and aging, shedding light on potential mechanisms that may be helpful in the detection of physiological neurodegeneration processes and neurodegenerative diseases such as Alzheimer's disease.

The relationship between alexithymia, sensory phenotype and neurophysiological parameters in patients with chronic upper limb neuropathy.

In this study, we investigated the relationship between sensory abnormalities evaluated by quantitative sensory testing (QST) and alexithymia, depression and anxiety in patients with neuropathic pain involving the upper limbs. We enrolled 62 patients (34 with carpal tunnel syndrome, 7 with brachial plexopathy, 3 with cervical painful radiculopathy, 5 with ulnar entrapment neuropathy at elbow and 13 with post-burn hypertrophic scars) and 48 healthy controls. All underwent nerve conduction studies (NCS), evaluation of cold, heat pain and vibration detection threshold (VDT) by QST and evaluation of alexithymia by Toronto Alexithymia Scale (TAS-20), depression by Beck Depression Inventory II (BDI-II), anxiety by State-Trait Anxiety Inventory (STAI-Y), level of psychological distress by 12-item General Health Questionnaire (GHQ-12) and perceived social support by the Multidimensional Scale of Perceived Social Support (MSPSS). The general linear model analysis revealed a significant relationship between TAS-20 overall and TAS-20 sub-score for difficulty identifying feelings and VDT z-scores in the left index with no interaction by year of education and sensory NCS results. Our results demonstrated the association between impairment of vibratory sensation of the left hand, reflecting cutaneous mechanoceptor dysfunction, and alexithymia, particularly the difficulty to identify feelings. The importance of delivering to patients with neuropathic pain personalized care that takes into account not only the neurophysiological aspects but also the aspects of mental functioning is discussed.

Three-dimensional virtual imaging of renal tumours: a new tool to improve the accuracy of nephrometry scores.

OBJECTIVES: To apply the standard PADUA and RENAL nephrometry score variables to three-dimensional (3D) virtual models (VMs) produced from standard bi-dimensional imaging, thereby creating three-dimensional (3D)-based (PADUA and RENAL) nephrometry scores/categories for the reclassification of the surgical complexity of renal masses, and to compare the new 3D nephrometry score/category with the standard 2D-based nephrometry score/category, in order to evaluate their predictive role for postoperative complications. MATERIALS AND METHODS: All patients with localized renal tumours scheduled for minimally invasive partial nephrectomy (PN) between September 2016 and September 2018 underwent 3D and 2D nephrometry score/category assessments preoperatively. After nephrometry score/category evaluation, all the patients underwent surgery. Chi-squared tests were used to evaluate the individual patients' grouping on the basis of the imaging tool (3D VMs and 2D imaging) used to assess the nephrometry score/category, while Cohen's κ coefficient was used to test the concordance between classifications. Receiver-operating characteristic curves were produced to evaluate the sensitivity and specificity of the 3D nephrometry score/category vs the 2D nephrometry score/category in predicting the occurrence of postoperative complications. A general linear model was used to perform multivariable analyses to identify predictors of overall and major postoperative complications. RESULTS: A total of 101 patients were included in the study. The evaluation of PADUA and RENAL nephrometry scores via 3D VMs showed a downgrading in comparison with the same scores evaluated with 2D imaging in 48.5% and 52.4% of the cases. Similar results were obtained for nephrometry categories (29.7% and 30.7% for PADUA risk and RENAL complexity categories, respectively). The 3D nephrometry score/category demonstrated better accuracy than the 2D nephrometry score/category in predicting overall and major postoperative complications (differences in areas under the curve for each nephrometry score/category were statistically significant comparing the 3D VMs with 2D imaging assessment). Multivariable analyses confirmed 3D PADUA/RENAL nephrometry category as the only independent predictors of overall (P = 0.007; P = 0.003) and major postoperative complications (P = 0.03; P = 0.003). CONCLUSIONS: In the present study, we showed that 3D VMs were more precise than 2D standard imaging in evaluating the surgical complexity of renal masses according to nephrometry score/category. This was attributable to a better perception of tumour depth and its relationships with intrarenal structures using the 3D VM, as confirmed by the higher accuracy of the 3D VM in predicting postoperative complications.

Total anatomical reconstruction during robot-assisted radical prostatectomy: focus on urinary continence recovery and related complications after 1000 procedures.

OBJECTIVES: To present the functional and oncological outcomes after ≥1 year of follow-up, following an experience of >1000 robot-assisted radical prostatectomies (RARPs) with our standardised total anatomical reconstruction (TAR) technique. To evaluate which factors influence postoperative continence recovery in order to obtain a nomogram to predict the risk of postoperative urinary incontinence (UI). PATIENTS AND METHODS: The enrolment phase began in June 2013 and ended in May 2017. Patients were prospectively included in the study with the following inclusion criteria: (i) localised prostate cancer (clinical stages cT1-3, cN0, cM0); (ii) indication for RP; and (iii) preoperative multiparametric prostate magnetic resonance imaging. All patients underwent RARP with the TAR technique done at the end of the demolitive phase. The continence rates were assessed at 24 h, and 1, 4, 12, 24 and 48 weeks after catheter removal. Patients were defined as continent if they answered 'zero pad' or 'one safety pad' per day. A logistic regression model was used to evaluate the potential impact of some pre- and intraoperative factors on postoperative urinary continence recovery. Model discrimination was assessed using an area under (AUC) the receiver operating characteristic (ROC) curve. A nomogram to predict the risk of postoperative UI after RARP with the TAR technique was generated based on the logistic model. RESULTS: In all, 1008 patients were enrolled in our study. At 24 h, and 1, 4, 12, 24 and 48 weeks after catheter removal, 621 (61.61%), 594 (58.93%), 803 (79.66%), 912 (90.48%), 950 (94.25%) and 956 (94.84%) patients were continent, respectively. In the logistic regression model, the variables analysed had a higher impact on continence recovery at 4 and 12 weeks. At 4 weeks, the postoperative odds of urinary continence recovery increased with the absence of diabetes [odds ratio (OR) 2.76, 95% confidence interval (CI) 1.41-5.41] and D'Amico low vs high risk (OR 2.01, 95% CI 1.01-3.99). At 12 weeks, urinary continence increased with the absence of diabetes (OR 3.01, 95% CI 1.23-7.35), D'Amico low vs high risk (OR 4.04, 95% CI 1.56-10.47), and D'Amico intermediate vs high risk (OR 3.33, 95% CI 1.66-6.70). ROC curves were drawn and an AUC value of 61.9% (95% CI 57.49-66.36) at 4 weeks and 63.8% (95% CI 58.03-69.65) at 12 weeks were computed. Based on these parameters, two nomograms (at 4 and 12 weeks postoperatively) were generated. CONCLUSION: The TAR technique conferred excellent results in the early recovery of urinary continence. Two nomograms were created, to predict preoperatively the postoperative odds of urinary continence recovery at 4 and 12 weeks after RARP by integrating the presence of diabetes and D'Amico risk classification.

Use of chitosan membranes after nerve-sparing radical prostatectomy improves early recovery of sexual potency: results of a comparative study.

OBJECTIVES: To evaluate the 1-year efficacy of chitosan membrane (ChiMe) application on the neurovascular bundles (NVBs) after nerve-sparing (NS) robot-assisted radical prostatectomy (RARP) in potency recovery rate. To compare the results with those of a contemporary cohort of patients who did not benefit from chitosan use. PATIENTS AND METHODS: Patients in the ChiMe group were enrolled at our institution from July 2015 to September 2016 in a preliminary phase II study. All of them underwent NS-RARP with ChiMe applied on the NVBs and were followed over time to complete a 1-year follow-up. The control group was composed of patients who underwent NS-RARP at our institution without the application of ChiMe from January 2015. The patients were further classified into two groups based on the amount of nerves spared: Group A, comprised patients who underwent a monolateral or bilateral full NS; Group B, comprised patients in which a full NS was not performed. The demographics, peri- and postoperative data, and complications were recorded and compared. Potency recovery was recorded for Group A vs Group B in both the ChiMe and the control groups. RESULTS: In all, 136 patients were enrolled in the ChiMe group and 334 patients in the control group. There were no differences between groups in terms of baseline variables. Based on the amount of nerves preserved, 183 patients were included in Group A and 287 in Group B. Odds ratios at different time points showed that the only two factors influencing potency recovery were the amount of nerves preserved (Group A vs Group B) and the application or not of ChiMe on the NVBs spared. Comparing the ChiMe vs control groups at different time points, we found a statistically significant improvement in the potency recovery rate in the ChiMe group at 1 month (36.76% vs 25.88%; P = 0.02) and 2 months (52.2% vs 39.22%; P = 0.01) after surgery, showing a favourable trend at every time point of the entire follow-up period, even if not significant after the second postoperative month. In Group A, the log-rank test showed a statistically significant difference between the ChiMe vs control groups (P = 0.02), in particular at 1 and 2 months after surgery (P = 0.02 and P = 0.01, respectively). CONCLUSION: The application of ChiMe on the NVBs resulted in a higher potency recovery rate at 1 and 2 months after a bilateral or monolateral full NS-RARP. A trend of a higher and shorter potency recovery rate showed it to be favourable to use ChiMe, even in the cohort of patients who did not undergo a full NS procedure.

From Micro- to Nano-Multifunctional Theranostic Platform: Effective Ultrasound Imaging Is Not Just a Matter of Scale.

Ultrasound Contrast Agents (UCAs) consisting of gas-filled-coated Microbubbles (MBs) with diameters between 1 and 10 µm have been used for a number of decades in diagnostic imaging. In recent years, submicron contrast agents have proven to be a viable alternative to MBs for ultrasound (US)-based applications for their capability to extravasate and accumulate in the tumor tissue via the enhanced permeability and retention effect. After a short overview of the more recent approaches to ultrasound-mediated imaging and therapeutics at the nanoscale, phase-change contrast agents (PCCAs), which can be phase-transitioned into highly echogenic MBs by means of US, are here presented. The phenomenon of acoustic droplet vaporization (ADV) to produce bubbles is widely investigated for both imaging and therapeutic applications to develop promising theranostic platforms.

'In Vitro', 'In Vivo' and 'In Silico' Investigation of the Anticancer Effectiveness of Oxygen-Loaded Chitosan-Shelled Nanodroplets as Potential Drug Vector.

PURPOSE: Chitosan-shelled/decafluoropentane-cored oxygen-loaded nanodroplets (OLN) are a new class of nanodevices to effectively deliver anti-cancer drugs to tumoral cells. This study investigated their antitumoral effects 'per se', using a mathematical model validated on experimental data. METHODS: OLN were prepared and characterized either in vitro or in vivo. TUBO cells, established from a lobular carcinoma of a BALB-neuT mouse, were investigated following 48 h of incubation in the absence/presence of different concentrations of OLN. OLN internalization, cell viability, necrosis, apoptosis, cell cycle and reactive oxygen species (ROS) production were checked as described in the Method section. In vivo tumor growth was evaluated after subcutaneous transplant in BALB/c mice of TUBO cells either without treatment or after 24 h incubation with 10% v/v OLN. RESULTS: OLN showed sizes of about 350 nm and a positive surface charge (45 mV). Dose-dependent TUBO cell death through ROS-triggered apoptosis following OLN internalization was detected. A mathematical model predicting the effects of OLN uptake was validated on both in vitro and in vivo results. CONCLUSIONS: Due to their intrinsic toxicity OLN might be considered an adjuvant tool suitable to deliver their therapeutic cargo intracellularly and may be proposed as promising combined delivery system.

Magnetic Nanoparticles in the Central Nervous System: Targeting Principles, Applications and Safety Issues.

One of the most challenging goals in pharmacological research is overcoming the Blood Brain Barrier (BBB) to deliver drugs to the Central Nervous System (CNS). The use of physical means, such as steady and alternating magnetic fields to drive nanocarriers with proper magnetic characteristics may prove to be a useful strategy. The present review aims at providing an up-to-date picture of the applications of magnetic-driven nanotheranostics agents to the CNS. Although well consolidated on physical ground, some of the techniques described herein are still under investigation on in vitro or in silico models, while others have already entered in-or are close to-clinical validation. The review provides a concise overview of the physical principles underlying the behavior of magnetic nanoparticles (MNPs) interacting with an external magnetic field. Thereafter we describe the physiological pathways by which a substance can reach the brain from the bloodstream and then we focus on those MNP applications that aim at a nondestructive crossing of the BBB such as static magnetic fields to facilitate the passage of drugs and alternating magnetic fields to increment BBB permeability by magnetic heating. In conclusion, we briefly cite the most notable biomedical applications of MNPs and some relevant remarks about their safety and potential toxicity.

[Admission test to the degree course in Medicine and Surgery and university career: the experience in the campuses of Piedmont Region (Northern Italy)]. / Test di ammissione al corso di laurea in Medicina e chirurgia e carriera universitaria: l'esperienza nelle sedi piemontesi.

OBJECTIVES: to consider the admission test to the degree course in Medicine and Surgery in the three campus of Piedmont Region (Northern Italy) in order to discuss the ability of this test to predict the academic outcome of the students. DESIGN: cohort study considering all the students enrolled in the first year of medicine during the academic year 2014-2015. Their academic career is monitored during the period January 2015-February 2016. SETTING AND PARTICIPANTS: a total of 781 students is considered and divided into two groups: regular (registered after passing the admission test; n. 605) and TAR (registered after court decision and having won the case in tribunal; n. 176). MAIN OUTCOME MEASURES: the study is based on three indicators of performance: A1. at least one of the required exams in the first year passed; A2. at least half of the required exams in the first year passed; A3. all the exams required in the first year passed. Statistical analyses are based on: positive predictive value and relative 95% confidence interval; odds ratio and relative 95% confidence intervals, adjusted by sex, age, high school type, and vote estimated by logistic regression models. RESULTS: the results highlight the good prediction of the admission test that remains significant even after adjustment for the confounding factors considered. CONCLUSIONS: the major limits are the short period of observation and the restricted number of campus considered. However, this analysis confirms the importance of the admission test. In fact, students with low scores in the test could show serious disadvantages in passing the exams (in the appointed time) in the first year.

Emotion Processing in Peripheral Neuropathic Pain: An Observational Study.

BACKGROUND: In clinical practice, the implementation of tailored treatment is crucial for assessing the patient's emotional processing profile. Here, we investigate all three levels of analysis characterizing emotion processing, i.e., recognition, representation, and regulation, in patients with peripheral neuropathic pain (PNP). METHODS: Sixty-two patients and forty-eight healthy controls underwent quantitative sensory testing, i.e., psychophysical tests to assess somatosensory functions such as perception of cold (CDT), heat-induced pain (HPT), and vibration (VDT), as well as three standardized tasks to assess emotional processing: (1) the Ekman 60-Faces Test (EK-60F) to assess recognition of basic facial emotions, (2) the Reading the Mind in the Eyes Test (RME) to assess the ability to represent the feelings of another person by observing their eyes, and (3) the 20-item Toronto Alexithymia Scale (TAS-20) to assess emotional dysregulation, i.e., alexithymia. RESULTS: General Linear Model analysis revealed a significant relationship between left index finger VDT z-scores in PNP patients with alexithymia. The RME correlated with VDT z-scores of the left little finger and overall score for the EK-60F. CONCLUSIONS: In patients with PNP, emotion processing is impaired, which emphasizes the importance of assessing these abilities appropriately in these patients. In this way, clinicians can tailor treatment to the needs of individual patients.

A Three-step Etch-and-Rinse vs a Universal Adhesive in Nanohybrid Composite Anterior Restorations: A Retrospective Clinical Evaluation.

PURPOSE: To retrospectively evaluate the clinical behavior of direct anterior composite restorations performed with a universal adhesive or with a three-step etch-and-rinse (E&R) adhesive. MATERIAL AND METHODS: Patients were randomly treated with a three-step E&R adhesive (Optibond FL, Kerr) or a universal adhesive (Clearfil Universal Bond Quick, Kuraray Noritake) applied in E&R mode. All restorations were performed with a nanohybrid composite (ClearFil Majesty ES-2, Kuraray Noritake) by the same experienced operator. Two calibrated examiners evaluated the restorations using a dental mirror and explorer, in accordance with modified United States Public Health Service (USPHS) procedures. Clinical events were registered and classified as either failure (F), survival (SR), or success (S). RESULTS: 168 restorations were evaluated in 90 patients with an average follow-up period of 37.9 (± 22.9) months. A total of 132 restorations were performed on vital teeth, and 36 were performed on endodontically treated teeth (ETT). A total of 128 Class-IV and 40 Class-III restorations were performed. In 89 restorations, a three-step E&R adhesive was applied (14 Class-III and 75 Class-IV), while in 79, a universal adhesive was used (26 Class-III and 53 Class-IV, p = 0.0091). A Cox regression analysis was performed (p < 0.05) to analyze which factors were involved in the failure of the restorations, considering failure (F) as restorations that needed re-intervention at the follow-up period of 37.9 (± 22.9) months. No statistically significant differences were observed when considering parameters directly involved with the adhesives tested. Endodontically treated teeth were more prone to fractures (p = 0.0006) compared to vital teeth. Restorations made with universal adhesives failed by fracturing significantly more frequently (p = 0.0234), while restorations made on endodontically treated teeth had a significantly worse outcome (p = 0.0001). Restorations made on canines also failed significantly more frequently (HR = 3.8, 95% CI = 1.4-10.1, p = 0.0062). CONCLUSIONS: Based on the obtained results, both the universal adhesive and the three-step E&R adhesive proved to be good treatment choices for direct anterior restorations after 37.9 (± 22.9) months of follow-up. Tooth vitality seems fundamental for the prognosis of a direct anterior composite restoration over time.

Combining Blue Light and Yellow Curcumin to Obtain a "Green" Tool for Berry Preservation against Bacterial Contamination: A Preliminary Investigation.

Background: According to recent studies, tens of millions of tons of fruit are wasted each year in Europe in primary production and home/service consumption. Among fruits, berries are most critical because they have a shorter shelf life and a softer, more delicate, and often edible skin. Curcumin is a natural polyphenolic compound extracted from the spice turmeric (Curcuma longa L.) which exhibits antioxidant, photophysical, and antimicrobial properties that can be further enhanced by photodynamic inactivation of pathogens when irradiated with blue or ultraviolet light. Materials and methods: Multiple experiments were performed in which berry samples were sprayed with a complex of ß-cyclodextrin containing 0.5 or 1 mg/mL of curcumin. Photodynamic inactivation was induced by irradiation with blue LED light. Antimicrobial effectiveness was assessed with microbiological assays. The expected effects of oxidation, curcumin solution deterioration, and alteration of the volatile compounds were investigated as well. Results: The treatment with photoactivated curcumin solutions reduced the bacterial load (3.1 vs. 2.5 colony forming units/mL (UFC/ml) in the control and treated groups; p-value = 0.01), without altering the fruit organoleptic and antioxidant properties. Conclusions: The explored method is a promising approach to extend berries' shelf life in an easy and green way. However, further investigations of the preservation and general properties of treated berries are still needed.

Syringomyelia Associated with Chiari 1 Malformation in Adults: Positive Outcome Predictors after Posterior Fossa Decompression with Duraplasty.

BACKGROUND: Syringomyelia (Syr) in patients with Chiari 1 malformation (CM1) may be attributable to abnormal dynamics of cerebrospinal fluid (CSF) in the upper cervical segment; fourth ventricle enlargement has been reported in association with a worse clinical and radiological presentation, independently of the posterior fossa volume. In this study, we analyzed presurgery hydrodynamic markers to evaluate if their changes could be associated with clinical and radiological improvement after posterior fossa decompression and duraplasty (PFDD). As a primary endpoint, we aimed to correlate improvement in the fourth ventricle area with positive clinical outcomes. METHODS: In total, in this study, we enrolled 36 consecutive adults with Syr and CM1 who were followed by a multidisciplinary team. All the patients were prospectively evaluated with clinical scales and neuroimaging, including CSF flow, the fourth ventricle area, and the Vaquero Index by using a phase-contrast MRI before (T0) and after surgical treatment (T1-Tlast, with a range of 12-108 months). The CSF flow at the craniocervical junction (CCJ), the fourth ventricle area, and the Vaquero Index changes were statistically analyzed and compared to the clinical and quality of life improvement after surgery. The good outcome prediction ability of presurgical radiological variables was tested. RESULTS: Surgery was associated with positive clinical and radiological outcomes in more than 90% of cases. The fourth ventricle area significantly reduced after surgery (T0-Tlast, p = 0.0093), but no significant associations with clinical improvement were found. The presurgical presence of CSF flow at the CCJ was able to predict a good outcome (AUC = 0.68, 95% CI 0.50-0.87 and LH+ = 2.1, IC 95% 1.16-3.07) and was also significantly associated with post-surgical pain relief (rho = 0.61 and p = 0.0144). CONCLUSIONS: Presurgery CSF flow at the CCJ is proposed as a radiological marker with the ability to predict a positive outcome after PFDD in adults with syringomyelia and CM1. Measurements of the fourth ventricle area could be useful additional information for evaluating surgical long-term follow-up; further experience on larger cohorts is required to better define the prognostic yield of this radiological parameter.

Development of a novel nomogram to identify the candidate to extended pelvic lymph node dissection in patients who underwent mpMRI and target biopsy only.

BACKGROUND: Nowadays a tool able to predict the risk of lymph-node invasion (LNI) in patients underwent target biopsy (TB) only before radical prostatectomy (RP) is still lacking. Our aim is to develop a model based on mp-MRI and target biopsy (TB) alone able to predict the risk of LNI. METHODS: We retrospectively extracted data of patients with preoperative positive mp-MRI and TB only who underwent RARP with ePLND from April 2014 to March 2020. A logistic regression model was performed to evaluate the impact of pre- and intra-operative factors on the risk of LNI. Model discrimination was assessed using an area under (AUC) the ROC curve. A nomogram, and its calibration plot, to predict the risk of LNI were generated based on the logistic model. A validation of the model was done using a similar cohort. RESULTS: 461 patients were included, of which 52 (11.27) had LNI. After logistic regression analysis and multivariable model DRE, PI-RADS, seminal vesicle invasion, PSA and worst GS at I and II target lesions were significant predictors of LNI. The AUC was 0.74 [0.67-0.81] 95% CI. The calibration plot shows that our model is very close to the ideal one which is in the 95% CI. After the creation of a visual nomogram, the cut-off to discriminate between the risk or not of LNI was set with Youden index at 60 points that correspond to a risk of LNI of 7%. The model applied on a similar cohort shown a LH+ of 2.58 [2.17-2.98] 95% CI. CONCLUSIONS: Our nomogram for patients undergoing MRI-TB only takes into account clinical stage, SVI at MRI, biopsy Gleason pattern and PSA and it is able to identify patients with risk of LNI when a score higher than 7% is achieved.

Psychophysiological and Neurophysiological Correlates of Dropping Objects from Hands in Carpal Tunnel Syndrome.

BACKGROUND: Dropping objects from hands (DOH) is a common symptom of carpal tunnel syndrome (CTS). We evaluated the clinical, neurophysiological, and psychophysiological features of 120 CTS patients to elucidate the DOH pathophysiology. Forty-nine healthy controls were included. METHODS: In the patients, the Boston Carpal Tunnel Questionnaire (BCTQ), the Douleur Neuropathique 4 questions (DN4), and a numeric rating scale for pain (NRS) were evaluated. In patients and controls, we evaluated bilateral median and ulnar motor and sensory nerve conduction studies, cutaneous silent period and cutaneomuscular reflexes (CMR) of the abductor pollicis brevis, cold-detection threshold (CDT) and heat-pain detection threshold (HPT) at the index, little finger, and dorsum of the hand, and vibratory detection threshold at the index and little finger by quantitative sensory testing. RESULTS: CTS with DOH had higher BCTQ, DN4 and NRS, lower median sensory action potential, longer CMR duration, lower CDT and higher HPT at all tested sites than controls and CTS without DOH. Predictive features for DOH were abnormal CDT and HPT at the right index and dorsum (OR: 3.88, p: 0.03) or at the little finger (OR: 3.27, p: 0.04) and a DN4 higher than 4 (OR: 2.16, p < 0.0001). CONCLUSIONS: Thermal hypoesthesia in median and extra-median innervated territories and neuropathic pain are predictive of DOH in CTS.

Three-dimensional automatic artificial intelligence driven augmented-reality selective biopsy during nerve-sparing robot-assisted radical prostatectomy: A feasibility and accuracy study.

Objective: To evaluate the accuracy of our new three-dimensional (3D) automatic augmented reality (AAR) system guided by artificial intelligence in the identification of tumour's location at the level of the preserved neurovascular bundle (NVB) at the end of the extirpative phase of nerve-sparing robot-assisted radical prostatectomy. Methods: In this prospective study, we enrolled patients with prostate cancer (clinical stages cT1c-3, cN0, and cM0) with a positive index lesion at target biopsy, suspicious for capsular contact or extracapsular extension at preoperative multiparametric magnetic resonance imaging. Patients underwent robot-assisted radical prostatectomy at San Luigi Gonzaga Hospital (Orbassano, Turin, Italy), from December 2020 to December 2021. At the end of extirpative phase, thanks to our new AAR artificial intelligence driven system, the virtual prostate 3D model allowed to identify the tumour's location at the level of the preserved NVB and to perform a selective excisional biopsy, sparing the remaining portion of the bundle. Perioperative and postoperative data were evaluated, especially focusing on the positive surgical margin (PSM) rates, potency, continence recovery, and biochemical recurrence. Results: Thirty-four patients were enrolled. In 15 (44.1%) cases, the target lesion was in contact with the prostatic capsule at multiparametric magnetic resonance imaging (Wheeler grade L2) while in 19 (55.9%) cases extracapsular extension was detected (Wheeler grade L3). 3D AAR guided biopsies were negative in all pathological tumour stage 2 (pT2) patients while they revealed the presence of cancer in 14 cases in the pT3 cohort (14/16; 87.5%). PSM rates were 0% and 7.1% in the pathological stages pT2 and pT3 (<3 mm, Gleason score 3), respectively. Conclusion: With the proposed 3D AAR system, it is possible to correctly identify the lesion's location on the NVB in 87.5% of pT3 patients and perform a 3D-guided tailored nerve-sparing even in locally advanced diseases, without compromising the oncological safety in terms of PSM rates.

A prospective randomized controlled trial comparing target prostate biopsy alone approach vs. target plus standard in naïve patients with positive mpMRI.

BACKGROUND: In the era of mpMRI guided target fusion biopsy (FB), the role of concomitant standard biopsy (SB) in naïve patients still remains under scrutiny. The aim of this study was to compare the detection rate (DR) of clinically significant prostate cancer (csPCa) in biopsy naïve patients with positive mpMRI who underwent FB alone (Arm A) vs FB+SB (Arm B). Secondary objectives were to compare the incidence of complications, the overall PCa DR and the biopsy results with final pathological findings after robotic prostatectomy (RARP). METHODS: This is a single center prospective non-inferiority parallel two arms (1:1) randomized control trial (ISRCTN registry number ISRCTN60263108) which took place at San Luigi Gonzaga University Hospital, Orbassano (Turin, Italy) from 4/2019 to 10/2021. Eligible participants were all adults aged<75 years old, biopsy naïve, with serum PSA<15 ng/mL and positive mpMRI (Pi-Rads V.2>3). FB was performed under ultrasound guidance using the BioJet fusion system; four to six target samples were obtained for each index lesion. SB was performed in accordance with the protocol by Rodríguez-Covarrubias. RARP with total anatomical reconstruction was carried out when indicated. DR of PCa and csPCA (Gleason Score >7) were evaluated. Post-biopsy complications according to Clavien-Dindo were recorded. Concordance between biopsy and RARP pathological findings was evaluated. Fisher's Exact test and Mann-Whitney test were applied; furthermore, Logistic Principal Component Analysis (LogPCA) and Pearson's correlation method, in terms of correlation funnel plots, were performed to explore data in a multivariate way. RESULTS: 201 and 193 patients were enrolled in Arm A and B, respectively. csPCa DR was 60.2% vs. 60.6% in Arm A and B respectively (Δ 0.4%; P=0.93); whilst overall PCa DR was 63.7% vs. 71.0% (Δ 7.3%; P=0.12). However, in a target only setting, the addition of SB homolaterally to the index lesion reaching a non-inferior performance compared to the combined sampling (Δ PCa DR 3%). Although the differences of 7.3% in PCa DR, during RARP were registered similar nerve sparing rate (P=0.89), positive surgical margins (P=0.67) and rate of significant upgrading (P=0.12). LogPCA model showed no distinction between the two cohorts; and Pearson's correlation values turned to be between -0.5 and +0.5. In Arm B, the lesion diameter <10 mm is the only predictive variable of positive SB only for PCa (P=0.04), with an additional value +3% for PCa DR. CONCLUSIONS: In biopsy naïve patients, FB alone is not inferior to FB+SB in detecting csPCa (Δ csPCa DR 0.4%). Δ 7.3% in overall PCa DR was registered between the two Arms, however the addition of further standard samples homolaterally to mp-MRI index lesion improved the overall PCa DR of FB only sampling (Δ PCa DR 3%). The omission of SB did not influence the post-surgical outcomes in terms of NS approach, PSMr and upgrading/downgrading.