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Background and Objective: We analysed gender trends for urology trainees and consultants across nine European countries (Spain, UK, Netherlands, Norway, Germany, France, Belgium, Italy, and Switzerland) over a 10-yr period (2012-2022) to gain insight into gender dynamics in urology and determine if there is increasing representation of women in the profession. This information will help in the development of more effective strategies to promote gender equality., Methods: Data from the past decade were collected, encompassing trainee and consultant records nationally. The project focused on gender demographics within the field of urology, looking at trends in the nine countries. Information was obtained from national registries and supplemented with additional data sources where necessary., Key Findings and Limitations: Our results reveal significant variations in gender composition of urology trainees, displaying a slight increase in the presence of female trainees across most countries. This trend was particularly remarkable in Spain and Belgium where the proportion of female urologists exceeded 50%, indicating a potential generational shift within the field. Furthermore, among consultants, there was a global annual increase of 6.7% in female representation, with notable rises in the UK, France, Swiss and Belgium. These trends were also reflected in the membership affiliation data of the European Association of Urology during the same timeframe., Conclusions and Clinical Implications: The observed growth in female trainees and consultants offers valuable insights for educational and workforce planning. It is important to understand the evolving dynamics in the field of urology, especially for trainee demographics. Furthermore, the potential engagement of this with more countries could provide a comprehensive view of urology trends across Europe and worldwide., Patient Summary: We looked at the proportion of urology trainees and consultants who are women across Europe. We found that overall, the percentage of females in these roles increased from 2012 to 2022, especially for urology trainees, but there are differences by country. Even if these trends continue, it will take many years before there is equal representation of men and women doctors in urology., (Copyright © 2024 European Association of Urology. All rights reserved.)

To investigate two different approaches to determine patient risk to develop cardiac events: the burden of coronary atherosclerosis, as assessed by the Gensini score, and plaque morphology, as assessed by intracoronary optical coherence tomography (OCT). We assessed the Gensini score and OCT features of plaque vulnerability in 847 patients from the CLIMA registry. Patients were divided into four Gensini quartiles. The main study endpoint was the 1-year composite of cardiac death, myocardial infarction (MI) and/or target vessel revascularization (TVR). A total of 56 patients (6.6%) experienced the one-year main composite endpoint. The composite endpoint was significantly affected by the Gensini score (hazard ratio [HR] 1.42, 95% confidence interval [CI] 1.11-1.81, p = 0.005), with a low incidence in the first Gensini quartile (Q1 1.3%) and a higher incidence in the remaining groups (Q2 8.3%, Q3 8.9% and Q4 8.3%). At the multivariable analysis, the combined four OCT criteria (HR 6.4, 95%CI 3.0-13.7, p < 0.001), thin fibrous cap (HR 2.9, 95%CI 1.7-5.0, p < 0.001), lipid arc > 180° (HR 2.1, 95%CI 1.2-3.6, p = 0.010), minimum lumen area < 3.5 mm 2 (HR 1.7, 95%CI 1.01-3.0, p = 0.047) and the Gensini score (HR 1.4, 95%CI 1.1-1.8, p = 0.017) were independent predictors of the main composite endpoint. In this post-hoc analysis of the CLIMA study, the burden of coronary atherosclerosis as assessed by the Gensini score and OCT plaque characteristics were independent predictors of cardiac events. Patients with the largest atherosclerosis burden and with plaque vulnerability by OCT were at the highest risk of poor outcome. Clinicaltrials.gov identifier: NCT02883088., (© 2024. The Author(s), under exclusive licence to Springer Nature B.V.)

Background: Inframalleolar bypass still preserves its role in the modern endovascular era. Aim of this study was to evaluate the mid-term outcomes of "short" inframalleolar vein bypasses in patients with chronic limb-threatening ischemia (CLTI) after the previously failed tibial endovascular recanalization., Methods: Between January 2015 and December 2021,107 CLTI patients in 3 Italian Departments of Vascular Surgery underwent "short" inframalleolar vein bypass after failed tibial endovascular recanalization. Early (30-day) and 3-year outcomes were evaluated in terms of survival, primary patency, primary assisted patency, secondary patency, and amputation-free survival. Univariate analysis of the perioperative factors affecting outcomes were performed by the means of log-rank test. The associations of procedure variables were sought based on a multivariate Cox regression analysis., Results: Distal anastomosis (inframalleolar) was mostly performed on dorsal pedis (64, 59.8%). At 30 days, bypass occlusion was recorded in 5 cases (4.6%). The mean follow-up period was 20.5 ± 17.9 months. The estimated 3-year overall survival was 66.7%. Three-year estimates of primary patency, primary assisted patency, secondary patency, and amputation-free survival were 68.5%, 70.1%, 70.2%, and 76.7%, respectively. Multivariate analysis showed a negative association of insulin treatment with primary patency (HR 4.3, P = 0.04), primary assisted patency (HR 5.1, P = 0.02), and secondary patency (HR 5.1, P = 0.02). The negative association of long-term corticosteroid use was also found with primary patency (HR 7.8, P = 0.005), primary assisted patency (HR 8.7, P = 0.003), secondary patency (HR 8.7, P = 0.003), and amputation-free survival (HR 3.9, P = 0.05)., Conclusions: Short" vein bypasses to the foot arteries in CLTI patients yielded good mid-term overall patency and limb salvage rates after a failed tibial endovascular recanalization. Insulin-dependent diabetes mellitus and long-term corticosteroid use seemed to affect the outcomes., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Objective: A study analyzing perioperative outcomes related to a sudden switch from 3D to 2D-4K technology for laparoscopic sacral colpopexy by expert pelvic surgeons: are we addicted to technology?, Material and Methods: After a sudden transition from 3D to 2D-4K laparoscopic technology, a total of 115 consecutive pelvic prolapse patients who underwent sacral colpopexy from June 2020 to September 2021 were retrospectively assessed from our database. Perioperative parameters, operative times (OT), and intraoperative difficulty scales were assessed. One-year follow-ups were analyzed for the study. Primary endpoints were OT; secondary endpoint was the evaluation of complications linked to this procedure., Results: We found statistical differences in OT and intraoperative difficulty scales between medians of the last 3D procedures and the first ten 2D-4K surgeries, without differences between operators. Only after more than 20 surgeries, we observed no significant differences between 3D and 2D-4K sacral colpopexy. We observed no statistical differences in terms of anatomic failure, PGI-I, and intra-postoperative complications., Conclusion: The transition of urogynecology from an exclusive vaginal approach to 2D-3D-4K laparoscopy significantly increased the level of technology necessary for surgical treatment of prolapse. This could, as a result, lead to pelvic surgeons becoming increasingly dependent on technology.

(1) Background: Musculoskeletal disorders of the upper limbs are a common medical condition among dental hygienists and dentists, making them a common occupational risk for dental professionals. The purpose of the work was to collect information about the dental professions and their habits to highlight what can be good practices to be carried out to prevent any musculoskeletal disorders. (2) Methods: To identify habits and problems inherent in the professional activity of dental hygienists and dentists, a questionnaire was formulated on the use of enlarging systems. (3) Results: The questionnaire was completed by 241 dental professionals. As for the use of magnifiers, 72.6% of participants use them: among dental hygienists, 67.8% use magnifiers, among dentists, 80.9% use magnifiers; there is a statistically significant difference. There is no statistically significant difference between professions regarding muscle disorders. (4) Conclusions: For a clearer assessment, it would be appropriate to submit the questionnaire to a wider sample of professionals, to define better the correlation between musculoskeletal disorders, work activity and the type of enlarging systems used.

Objective: To conduct a systematic review (SR) of literature to assess the existing evidence concerning the success and complications of endourological ex vivo stone surgeries., Methods: Eligible studies for inclusion focused on investigating the success and/or complications related to endourological ex vivo surgeries in donors with nephrolithiasis. A SR was undertaken in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. The search included databases of Web of Science, PubMed, and Scopus and only article in English were included. Studies published between 2002 and 2023 included in this SR., Results: After screening 1726 abstracts, this SR included 16 studies with a total of 209 patients. The mean stone size was 5.6 mm and majority of kidneys contained single stones, located in the lower calyx. After ex vivo endourological stone surgeries, the average stone-free rate was found to be 95.4%. The mean duration of ex vivo surgery was 17.3 minutes. Regarding intraoperative complications, two patients (1%) experienced mucosal injuries during pneumatic lithotripsy. As for postoperative complications, two patients (1%) experienced vascular complications. In terms of urological complications, hematuria was observed in 24 patients (11.5%), while one patient (0.5%) experienced clot formation in renal pelvis. Seven patients (3.3%) had urinary tract infections, and three patients (1.4%) developed urolithiasis during the follow-up. Additionally, one patient (0.5%) experienced complete occlusion of ureteroneocystostomy and required revision., Conclusion: Given the advancements in current technology and techniques, endourological ex vivo stone surgeries are increasingly recognized as an effective and safe option for donors with nephrolithiasis., Trial Registration: This systematic review was registered under the protocol registration number CRD42024538384/PROSPERO., Competing Interests: Declaration of Competing Interest The authors have no conflict of interest to declare., (Copyright © 2024 Elsevier Inc. All rights reserved.)

The search for reliable and easily accessible biomarkers in Parkinson's disease is receiving a growing emphasis, to detect neurodegeneration from the prodromal phase and to enforce disease-modifying therapies. Despite the need for non-invasively accessible biomarkers, the majority of the studies have pointed to cerebrospinal fluid or peripheral biopsies biomarkers, which require invasive collection procedures. Saliva represents an easily accessible biofluid and an incredibly wide source of molecular biomarkers. In the present study, after presenting the morphological and biological bases for looking at saliva in the search of biomarkers for Parkinson's disease, we systematically reviewed the results achieved so far in the saliva of different cohorts of Parkinson's disease patients. A comprehensive literature search on PubMed and SCOPUS led to the discovery of 289 articles. After screening and exclusion, 34 relevant articles were derived for systematic review. Alpha-synuclein, the histopathological hallmark of Parkinson's disease, has been the most investigated Parkinson's disease biomarker in saliva, with oligomeric alpha-synuclein consistently found increased in Parkinson's disease patients in comparison to healthy controls, while conflicting results have been reported regarding the levels of total alpha-synuclein and phosphorylated alpha-synuclein, and few studies described an increased oligomeric alpha-synuclein/total alpha-synuclein ratio in Parkinson's disease. Beyond alpha-synuclein, other biomarkers targeting different molecular pathways have been explored in the saliva of Parkinson's disease patients: total tau, phosphorylated tau, amyloid-β1-42 (pathological protein aggregation biomarkers); DJ-1, heme-oxygenase-1, metabolites (altered energy homeostasis biomarkers); MAPLC-3beta (aberrant proteostasis biomarker); cortisol, tumor necrosis factor-alpha (inflammation biomarkers); DNA methylation, miRNA (DNA/RNA defects biomarkers); acetylcholinesterase activity (synaptic and neuronal network dysfunction biomarkers); Raman spectra, proteome, and caffeine. Despite a few studies investigating biomarkers targeting molecular pathways different from alpha-synuclein in Parkinson's disease, these results should be replicated and observed in studies on larger cohorts, considering the potential role of these biomarkers in determining the molecular variance among Parkinson's disease subtypes. Although the need for standardization in sample collection and processing, salivary-based biomarkers studies have reported encouraging results, calling for large-scale longitudinal studies and multicentric assessments, given the great molecular potentials and the non-invasive accessibility of saliva., (Copyright © 2024 Copyright: © 2024 Neural Regeneration Research.)

Non-bacterial thrombotic endocarditis (NBTE) is a form of non-infective endocarditis characterized by the deposition of sterile fibrin and platelets on cardiac valves. Even though some studies have identified important pathophysiological features, many aspects remain poorly understood. Given its wide availability, transthoracic echocardiography is typically the initial diagnostic approach to the patient. Additionally, recent technological advancements in transesophageal echocardiography, such as three-dimensional and multiplanar reconstruction analysis, have significantly improved diagnostic accuracy over time. By presenting our case series and performing a literature review, we focused on the main pathophysiologic, diagnostic, and therapeutic aspects of this rare but potentially life-threatening disease.

Oligomeric species arising during the aggregation of α-synuclein are implicated as a major source of toxicity in Parkinson's disease, and thus a major potential drug target. However, both their mechanism of formation and role in aggregation are largely unresolved. Here we show that, at physiological pH and in the absence of lipid membranes, α-synuclein aggregates form by secondary nucleation, rather than simple primary nucleation, and that this process is enhanced by agitation. Moreover, using a combination of single molecule and bulk level techniques, we identify secondary nucleation on the surfaces of existing fibrils, rather than formation directly from monomers, as the dominant source of oligomers. Our results highlight secondary nucleation as not only the key source of oligomers, but also the main mechanism of aggregate formation, and show that these processes take place under conditions which recapitulate the neutral pH and ionic strength of the cytosol., (© 2024. The Author(s).)

Dropped head syndrome (DHS) is characterized by severe forward flexion of the cervical spine due to an imbalance in neck muscle tone. This condition can be linked to various neuromuscular diseases, including myasthenia gravis (MG). On the other hand, Parkinson's disease (PD) patients may show a clinically indistinguishable picture named antecollis, which is caused by increased axial tone, but without muscle weakness. Differentiating between DHS and antecollis is crucial due to their distinct treatment requirements. We present the case of a 71-year-old White male with a one-month history of severe neck flexion, mild dysphagia, and dysphonia. His medical history included diabetes mellitus, coronary artery disease, arterial hypertension, and mild cervical spondylosis. Neurological examination revealed features of Parkinsonism, including hypomimia, asymmetric rigidity, and reduced arm swing. There was significant weakness in his neck extensor muscles, with no signs of ptosis or diplopia. Brain/spine MRI scans were unremarkable, but electromyography showed a reduced compound muscle action potentials amplitude in repetitive nerve stimulation, consistent with MG. High-titer acetylcholine receptor antibodies confirmed the diagnosis. Treatment with pyridostigmine (60 to 120 mg/day) and plasma exchange (daily, for five consecutive days) improved the patient's general condition and neck posture. Concurrently, the patient was diagnosed with PD based on established clinical criteria and improved with carbidopa/levodopa therapy (up to 150/600 mg/daily). This case highlights the rare co-occurrence of MG and PD, emphasizing the need for thorough clinical, neurophysiological, and laboratory evaluations in complex DHS presentations. Managing MG's life-threatening aspects and addressing PD symptoms requires a tailored approach, showcasing the critical role of neurophysiology in accurate diagnosis and effective treatment., Competing Interests: The authors declare no conflicts of interest related to the present work. Dr. Luca Marsili has received honoraria from the International Association of Parkinsonism and Related Disorders (IAPRD) Society for social media and web support. Dr. Carlo Colosimo received grants from Ipsen and Royalties from Oxford University Press and Cambridge University Press unrelated to the present research. All other authors report no conflicts of interest.

Xerosydryle belongs to a new category of materials resulting from the interaction of water with various hydrophilic polymers. These materials can exhibit different properties depending on the kind of polymer-water interaction. Previous research confirmed the existence of a solid manifestation of water at room temperature. The thermal properties of dissolved xerosydryle in water are similar to those of biological macromolecules during denaturation but with greater stability. This study investigated the biological effect of xerosydryle on a living system for the first time, using a seed germination model. The interaction was evaluated using physiological assays such as chlorophyll shifts, potassium (re)uptake during the onset of germination and a transcriptome approach. Seeds were treated with samples of xerosydryle and distilled water. Transcriptome analysis of germinating seeds highlighted differences (up- and down-regulated genes) between seeds treated with xerosydryle and those treated with distilled water. Overall, the experiments performed indicate that xerosydryle, even at low concentrations, interferes with seedling growth in a manner similar to an osmotic modulator. This work paves the way for a more comprehensive exploration of the active biological role of xerosydryle and similar compounds on living matter and opens up speculation on the interactions at the boundaries between physics, chemistry, and biology.

Background: Stone nomogram by Micali et al., able topredict treatment failure of shock-wave lithotripsy (SWL), retrograde intrarenal surgery (RIRS) and percutaneous nephrolithotomy (PNL) in the management of single 1-2 cm renal stones, was developed on 2605 patients and showed a high predictive accuracy, with an area under ROC curve of 0.793 at internal validation. The aim of the present study is to externally validate the model to assess whether it displayed a satisfactory predictive performance if applied to different populations., Methods: External validation was retrospectively performed on 3025 patients who underwent an active stone treatment from December 2010 to June 2021 in 26 centers from four countries (Italy, USA, Spain, Argentina). Collected variables included: age, gender, previous renal surgery, preoperative urine culture, hydronephrosis, stone side, site, density, skin-to-stone distance. Treatment failure was the defined outcome (residual fragments >4 mm at three months CT-scan)., Results: Model discrimination in external validation datasets showed an area under ROC curve of 0.66 (95% 0.59-0.68) with adequate calibration. The retrospective fashion of the study and the lack of generalizability of the tool towards populations from Asia, Africa or Oceania represent limitations of the current analysis., Conclusions: According to the current findings, Micali's nomogram can be used for treatment prediction after SWL, RIRS and PNL; however, a lower discrimination performance than the one at internal validation should be acknowledged, reflecting geographical, temporal and domain limitation of external validation studies. Further prospective evaluation is required to refine and improve the nomogram findings and to validate its clinical value.

Obesity and type 2 diabetes cause a loss in brown adipose tissue (BAT) activity, but the molecular mechanisms that drive BAT cell remodeling remain largely unexplored. Using a multilayered approach, we comprehensively mapped a reorganization in BAT cells. We uncovered a subset of macrophages as lipid-associated macrophages (LAMs), which were massively increased in genetic and dietary model of BAT expansion. LAMs participate in this scenario by capturing extracellular vesicles carrying damaged lipids and mitochondria released from metabolically stressed brown adipocytes. CD36 scavenger receptor drove LAM phenotype, and CD36-deficient LAMs were able to increase brown fat genes in adipocytes. LAMs released transforming growth factor β1 (TGF-β1), which promoted the loss of brown adipocyte identity through aldehyde dehydrogenase 1 family member A1 (Aldh1a1) induction. These findings unfold cell dynamic changes in BAT during obesity and identify LAMs as key responders to tissue metabolic stress and drivers of loss of brown adipocyte identity., Competing Interests: Declaration of interests J.R.B. is a member of the Scientific Advisory Board and receives research support from LUCA Sciences, Inc., has consulted for DeciBio within the past 12 months, receives royalties from Springer Nature Group, and is an inventor on pending patent applications related to the treatment of metabolic diseases and immunoassay diagnostics., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Objectives: To understand how best to further reduce the inappropriate use of pre-surgical androgen deprivation therapy (ADT), we investigated the determinants (influences) of ADT prescribing in urologists in two European countries using an established behavioural science approach. Additionally, we sought to understand how resource limitations caused by COVID-19 influenced this practice. Identification of key determinants, of undistributed and disrupted practice, will aid development of future strategies to reduce inappropriate ADT prescribing in current and future resource-limited settings., Participants and Methods: We conducted semi-structured qualitative interviews with urologists practicing in Italy and the UK from February to July 2022. Interviews focussed on undisrupted (usual) practice and disrupted practice (changes made during COVID-19 restrictions). Codes were generated inductively and were mapped to the 14 domains of the Theoretical Domains Framework. Relevant domains of influence were identified, and the similarities and differences between the UK and Italy were distinguished., Results: We identified 10 domains that were influential to ADT prescribing in the UK and eight in Italy. The role of guidance and evidence, the cancer care setting, the patients and the urologist's beliefs and experiences were identified as areas that were influential to ADT prescribing before surgery. Twenty-one similarities and 22 differences between the UK and Italy, for usual and COVID-19 practice, were identified across these 10 domains., Conclusion: Similarities and differences influencing ADT prescribing prior to surgery should be considered in behavioural strategy development and tailoring to reduce inappropriate ADT use. We gained an understanding of usual, undistributed care and resource-limited or disrupted care due to COVID-19 in two European countries. This gives an indication of how influences on ADT prescribing may change in future resource-limited circumstances and where efforts can be focused now and in future., Competing Interests: Monique J. Robool, Steven MacLennan and Jennifer Dunsmore have received an EAU Research Foundation seeding grant. Steven MacLennan and Jennifer Dunsmore secured the University of Aberdeen Elphinstone PhD Student Scholarship and stipend funds from Cancer Research Aberdeen and North East Scotland (CRANES), Registered charity number: SC034542. Philip Cornford is the Chair of the EAU Prostate Cancer Panel and receives consulting fees from AstraZeneca, Ipsen, Janssen; payments or honoraria for lectures/ events from Accord, Bayer and Ipsen; and support to attend meetings from Ipsen, Jassen and Bayer. Francesco Esperto is a board member for YAU endourology and stones group, YOU, SIU and EBU. Nicola Pavan receives consulting fees for Ipsen and Ferring and payments or honoraria for lectures/events from Accord. Ted A. Skolarus received grant from the US National Institutes of Health National Cancer Institute R37 CA222885: De‐implementation of low value castration for men with prostate cancer and participates on the Data Safety and Monitoring Board: US NHBLI U01HL159880 Eliminating Monitor Overuse (EMO) Hybrid Effectiveness‐Deimplementation Trial, Children's Hospital of Philadelphia, Perelman School of Medicine, University of Pennsylvania. James N'Dow, María J. Ribal and Sara J. MacLennan do not have any conflict of interests to declare., (© 2024 The Author(s). BJUI Compass published by John Wiley & Sons Ltd on behalf of BJU International Company.)

Purpose: To present the results of the first multi-centre real-world validation of autoplanning for whole breast irradiation after breast-sparing surgery, encompassing high complexity cases (e.g. with a boost or regional lymph nodes) and a wide range of clinical practices., Methods: The 24 participating centers each included 10 IMRT/VMAT/Tomotherapy patients, previously treated with a manually generated plan ('manplan'). There were no restrictions regarding case complexity, planning aims, plan evaluation parameters and criteria, fractionation, treatment planning system or treatment machine/technique. In addition to dosimetric comparisons of autoplans with manplans, blinded plan scoring/ranking was conducted by a clinician from the treating center. Autoplanning was performed using a single configuration for all patients in all centres. Deliverability was verified through measurements at delivery units., Results: Target dosimetry showed comparability, while reductions in OAR dose parameters were 21.4 % for heart D mean , 16.7 % for ipsilateral lung D mean , and 101.9 %, 45.5 %, and 35.7 % for contralateral breast D 0.03cc , D 5% and D mean , respectively (all p < 0.001). Among the 240 patients included, the clinicians preferred the autoplan for 119 patients, with manplans preferred for 96 cases (p = 0.01). Per centre there were on average 5.0 ± 2.9 (1SD) patients with a preferred autoplan (range [0-10]), compared to 4.0 ± 2.7 with a preferred manplan ([0,9]). No differences were observed regarding deliverability., Conclusion: The automation significantly reduced the hands-on planning workload compared to manual planning, while also achieving an overall superiority. However, fine-tuning of the autoplanning configuration prior to clinical implementation may be necessary in some centres to enhance clinicians' satisfaction with the generated autoplans., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: (1) All authors have participated in (a) conception and design, or analysis and interpretation of the data; (b) drafting the article or revising it critically for important intellectual content; and (c) approval of the final version. (2) This manuscript has not been submitted to, nor is under review at, another journal or other publishing venue. (3) Stefania Zara is employees of the company “Tecnologie Avanzate TA Srl” that distributes the software RayStation in Italy; this company supports the group in terms of collecting data. Data were analyzed objectively and independently from the vendor; (4) Remaining authors have no affiliation with any organization with a direct or indirect financial interest in the subject matter discussed in the manuscript., (Copyright © 2024 Associazione Italiana di Fisica Medica e Sanitaria. Published by Elsevier Ltd. All rights reserved.)

Background: 22q11.2 deletion syndrome (22q11.2DS) has been linked to an increased risk of early-onset Parkinson's disease. However, the pathophysiological mechanisms underlying parkinsonism remain poorly understood., Objective: The objective is to investigate salivary total α-synuclein levels in 22q11.2DS patients with and without parkinsonian motor signs., Methods: This cross-sectional study included 10 patients with 22q11.2DS with parkinsonism (Park+), ten 22q11.2DS patients without parkinsonism (Park-), and 10 age and sex-comparable healthy subjects (HS). Salivary and serum α-synuclein levels were measured using enzyme-linked immunosorbent assay., Results: Salivary total α-synuclein concentration was significantly lower in Park (+) patients than in Park (-) patients and HS (P = 0.007). In addition, salivary α-synuclein showed good accuracy in discriminating Park (+) from Park (-) patients (area under the curve = 0.86) and correlated with motor severity and cognitive impairment., Conclusion: This exploratory study suggests that the parkinsonian phenotype of 22q11.2DS is associated with a reduced concentration of monomeric α-synuclein in biological fluids., (© 2024 International Parkinson and Movement Disorder Society.)

Parkinson's disease is a progressive neurodegenerative disorder characterized by the deposition of misfolded alpha-synuclein in different regions of the central and peripheral nervous system. Motor impairment represents the signature clinical expression of Parkinson's disease. Nevertheless, non-motor symptoms are invariably present at different stages of the disease and constitute an important therapeutic challenge with a high impact for the patients' quality of life. Among non-motor symptoms, pain is frequently experienced by patients, being present in a range of 24-85% of Parkinson's disease population. Moreover, in more than 5% of patients, pain represents the first clinical manifestation, preceding by decades the exordium of motor symptoms. Pain implies a complex biopsychosocial experience with a downstream complex anatomical network involved in pain perception, modulation, and processing. Interestingly, all the anatomical areas involved in pain network can be affected by a-synuclein pathology, suggesting that pathophysiology of pain in Parkinson's disease encompasses a 'pain spectrum', involving different anatomical and neurochemical substrates. Here the various anatomical sites recruited in pain perception, modulation and processing are discussed, highlighting the consequences of their possible degeneration in course of Parkinson's disease. Starting from peripheral small fibres neuropathy and pathological alterations at the level of the posterior laminae of the spinal cord, we then describe the multifaceted role of noradrenaline and dopamine loss in driving dysregulated pain perception. Finally, we focus on the possible role of the intertwined circuits between amygdala, nucleus accumbens and habenula in determining the psycho-emotional, autonomic and cognitive experience of pain in Parkinson's disease. This narrative review provides the first anatomically driven comprehension of pain in Parkinson's disease, aiming at fostering new insights for personalized clinical diagnosis and therapeutic interventions., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Guarantors of Brain.)

Background: The optimal treatment for metastatic colorectal cancer (mCRC) beyond second line is still questioned. Besides the standard of care agents (regorafenib, REG, or trifluridine/tipiracil, FTD/TPI), chemotherapy rechallenge or reintroduction (CTr/r) are commonly considered in clinical practice, despite weak supporting evidence. The prognostic performance of CTr/r, REG and FTD/TPI in this setting are herein evaluated., Patients and Methods: PROSERpYNa is a multicenter, observational, retrospective study, in which patients with refractory mCRC, progressing after at least 2 lines of CT, treated with CTr/r, REG or FTD/TPI, are considered eligible and were enrolled in 2 independent data sets (exploratory and validation). Primary endpoint was overall survival (OS); secondary endpoints were investigator-assessed progression-free survival (PFS), objective response rate (RR) and safety. A propensity score adjustment was accomplished for survival analyses., Results: Data referring to patients treated between Jan-10 and Jan-19 from 3 Italian institutions were gathered (341 and 181 treatments for exploratory and validation data sets respectively). In the exploratory cohort, median OS (18.5 vs. 6.5 months), PFS (6.1 vs. 3.5 months) and RR (28.6% vs. 1.4%) were significantly longer for CTr/r compared to REG/FTD/TPI. Survival benefits were retained at the propensity score analysis, adjusted for independent prognostic factors identified at multivariate analysis. Moreover, these results were confirmed within the validation cohort analyses., Conclusions: Although the retrospective fashion, CTr/r proved to be a valuable option in this setting in a real-world context, providing superior outcomes compared to standard of care agents at the price of a moderate toxicity., Competing Interests: Disclosure MAC reports consulting or advisory role for Merck, SERVIER and Pierre Fabre. AO reports consulting or advisory role for Novartis, Lilly, Pfizer, Amgen, Daiichi Sankyo, Gilead. LS reports consulting or advisory role for Pierre-Fabre, AstraZeneca, Bayer, SERVIER, Merck, Amgen. CP reports consulting or advisory role for Amgen, SERVIER and Eli-Lilly. DS reports consulting or advisory role for Amgen, Janssen, Astellas, Bayer, Novartis, Merck, MSD, BMS, Eisai, Ipsen, AstraZeneca, Sanofi, Seagen, and Daiichi Sankyo. EB reports personal fees, nonfinancial support and other from MSD, AstraZeneca, Pfizer, Eli-Lilly, BMS, Novartis and Roche; and grants from AstraZeneca and Roche, outside the submitted work. All other authors declare that they have no conflict of interest., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: While the addition of androgen receptor signaling inhibitors (ARSIs) to androgen deprivation therapy (ADT) results in better of overall survival in patients with metastatic hormone-sensitive prostate cancer (mHSPC), information regarding health related quality of life (HR-QoL) is sparse. We aimed at summarizing current evidence on the impact of ARSIs on HR-QoL., Methods: We performed a systematic review of the published literature on PubMed/EMBASE, Web of Science, SCOPUS, and the Cochrane libraries between January 2011 and April 2022. We included only phase III randomized controlled trials (RCT), which were selected according to the PRISMA guidelines. We aimed at evaluating differences in HR-QoL, assessed by validated patient reported outcomes instruments. We analyzed global scores and sub-domains such as sexual functioning, urinary symptoms, bowel symptoms, pain/fatigue, emotional and social/family wellbeing. We reported data descriptively., Results: Six RCTs were included: two used enzalutamide with ADT as intervention arms (ARCHES, ENZAMET); one used apalutamide with ADT (TITAN); two abiraterone acetate and prednisone (AAP) with ADT (STAMPEDE, LATITUDE); and one darolutamide with ADT (ARASENS). Enzalutamide or AAP with ADT increase overall HR-QoL in comparison with ADT alone, ADT with first generation nonsteroideal anti-androgens or ADT with docetaxel, whereas apalutamide and darolutamide with ADT maintain HR-QoL similarly to ADT alone or ADT with docetaxel, respectively. Time to first deterioration of pain was longer with combination therapy with enzalutamide, AAP or darolutamide, but not with apalutamide. No worsening of emotional wellbeing was reported from the addition of ARSIs to ADT than ADT alone., Conclusions: The addition of ARSIs to ADT in mHSPC tends to increase overall HR-QoL and prolong time to first deterioration of pain/fatigue compared with ADT alone, ADT with first generation nonsteroideal anti-androgens, and ADT with docetaxel. ARSIs show a complex interaction with remaining HR-QoL domains. We advocate a standardization of HR-QoL measurement and reporting to allow further comparisons., (© 2023. The Author(s), under exclusive licence to Springer Nature Limited.)

Background: The aim of this study was to evaluate effectiveness and safety of laparoscopic lateral suspension in women affected by high grade uterine prolapse associated to anterior defect. The secondary endpoint is to evaluate mid-term impact on Quality of Life and sexual function., Methods: A multicenter retrospective study on women undergoing laparoscopic lateral suspension for uterine prolapse ≥III stage was performed. We included 174 women, but due to exclusion criteria, 134 patients were enrolled for this study. Preoperative evaluation consisted of an urogynecological interview, clinical exam, 3-day voiding diary and urodynamic testing; the prolapse Quality of Life Questionnaire was used to quantify the impact of prolapse symptoms on Quality of Life and the Pelvic Organ Prolapse/Urinary Incontinence Sexual Questionnaire short form, the Female Sexual Function Index and the Female Sexual Distress Scale were administered to evaluate sexual function before surgical intervention and at median follow-up of 3.8 years., Results: We included 134 women with uterine prolapse ≥III stage. All patients underwent laparoscopic lateral suspension, 8 also posterior colporrhaphy and 5 also transobturator tape insertion. POP-Q classification score for anterior and apical compartment showed a significant average decrease. The surveys administered to patients showed an improvement in Quality of Life, an increase in the number of monthly intercourses and a significant improvement in sexual life after surgery., Conclusions: Laparoscopic lateral suspension for pelvic organ prolapse correction is a safe and effective technique for uterine and anterior associated defect. Quality of Life and sexual function significantly improved after surgery.

Aim: Diffuse large B-cell lymphoma (DLBCL) is the most common B-cell non-Hodgkin lymphoma (NHL). Despite the availability of clinical and molecular algorithms applied for the prediction of prognosis, in up to 30%-40% of patients, intrinsic or acquired drug resistance occurs. Constitutional genetics may help to predict R-CHOP resistance. This study aimed to validate previously identified single nucleotide polymorphisms (SNPs) in the literature as potential predictors of R-CHOP resistance in DLBCL patients, SNPs. Methods: Twenty SNPs, involved in R-CHOP pharmacokinetics/pharmacodynamics or other pathobiological processes, were investigated in 185 stage I-IV DLBCL patients included in a multi-institution pharmacogenetic study to validate their previously identified correlations with resistance to R-CHOP. Results: Correlations between rs2010963 ( VEGFA gene) and sex ( P = 0.046), and rs1625895 ( TP53 gene) and stage ( P = 0.003) were shown. After multivariate analyses, a concordant effect (i.e., increased risk of disease progression and death) was observed for rs1883112 ( NCF4 gene) and rs1800871 ( IL10 gene). When patients were grouped according to the revised International Prognostic Index (R-IPI), both these SNPs further discriminated progression-free survival (PFS) and overall survival (OS) of the R-IPI-1-2 subgroup. Overall, patients harboring the rare allele showed shorter PFS and OS compared with wild-type patients. Conclusions: Two out of the 20 study SNPs were validated. Thus, these results support the role of previously identified rs1883112 and rs1800871 in predicting DLBCL resistance to R-CHOP and highlight their ability to further discriminate the prognosis of R-IPI-1-2 patients. These data point to the need to also focus on host genetics for a more comprehensive assessment of DLBCL patient outcomes in future prospective trials., Competing Interests: Mini E is an Editorial Board Member of the journal Cancer Drug Resistance, while the other authors have declared that they have no conflicts of interest., (© The Author(s) 2024.)

Saliva is a convenient and accessible biofluid that has potential as a future diagnostic tool for Parkinson's disease. Candidate diagnostic tests for Parkinson's disease to date have predominantly focused on measurements of α-synuclein in CSF, but there is a need for accurate tests utilizing more easily accessible sample types. Prior studies utilizing saliva have used bulk measurements of salivary α-synuclein to provide diagnostic insight. Aggregate structure may influence the contribution of α-synuclein to disease pathology. Single-molecule approaches can characterize the structure of individual aggregates present in the biofluid and may, therefore, provide greater insight than bulk measurements. We have employed an antibody-based single-molecule pulldown assay to quantify salivary α-synuclein and amyloid-β peptide aggregate numbers and subsequently super-resolved captured aggregates using direct Stochastic Optical Reconstruction Microscopy to describe their morphological features. We show that the salivary α-synuclein aggregate/amyloid-β aggregate ratio is increased almost 2-fold in patients with Parkinson's disease ( n = 20) compared with controls ( n = 20, P < 0.05). Morphological information also provides insight, with saliva from patients with Parkinson's disease containing a greater proportion of larger and more fibrillar amyloid-β aggregates than control saliva ( P < 0.05). Furthermore, the combination of count and morphology data provides greater diagnostic value than either measure alone, distinguishing between patients with Parkinson's disease ( n = 17) and controls ( n = 18) with a high degree of accuracy (area under the curve = 0.87, P < 0.001) and a larger dynamic range. We, therefore, demonstrate for the first time the application of highly sensitive single-molecule imaging techniques to saliva. In addition, we show that aggregates present within saliva retain relevant structural information, further expanding the potential utility of saliva-based diagnostic methods., Competing Interests: The authors report no competing interests., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Guarantors of Brain.)

The increase in practices related to enhancing penile size can be attributed to the belief that an improved genital appearance contributes to a man's virility, coupled with an altered self-perception of his body. It is crucial to tailor interventions to meet the genuine needs of patients by thoroughly assessing their history, psychological state, and potential surgical benefits, all while considering the associated risks of complications. This systematic review aims to summarize the available evidence on outcomes, complications, and quality of life after penile augmentation surgery, examining both minimally invasive and more radical techniques. A search of the PubMed and Scopus databases, focusing on English-language papers published in the last 15 years, was performed in December 2023. Papers discussing surgery in animal models and case reports were excluded from the present study unless further evaluated in a follow-up case series. The primary outcomes were changes in penile dimensions, specifically in terms of length and girth, as well as the incidence of surgical complications and the impact on quality of life. A total of 1670 articles were retrieved from the search and 46 were included for analysis. Procedures for penile length perceived enhancements include lipoplasty, skin reconstruction plasty, V-Y and Z plasty, flap reconstruction, scrotoplasty, ventral phalloplasty, and suspensory ligament release; techniques for increasing corporal penile length include penile disassembly, total phalloplasty, and sliding elongation. Finally, penile girth enhancement may be performed using soft tissue fillers, grafting procedures, biodegradable scaffolds, and Penuma ® . In conclusion, while penile augmentation surgeries offer potential solutions for individuals concerned about genital size, the risks and complexities need to be accounted for.

Background: Different studies have shown the key role of endoplasmic reticulum (ER) stress in autoimmune and chronic inflammatory disorders, as well as in neurodegenerative diseases. ER stress leads to the formation of misfolded proteins which affect the secretion of different cell types that are crucial for the intestinal homeostasis., Purpose: In this review, we discuss the role of ER stress and its involvement in the development of inflammatory bowel diseases, chronic conditions that can cause severe damage of the gastrointestinal tract, focusing on the alteration of Paneth cells and goblet cells (the principal secretory phenotypes of the intestinal epithelial cells). ER stress is also discussed in the context of neurodegenerative diseases, in which protein misfolding represents the signature mechanism. ER stress in the bowel and consequent accumulation of misfolded proteins might represent a bridge between bowel inflammation and neurodegeneration along the gut-to-brain axis, affecting intestinal epithelial homeostasis and the equilibrium of the commensal microbiota. Targeting intestinal ER stress could foster future studies for designing new biomarkers and new therapeutic approaches for neurodegenerative disorders., (© 2024 The Authors. Neurogastroenterology & Motility published by John Wiley & Sons Ltd.)

Oligomeric alpha-synuclein (α-syn) in saliva and phosphorylated α-syn deposits in the skin have emerged as promising diagnostic biomarkers for Parkinson's disease (PD). This study aimed to assess and compare the diagnostic value of these biomarkers in discriminating between 38 PD patients and 24 healthy subjects (HSs) using easily accessible biological samples. Additionally, the study sought to determine the diagnostic potential of combining these biomarkers and to explore their correlations with clinical features. Salivary oligomeric α-syn levels were quantified using competitive ELISA, while skin biopsies were analyzed through immunofluorescence to detect phosphorylated α-syn at Ser129 (p-S129). Both biomarkers individually were accurate in discriminating PD patients from HSs, with a modest agreement between them. The combined positivity of salivary α-syn oligomers and skin p-S129 aggregates differentiated PD patients from HSs with an excellent discriminative ability with an AUC of 0.9095. The modest agreement observed between salivary and skin biomarkers individually suggests that they may reflect different aspects of PD pathology, thus providing complementary information when combined. This study's results highlight the potential of utilizing a multimodal biomarker approach to enhance diagnostic accuracy in PD.

Purpose: To evaluate the impact of ureteroscope position within renal cavities as well as different locations of the tip of the ureteral access sheath (UAS) on fluid dynamics during retrograde intrarenal surgery (RIRS)., Materials and Methods: A prospective observational clinical study was performed. Measurements with a flexible ureteroscope placed in the upper, middle and lower calyces were obtained with the tip of the UAS placed either 2 cm below the pyelo-ureteric junction (PUJ), or at the level of the iliac crest., Results: 74 patients were included. The outflow rates from the middle and upper calyxes were statistically significantly higher compared to the lower calyx, both with the UAS close to the pyelo-ureteric junction and at the iliac crest. When the UAS was withdrawn and positioned at the level of the iliac crest, a significant decrease in outflow rates from the upper (40.1 ± 4.3 ml/min vs 35.8 ± 4.1 ml/min) and middle calyces (40.6 ± 4.0 ml/min vs 36.8 ± 4.6 ml/min) and an increase in the outflow from the lower calyx (28.5 ± 3.3 ml/min vs 33.7 ± 5.7 ml/min) were noted., Conclusions: Our study showed that higher fluid outflow rates are observed from upper and middle calyces compared to lower calyx. This was true when the UAS was positioned 2 cm below the PUJ and at the iliac crest. Significant worsening of fluid dynamics from upper and middle calyces was observed when the UAS was placed distally at the level of the iliac crest. While the difference was statistically significant, the absolute change was not significant. In contrast, for lower calyces, a statistically significant improvement was documented., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Dealing with acute cholecystitis in high-risk, critically ill, and unfit-for-surgery patients is frequent during daily practice and requires complex management. Several procedures exist to postpone and/or prevent surgical intervention in those patients who temporarily or definitively cannot undergo surgery. After a systematic review of the literature, an expert panel from the Italian Society of Emergency Surgery and Trauma (SICUT) discussed the different issues and statements in subsequent rounds. The final version of the statements was discussed during the annual meeting in Rome (September 2022). The present paper presents the definitive conclusions of the discussion. Fifteen statements based on the literature evidence were provided. The statements gave precise indications regarding the decisional process and the management of patients who cannot temporarily or definitively undergo cholecystectomy for acute cholecystitis. Acute cholecystitis management in high-risk, critically ill, and unfit-for-surgery patients should be multidisciplinary. The different gallbladder drainage methods must be tailored according to each patient and based on the expertise of the hospital. Percutaneous gallbladder drainage is recommended as the first choice as a bridge to surgery or in severely physiologically deranged patients. Endoscopic gallbladder drainage (cholecystoduodenostomy and cholecystogastrostomy) is suggested as a second-line alternative especially as a definitive procedure for those patients not amenable to surgical management. Trans-papillary gallbladder drainage is the last option to be reserved only to those unfit for other techniques. Delayed laparoscopic cholecystectomy in patients with percutaneous gallbladder drainage is suggested in all those patients recovering from the conditions that previously discouraged surgical intervention after at least 6 weeks from the gallbladder drainage., (© 2023. Italian Society of Surgery (SIC).)

Background: Currently, the landscape of surgical training is undergoing rapid evolution, marked by the initial implementation of standardized surgical training programs, which are further facilitated by the emergence of new technologies. However, this proliferation is uneven across various countries and hospitals., Objective: To offer a comprehensive overview of the existing surgical training programs throughout Europe, with a specific focus on the accessibility of simulation resources and standardized surgical programs., Design Setting and Participants: A dedicated survey was designed and spread in May 2022 via the European Association of Urology (EAU) mail list, to Young Urologist Office (YUO), Junior membership, European Urology Residents Education Program participants between 2014 and 2022, and other urologists under 40 yr, and via the EAU Newsletter., Intervention: A 64-item, online-based survey in accordance with the Checklist for Reporting Results of Internet E-Surveys (CHERRIES) using the platform of Survey Monkey (Portland, OR, USA) was realized., Outcome Measurements and Statistical Analysis: The study involved an assessment of the demographic characteristics. Additionally, it explored the type of center, availability of various surgical approaches, presence of training infrastructure, participation in courses, organization of training, and participants' satisfaction with the training program. The level of satisfaction was evaluated using a Likert-5 scale. The subsequent sections delved into surgical training within the realms of open, laparoscopic, robotic, and endoscopic surgery, each explored separately. Finally, the investigation encompassed the presence of a structured training course and the availability of a duly validated final evaluation process., Results and Limitations: There were 375 responders with a completion rate of 82%. Among them, 75% were identified as male, 50.6% were young urologists, 31.7% were senior residents, and 17.6% were junior residents. A significant majority of participants (69.6%) were affiliated with academic centers. Regarding the presence of dry lab training facilities, only 50.3% of respondents indicated its availability. Among these centers, 46.7% were primarily focused on laparoscopy training. The availability of virtual and wet lab training centers was even more limited, with rates of 31.5% and 16.2%, respectively. Direct patient involvement was reported in 80.5% of cases for open surgery, 58.8% for laparoscopy, 25.0% for robotics, and 78.6% for endourology. It is worth noting that in <25% of instances, training followed a well-defined standardized program comprising both preclinical and clinical modular phases. Finally, the analysis of participant feedback showed that 49.7% of respondents expressed a satisfaction rating of either 4 or 5 points with respect to the training program. The limitations of our study include the low response rate, predominance of participants from academic centers, and absence of responses from individuals not affiliated with the EAU network., Conclusions: The current distribution of surgical training centers falls short of ensuring widespread access to standardized training programs. Although dry lab facilities are relatively well spread, the availability of wet lab resources remains restricted. Additionally, it appears that many trainees' initial exposure to surgery occurs directly with patients. There is a pressing need for continued endeavors to establish uniform training routes and assessment techniques across various surgical methodologies., Patient Summary: Nowadays, the surgical training landscape is heterogeneous across different countries. The implementation of a standardized training methodology to enhance the overall quality of surgical training and thereby improving patient outcomes is needed., (© 2024 The Authors.)

Background: Castleman disease (CD) comprises a group of rare and heterogeneous haematological disorders, including unicentric (UCD) and multicentric (MCD) forms, the latter further subdivided into HHV8-MCD, POEMS-MCD and idiopathic-MCD (iMCD). However, according to the Castleman Disease Collaborative Network guidelines, the diagnosis of CD can only be achieved through collaboration between clinicians and pathologists., Methods: We applied these clinical and pathological criteria and implement with clonality testing to a retrospective cohort of 48 adult and paediatric Italian patients diagnosed with reactive lymphadenitis with CD-like histological features., Results: We confirmed the diagnosis of CD in 60% (29/48) of the cases, including 12 (41%) UCD and 17 (59%; five HHV8-MCD, three POEMS-MCD and nine iMCD) MCD. Of the remaining 19 cases (40%) with multiple lymphadenopathy, 5 (26%) were classified as autoimmune diseases, 1 (5%) as autoimmune lymphoproliferative disorder, 1 (5%) as IgG4-related disease, 11 (83%) as reactive lymphadenitis and 1 (5%) as nodal marginal zone lymphoma., Conclusions: Our study emphasizes the importance of the multidisciplinary approach to reactive lymphadenitis with CD-like features in order to achieve a definitive diagnosis and choose the appropriate treatment., (© 2023 The Authors. British Journal of Haematology published by British Society for Haematology and John Wiley & Sons Ltd.)

Background: The patient selection for optimal adjuvant therapy in gastrointestinal stromal tumors (GISTs) is provided by nomogram based on tumor size, mitotic index, tumor location, and tumor rupture. Although mutational status is not currently used to risk assessment, tumor genotype showed a prognostic influence on natural history and tumor relapse. Innovative measures, such as KIT/PDGFRA-mutant-specific variant allele frequency (VAF) levels detection from next-generation sequencing (NGS), may act as a surrogate of tumor burden and correlate with prognosis and overall survival of patients with GIST, helping the choice for adjuvant treatment., Patients and Methods: This was a multicenter, hospital-based, retrospective/prospective cohort study to investigate the prognostic role of KIT or PDGFRA-VAF of GIST in patients with radically resected localized disease. In the current manuscript, we present the results from the retrospective phase of the study., Results: Two-hundred (200) patients with GIST between 2015 and 2022 afferent to 6 Italian Oncologic Centers in the EURACAN Network were included in the study. The receiver operating characteristic (ROC) curves analysis was used to classify "low" vs. "high" VAF values, further normalized on neoplastic cellularity (nVAF). When RFS between the low and high nVAF groups were compared, patients with GIST with KIT/PDGFRA nVAF > 50% showed less favorable RFS than patients in the group of nVAF ≤ 50% (2-year RFS, 72.6% vs. 93%, respectively; P = .003). The multivariable Cox regression model confirmed these results. In the homogeneous sub-population of intermediate-risk, patients with KIT-mutated GIST, the presence of nVAF >50% was statistically associated with higher disease recurrence., Conclusion: In our study, we demonstrated that higher nVAF levels were independent predictors of GIST prognosis and survival in localized GIST patients with tumors harboring KIT or PDGFRA mutations. In the cohort of intermediate-risk patients, nVAF could be helpful to improve prognostication and the use of adjuvant imatinib., (© The Author(s) 2023. Published by Oxford University Press.)

Background: Both clinicians and patients use social media to post about health care issues such as kidney stone disease, but their perspectives may differ., Objective: To evaluate content and themes regarding kidney stone surgery shared by patients and urologists on Instagram., Design Setting and Participants: A search was performed on Instagram using the term "kidney stone surgery". The first 100 posts from individuals who were clearly identified as a patient were assessed. We also assessed 100 posts from self-identified urologists., Outcome Measurements and Statistical Analysis: A previously published system was applied as a framework for categorizing the information collected. Outcomes of interested included pain, recovery, and costs., Results and Limitations: Some 71% of the patients were female and most of their posts (52%) were shared postoperatively. The most common themes covered in patient posts were the need for multiple operative sessions (45%), pain (43%), and recovery (42%). Other themes included activities of daily life (18%), return to work (11%), nervousness (16%), stent issues (31%), stent on a string (5%), diet and prevention (9%), gratitude for health care services (10%), disease recurrence (18%), and costs (10%). Some 94% of the urologists were male and their posts covered the following domains: recovery (11%), stent issues (3%), pain (1%), stent on a string (1%), gratitude for health care services (1%), and recurrence 1%. Among the posts from urologists, 79% included self-promotion and 52% covered new technology. Overall, 10% contained false information. The majority of the posts with surgical images had no clear statement regarding patient consent (97%)., Conclusions: Kidney stone surgery can affect many areas of a patient's quality of life. Most of the posts shared by patients were negative. Posts shared by urologists do not reflect the same themes. Moreover, there appears to be poor adherence to European Association of Urology recommendations regarding online professional conduct., Patient Summary: Many patients use social media to share their experiences of kidney stone surgery. Posts are largely related to quality-of-life issues and are mostly negative. While urologists also use social media, the content they post on professional accounts is mostly focused on new technology and career promotion., (© 2023 The Author(s).)

Radical prostatectomy significantly impacts the inherent anatomy of the male pelvis and the functional mechanisms of urinary continence. Incontinence has a considerable negative influence on the quality of life of patients, as well as their social and psychological wellbeing. Numerous surgical techniques have been demonstrated to support the preservation of continence during robot-assisted radical prostatectomy (RARP). In this in-depth analysis, we give a general summary of the surgical techniques used in RARP and their impact on incontinence rates., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2023 Katsimperis, Juliebø-Jones, Ta, Tandogdu, Al-Bermani, Bellos, Esperto, Tonyali, Mitsogiannis, Skolarikos, Varkarakis, Somani and Tzelves.)

Background: Two surgical techniques were compared : Standard BIO-RSA, performed with a glenoid eccentric reaming along with a cylindric bone graft augmentation vs. the Angled BIO-RSA, performed with a glenoid concentric reaming and a defect correction with an angled bone graft., Methods: Patients undergoing RSA from January 2016 to April 2019, with one of the two techniques being performed, were retrospectively reviewed. Glenoids were classified according to Favard. Clinical (Constant-Murley, VAS and ROM) and radiographic (superior tilt correction) data were collected pre-operatively and at 12 months post-operatively., Results: 141 shoulders were included. Angled BIO-RSA group showed statistically significant better outcomes in terms of forward flexion (149.9° Vs 139.3°) and abduction (136.4° Vs 126.7°). The use of an Angled BIO-RSA showed a statistically significant better superior tilt correction (1.252° Vs 4.09°). Angled BIO-RSA, leads to a better inclination correction and a mean postoperative tilt value inferior to 5° in E1 and E3 differently from standard BIO-RSA., Discussion: Both techniques were able to correct glenoid superior inclination with excellent postoperative short-term results. However, angled BIO-RSA technique appears to be more effective in ensuring a correct inclination of the prosthetic glenoid component with better clinical outcomes., Competing Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2021.)

Cholangiocytes, the epithelial cells that line the biliary tree, can proliferate under the stimulation of several factors through both autocrine and paracrine pathways. The cocaine-amphetamine-regulated-transcript (CART) peptide has several physiological functions, and it is widely expressed in several organs. CART increases the survival of hippocampal neurons by upregulating brain-derived neurotrophic factor (BDNF), whose expression has been correlated to the proliferation rate of cholangiocytes. In the present study, we aimed to evaluate the expression of CART and its role in modulating cholangiocyte proliferation in healthy and bile duct ligated (BDL) rats in vivo, as well as in cultured normal rat cholangiocytes (NRC) in vitro. Liver samples from both healthy and BDL (1 week) rats, were analyzed by immunohistochemistry and immunofluorescence for CART, CK19, TrkB and p75NTR BDNF receptors. PCNA staining was used to evaluate the proliferation of the cholangiocytes, whereas TUNEL assay was used to evaluate biliary apoptosis. NRC treated or not with CART were used to confirm the role of CART on cholangiocytes proliferation and the secretion of BDNF. Cholangiocytes proliferation, apoptosis, CART and TrkB expression were increased in BDL rats, compared to control rats. We found a higher expression of TrkB and p75NTR, which could be correlated with the proliferation rate of biliary tree during BDL. The in vitro study demonstrated increased BDNF secretion by NRC after treatment with CART compared with control cells. As previously reported, proliferating cholangiocytes acquire a neuroendocrine phenotype, modulated by several factors, including neurotrophins. Accordingly, CART may play a key role in the remodeling of biliary epithelium during cholestasis by modulating the secretion of BDNF.

Objective: In a previous study, we reported an increase of nasal nerve growth factor (NGF) in patients treated with high-pressure administration of sterile saline isotonic solution (HPpSIS). Herein we characterized the nasal mucosa in terms of innate immune response and cytokine signature, including antiviral properties. Potential NGF and antiviral benefits of HPpSIS were also discussed., Patients and Methods: Twenty (20) patients (11 males, 9 females; age range 30-75 years old) underwent HPpSIS and nasal samples were collected before and after treatment. Nasal scraping was used for morphological (smears and Quick May-Grunwald Giemsa staining, MGG), biochemical (Histamine, Serotonin; ELISA) and molecular (messenger RNA, mRNA) analyses. Amplification of transcripts specific for Toll-like receptor (TLR) 3 (TLR3), TLR7, TLR9, Interleukin-(IL) 18 (IL18), IL13, IL12, eosinophil-derived neurotoxin (EDN), Eosinophil Cationic Protein (ECP), γ Interferon (γIFN), tryptase and serotonin was performed using the 2-step real-time Reverse Transcription Polymerase Chain Reaction (RT-PCR). Clinical and laboratory data were analyzed and compared., Results: The clinical evaluation showed a protective effect of our therapy. Smears showed the presence of leucocytes, eosinophils (EOs) and mast cells (MCs), and increased immunoreactivity for ECP/RNase3 and EDN after HPpSIS. ELISA showed increased levels of Serotonin and EDN associated with unchanged levels of substance P(SP) and histamine. Increased eosinophil-derived neurotoxin eosinophil-derived neurotoxin (EDN) levels were confirmed by in situ fluorescent analysis. HPpSIS induced the upregulation of TLR3, TLR7 and TLR9 transcripts, while no changes were observed for Intercellular Adhesion Molecule 1 (ICAM1), IL18, Interleukin-15 (IL15) and IL12 transcripts nor for Interleukin-6 (IL6) and IL13. No changes were also observed for γIFN and EDN/RNase2 transcripts, while ECP/RNase3 transcripts were significantly upregulated after HPpSIS. Finally, tryptase transcripts were unchanged while serotonin transcripts were significantly increased after HPpSIS., Conclusions: The clinical and biomolecular changes observed at the nasal mucosa due to HpSS treatment suggest the activation of an innate surveillance, by means of TLR transcription, and a possible anti-viral response due to EDN upregulation. It remains to be verified if NGF, known to be released locally upon HpSIS treatment, might in part be responsible for this local activation.

Background: Tenodesis of the long head of the biceps (LHB) is commonly undertaken during arthroscopic rotator cuff repair. We assessed the clinical and structural outcomes after high arthroscopic tenodesis (HAT) or mini-open subpectoral tenodesis (ST). We hypothesized that the clinical and structural results after HAT and ST are similar., Methods: We included 40 patients with rotator cuff tear and LHB tendinopathy. Twenty patients (7 women and 13 men; mean age: 57.9 years; range: 56-63 years) were treated using HAT, and 20 patients (8 women and 12 men; mean age: 58.5 years; range: 55-64 years) were treated using ST. Functional evaluation was performed preoperatively and at 6 weeks, 6 months, and 1 year after surgery, using the Constant Murley Score and Simple Shoulder Test scores; the LHB was evaluated using the LHB score. A Visual Analogue Scale was administered to all patients preoperatively and 2 days after surgery., Results: The postoperative total and pain subscale's Constant scores were significantly higher in the ST group. Moreover, 2 LHB score values were significantly different between the groups. The postoperative LHB total score in the ST and HAT groups averaged 86.9 ± 4.1 (mean ± SD) points and 73.3 ± 6.4 points, respectively. The Pain/Cramps subscale in the ST and HAT groups averaged 47.1 ± 5.9 and 33.2 ± 4.6 points, respectively. The 2 groups showed no difference in Visual Analogue Scale values (5.5 in the HAT group; 5.8 in the ST group) postoperatively. One patient in the HAT group reported a secondary onset of Popeye deformity., Conclusion: Both high arthroscopic and mini-open ST of the LHB tendon produced reliably good functional results, but the ST group was associated with better postoperative clinical outcomes., Competing Interests: Competing interests The authors declare that they have no competing interests., (Copyright © 2020. Production and hosting by Elsevier B.V.)

Background: The aim of this study was to demonstrate that the implementation of remote medical care in the management of patients suffering from specific urogynecological diseases can be a valid alternative to outpatient visits leading to a huge saving of resources which can be used for real emergencies. Therefore, the primary aim of this study was to demonstrate that patients treated with telehealth had the same improvement in symptoms and Quality of Life as those treated with outpatient visits., Methods: Observational analysis on women with urogynecological diseases was performed during restrictive measures period. One group of patients was assessed in the clinic and one group by video consultations. The population answered Female Sexual Function Index (FSFI), Female Sexual Distress Scale (FSDS), the Overactive Bladder Questionnaire Symptoms and Health-Related Quality of Life Short-Form Symptoms (OAB-Q), Prolapse Quality of Life Questionnaire (P-QoL), the Pelvic Pain and Urinary/Frequency Patient Symptom Scale (PUF) scores, the Short Form Health Survey questionnaires (SF-36) during the first visit and after 12 weeks. The primary endpoint was to evaluate the change in symptoms after the outpatient and telemedicine visit. The secondary endpoint was the evaluation of the telemedicine impact on the Quality of Life and sexual function., Results: One hundred twenty-five patients were considered. Symptoms of overactive bladder, genitourinary syndrome, and recurrent urinary infections improved significantly in both groups with no significant differences. Sexual activity increased significantly in both groups with a significant change in FSFI and FSDS values. The SF-36 showed a significant change 12 weeks after the visit in both groups., Conclusions: Telemedicine is equally useful and effective as the outpatient visits in patients suffering from urogynecological diseases.

Objective: Local anesthesia for single incision slings has shown a good objective and subjective cure rate in women with stress urinary incontinence. The aim of the present study was to verify the efficacy and safety of local anesthesia during Altis ® single incision placement., Material and Methods: One hundred sixty-six consecutive patients (83 patients for each group: local resp. spinal anesthesia) were selected from our database for this retrospective study among women who underwent an Altis ® implantation for SUI from September 2016 to June 2021, after unsuccessful previous conservative treatment. Primary endpoints were objective and subjective cure rates; secondary endpoint was the evaluation of complications linked to this procedure., Results: A total of 155 included patients completed our 12 months follow-up. Baseline characteristics were similar between the groups. Operative time (percentage difference of 50%; p < 0.05 ) and the Intraoperative Difficulty Scale resulted lower in spinal patients. No differences were found between populations in terms of objective (cough stress test and urodynamics) and subjective (PGI-I and FSDS questionnaires) cure rate and postoperative complications., Conclusion: Local anesthesia for Altis ® implantation could be considered a safe alternative to spinal anesthesia and an effective opportunity to avoid general anesthesia, increasing the possibility of outpatient implantation of this sling system.

Background: Treatment of cancer pain remains suboptimal worldwide. In Italy, a law requires that pain be regularly assessed and reported in both medical and nursing records. Aim: To provide a homogeneous form to get exhaustive clinical information in the clinical report according to Italian legislation. Methods: A board, including oncologists and pain therapists, designed a form to report the pain characteristics of cancer patients in Italy in clinical records. The form was voted on through a Delphi process among directors of 18 clinical oncology specialization schools in Italy to obtain agreement on its content. Results: A form useful for collecting and reporting comprehensive and homogeneous information on pain among oncologists in Italy was produced. Conclusion: The development of common strategies for pain management can be improved by using this tool.

Background and Objectives : Photo/chrono-aging is usually expressed as facial discolouration, wrinkles, redness, elastosis, laxity, and dehydration, thus representing major signs of ageing that often lead to a negative phycological impact on a patient's quality of life. Several types of treatment have been tested during the last decade, especially laser treatments. This article aims to share our experience in the treatment of photoaging with a new 675 nm laser source system on facial chrono-ageing. Materials and Methods : Thirty-five (35) patients were treated with the 675 nm laser device: 32 females (mean age 49 years) and 3 men (mean age 57 years), with Fitzpatrick skin types I-III (9% type I, 43% type II, 48% type III), facial wrinkles and hyperpigmented spots. The efficacy of this treatment was assessed using the Modified Fitzpatrick Wrinkles Scale (FWS), which was calculated before starting the treatment and after 6 months. The pain was evaluated using the VAS Pain Scale. Results : All 35 patients showed a significant improvement in facial wrinkles according to the FWS (from 1.96 to 1.73 at the 3-month follow-up, up to a value of 1.43 at 6 months). In a small group of patients, it was observed that 44% of them showed vascular moderate improvement and that 13% showed a vascular marked improvement after treatment. No side effects were detected except a mild erythematous rash in two patients, and the VAS Pain scale was assessed at 1.17. Conclusions : Red Touch allows a uniform and stable result to be achieved over time with minimum discomfort.

The COVID-19 pandemic has impacted urology residents and their training. However, several new technologies or knowledge platforms as social media (SoMe) and web-based learning solutions have filled this gap. Therefore, we aimed to analyze resident's learning curves of new learning modalities, identify the evidence that is provided in the literature, and evaluate the possible impact of such solutions in the future. We conducted a non-systematic literature search using Medline, PubMed, and Embase. In addition, online resources of national and international urology resident societies were queried. The identified paper described SoMe, webinars, podcasts, pre-recorded surgical videos, educational platforms, and mobile apps in the field of urology that are used to gain access to information, teach and provide feedback to residents, and were used under the conditions of the pandemic. The application of those technologies harbors the risk of mis- and disinformation, but have the potential to provide access to education and validated knowledge, training, and feedback and thereby might democratize training of residents in urology globally.

Background: Distal upper limb tremor during walking (TW) is frequently observed in Parkinson's disease (PD) but its clinical features are unknown., Objective: To characterize the occurrence and the clinical features of TW in comparison to the other types of tremors in PD., Methods: Fifty-one PD patients with rest tremor were evaluated off- and on-treatment. Occurrence, body distribution, severity and latency of TW and of other tremor types were assessed., Results: TW was present in 78% of the PD patients examined. TW body distribution and severity were similar to those of rest and re-emergent tremor but different from the postural tremor presented by the same patients. TW latency, observed in 85% of patients, was on average 5.8 s. Dopaminergic treatment significantly improved TW, rest, and re-emergent tremor severity but left TW latency unaffected., Conclusions: TW is a frequent motor sign in PD and is likely a clinical variant of rest tremor., (© 2023 The Authors. Movement Disorders Clinical Practice published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.)

Background: The aim of this study was to compare the efficacy of vaginal native tissue repair (VNTR) combined with tension-free transobturator tape (TVT-O) or pelvic floor muscle training (PFMT) in terms of quality of life (QoL) and sexual function (SF) in women affected by anterior defect and occult stress urinary incontinence (OSUI)., Methods: One hundred forty-seven patients with symptomatic anterior defect with OSUI underwent VNTR. In 71 patients TVT-O was inserted and 76 underwent PFMT after surgery. Clinical exam, 3-day voiding diary and urodynamic testing were evaluated in preoperative and postoperative times. Specific questionnaires were also administered, in order to indagate disease perception and the impact on QoL and SF., Results: Nine patients had postoperative pain in the TVT-O group vs. 0 patients in the PMFT group (P=0.001) and 7 patients reported de novo urgency vs. 3 in the two groups, respectively. At 12 weeks follow-up (FU), the first voiding desire was at 88.12+19.70 mL in VNTR+TOT vs. 102.29+19.13 (P=0.03); the mean number of voids (24 hours) was 9.95±2.66 vs. 6.14±1.77 (P=0.04), respectively. No significant differences in terms of QoL and SF were shown., Conclusions: This retrospective study suggests that VNTR+TVT-O and VNTR+PMFT have the same efficacy in terms of QoL and SF, with several post-operative complications, even if minor, in patients treated with combined surgery.

Competing Interests: We declare no competing interests.