European Tertiary Referral Centers Research Articles

Cochlear Implantation in Single-Sided Deafness and Asymmetric Hearing Loss: 12 Months Follow-up Results of a European Multicenter Evaluation.

People with single-sided deafness (SSD) or asymmetric hearing loss (AHL) have particular difficulty understanding speech in noisy listening situations and in sound localization. The objective of this multicenter study is to evaluate the effect of a cochlear implant (CI) in adults with single-sided deafness (SSD) or asymmetric hearing loss (AHL), particularly regarding sound localization and speech intelligibility with additional interest in electric-acoustic pitch matching. A prospective longitudinal study at 7 European tertiary referral centers was conducted including 19 SSD and 16 AHL subjects undergoing cochlear implantation. Sound localization accuracy was investigated in terms of root mean square error and signed bias before and after implantation. Speech recognition in quiet and speech reception thresholds in noise for several spatial configurations were assessed preoperatively and at several post-activation time points. Pitch perception with CI was tracked using pitch matching. Data up to 12 months post activation were collected. In both SSD and AHL subjects, CI significantly improved sound localization for sound sources on the implant side, and thus overall sound localization. Speech recognition in quiet with the implant ear improved significantly. In noise, a significant head shadow effect was found for SSD subjects only. However, the evaluation of AHL subjects was limited by the small sample size. No uniform development of pitch perception with the implant ear was observed. The benefits shown in this study confirm and expand the existing body of evidence for the effectiveness of CI in SSD and AHL. Particularly, improved localization was shown to result from increased localization accuracy on the implant side.

External validation and comparison of magnetic resonance imaging-based risk prediction models for prostate biopsy stratification.

Magnetic resonance imaging (MRI) is a promising tool for risk assessment, potentially reducing the burden of unnecessary prostate biopsies. Risk prediction models that incorporate MRI data have gained attention, but their external validation and comparison are essential for guiding clinical practice. The aim is to externally validate and compare risk prediction models for the diagnosis of clinically significant prostate cancer (csPCa). A cohort of 4606 patients across fifteen European tertiary referral centers were identified from a prospective maintained database between January 2016 and April 2023. Transrectal or transperineal image-fusion MRI-targeted and systematic biopsies for PI-RADS score of ≥ 3 or ≥ 2 depending on patient characteristics and physician preferences. Probabilities for csPCa, defined as International Society of Urological Pathology (ISUP) grade ≥ 2, were calculated for each patients using eight models. Performance was characterized by area under the receiver operating characteristic curve (AUC), calibration, and net benefit. Subgroup analyses were performed across various clinically relevant subgroups. Overall, csPCa was detected in 2154 (47%) patients. The models exhibited satisfactory performance, demonstrating good discrimination (AUC ranging from 0.75 to 0.78, p < 0.001), adequate calibration, and high net benefit. The model described by Alberts showed the highest clinical utility for threshold probabilities between 10 and 20%. Subgroup analyses highlighted variations in models' performance, particularly when stratified according to PSA level, biopsy technique and PI-RADS version. We report a comprehensive external validation of risk prediction models for csPCa diagnosis in patients who underwent MRI-targeted and systematic biopsies. The model by Alberts demonstrated superior clinical utility and should be favored when determining the need for a prostate biopsy.

Clinical Impact of Digitalis Therapy in a Large Multicenter Cohort of CRT-Recipients.

(1) Introduction: Digitalis use in patients with severe heart failure is controversial. We assessed the effects of digitalis therapy on mortality in a large, observational study in recipients of cardiac resynchronization therapy (CRT). (2) Methods: Consecutive patients receiving a CRT-defibrillator in three European tertiary referral centers were enrolled and followed-up for a mean 37 months ± 28 months. Digitalis use was assessed at the time of CRT implantation. A multivariate Cox-regression model and propensity score matching were used to determine all-cause mortality as the primary endpoint. CRT-response (defined as improvement of ≥1 NYHA class), echocardiographic improvement (defined as improvement of LVEF of ≥ 5%) and incidence of ICD shocks and rehospitalization were assessed as secondary endpoints in a subgroup of patients. (3) Results: The study comprised 552 CRT-recipients with standard indications, including 219 patients (40%) treated with digitalis. Compared to patients without digitalis, they had more often atrial fibrillation, poorer LVEF and a higher NYHA class (all p ≤ 0.002). Crude analysis of all-cause mortality demonstrated a similar relative risk of death for patients with and without digitalis (HR = 1.14; 95% CI 0.88-1.5; p = 0.40). After adjustment for independent predictors of mortality, digitalis therapy did not alter the risk for death (adjusted HR = 1.04; 95% CI 0.75-1.45; p = 0.82). Furthermore, in comparison to 286 propensity-score-matched patients, mortality was not affected by digitalis intake (propensity-adjusted HR = 1.11; 95% CI 0.72-1.70; p = 0.64). A CRT-response was predominant in digitalis non-users, concerning both improvement of HF symptoms and LVEF (NYHA p < 0.01; LVEF p < 0.01), while patients on digitalis had more often ventricular tachyarrhythmias requiring ICD shock (p = 0.01); although, rehospitalization for cardiac reasons was significantly lower among digitalis users compared to digitalis non-users (HR = 0.58; 95% C. I. 0.40-0.85; p = 0.01). (4) Conclusions: Digitalis therapy had no effect on mortality, but was associated with a reduced response to CRT and increased susceptibility to ventricular arrhythmias requiring ICD shock treatment. Although, digitalis administration positively altered the likelihood for cardiac rehospitalization during follow-up.

Physician Made Bovine Pericardial Tube Grafts in Aortic Infection: A European Multicentre Study

This study examines outcome and durability of physician made bovine pericardial tube grafts in aortic infections in all anatomical locations. This was a retrospective and prospective international multicentre study. Peri-operative and long term outcomes of patients undergoing in situ aortic reconstruction for native or graft infections with physician made bovine pericardial tube grafts between January 2008 and December 2020 in four European tertiary referral centres were analysed. The primary endpoint was recurrent aortic infection. Secondary endpoints were persistent infection, aortic re-operation for infection, graft related complications, and death. One hundred and sixty eight patients (77% male, mean age 67 ± 11 years) were identified: 38 (23%) with native and 130 (77%) with aortic graft infection. The thirty day mortality rate was 15% (n= 26) overall, 11% (n= 4), and 17% (n= 22) for native and aortic graft infections, respectively (p= .45). Median follow up was 26 months (interquartile range [IQR] 10, 51). Estimated survival at one, two, three, and five years was 64%, 60%, 57%, and 50%, and significantly better for native (81%, 77%, 77%, and 69%) than for graft infections (58%, 55%, 51%, and 44%; p= .011). Nine patients (5.3%) had persistent infection and 10 patients (6%) had aortic re-infection after a median of 10 months (IQR 5, 22), resulting in an estimated freedom from re-infection at one, two, three, and five years of 94%, 92%, 90%, and 86%. Estimated freedom from graft complications at one, two, three, and five years was 91%, 89%, 87%, and 87%. This multicentre study demonstrates low re-infection rates when using physician made bovine pericardial tube grafts, comparable to those of other biological grafts. The rate of graft complications, mainly anastomotic aneurysms and stenoses, was low, while graft degeneration was absent. Physician made bovine pericardial tube grafts are an excellent tool for in situ reconstruction in the setting of native aortic infection or aortic graft infection.

Artificial Intelligence Tools for the Diagnosis of Eosinophilic Esophagitis in Adults Reporting Dysphagia: Development, External Validation, and Software Creation for Point-of-Care Use

Despite increased awareness of eosinophilic esophagitis (EoE), the diagnostic delay has remained stable over the past 3 decades. There is a need to improve the diagnostic performance and optimize resources allocation in the setting of EoE. We developed and validated 2 point-of-care machine learning (ML) tools to predict a diagnosis of EoE before histology results during office visits. We conducted a multicenter study in 3 European tertiary referral centers for EoE. We built predictive ML models using retrospectively extracted clinical and esophagogastroduodenoscopy (EGDS) data collected from 273 EoE and 55 non-EoE dysphagia patients. We validated the models on an independent cohort of 93 consecutive patients with dysphagia undergoing EGDS with biopsies at 2 different centers. Models' performance was assessed by area under the curve (AUC), sensitivity, specificity, and positive and negative predictive values (PPV and NPV). The models were integrated into a point-of-care software package. The model trained on clinical data alone showed an AUC of 0.90 and a sensitivity, specificity, PPV, and NPV of 0.90, 0.75, 0.80, and 0.87, respectively, for the diagnosis of EoE in the external validation cohort. The model trained on a combination of clinical and endoscopic data showed an AUC of 0.94, and a sensitivity, specificity, PPV, and NPV of 0.94, 0.68, 0.77, and 0.91, respectively, in the external validation cohort. Our software-integrated models (https://webapplicationing.shinyapps.io/PointOfCare-EoE/) can be used at point-of-care to improve the diagnostic workup of EoE and optimize resources allocation.

External validation of nomograms including MRI features for the prediction of side-specific extraprostatic extension.

Prediction of side-specific extraprostatic extension (EPE) is crucial in selecting patients for nerve-sparing radical prostatectomy (RP). Multiple nomograms, which include magnetic resonance imaging (MRI) information, are available predict side-specific EPE. It is crucial that the accuracy of these nomograms is assessed with external validation to ensure they can be used in clinical practice to support medical decision-making. Data of prostate cancer (PCa) patients that underwent robot-assisted RP (RARP) from 2017 to 2021 at four European tertiary referral centers were collected retrospectively. Four previously developed nomograms for the prediction of side-specific EPE were identified and externally validated. Discrimination (area under the curve [AUC]), calibration and net benefit of four nomograms were assessed. To assess the strongest predictor among the MRI features included in all nomograms, we evaluated their association with side-specific EPE using multivariate regression analysis and Akaike Information Criterion (AIC). This study involved 773 patients with a total of 1546 prostate lobes. EPE was found in 338 (22%) lobes. The AUCs of the models predicting EPE ranged from 72.2% (95% CI 69.1-72.3%) (Wibmer) to 75.5% (95% CI 72.5-78.5%) (Nyarangi-Dix). The nomogram with the highest AUC varied across the cohorts. The Soeterik, Nyarangi-Dix, and Martini nomograms demonstrated fair to good calibration for clinically most relevant thresholds between 5 and 30%. In contrast, the Wibmer nomogram showed substantial overestimation of EPE risk for thresholds above 25%. The Nyarangi-Dix nomogram demonstrated a higher net benefit for risk thresholds between 20 and 30% when compared to the other three nomograms. Of all MRI features, the European Society of Urogenital Radiology score and tumor capsule contact length showed the highest AUCs and lowest AIC. The Nyarangi-Dix, Martini and Soeterik nomograms resulted in accurate EPE prediction and are therefore suitable to support medical decision-making.

Risk stratification for early biochemical recurrence of prostate cancer in the era of multiparametric magnetic resonance imagining-targeted biopsy.

Multiparametric magnetic resonance imaging (MRI) and MRI-targeted biopsy are nowadays recommended in the prostate cancer (PCa) diagnostic pathway. Ploussard and Mazzone have integrated these tools into novel risk classification systems predicting the risk of early biochemical recurrence (eBCR) in PCa patients who underwent radical prostatectomy (RP). We aimed to assess available risk classification systems and to define the best-performing. Data on 1371 patients diagnosed by MRI-targeted biopsy and treated by RP between 2014 and 2022 at eight European tertiary referral centers were analyzed. Risk classifications systems included were the European Association of Urology (EAU) and National Comprehensive Cancer Network (NCCN) risk groups, the Cancer of the Prostate Risk Assessment (CAPRA) score, the International Staging Collaboration for Cancer of the Prostate (STAR-CAP) classification, the Ploussard and Mazzone models, and ISUP grade group. Kaplan-Meier analyses were used to compare eBCR among risk classification systems. Performance was assessed in terms of discrimination quantified using Harrell's c-index, calibration, and decision curve analysis(DCA). Overall, 152 (11%) patients had eBCR at a median follow-up of 31 months (interquartile range: 19-45). The 3-year eBCR-free survival rate was 91% (95% confidence interval [CI]: 89-93). For each risk classification system, a significant difference among survival probabilities was observed (log-rank test p < 0.05) except for NCCN classification (p = 0.06). The highest discrimination was obtained with the STAR-CAP classification (c-index 66%) compared to CAPRA score (63% vs. 66%, p = 0.2), ISUP grade group (62% vs. 66, p = 0.07), Ploussard (61% vs. 66%, p = 0.003) and Mazzone models (59% vs. 66%, p = 0.02), andEAU (57% vs. 66%, p < 0.001) and NCCN (57% vs. 66%, p < 0.001) risk groups. Risk classification systems demonstrated good calibration characteristics. At DCA, the CAPRA score showed the highest net benefit at a probability threshold of 9%-15%. The performance of risk classification systems using MRI and MRI-targeted information was less optimistic when tested in a contemporary set of patients. CAPRA score and STAR-CAP classification were the best-performing and should be preferred for treatment decision-making.

The outcomes of pics technique for the management of end-stage peyronie's disease

To present the surgical, the functional and patients’ reported outcomes (PROs) of PICS technique in multicentric series of patients affected by end-stage PD. Patients underwent an IPP implantation followed by PICS technique were recruited in two European tertiary referral center. The primary endpoint of the study was the achievement of a complete straightening of the penis. The secondary endpoints were surgical, functional and PROs. The International Index of Erectile Function (IIEF-5), the Sexual Encounter profile questions 2 and 3 (SEP 2 and SEP 3) and the Erectile Dysfunction Inventory of Treatment Satisfaction (EDITS) were used to assess patients’ erectile function. The PICS technique was used in 37 patients. Median patient age was 62 years (IQR 57-70 years). Residual curvature after IPP was 60° (IQR 50–70°). Operative time was 100 minutes (IQR 90–120). Median follow-up resulted of 14 months (IQR 12–17). 27 of 37 patients (72.9%) achieved a totally straight penis. 6 patients (16.2 %) experienced a residual penile curvature: of 10° in 3 patients, 15° in 1 patient and 20° in 2 patients. The residual curvature did not interfere with sexual intercourse in any of the cases. No intraoperative complications were detected. 9 of 37 patients (24.3%) developed an early postoperative complications: 3 (8.1%) manifested a transient fever and 6 (16.2%) experienced a genital hematoma. We detected a single case (2.7%) of acute infection requiring a removal of the IPP. No cases of IPP mechanical failure were described. Median IIEF-5 score increased from 10 (8-12) in postoperative settings to 23.5 (22.2-25) at 12 months follow-up. SEP 2-3 increased from 5 (13.5%) and 0 (0%) to 34 (91.9) in both domains. EDITS scored 25 (21.2-29.5) at 12 months follow-up. The PICS technique represents a safe and effective approach to manage residual penile curvature during IPP placement in patients with end-stage PD. None

Surgical Treatment of Spinal Meningiomas in the Elderly (≥75 Years): Which Factors Affect the Neurological Outcome? An International Multicentric Study of 72 Cases.

Simple SummarySpinal meningiomas (SMs) are slow growing lesions, often occurring in middle- and old-aged patients. Few data about age-related prognostic factors are available in the literature to date. We analyzed a series of elderly patients undergoing surgery for a SM in the last twenty years in four different European tertiary referral centers. This work aimed to assess the surgical outcome and to identify possible outcome predictors. In this international multicentric retrospective study involving 72 patients older than ≥75 years, we highlight that functional preoperative score (according to modified McCormick scale) and age at surgery correlate with functional outcome.(1) Background: With the increasing life expectancy in the Western world, an increasing number of old patients presents with spinal meningioma. Considering the benign nature of these tumors, the functional outcome remains of great importance, since more people reach old age in general conditions of well-being and satisfactory autonomy. (2) Methods: We conducted an international multicenter retrospective study to investigate demographic, clinical and radiological data in a population of elderly patients (≥75 years of age) undergoing surgery for SM from January 2000 to December 2020 in four European referral centers. The aim was to identify prognostic and predictive factors for a good postoperative functional outcome. (3) Results: 72 patients were included in the study. Complete tumor resection (Simpson I or II) was achieved in 67 (95.7%) cases. Intraoperative complications were reported in 7 (9.9%) patients while postoperative complications were found in 12 (16.7%). An excellent general postoperative status (McCormick I and II) was achieved in 65.3%. Overall, surgical resection had a good impact on patients’ functional outcome (86.1% either showing an improvement or maintaining a good preoperative status). Uni- and multivariate analyses found that both age and preoperative modified McCormick independently correlated with relative outcome (coeff = −0.058, p = 0.0251; coeff = 0.597, p < 0.0001) and with postoperative status (coeff = 0.058, p = 0.02507; coeff = 0.402, p = 0.00027), respectively. (4) Conclusions: Age and preoperative modified McCormick were found to be independent prognostic factors. Nevertheless, advanced age (≥75), per se, did not seem to contraindicate surgery, even in those with severe preoperative neurological deficits. The functional results sustain the need for surgical resection of SM in the elderly.

MP031 - Results of ureteroscopy and laser fragmentation (URSL) in extremes of age (less than or equal to 10 years and more than or equal to 80 years): Comparative outcomes from 2 European tertiary referral centers.

MP031 - Results of ureteroscopy and laser fragmentation (URSL) in extremes of age (less than or equal to 10 years and more than or equal to 80 years): Comparative outcomes from 2 European tertiary referral centers.

Semi-closed-circuit vacuum-assisted mini percutaneous nephrolithotomy in the pediatric population: the initial experience of two tertiary referral centers.

Percutaneous nephrolithotomy (PCNL) is the gold-standard for complex renal stones treatment in the pediatric population. While the miniaturization of PCNL reduces the risk of bleeding, it can hinder surgical and functional outcomes. The aim of the study was to assess the safety and feasibility of semi-closed-circuit vacuum-assisted Mini-PCNL (vmPCNL) in pediatric patients. From January 2017 to December 2018, we prospectively collected data on consecutive vmPCNLs from two European tertiary referral centers. The procedure was performed with the ClearPetra® (Well Lead Medical Co., Ltd., Guangzhou, China) access sheath equipped with a lateral arm connected to the aspiration system (pressure setting ~120-150 cmH<inf>2</inf>O) by a 200 Ml plastic stone collector. Pre-, intra- and postoperative data and costs were analyzed. The stone-free rate (SFR) was defined as absence of residual fragments >4 mm with either ultrasound or kidney, ureter, and bladder X-ray. Eighteen vmPCNLs were performed in 16 renal units of 13 children. The median age was 119 months (IQR: 97-160) and the weight was 29 Kg (IQR: 25-40). The median cumulative stone size was 32 mm (22-46) with 8 (44.4%) cases of staghorn stones. The OT was 128 min (IQR: 99-167). The basketing was unnecessary in 6/18 (33%) cases. Neither intra-operative complications nor blood transfusions occurred. Postoperative fever was observed in 5/18 (27.8%) cases; in one case a double J ureteral stent was placed for concomitant hydronephrosis. The SFR was 81.3% (13/16), rising to 93.8% (15/16) after ancillary procedures. The materials costs of a vmPCNL (734.8 €) were comparable to mini-PCNL using a reusable set (710.7 €). The vmPCNL seems to be sustainable, safe and feasible for kidney stones treatment in the pediatric population.

Primary renal sarcomas: imaging features and discrimination from non-sarcoma renal tumors

ObjectivesTo assess imaging features of primary renal sarcomas in order to better discriminate them from non-sarcoma renal tumors.MethodsAdult patients diagnosed with renal sarcomas from 1995 to 2018 were included from 11 European tertiary referral centers (Germany, Belgium, Turkey). Renal sarcomas were 1:4 compared to patients with non-sarcoma renal tumors. CT/MRI findings were assessed using 21 predefined imaging features. A random forest model was trained to predict “renal sarcoma vs. non-sarcoma renal tumors” based on demographics and imaging features.Resultsn = 34 renal sarcomas were included and compared to n = 136 non-sarcoma renal tumors. Renal sarcomas manifested in younger patients (median 55 vs. 67 years, p < 0.01) and were more complex (high RENAL score complexity 79.4% vs. 25.7%, p < 0.01). Renal sarcomas were larger (median diameter 108 vs. 43 mm, p < 0.01) with irregular shape and ill-defined margins, and more frequently demonstrated invasion of the renal vein or inferior vena cava, tumor necrosis, direct invasion of adjacent organs, and contact to renal artery or vein, compared to non-sarcoma renal tumors (p < 0.05, each). The random forest algorithm yielded a median AUC = 93.8% to predict renal sarcoma histology, with sensitivity, specificity, and positive predictive value of 90.4%, 76.5%, and 93.9%, respectively. Tumor diameter and RENAL score were the most relevant imaging features for renal sarcoma identification.ConclusionRenal sarcomas are rare tumors commonly manifesting as large masses in young patients. A random forest model using demographics and imaging features shows good diagnostic accuracy for discrimination of renal sarcomas from non-sarcoma renal tumors, which might aid in clinical decision-making.Key Points• Renal sarcomas commonly manifest in younger patients as large, complex renal masses.• Compared to non-sarcoma renal tumors, renal sarcomas more frequently demonstrated invasion of the renal vein or inferior vena cava, tumor necrosis, direct invasion of adjacent organs, and contact to renal artery or vein.• Using demographics and standardized imaging features, a random forest showed excellent diagnostic performance for discrimination of sarcoma vs. non-sarcoma renal tumors (AUC = 93.8%, sensitivity = 90.4%, specificity = 76.5%, and PPV = 93.9%).

Safety of Esophageal Cancer Surgery During the First Wave of the COVID-19 Pandemic in Europe: A Multicenter Study

BackgroundMany hospitals postponed elective surgical care during the first wave of the coronavirus disease 2019 (COVID-19) pandemic. Some centers continued elective surgery, including esophageal cancer surgery, with the use of preoperative screening methods; however, there is no evidence supporting the safety of this strategy as postoperative outcomes after esophageal cancer surgery during the COVID-19 pandemic have not yet been investigated.MethodsThis multicenter study in four European tertiary esophageal cancer referral centers included consecutive adult patients undergoing elective esophageal cancer surgery from a prospectively maintained database in a COVID-19 pandemic cohort (1 March 2020–31 May 2020) and a control cohort (1 October 2019–29 February 2020). The primary outcome was the rate of respiratory failure requiring mechanical ventilation.ResultsThe COVID-19 cohort consisted of 139 patients, versus 168 patients in the control cohort. There was no difference in the rate of respiratory failure requiring mechanical ventilation (13.7% vs. 8.3%, p = 0.127) and number of pulmonary complications (32.4% vs. 29.9%, p = 0.646) between the COVID-19 cohort and the control cohort. Overall, postoperative morbidity and mortality rates were comparable between both cohorts. History taking and reverse transcription polymerase chain reaction (RT-PCR) were used as preoperative screening methods to detect a possible severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in all centers. No patients were diagnosed with COVID-19 pre- or postoperatively.ConclusionEsophageal cancer surgery during the first wave of the COVID-19 pandemic was not associated with an increase in pulmonary complications as no patients were diagnosed with COVID-19. Esophageal cancer surgery can be performed safely with the use of adequate preoperative SARS-CoV-2 screening methods.

Clinicopathological correlates, oncological impact, and validation of Oncotype DX™ in a European Tertiary Referral Centre.

Oncotype DX™ (ODX) score estimates prognosis and predicts breast cancer recurrence. It also individualizes patient adjuvant chemotherapy prescription in breast cancer. This assay relies on genetic and molecular markers; the clinicopathological phenotype of which are tested routinely. The aim of this study was determine whether clinicopathological and immunohistochemical information predicts ODX recurrence score (RS). Secondly, to assess the impact on adjuvant chemotherapy (AC) and oncological outcome of ODX testing in patients in a European tertiary referral center. Estrogen receptor positive (ER+), human epidermal growth factor receptor-2 negative (HER2-), lymph node negative (LN-), and female breast cancer patients with ODX testing performed between 2007 and 2015 were categorized into low- (<11), intermediate- (11-25), and high-risk (>25) groups. Clinicopathological and immunohistochemical correlates of RS were determined. Predictors of RS were assessed using binary logistic regression. Oncological outcome was assessed using Kaplan-Meier and Cox regression analyses. ODX was performed in 400 consecutive ER+LN- patients. Median follow-up was 74.1months (3.0-144.4). Low grade (odds ratio [OR]:2.39; 95% confidence interval [CI]:1.04-5.51, p=0.041) independently predicted low ODX, while high grade (OR:2.04; 95% CI: 1.19-3.49, p=0.009) and reduced progesterone receptor (PgR) expression (OR: 2.57, 95% CI: 1.42-4.65, p=0.002) independently predicted high ODX. Omission of AC in intermediate- (p=0.159) and high-risk (p=0.702) groups did not negatively impact survival. In conclusion, tumor grade independently predicts low and high RS, while PgR negativity predicts high RS. ODX reduced AC prescription without compromising oncological outcome.

Comparison of treatments and outcomes of children with juvenile dermatomyositis followed at two European tertiary care referral centers

To compare the treatment approaches and disease outcomes of children with JDM followed in two European tertiary care peadiatric rheumatology centres. The medical notes of patients with JDM seen at Istituto Giannina Gaslini (IGG) of Genoa, Italy or Great Ormond Street Hospital (GOSH) of London, UK between January 2000 and December 2015 within 6 months after disease onset and followed for at least 6 months were reviewed. Demographic, clinical and therapeutic data were collected. At each visit, the caring physician was asked to rate the disease state subjectively. A total of 127 patients were included, 88 at GOSH and 39 at IGG. At 24 months, the median values of muscle strength and disease activity were at the normal end of the scale and around three quarters of patients were said to have inactive disease. Also, at 2 years, 38.6% and 36% of British and Italian patients, respectively, had damage. Cyclophosphamide, azathioprine, infliximab, rituximab and mycophenolate mofetil were used more frequently by UK physicians, whereas ciclosporin, intravenous immunoglobulin and hydroxychloroquine were prescribed by Italian physicians. This study shows a significant difference in the choice of medications between pediatric rheumatologists practising in the two centres. Despite this, a high proportion of patients had inactive disease at 2 years and there was a low frequency of damage: modern treatments have improved outcomes.

Current use of cardiac magnetic resonance in tertiary referral centres for the diagnosis of cardiomyopathy: the ESC EORP Cardiomyopathy/Myocarditis Registry.

Aims Cardiac magnetic resonance (CMR) is recommended in the diagnosis of cardiomyopathies, but it is time-consuming, expensive, and limited in availability in some European regions. The aim of this study was to determine the use of CMR in cardiomyopathy patients enrolled into the European Society of Cardiology (ESC) cardiomyopathy registry [part of the EURObservational Research Programme (EORP)].Methods and results Three thousand, two hundred, and eight consecutive adult patients (34.6% female; median age: 53.0 ± 15 years) with cardiomyopathy were studied: 1260 with dilated (DCM), 1739 with hypertrophic (HCM), 66 with restrictive (RCM), and 143 with arrhythmogenic right ventricular cardiomyopathy (ARVC). CMR scans were performed at baseline in only 29.4% of patients. CMR utilization was variable according to cardiomyopathy subtypes: from 51.1% in ARVC to 36.4% in RCM, 33.8% in HCM, and 20.6% in DCM (P < 0.001). CMR use in tertiary referral centres located in different European countries varied from 1% to 63.2%. Patients undergoing CMR were younger, less symptomatic, less frequently had implantable cardioverter-defibrillator (ICD)/pacemaker implanted, had fewer cardiovascular risk factors and comorbidities (P < 0.001). In 28.6% of patients, CMR was used along with transthoracic echocardiography (TTE); 67.6% patients underwent TTE alone, and 0.9% only CMR.Conclusion Less than one-third of patients enrolled in the registry underwent CMR and the use varied greatly between cardiomyopathy subtypes, clinical profiles of patients, and European tertiary referral centres. This gap with current guidelines needs to be considered carefully by scientific societies to promote wider availability and use of CMR in patients with cardiomyopathies.

Has the COVID-19 outbreak changed the way we are treating prostate cancer? An EAU - YAU Prostate Cancer Working Group multi-institutional study.

IntroductionThe COVID-19 outbreak has become the dominant issue throughout the world whilst the governments, nations and health services are trying to deal with its impact. The aim of our study is to assess the impact of COVID-19 on patients treated with radical prostatectomy (RP) for prostate cancer (PCa) at European referral centers in terms of surgical volume (SV), waiting list meant as time from biopsy to surgery (WL) and risk of adverse pathologic findings at RP due to the selection of men with more adverse disease characteristics at final pathology.Material and methodsConsecutive patients with a diagnosis of histologically proven PCa treated with RP between March 2020 (WHO declaration of pandemic) and December 2020 were identified. Patients with metastatic disease not eligible to local treatment and recurrent prostate cancer after RP or RT were excluded. Patients treated at the same institutions between March 2019 and December 2019 were considered as the control group. Multivariable logistic regression analysis tested the impact of the COVID-19 outbreak on the risk of adverse pathologic findings at RP after adjusting for confounders. The percentage change of SV and WL was assessed comparing the months of pandemic with the equivalent timespan of the previous year.ResultsA total of 2,574 patients treated with RP (927 cases and 1647 controls) were identified in 8 European tertiary referral centers. At multivariable analysis patients who were treated during the pandemic had higher risk of extra prostatic disease (OR:1.35, p = 0.038) and lymph node invasion (LNI) (OR:1.72, p = 0.048). An average 23% reduction of the SV with the equivalent timespan of the previous year allowed an illusory reduction of the WL after the peak gained during the first wave of COVID-19.ConclusionsOur results showed that the COVID-19 outbreak resulted in a delay in the administration of curative-intent therapies in patients with localized PCa. This, in turn, resulted in a stage migration phenomenon with a potential impact on oncologic control.

Clinical Phenotype and Course of PDE6A-Associated Retinitis Pigmentosa Disease, Characterized in Preparation for a Gene Supplementation Trial

Treatment trials require sound knowledge on the natural course of disease. To assess clinical features, genetic findings, and genotype-phenotype correlations in patients with retinitis pigmentosa (RP) associated with biallelic sequence variations in the PDE6A gene in preparation for a gene supplementation trial. This prospective, longitudinal, observational cohort study was conducted from January 2001 to December 2019 in a single center (Centre for Ophthalmology of the University of Tübingen, Germany) with patients recruited multinationally from 12 collaborating European tertiary referral centers. Patients with retinitis pigmentosa, sequence variants in PDE6A, and the ability to provide informed consent were included. Comprehensive ophthalmological examinations; validation of compound heterozygosity and biallelism by familial segregation analysis, allelic cloning, or assessment of next-generation sequencing-read data, where possible. Genetic findings and clinical features describing the entire cohort and comparing patients harboring the 2 most common disease-causing variants in a homozygous state (c.304C>A;p.(R102S) and c.998 + 1G>A;p.?). Fifty-seven patients (32 female patients [56%]; mean [SD], 40 [14] years) from 44 families were included. All patients completed the study. Thirty patients were homozygous for disease-causing alleles. Twenty-seven patients were heterozygous for 2 different PDE6A variants each. The most frequently observed alleles were c.304C>A;p.(R102S), c.998 + 1G>A;p.?, and c.2053G>A;p.(V685M). The mean (SD) best-corrected visual acuity was 0.43 (0.48) logMAR (Snellen equivalent, 20/50). The median visual field area with object III4e was 660 square degrees (5th and 95th percentiles, 76 and 11 019 square degrees; 25th and 75th percentiles, 255 and 3923 square degrees). Dark-adapted and light-adapted full-field electroretinography showed no responses in 88 of 108 eyes (81.5%). Sixty-nine of 108 eyes (62.9%) showed additional findings on optical coherence tomography imaging (eg, cystoid macular edema or macular atrophy). The variant c.998 + 1G>A;p.? led to a more severe phenotype when compared with the variant c.304C>A;p.(R102S). Seventeen of the PDE6A variants found in these patients appeared to be novel. Regarding the clinical findings, disease was highly symmetrical between the right and left eyes and visual impairment was mild or moderate in 90% of patients, providing a window of opportunity for gene therapy.

Semi-closed-circuit vacuum-assisted mini percutaneous nephrolithotomy in the pediatric population: the initial experience of two tertiary referral centers

Percutaneous nephrolithotomy (PCNL) is the gold-standard for complex renal stones treatment in the pediatric population. While the miniaturization of PCNL reduces the risk of bleeding, it can hinder surgical and functional outcomes. The aim of the study was to assess the safety and feasibility of semi-closed-circuit vacuum-assisted Mini-PCNL (vmPCNL) in pediatric patients. From January 2017 to December 2018, we prospectively collected data on consecutive vmPCNLs from two European tertiary referral centers. The procedure was performed with the ClearPetra® (Well Lead Medical Co., Ltd., Guangzhou, China) access sheath equipped with a lateral arm connected to the aspiration system (pressure setting ~120-150 cmH<inf>2</inf>O) by a 200 Ml plastic stone collector. Pre-, intra- and postoperative data and costs were analyzed. The stone-free rate (SFR) was defined as absence of residual fragments >4 mm with either ultrasound or kidney, ureter, and bladder X-ray. Eighteen vmPCNLs were performed in 16 renal units of 13 children. The median age was 119 months (IQR: 97-160) and the weight was 29 Kg (IQR: 25-40). The median cumulative stone size was 32 mm (22-46) with 8 (44.4%) cases of staghorn stones. The OT was 128 min (IQR: 99-167). The basketing was unnecessary in 6/18 (33%) cases. Neither intra-operative complications nor blood transfusions occurred. Postoperative fever was observed in 5/18 (27.8%) cases; in one case a double J ureteral stent was placed for concomitant hydronephrosis. The SFR was 81.3% (13/16), rising to 93.8% (15/16) after ancillary procedures. The materials costs of a vmPCNL (734.8 €) were comparable to mini-PCNL using a reusable set (710.7 €). The vmPCNL seems to be sustainable, safe and feasible for kidney stones treatment in the pediatric population.

Indications for and complications of pelvic lymph node dissection in prostate cancer: accuracy of available nomograms for the prediction of lymph node invasion.

To externally validate the currently available nomograms for predicting lymph node invasion (LNI) in patients with prostate cancer (PCa) and to assess the potential risk of complications of extended pelvic lymph node dissection (ePLND) when using the recommended threshold. A total of 14921 patients, who underwent radical prostatectomy with ePLND at eight European tertiary referral centres, were retrospectively identified. After exclusion of patients with incomplete biopsy or pathological data, 12009 were included. Of these, 609 had undergone multiparametic magnetic resonance imaging-targeted biopsies. Among ePLND-related complications we included lymphocele, lymphoedema, haemorrhage, infection and sepsis. The performances of the Memorial Sloan Kettering Cancer Centre (MSKCC), Briganti 2012, Briganti 2017, Briganti 2019, Partin 2016 and Yale models were evaluated using receiver-operating characteristic curve analysis (area under the curve [AUC]), calibration plots, and decision-curve analysis. Overall, 1158 patients (9.6%) had LNI, with a mean of 17.7 and 3.2 resected and positive nodes, respectively. No significant differences in AUCs were observed between the MSKCC (0.79), Briganti 2012 (0.79), Partin 2016 (0.78), Yale (0.80), Briganti 2017 (0.81) and Briganti 2019 (0.76) models. A direct comparison of older models showed that better discrimination was achieved with the MSKCC and Briganti 2012 nomograms. A tendency for underestimation was seen for all the older models, whereas the Briganti 2017 and 2019 nomograms tended to overestimate LNI risk. Decision-curve analysis showed a net benefit for all models, with a lower net benefit for the Partin 2016 and Briganti 2019 models. ePLND-related complications were experienced by 1027 patients (8.9%), and 12.6% of patients with pN1 disease. The currently available nomograms have similar performances and limitations in the prediction of LNI. Miscalibration was present, however, for all nomograms showing a net benefit. In patients with only systematic biopsy, the MSKCC and Briganti 2012 nomograms were superior in the prediction of LNI.