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Context Neurourological patients often encounter bacteriuria without any symptoms or may experience symptoms suspicious of urinary tract infections (UTIs). However, there is a lack of guidelines that unequivocally state the definition of UTIs in this specific patient group. Objective To present all used definitions of UTIs in neurourological patients. Evidence acquisition This systematic review was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) statement. Studies were identified by electronic search of Medline, Embase, Cochrane controlled trials databases, and clinicaltrial.gov without a time limitation (last search September 2020) and by screening of reference lists and reviews. The occurrences of the various UTI definitions were counted and the frequencies calculated. Evidence synthesis After screening 7164 abstracts, we included 32 studies enrolling a total of 8488 patients with a neurourological disorder who took part in an interventional clinical study. UTI definitions were heterogeneous. The concordance to predefined definitions was low. Conclusions Interventional clinical studies rarely report specific definitions for UTIs, and both clinical and laboratory criteria used are heterogeneous. A generally accepted UTI definition for neurourological patients is urgently needed. Patient summary Patients suffering from neurological disorders often experience symptoms in their lower urinary tract that resemble urinary tract infections. Furthermore, they can have positive urine cultures without symptoms (the so-called asymptomatic bacteriuria). However, clinical studies rarely report specific definitions for urinary tract infections, and when it is done, they are heterogeneous. A generally accepted urinary tract infection definition for neurourological patients is urgently needed. Take Home Message Interventional clinical studies on neurourological patients rarely report specific definitions for urinary tract infections (UTIs), and both clinical and laboratory criteria used are heterogeneous. A generally accepted UTI definition for neurourological patients is urgently needed.

OBJECTIVE The purpose of this first french guideline is to provide a clinical framework for the diagnosis, treatment and follow-up of anterior urethral strictures. The statements are established by the subgroup working on uro-genital reconstruction surgery (GURU) from the CAMS-AFU (Andrology and Sexual Medicine Committee from the French Association of Urology). MATERIAL AND METHODS These guidelines are adapted from the Male Urethral Stricture : American Urological Association Guideline 2016, updated by an additional bibliography from January 2016 to December 2019. Twenty-seven main scenarios seen in clinical practice are identified: from diagnosis, to treatment and follow-up. In addition, this guidelines are powered by anatomical diagrams, treatment algorithms, summaries and follow-up tables. RESULTS Anterior urethral strictures are a common condition (0,1 a 1,4 %) in men. The diagnosis is based on a trifecta including an examination with patient reported questionnaires, urethroscopy and retrograde urethrography with voiding cystourethrography. Short meatal stenosis can be treated by dilation or meatotomy, otherwise a urethroplasty can be performed. First line treatment of penile strictures is urethroplasty. Short bulbar strictures (

Introduction Cryptococcus spp. is a fungus responsible for 600,000 deaths per year worldwide, mainly in immunosuppressed subjects. However, 20% of cases occur in immunocompetent subjects. Neuropathic disorders involving the auditory nerve have been reported, but vestibular disorders have never been described in detail. We report the case of an immunocompetent man, who presented audiovestibular disorders leading to a diagnosis of cryptococcal meningitis. Case report A 39-year-old man was referred for balance disorders and right sensorineural hearing loss. He presented right vestibulo-saccular impairment and bilateral absence of auditory brainstem responses. Brain MRI was suggestive of cryptococcal meningitis. A cystic lesion in the right flocculus compressed the vestibulocochlear nerve. During monthly follow-up, pure tone audiometry gradually improved and speech audiometry in silence returned to normal. Partial resynchronization of the auditory afferent pathways was observed only on the contralateral side to vestibulocochlear nerve compression, while complete recovery of saccular function was observed. Discussion Cryptococcal meningitis in immunocompetent subjects may be accompanied by lesions of the auditory and vestibular afferent pathways. Recovery of hearing and balance was observed in response to medical treatment and early vestibular rehabilitation.

To evaluate the outcomes of ureteral reimplantation (UR) after failure of endoscopic treatment for symptomatic vesicoureteral reflux (VUR) in renal transplant recipients. We conducted a monocentric retrospective study that included all renal transplant recipients with failure of Deflux™ as first-line treatment of VUR from January 2007 to December 2020. Failure of Deflux™ was defined by: VUR on retrograde cystography and at least one acute pyelonephritis of the renal graft. The preferred surgical treatment was native ureteropyelostomy (NPUS) in the recent years. If the native ureter could not be used, ureteroneocystostomy (UNC) was performed. The primary outcome was the clinical efficacy of UR defined as the absence of acute graft pyelonephritis during follow-up. Out of 1565 kidney transplantations, 119 (7.6%) had symptomatic VUR treated with bulking agent. 35 (29.4%) had Deflux™ failure and were addressed to UR: 21/35 (60%) NPUS and 14/35 (40%) UNC. The median estimated blood loss, operative time, and length of stay were 120 mL, 90 min, and 7 days, respectively. After a median follow-up of 7.1 (IQR 4.1–9.8) years, UR was clinically successful in a total of 32 patients (91.4%): 20 (95.2%) and 12 (85.7%) patients in the NPUS and UNC groups, respectively (p = 0.55). Three (8.5%) high-grade complications have been reported. No nephrectomy of native kidney was required in the NPUS group. After failure of Deflux™ for VUR of renal graft, surgical treatment with native ureteropyelostomy or ureteroneocystostomy is associated to a high success rate and few high-grade complications.

Objectives This study sought to investigate patient intermediate-term outcomes after transcatheter pulmonary valve replacement (TPVR) with Edwards SAPIEN valve. Background The Edwards SAPIEN valve, initially designed for percutaneous aortic valve replacement, has been approved for TPVR in patients with dysfunctional right ventricular outflow tracts (RVOT), but only short-term follow-up has been reported. Methods From 2011 to 2016, 62 patients undergoing successful TPVR using the SAPIEN XT valve were consecutively included into the study. Primary efficacy and safety endpoints were defined as freedom from valve-reintervention and freedom from infective endocarditis at last follow-up, respectively. Results The primary efficacy outcome was met for 87.1% patients after a mean follow-up of 4.6 ± 1.8 years, corresponding to a freedom of reintervention at 5 years of 89% (95% CI 74.8-95.6%). Reinterventions were exclusively due to recurrent obstruction, no significant valvular regurgitation was observed. One case of infective endocarditis was reported, corresponding to a rate of 0.35% per patient-year (95% CI 0.01-2.00%). At 5 years, freedom from infective endocarditis was 98.4% (95% CI 89.1-99.8%). Six patients died or were transplanted due to advanced cardiac failure, without relationship with TPVR. In univariate analysis, reintervention was associated with young age, a smaller tube-graft, a higher pulmonary valve gradient after the procedure and a ratio of largest implanted stent diameter to invasive balloon conduit diameter over 1.35. Conclusions This study documents the mid-term safety and efficacy of the Edwards SAPIEN XT valve in patients with dysfunctional RVOT, and identifies a patient profile associated with an uncertain benefit-risk balance.

Objectives: To evaluate the risk of residual tumor and tumor upstaging during a second resection after primary complete transurethral resection of bladder tumor (TURBT) using photodynamic diagnosis (PDD) for high-risk nonmuscle invasive bladder cancer (NMIBC). Patients and Methods: From January 2014 to March 2020, a single-institutional study was conducted including consecutive patients with high-risk NMIBC (T1 and/or cis and/or high grade) who underwent a restaging transurethral resection (reTUR) within 12 weeks after a primary complete resection. Each TURBT was performed using blue light after intravesical instillation of hexaminolevulinate. The primary endpoint was detection of residual tumor at reTUR, proved with positive pathology report. Results: A total of 109 consecutive patients with high-risk NMIBC underwent reTUR after a primary complete blue light resection. Pathologic evaluation of the surgical specimens of the primary TURBT revealed stage T1 and high-grade tumors in 69 (68.3%) and 108 (99%) patients, respectively, and concomitant carcinoma in situ was found in 45 patients (41.3%). The median time to reTUR was 8 (6-10) weeks. Residual tumor was detected histopathologically in 64 of 109 patients (58.7%) at the second TURBT with PDD. In five of these patients (4.5%), initial T1 tumors were upstaged to T2 tumors. Conclusions: We examined a contemporary series of patients undergoing reTUR with PDD as management of high-risk NMIBC proven at the first blue light resection. We reported a 54.2% risk of disease persistence and a 4.5% risk of understaging in T1 tumors. These findings support that reTUR is still necessary after initial complete TURBT with PDD. Further studies are needed to assess the long-term oncologic outcomes of reTUR with PDD.

BACKGROUND In severe obesity, left ventricular (LV) and right ventricular (RV) remodeling and contractile dysfunction have been documented, but less is known regarding left atrial (LA) dysfunction and its association with LV/RV remodeling, especially in children. PURPOSE To assess the effects of severe childhood obesity on cardiac function by using multichamber strain analysis with MRI. STUDY TYPE Prospective. SUBJECTS Forty-five children aged 7-18 years (including 20 with severe obesity, defined as a body mass index values above the 99th percentile). FIELD STRENGTH 5 T. SEQUENCE Steady-state-free-precession (SSFP) images in short-axis views and longitudinal two- and four-chamber views. ASSESSMENT Cardiac strain measurements were derived from standard SSFP cine images by using a dedicated MR imaging feature tracking software. Inter- and intra-rater reliability were evaluated. STATISTICAL TESTS Independent sample t test, Spearman's correlation coefficient, principal component analysis, Bland-Altman analysis, and intra-class correlation coefficients (ICC). A P value

Three-dimensional (3-D) printed models are increasingly used to enhance understanding of complex anatomy in congenital heart disease. To assess feasibility and accuracy of 3-D printed models obtained from cardiac CT scans in young children with complex congenital heart diseases. We included children with conotruncal heart anomalies who were younger than 2 years and had a cardiac CT scan in the course of their follow-up. We used cardiac CT scan datasets to generate 3-D models. To assess the models’ accuracy, we compared four diameters for each child between the CT images and the printed models, including the largest diameters (Dmax) of ventricular septal defects and aortic annulus and their minimal diameters (Dmin). We obtained images from 14 children with a mean age of 5.5 months (range 1–24 months) and a mean weight of 6.7 kg (range 3.4–14.5 kg). We generated 3-D models for all children. Mean measurement difference between CT images and 3-D models was 0.13 mm for Dmin and 0.12 mm for Dmax for ventricular septal defect diameters, and it was 0.16 mm for Dmin and −0.13 mm for Dmax for aortic annulus diameter, indicating a non-clinically significant difference. Three-dimensional printed models could be feasibly generated from cardiac CT scans in a small pediatric population with complex congenital heart diseases. This technique is highly accurate and reliably reflects the same structural dimensions when compared to CT source images.

Background: The coronavirus disease 2019 (COVID-19) pandemic has led to a public health crisis. Only limited data are available on the characteristics and outcomes of patients hospitalized for COVID-19 in France. Aims: To investigate the characteristics, cardiovascular complications and outcomes of patients hospitalized for COVID-19 in France. Methods: The Critical COVID-19 France (CCF) study is a French nationwide study including all consecutive adults with a diagnosis of severe acute respiratory syndrome coronavirus 2 (SARS-Cov-2) infection hospitalized in 24 centres between 26 February and 20 April 2020. Patients admitted directly to intensive care were excluded. Clinical, biological and imaging parameters were systematically collected at hospital admission. The primary outcome was in-hospital death. Results: Of 2878 patients included (mean ± SD age 66.6 ± 17.0 years, 57.8% men), 360 (12.5%) died in the hospital setting, of which 7 (20.7%) were transferred to intensive care before death. The majority of patients had at least one (72.6%) or two (41.6%) cardiovascular risk factors, mostly hypertension (50.8%), obesity (30.3%), dyslipidaemia (28.0%) and diabetes (23.7%). In multivariable analysis, older age (hazard ratio [HR] 1.05, 95% confidence interval [CI] 1.03−1.06; P < 0.001), male sex (HR 1.69, 95% CI 1.11−2.57; P = 0.01), diabetes (HR 1.72, 95% CI 1.12−2.63; P = 0.01), chronic kidney failure (HR 1.57, 95% CI 1.02−2.41; P = 0.04), elevated troponin (HR 1.66, 95% CI 1.11−2.49; P = 0.01), elevated B-type natriuretic peptide or N-terminal pro-B-type natriuretic peptide (HR 1.69, 95% CI 1.0004−2.86; P = 0.049) and quick Sequential Organ Failure Assessment score ≥ 2 (HR 1.71, 95% CI 1.12−2.60; P = 0.01) were independently associated with in-hospital death. Conclusions: In this large nationwide cohort of patients hospitalized for COVID-19 in France, cardiovascular comorbidities and risk factors were associated with a substantial morbi-mortality burden.

Background and objectivesChronic pulmonic regurgitation (PR) following repair of congenital heart disease (CHD) impairs right ventricular function that impacts peak exercise cardiac index (pCI). We aimed to estimate in a non-invasive way pCI and peak oxygen consumption (pVO2) and to evaluate predictors of low pCI in patients with significant residual pulmonic regurgitation after CHD repair.MethodWe included 82 patients (median age 19 years (range 10–54 years)) with residual pulmonic regurgitation fraction >40%. All underwent cardiac MRI and cardiopulmonary testing with measurement of pCI by thoracic impedancemetry. Low pCI was defined 2.ResultsLow pCI was found in 18/82 patients. Peak indexed stroke volume (pSVi) tended to compensate chronotropic insufficiency only in patients with normal pCI (r=−0.31, p=0.01). Below 20 years of age, only 5/45 patients had low pCI but near-normal (≥6.5 L/min/m2). pVO2 (mL/kg/min) was correlated with pCI (r=0.58, p=0.0002) only in patients aged >20 years. Left ventricular stroke volume in MRI correlated with pSVi only in the group of patients with low pCI (r=0.54, p=0.02). No MRI measurements predicted low pCI. In multivariable analysis, only age predicted a low pCI (OR=1.082, 95% CI 1.035 to 1.131, p=0.001) with continuous increase of risk with age.ConclusionsIn patients with severe PR, pVO2 is a partial reflection of pCI. Risk of low pCI increases with age. No resting MRI measurement predicts low haemodynamic response to exercise. Probably more suitable to detect ventricular dysfunction, pCI measurement could be an additional parameter to take into account when considering pulmonic valve replacement.

Background While outcomes of intra-atrial reentrant/focal atrial tachycardia (IART/FAT) catheter ablation have considerably improved in adult congenital heart disease (ACHD), recurrences remain common with different circuits frequently encountered. Objective We aimed to assess the value of programmed atrial stimulation after successful clinical IART/FAT catheter ablation in patients with ACHD. Methods This is a retrospective study including all patients with ACHD undergoing IART/FAT catheter ablation in a tertiary center. After successful catheter ablation of clinical arrhythmia, survival free from arrhythmia recurrence was analyzed according to whether all inducible IARTs/FATs were targeted. Results From 2004 to 2020, 238 IART/FAT catheter ablation procedures were performed (mean age 44.1 ± 15.0 years; 61.3% men). Acute procedural success of clinical arrhythmia was achieved in 208 procedures (87.4%). Among 122 procedures with programmed atrial stimulation (58.7%), at least 1 other IART/FAT was induced in 61 patients (50%). All inducible IARTs/FATs were ablated in 54 patients (88.5%), whereas 7 patients (11.5%) presented with at least 1 nontargeted inducible IART/FAT. Patients with nontargeted inducible IART/FAT had a higher risk of atrial arrhythmia episodes than did inducible patients treated with ablation of all IARTs/FATs (hazard ratio 5.7; 95% confidence interval 1.7–18.4; P = .004), with 12-month atrial arrhythmias recurrence rates of 22.9% and 77.7%, respectively. Inducible patients with successful ablation of all IARTs/FATs had a risk of recurrence similar to that of noninducible patients (hazard ratio 0.6; 95% confidence interval 0.3–1.3; P = .215). Conclusion Beyond clinical IART/FAT catheter ablation in patients with ACHD, our findings suggest the interest of systematically targeting all remaining inducible arrhythmias, irrespective of whether previously documented.

Despite impressive improvement in long-term survival, adults with congenital heart disease (CHD) remain exposed to a significant cardiovascular morbidity over lifetime. Thromboembolic events (TE) are a major issue. Specific anatomic groups have been shown a particular high risk of TE, including cyanotic heart disease and Fontan circulation. Many intercurrent clinical factors add a substantial risk such as intracardiac medical devices, atrial arrhythmia, endocarditis, or pregnancy. Nevertheless, what is unknown exceeds what is known, especially regarding the management of this heterogenous patient population. Anticoagulation decision should always be individualized weighing balanced with the alternative risk of hemorrhagic complications. In this review, we aim to synthetize existing literature on TE in adults with CHD, discuss management issues, highlight gaps in knowledge, and intend to suggest high priority research.

Summary Background Closure of patent foramen ovale is well-managed in adults, but is performed less frequently in children. Aim To analyse all patent foramen ovale closures performed in the past 20 years in French paediatric centres. Methods Retrospective study of patent foramen ovale closures in children without cardiopathy in nine centres between 2000 and 2019. Results Forty-one procedures were carried out in children (median age: 14.9 years). Thirty-one patent foramen ovales were closed after a transient ischaemic attack or stroke, six for a left-to-right shunt and four for other reasons. Transthoracic echocardiography was used for 72.2% of the diagnoses and transoesophageal echocardiography for 27.8%. A substantial degree of shunting was found in 42.9% of patients and an atrial septal aneurysm in 56.2%. General anaesthesia with transoesophageal echocardiography guidance was performed in 68.3% of the procedures; local anaesthesia and transthoracic echocardiography or intracardiac echocardiography was performed in 31.7%. The success rate was 100%. The median fluoroscopy time was 4.14 minutes: 3.55 minutes with transoesophageal echocardiography; and 4.38 minutes with transthoracic echocardiography (P = 0.67). There was only one periprocedural complication (2.4%). Postoperatively, 80,5% of patients were treated with aspirin and 12,2% with an anticoagulant. The rate of complete occlusion was 56.8% immediately after the procedure, 68.6% at 1 year and 92.3% at the last follow-up. There were no delayed complications or cases of recurrent stroke during follow-up (median follow-up: 568 days). Conclusion Closure of patent foramen ovale in children appears to be safe and effective, as we noted a low rate of immediate complications, no delayed complications and no stroke recurrence in this indication.

OBJECTIVE To evaluate the renal function outcomes after selective trans-arterial embolization (SAE) of iatrogenic vascular lesions (IVL), including pseudoaneurysm and arteriovenous fistula, following partial nephrectomy (PN). MATERIALS AND METHODS A multi-institutional study was conducted including consecutive patients who underwent PN between January 2009 and March 2019. Two surgical approaches were used: open and robot-assisted PN. Patients with SAE were identified and matched (1:2) with patients without IVL. The matching criteria were age, gender, Charlson score, creatinine clearance, RENAL score, and tumor size. The primary outcome was the evolution of global renal function at 6-months postoperatively. RESULTS A total of 493 consecutive PN (360 open PN and 133 robot-assisted PN) were included. IVL occurred in 17 cases (3.4%) without statistical difference according to the surgical approach (P = .78). Patients from embolization group were matched to 34 cases without postoperative IVL. Groups were comparable concerning clinical, tumor and surgical characteristics. The clinical success of SAE, defined as the absence of recourse to a second embolization or a total nephrectomy, was obtained in 16 (94.1%) cases. No minor or major complications were reported after SAE. The preoperative estimated glomerular filtration rate (eGFR) was similar between control group (93 [85-102] ml/min) and embolization group (95 [83-102] ml/min) (P = .99). Median (IQR) eGFR between control group (87 [72-95] ml/min) and embolization group (83 [76-93] ml/min) at a follow-up of 6 months showed no significant difference (P = .73). CONCLUSION IVL are rare complications of PN. SAE is an effective and minimally invasive management tool, with no deleterious effect on global renal function.

International audience; OBJECTIVES: The aim of this study was to assess the diagnostic performances of (18)F-fluorodeoxyglucose ((18)F-FDG) positron emission tomography (PET)/computed tomography (CT) in congenital heart disease (CHD) patients with pulmonary prosthetic valve or conduit endocarditis (PPVE) suspicion. BACKGROUND: PPVE is a major issue in the growing CHD population. Diagnosis is challenging, and usual imaging tools are not always efficient or validated in this specific population. Particularly, the diagnostic yield of (18)F-FDG PET/CT remains poorly studied in PPVE. METHODS: A retrospective multicenter study was conducted in 8 French tertiary centers. Children and adult CHD patients who underwent (18)F-FDG PET/CT in the setting of PPVE suspicion between January 2010 and May 2020 were included. The cases were initially classified as definite, possible, or rejected PPVE regarding the modified Duke criteria and finally by the Endocarditis Team consensus. The result of (18)F-FDG PET/CT had been compared with final diagnosis consensus used as gold-standard in our study. RESULTS: A total of 66 cases of PPVE suspicion involving 59 patients (median age 23 years, 73% men) were included. Sensitivity, specificity, positive predictive value, and negative predictive value of (18)F-FDG PET/CT in PPVE suspicion were respectively: 79.1% (95% CI: 68.4%-91.4%), 72.7% (95% CI: 60.4%-85.0%), 91.9% (95% CI: 79.6%-100.0%), and 47.1% (95% CI: 34.8%-59.4%). (18)F-FDG PET/CT findings would help to correctly reclassify 57% (4 of 7) of possible PPVE to definite PPVE. CONCLUSIONS: Using (18)F-FDG PET/CT improves the diagnostic accuracy of the Duke criteria in CHD patients with suspected PPVE. Its high positive predictive value could be helpful in routine to shorten diagnosis and treatment delays and improve clinical outcomes.

Purpose/objective: The association of 3D Conformal External Beam Radiotherapy (3D-CEBRT) with adjuvant Androgen Deprivation Therapy (ADT) proved to treat patients with intermediate- and high-risk localized prostate cancer (IR and HR). However, older patients were underrepresented in literature. We aimed to report the oncological results and morbidity 3D-CEBRT +ADT in &ge, 80 years patients. Material and Methods: From June 1998 to July 2017, 101 patients &ge, 80 years were included in a tertiary center. The median age was 82 years. ADT was initiated 3 months prior 3D-CEBRT in all patients, with a total duration of 6 months for IR prostate cancer (group A, n = 41) and 15 months for HR prostate cancer (group B, n = 60). Endpoints included overall survival (OS), metastasis-free survival (DMFS), biochemical recurrence-free survival (BRFS) and toxicity. Results: Five years-OS was 95% and 86.7% in groups A and B, respectively. Cardiovascular events occurred in 22.8% of &ge, 80 years patients with no impact on OS. In the multivariate analysis, age &lt, 82 years, Karnofsky index and normalization of testosterone levels were significantly associated with better OS. Conclusion: Age &ge, 80 years should not be a limitation for the treatment of IR and HR prostate cancer patients with 3D-CEBRT and ADT, but cardiovascular monitoring and prevention are mandatory.

Aims While some concerns about vaccination-related pericarditis and/or myocarditis have been raised, no published data are available on pericarditis and/or myocarditis with mRNA COVID-19 vaccines in the age group of adolescents, particularly 12–15 years. The objective of this study was to determine whether the risk of reporting pericarditis and/or myocarditis with mRNA COVID-19 vaccines varied according to dose of vaccination, age, sex, and type of pericarditis and/or myocarditis in adolescents between 12 and 17 years. Methods and results We performed an observational study reviewing all reports of adolescents vaccinated with mRNA COVID-19 vaccines and recorded in VigiBase®, the World Health Organization global database of individual case safety reports. We included all reports registered between 1 January 2021 and 14 September 2021. Reporting odds ratios (RORs) with their 95% confidence interval (CI) were calculated to estimate the risk of reporting pericarditis and/or myocarditis. Among 4942 reports with mRNA COVID-19 vaccines in adolescents, we identified 242 pericarditis and/or myocarditis. Compared with the first dose of mRNA COVID-19 vaccines, the second dose was associated with an increased risk of reporting pericarditis and/or myocarditis (ROR 4.95; 95% CI 3.14, 7.89). The risk of reporting pericarditis and/or myocarditis was 10 times higher in boys than in girls and no difference between the two types of vaccines could be demonstrated. Conclusion This investigation including only adolescent data suggests for the first time that the second dose of mRNA COVID-19 vaccines increases the risk of reporting myocarditis/pericarditis compared with the first dose particularly in boys without significant difference between tozinameran and elasomeran.

In this issue of JEM, a paper by Kim et al. (2021. J. Exp. Med.https://doi.org/10.1084/jem.20211872), asking a simple question through a remarkable alliance of human and mouse genetics, demonstrates that a prevalent hematological condition can lead to osteoporosis. This work is important by virtue of the quality of its results and its implication for the relationship between bone and its marrow.

Background Three-dimensional (3D) printing technology enables the translation of 2-dimensional (2D) medical imaging into a physical replica of a patient’s individual anatomy and may enhance the understanding of congenital heart defects (CHD). We aimed to evaluate the usefulness of a spectrum of 3D-printed models in teaching CHD to medical students. Results We performed a prospective, randomized educational procedure to teach fifth year medical students four CHDs (atrial septal defect (ASD, n = 74), ventricular septal defect (VSD, n = 50), coarctation of aorta (CoA, n = 118) and tetralogy of Fallot (ToF, n = 105)). Students were randomized into printing groups or control groups. All students received the same 20 min lecture with projected digital 2D images. The printing groups also manipulated 3D printed models during the lecture. Both groups answered an objective survey (Multiple-choice questionnaire) twice, pre- and post-test, and completed a post-lecture subjective survey. Three hundred forty-seven students were included and both teaching groups for each CHD were comparable in age, sex and pre-test score. Overall, objective knowledge improved after the lecture and was higher in the printing group compared to the control group (16.3 ± 2.6 vs 14.8 ± 2.8 out of 20, p p = 0.0001 ASD group; p = 0.002 VSD group; p = 0.0005 CoA group; p = 0.003 ToF group). Students’ opinion of their understanding of CHDs was higher in the printing group compared to the control group (respectively 4.2 ± 0.5 vs 3.8 ± 0.4 out of 5, p Conclusion The use of 3D printed models in CHD lectures improve both objective knowledge and learner satisfaction for medical students. The practice should be mainstreamed.

OBJECTIVE: To define the phenotypic spectrum of phosphatidylinositol glycan class A protein (PIGA)-related congenital disorder of glycosylation (PIGA-CDG) and evaluate genotype-phenotype correlations.METHODS: Our cohort encompasses 40 affected males with a pathogenic PIGA variant. We performed a detailed phenotypic assessment, and in addition, we reviewed the available clinical data of 36 previously published cases and assessed the variant pathogenicity using bioinformatical approaches.RESULTS: Most individuals had hypotonia, moderate to profound global developmental delay, and intractable seizures. We found that PIGA-CDG spans from a pure neurological phenotype at the mild end to a Fryns syndrome-like phenotype. We found a high frequency of cardiac anomalies including structural anomalies and cardiomyopathy, and a high frequency of spontaneous death, especially in childhood. Comparative bioinformatical analysis of common variants, found in the healthy population, and pathogenic variants, identified in affected individuals, revealed a profound physiochemical dissimilarity of the substituted amino acids in variant constrained regions of the protein.SIGNIFICANCE: Our comprehensive analysis of the largest cohort of published and novel PIGA patients broadens the spectrum of PIGA-CDG. Our genotype-phenotype correlation facilitates the estimation on pathogenicity of variants with unknown clinical significance and prognosis for individuals with pathogenic variants in PIGA.

In our center, until 2018, MRI-targeted biopsy was underused. Since January 2018, we systematically performed MRI-targeted biopsy for suspicious PI-RADS ≥ 3 lesions in accordance to the recent guidelines. We hypothesized that the implementation of systematic prebiopsy MRI would increase the detection rate (DR) of prostate cancer (PCa) without increasing DR of clinically insignificant PCa (insignPCa). A retrospective study including consecutive men who underwent prostate biopsy for suspicion of PCa in our center between January 2017 and December 2018 was conducted. Combined biopsies were performed for suspicious MRI and systematic biopsies for nonsuspicious MRI. The primary outcome was to compare the DR of PCa per year. Secondary outcomes included DRs of clinically significant PCa (csPCa) and insignPCa between both years and outcomes of targeted vs systematic biopsies. A total of 306 men (152 in 2017 and 154 in 2018) were included. Respectively, median (IQR) age was 69 (63–75) vs 70 (65–76) years (p = 0.29) and median (IQR) PSA density was 0.17 (0.13–0.28) vs 0.17 (0.11–0.26) (p = 0.24). There was a significant increase in prebiopsy MRI performed (120 [78.9%] vs 143 [92.8%]; p

Arterial calcification is an important hallmark of cardiovascular disease and shares many similarities with skeletal mineralisation. The bone-specific protein osteocalcin (OCN) is an established marker of vascular smooth muscle cell (VSMC) osteochondrogenic trans-differentiation and a known regulator of glucose metabolism. However, the role of OCN in controlling arterial calcification is unclear. We hypothesised that OCN regulates calcification in VSMCs and sought to identify the underpinning signalling pathways. Immunohistochemistry revealed OCN co-localisation with VSMC calcification in human calcified carotid artery plaques. Additionally, 3 mM phosphate treatment stimulated OCN mRNA expression in cultured VSMCs (1.72 fold; p

To evaluate the intermediate-term efficacy and tolerance of statins in children and adolescents with familial hypercholesterolemia.A total of 131 children or adolescents treated with statins for familial hypercholesterolemia were prospectively included. The efficacy of treatment was established by the percentage of children who achieved low density lipoprotein-cholesterol (LDL-C) levels160 mg/dL during treatment. Treatment tolerance was evaluated by the occurrence of clinical or laboratory side effects, regularity of increases in height and weight, and pubertal development.The median duration of treatment with statins was 4 years. A median decrease of 32% in LDL-C levels was observed (P .0001). The therapeutic target (LDL-C160 mg/dL) was achieved in 67% of cases. Increases in height and weight and sexual maturation were not affected by the treatment. Minor side effects were reported for 24 (18.4%) patients including 3 cases of a clinically asymptomatic increase in creatine phosphokinase (CPK) levels, 2 cases of an increase in CPK levels with muscular symptoms, 14 cases of myalgia without an increase in CPK levels, 3 cases of abdominal pain, 1 case of dysuria, and 1 case of diffuse pain. None of these side effects led to the discontinuation of statin therapy, although a change of statin was required in 7 cases. This new statin was tolerated in all cases. No patients had abnormal liver function during treatment.The results of this large cohort confirm the intermediate-term safety and efficacy of statin therapy in children with familial hypercholesterolemia.

There have recent reports in the literature of increased rates of bladder recurrence (BR) after radical nephroureterectomy (RNU) when diagnostic flexible ureteroscopy (DFU) was performed before RNU. The technical heterogeneity of DFU was a major bias in these studies. Our purpose was to evaluate the impact of a standardized DFU technique before RNU on the risk of BR. A retrospective monocenter study including patients who underwent RNU for upper tract urothelial carcinoma (UTUC) between 2005 and 2017. 171 patients were identified. 78 patients were excluded owing to a history of bladder cancer before RNU or neo-adjuvant/adjuvant chemotherapy. 93 included patients were stratified according to pre-RNU ureteroscopy (DFU + 70 patients) or no pre-RNU ureteroscopy (DFU—23 patients). The standardized DFU technique consisted of systematic ureteral sheath (ch9–10), flexible ureteroscopy, biopsy, and drainage with a mono-J/bladder catheter to avoid contact of contaminated urine of the upper tract with the bladder. Epidemiological, initial staging, and postoperative tumoral characteristics were similar in both groups. Mean follow-up was 35 months [2–166], 47(50%) BR occurred with 41(87%) in the DFU + group, and pre-RNU–DFU was an independent predictive factor of BR (OR = 4[1.4–11.9], P = 0.01) (Cox regression model). The characteristics of BR were similar in both groups, although BR occurred earlier in DFU + (427 days vs. 226 days (P = 0.07)). Bladder recurrence after diagnostic ureteroscopy + nephroureterectomy was high despite technical precautions to avoid contact of bladder mucosa with contaminated urine from the upper urinary tract. Post-DFU endovesical instillation should be investigated.

Background Multiple sclerosis (MS) and its animal model, experimental autoimmune encephalomyelitis (EAE), are inflammatory demyelinating and neurodegenerative diseases of the CNS. Although recent studies suggest the neuroprotective effects of oligodendrocytes in neurodegenerative diseases, it remains unknown whether oligodendrocyte death induced by inflammatory attacks contributes to neurodegeneration in MS and EAE. Upon endoplasmic reticulum (ER) stress, activation of pancreatic ER kinase (PERK) promotes cell survival through induction of activating transcription factor 4 (ATF4) by phosphorylating eukaryotic translation initiation factor 2α (eIF2α). We have generated a mouse model that allows for temporally controlled activation of PERK specifically in oligodendrocytes. Our previous study has demonstrated that PERK activation specifically in oligodendrocytes attenuates EAE disease severity and ameliorates EAE-induced oligodendrocyte apoptosis, demyelination, and axon degeneration, without altering inflammation. Methods We determined whether oligodendrocyte-specific PERK activation reduced neuron loss in the CNS of EAE mice using the mouse model that allows for temporally controlled activation of PERK specifically in oligodendrocytes. We further generated a mouse model that allows for inactivation of ATF4 specifically in oligodendrocytes, and determined the effects of ATF4 inactivation in oligodendrocytes on mice undergoing EAE. Results We showed that protection of oligodendrocytes resulting from PERK activation led to attenuation of neuron loss in the CNS gray matter of EAE mice. Surprisingly, we found that ATF4 inactivation specifically in oligodendrocytes did not alter EAE disease severity and had no effect on oligodendrocyte loss, demyelination, axon degeneration, neuron loss, and inflammation in EAE mice. Conclusions These findings suggest the neuroprotective effects of PERK activation in oligodendrocytes in EAE, and rule out the involvement of ATF4 in oligodendrocytes in the development of EAE. These results imply that the protective effects of PERK activation in oligodendrocytes in MS and EAE are not mediated by ATF4.

Aims The European Society of Cardiology (ESC) EURObservational Research Programme (EORP)-Atrial Fibrillation (AF) III Registry aims to identify contemporary patterns in AF management in clinical practice, assess their compliance with the 2016 ESC AF Guidelines, identify major gaps in guideline implementation, characterize the clinical practice settings associated with good vs. poor guideline implementation and assess and compare the 1-year outcome of guideline-adherent vs. guideline non-adherent management strategies. Methods and results Consecutive adult AF patients (n = 8306) were enrolled between 1 July 2018 and 15 July 2019, and individual patient data were prospectively collected across 192 centres and 31 participating countries during the 3-month enrolment period per centre. The Registry collected baseline and 1-year follow-up data in the eight main domains: patient demographic/enrolment setting, AF diagnosis/characterization, diagnostic assessment, stroke prevention treatments, arrhythmia-directed therapies, integrated AF management, major outcomes (death, non-fatal stroke or systemic embolic event, and non-fatal bleeding event), and the quality of life questionnaire. Conclusion The EORP-AF III Registry is an international, prospective registry of care and outcomes of patients treated for AF, which will provide insights into the contemporary patterns in AF management, ESC AF Guidelines implementation in routine practice and barriers to optimal management of this highly prevalent arrhythmia.

Objectives: To compare the detection rate of BCG refractory tumors between white light cystoscopy (WL-C) and Photodynamic Diagnosis cystoscopy (PDD-C). Methods: We performed a monocentric retrospec...

Summary Background Although cardiovascular comorbidities seem to be strongly associated with worse outcomes in patients with coronavirus disease 2019 (COVID-19), data regarding patients with preexisting heart failure are limited. Aims To investigate the incidence, characteristics and clinical outcomes of patients with COVID-19 with a history of heart failure with preserved or reduced ejection fraction. Methods We performed an observational multicentre study including all patients hospitalized for COVID-19 across 24 centres in France from 26 February to 20 April 2020. The primary endpoint was a composite of in-hospital death or need for orotracheal intubation. Results Overall, 2809 patients (mean age 66.4 ± 16.9 years) were included. Three hundred and seventeen patients (11.2%) had a history of heart failure; among them, 49.2% had heart failure with reduced ejection fraction and 50.8% had heart failure with preserved ejection fraction. COVID-19 severity at admission, defined by a quick sequential organ failure assessment score > 1, was similar in patients with versus without a history of heart failure. Before and after adjustment for age, male sex, cardiovascular comorbidities and quick sequential organ failure assessment score, history of heart failure was associated with the primary endpoint (hazard ratio [HR]: 1.41, 95% confidence interval [CI]: 1.06–1.90; P = 0.02). This result seemed to be mainly driven by a history of heart failure with preserved ejection fraction (HR: 1.61, 95% CI: 1.13–2.27; P = 0.01) rather than heart failure with reduced ejection fraction (HR: 1.19, 95% CI: 0.79–1.81; P = 0.41). Conclusions History of heart failure in patients with COVID-19 was associated with a higher risk of in-hospital death or orotracheal intubation. These findings suggest that patients with a history of heart failure, particularly heart failure with preserved ejection fraction, should be considered at high risk of clinical deterioration.

Background. – Although women account for up to half of patients hospitalized for coronavirus disease 2019 (COVID-19), no specific data have been reported in this population. Aims. − To assess the burden and impact of cardiovascular comorbidities in women with COVID-19. Methods. − All consecutive patients hospitalized for COVID-19 across 24 hospitals from 26 February to 20 April 2020 were included. The primary composite outcome was transfer to an intensive care unit or in-hospital death. Results. − Among 2878 patients, 1212 (42.1%) were women. Women were older (68.3 ± 18.0 vs 65.4 ± 16.0 years; P < 0.001), but had less prevalent cardiovascular comorbidities than men. Among women, 276 (22.8%) experienced the primary outcome, including 161 (13.3%) transfers to an intensive care unit and 115 (9.5%) deaths without transfer to intensive care unit. The rate of in-hospital death or transfer to an intensive care unit was lower in women versus men (crude hazard ratio [HR] 0.62, 95% confidence interval [CI] 0.53–0.72). Age (adjusted HR 1.05 per 5-year increase, 95% CI 1.01–1.10), body mass index (adjusted HR 1.06 per 2-unit increase, 95% CI 1.02–1.10), chronic kidney disease (adjusted HR 1.57, 95% CI 1.11–2.22) and heart failure (adjusted HR 1.52, 95% CI 1.04–2.22) were independently associated with the primary outcome in women. Elevated B-type natriuretic peptide/N-terminal prohormone of B-type natriuretic peptide (adjusted HR 2.41, 95% CI 1.70–3.44) and troponin (adjusted HR 2.00, 95% CI 1.39–2.88) concentrations at admission were also associated with the primary outcome, even in women free of previous coronary artery disease or heart failure. Conclusions. – Although female sex was associated with a lower risk of transfer to an intensive care unit or in-hospital death, COVID-19 remained associated with considerable morbimortality in women, especially in those with cardiovascular diseases.

Background With the emergence of coronary computed tomography (CT) angiography, anomalous aortic origin of a coronary artery (ANOCOR) is more frequently diagnosed. Fractional flow reserve derived from CT (FFRCT) is a noninvasive functional test providing anatomical and functional evaluation of the overall coronary tree. These unique features of anatomical and functional evaluation derived from CT could help for the management of patients with ANOCOR. We aimed to retrospectively evaluate the physiological and clinical impact of FFRCT analysis in the ANOCOR registry population. Methods and Results The ANOCOR registry included patients with ANOCOR detected during invasive coronary angiography or coronary CT angiography between January 2010 and January 2013, with a planned 5‐year follow‐up. We retrospectively performed FFRCT analysis in patients with coronary CT angiography of adequate quality. Follow‐up was performed with a clinical composite end point (cardiac death, myocardial infarction, and unplanned revascularization). We obtained successful FFRCT analyses and 5‐year clinical follow‐up in 54 patients (average age, 60±13 years). Thirty‐eight (70%) patients had conservative treatment, and 16 (30%) patients had coronary revascularization after coronary CT angiography. The presence of an ANOCOR course was associated with a moderate reduction of FFRCT value from 1.0 at the ostium to 0.90±0.10 downstream the ectopic course and 0.82±0.11 distally. No significant difference in FFRCT values was identified between at‐risk and not at‐risk ANOCOR. After a 5‐year follow‐up, only one unplanned percutaneous revascularization was reported. Conclusions The presence of ANOCOR was associated with a moderate hemodynamic decrease of FFRCT values and associated with a low risk of cardiovascular events after a 5‐year follow‐up in this middle‐aged population.

De novo missense variants in KCNH1 encoding Kv10.1 are responsible for two clinically recognisable phenotypes: Temple-Baraitser syndrome (TBS) and Zimmermann-Laband syndrome (ZLS). The clinical overlap between these two syndromes suggests that they belong to a spectrum of KCNH1-related encephalopathies. Affected patients have severe intellectual disability (ID) with or without epilepsy, hypertrichosis and distinctive features such as gingival hyperplasia and nail hypoplasia/aplasia (present in 20/23 reported cases).We report a series of seven patients with ID and de novo pathogenic KCNH1 variants identified by whole-exome sequencing or an epilepsy gene panel in whom the diagnosis of TBS/ZLS had not been first considered. Four of these variants, p.(Thr294Met), p.(Ala492Asp), p.(Thr493Asn) and p.(Gly496Arg), were located in the transmembrane domains S3 and S6 of Kv10.1 and one, p.(Arg693Gln), in its C-terminal cyclic nucleotide-binding homology domain (CNBHD). Clinical reappraisal by the referring clinical geneticists confirmed the absence of the distinctive gingival and nail features of TBS/ZLS.Our study expands the phenotypical spectrum of KCNH1-related encephalopathies to individuals with an attenuated extraneurological phenotype preventing a clinical diagnosis of TBS or ZLS. This subtype may be related to recurrent substitutions of the Gly496, suggesting a genotype–phenotype correlation and, possibly, to variants in the CNBHD domain.

Background:BRCC3/MTCP1 deletions are associated with a rare familial moyamoya angiopathy with extracranial manifestations.Case: We report the case of an adolescent male presenting with progressive and symptomatic moyamoya angiopathy and severe dilated cardiomyopathy caused by a hemizygous deletion of BRCC3/MTCP1. He was treated for renovascular hypertension by left kidney homograft and right nephrectomy in infancy and had other syndromic features, including cryptorchidism, growth hormone deficiency, and facial dysmorphism. Due to worsening of the neurological and cardiac condition, he was treated by a direct superficial temporal artery to middle cerebral artery bypass to enable successful cardiac transplant without cerebral damage.Conclusions:BRCC3-related moyamoya is a devastating disease with severe heart and brain complications. This case shows that aggressive management with cerebral revascularization to allow cardiac transplant is feasible and efficient despite end-stage heart failure.

This new and easily reproducible pulmonary valve-sparing technique for the correction of Tetralogy of Fallot is based on a conservative management of the native pulmonary valve to preserve its growth potential. From July 2015 to December 2019, 67 children presenting with a Tetralogy of Fallot were operated consecutively in a single centre using this technique in all cases. A T-shaped infundibulotomy is used to release the anterior pulmonary annulus from any muscular attachment. After myocardial resection and ventricular septal defect closure, an extensive commissurotomy is achieved. Finally, the right ventricular outflow tract remodelling is completed by a shield-shaped bovine patch with an oversized square superior edge, attached directly on the pulmonary valve annulus, with an effect of systolic traction. Sixty patients (89.5%) had a Tetralogy of Fallot repair with preservation of the pulmonary valve. To date, with a median follow-up of 38.2 [14–64] months, no patient has needed a surgical or interventional procedure for pulmonary valve stenosis or regurgitation, with low residual gradients. This procedure could provide a significant increase in native pulmonary valve preservation. Long-term studies are needed to assess pulmonary valve growth and the consequent reduction in surgical or interventional reoperations.

Context Unlike homozygous variants, the implication of heterozygous variants on the leptin–melanocortin pathway in severe obesity has not been established. Objective To describe the frequency, the phenotype, and the genotype–phenotype relationship for heterozygous variants in LEP, LEPR, POMC, and PCSK1 in severe obesity. Methods In this retrospective study, genotyping was performed on at least 1 of the LEP, LEPR, POMC, and PCSK1 genes in 1486 probands with severe obesity (600 children, 886 adults). The phenotype was collected in 60 subjects with heterozygous variants and 16 with homozygous variants. We analyzed variant frequency, body mass index (BMI), age of obesity onset, food impulsivity, and endocrine abnormalities. Results The frequency of subjects with homozygous variants was 1.7% (n = 26), and 6.7% (n = 100) with heterozygous variants. Adults with homozygous variants had a higher BMI (66 vs 53 kg/m2, P = .015), an earlier onset of obesity (0.4 vs 5.4 years, P < .001), more often food impulsivity (83% vs 42%, P = .04), and endocrine abnormalities (75% vs 26%, P < .01). The BMI was higher for subjects with high-impact heterozygous variants (61 vs 50 kg/m², P = .045) and those with a second heterozygous variant on the pathway (65 vs 49 kg/m², P < .01). In children, no significant differences were found for the age of obesity onset and BMI. Conclusion Heterozygous variants in LEP, LEPR, POMC, and PCSK1 are frequent in severe obesity and sometimes associated with a phenotype close to that of homozygotes. These data suggest a systematic search for variants in severe early-onset obesity, to discuss therapy that targets this key pathway.

Background Percutaneous treatment of native coarctation (coA), gold standard in adult patients, is still debated in children. We aim to report the French multicentre experience. Methods All patients aged 1 to 18 yrs with native coA, treated percutaneously between 01/2000 and 12/2018, were included in this multcentric (9 centres) retrospective survey. Results One hundred and thirty three children (34 female) were included. Indication for treatment was hypertension in 109, exercise hypertension in 8 and other reasons in 16 patients. Mean age at intervention was 11.5 ± 3.9 years, mean weight 41 ± 18 kg. Procedure consisted of isolated balloon dilatation in 5 (mean age 2,63 yrs, mean weight 12 kg), balloon dilatation followed by stent implantation in 8 (mean age 11 yrs, mean weight 37 kg), and immediate stent implantation in 120 (mean age 12 yrs, mean weight 43 kg). Stents used (n = 124/128) were covered in 43, non-covered in 77, including 38 open cell stents. Invasive gradient across coA dropped from 28 mmHg (range 5 to 64) at baseline (n = 124) to 3 mmHg (range -5 to 20) after intervention (n = 105). Three associated lesions were treated: 1 PDA closure, 1 aortic valvuloplasty and 1 left SVC occlusion. Serious vascular complications occurred in 8 patients (6%) (3 pseudo-aneurysms, 2 dissections, 2 stenosis and 1 occlusion) requiring surgery in 2. Reintervention was performed in 22%: 2 patients had surgery, 28 were treated percutaneously (14 balloon dilatations, 14 stent implantations). Mean follow-up reached 4.9 ± 4.7 years. At latest follow-up, 25% remained hypertensive with 15 patients (11%) on anti-hypertensive medication. MRI, CTscan or fluoroscopy imaging, are available in 52 patients during follow-up (39%). Rate of aneurysm formation, stent fracture and risks factors for reintervention or residual hypertension will be presented. Conclusions Percutaneous treatment of native coarctation was safe and efficient in our french population. Close follow-up is required for longer-term results.

Objectives This study sought to investigate patient intermediate-term outcomes after transcatheter pulmonary valve replacement (TPVR) with Edwards SAPIEN valve. Background The Edwards SAPIEN valve, initially designed for percutaneous aortic valve replacement, has been approved for TPVR in patients with dysfunctional right ventricular outflow tracts (RVOT), but only short-term follow-up has been reported. Methods From 2011 to 2016, 62 patients undergoing successful TPVR using the SAPIEN XT valve were consecutively included into the study. Primary efficacy and safety endpoints were defined as freedom from valve-reintervention and freedom from infective endocarditis at last follow-up, respectively. Results The primary efficacy outcome was met for 87,1% patients after a mean follow-up of 55 ± 21 months, corresponding to a freedom of reintervention at 5 years of 89% (95% CI 74.8–95.6%). Reinterventions were exclusively due to recurrent obstruction, no significant valvular insufficiency was observed. One case of infective endocarditis was reported, corresponding to a rate of 0.35% per patient-year (95% CI 0.01–2.00%). At 5 years freedom from infective endocarditis was 98.4% (95% CI 89.1–99.8%) ( Fig. 1 ). Six patients died or were transplanted due to advanced cardiac failure, without relationship with TPVR. In univariate analysis, reintervention was associated with young age, a smaller tube-graft, a higher pulmonary valve gradient after the procedure and a ratio of largest implanted stent diameter to invasive balloon conduit diameter over 1.35. Conclusions This study confirms the mid-term safety and efficacy of the Edwards SAPIEN XT valve in patients with dysfunctional RVOT, and identifies a patient profile associated with an uncertain benefit-risk balance.

Introduction Congenitally corrected transposition of the great arteries (ccTGA) is a rare disease of unknown aetiology. We aimed to better understand familial recurrence pattern. Methods An international, multicentre, retrospective cohort study was conducted in 29 tertiary hospitals in 6 countries between 1990 and 2018, leading to investigate 1043 unrelated ccTGA probands. Results Atrioventricular block at diagnosis and laterality defects were observed in 35.4% and 29.9%, respectively. ccTGA associated with primary ciliary dyskinesia in 10 patients. Parental consanguinity was noted in 3.4% cases. A congenital heart defect was diagnosed in 81 relatives from 69 families, 58% of them being first-degree relatives, including 28 siblings. The most prevalent defects in relatives were dextro-transposition of the great arteries (d-TGA: 28.4%), laterality defects (13.6%) and ccTGA (11.1%); 36 new familial clusters were described, including 8 pedigrees with concordant familial aggregation of ccTGA, 19 pedigrees with familial co-segregation of ccTGA and d-TGA and 9 familial co-segregation of ccTGA and laterality defects. In one family there was co-segregation of ccTGA, d-TGA and heterotaxy syndrome in 3 distinct relatives. Conclusion ccTGA is not always a sporadic congenital heart defect. Familial clusters as well as evidence of an association between ccTGA, d-TGA, laterality defects and in some cases primary ciliary dyskinesia strongly suggest a common pathogenetic pathway involving laterality genes in the pathophysiology of ccTGA.

International audience; Interventional radiology plays an important and increasing role in cancer treatment. Follow-up is important to be able to assess treatment success and detect locoregional and distant recurrence and recommendations for follow-up are needed. At ECIO 2018, a joint ECIO-ESOI session was organized to establish follow-up recommendations for oncologic intervention in liver, renal, and lung cancer. Treatments included thermal ablation, TACE, and TARE. In total five topics were evaluated: ablation in colorectal liver metastases (CRLM), TARE in CRLM, TACE and TARE in HCC, ablation in renal cancer, and ablation in lung cancer. Evaluated modalities were FDG-PET-CT, CT, MRI, and (contrast-enhanced) ultrasound. Prior to the session, five experts were selected and performed a systematic review and presented statements, which were voted on in a telephone conference prior to the meeting by all panelists. These statements were presented and discussed at the ECIO-ESOI session at ECIO 2018. This paper presents the recommendations that followed from these initiatives. Based on expert opinions and the available evidence, follow-up schedules were proposed for liver cancer, renal cancer, and lung cancer. FDG-PET-CT, CT, and MRI are the recommended modalities, but one should beware of false-positive signs of residual tumor or recurrence due to inflammation early after the intervention. There is a need for prospective preferably multicenter studies to validate new techniques and new response criteria. This paper presents recommendations that can be used in clinical practice to perform the follow-up of patients with liver, lung, and renal cancer who were treated with interventional locoregional therapies.

The long-term prospective multi-centre nationwide (French) observational study FRANCISCO will provide new information on perimembranous ventricular septal defect with left ventricular overload but no pulmonary hypertension in children older than 1 year. Outcomes will be compared according to treatment strategy (watchful waiting, surgical closure, or percutaneous closure) and anatomic features of the defect. The results are expected to provide additional guidance about the optimal treatment of this specific population, which is unclear at present. Background The management of paediatric isolated perimembranous ventricular septal defect (pmVSD) with left ventricle (LV) volume overload but no pulmonary arterial hypertension (PAH) remains controversial. Three therapeutic approaches are considered: watchful waiting, surgical closure, and percutaneous closure. We aim to investigate the long-term outcomes of these patients according to anatomic pmVSD characteristics and treatment strategy. Methods The Filiale de Cardiologie Pediatrique et Congenitale (FCPC) designed the FRANCISCO registry, a long-term prospective nationwide multi-centre observational cohort study sponsored by the French Society of Cardiology, which enrolled, over 2 years (2018–2020), patients older than 1 year who had isolated pmVSD with LV volume overload. Prevalent complications related to pmVSD at baseline were exclusion criteria. Clinical, echocardiographic, and functional data will be collected at inclusion then after 1, 5, and 10 years. A core lab will analyse all baseline echocardiographic data to depict anatomical pmVSD features. The primary outcome is the 5-year incidence of cardiovascular events (infective endocarditis, sub-aortic stenosis, aortic regurgitation, right ventricular outflow tract stenosis, tricuspid regurgitation, PAH, arrhythmia, stroke, haemolysis, heart failure, or death from a cardiovascular event). We plan to enrol 200 patients, given the 10% estimated 5-year incidence of cardiovascular events with a 95% confidence interval of ±5%. Associations linking anatomical pmVSD features and treatment strategy to the incidence of complications will be assessed. Conclusions The FRANSCICO study will provide the long-term incidence of complications in patients older than 1 year with pmVSD and LV volume overload. The results are expected to improve guidance for treatment decisions.

International audience; Background The COCCINELLE study is a nationwide retrospective French cohort set up to evaluate the risk of radiation associated cancer in patients who undergone cardiac catheterization (CC) procedures for diagnosis or treatment of congenital heart disease during childhood [1].Material and methods Children who undergone CC procedures from 01/01/2000 to 31/12/2013 before the age of 16 in one of the 15 pediatric cardiology departments which perform pediatric CC in mainland France were included. The follow-up started at the date of the first recorded CC procedure until the exit date, i.e. the date of death, the date of first cancer diagnosis, the date of the 18th birthday, or the 31/12/2015, whichever occurred first. The cohort was linked to the National Childhood Cancer Registry to identify patients diagnosed with cancer and with the French National Directory for the Identification of Natural Persons to retrieve the patients’ vital status. An external comparison was conducted using standardized incidence ratios (SIR). Breslow and Day’s approximation was used to estimate 95% confidence intervals (CI) for the SIRs [2]. Results A total of 17,104 children were included in the cohort and followed for 110,335 person-years, with 22,227 CC procedures collected. Among the patients, 81.6 % received only one procedure. Fifty-nine cancer cases were observed in the cohort. SIRs were increased for all-cancer (SIR = 3.8, 95% CI 2.9, 4.9), leukemia (SIR = 3.3, 95% CI 2.0, 5.4), lymphoma (SIR = 14.9, 95% CI 9.9, 22.5) and solid cancers excluding central nervous system tumors (SIR = 3.3, 95% CI 2.0, 5.5) compared with the general population. Conclusion Increased risks of cancer were observed. Potential explanations include shared genetic or environmental factors, immunosuppression drugs, and exposure to medical ionizing radiation procedures. The dose-response analysis between ionizing radiation doses received during CCs and cancer occurrence will allow to address this question.Keywords: Ionizing radiation, cardiac catheterization, congenital heart disease, cancerCompeting interestsThe authors declare that they have no competing of interest.References1.Baysson H, Nkoumazok B, Barnaoui S, Réhel J, Girodon B, Milani G, Boudjemline Y, Bonnet D, Laurier D, Bernier M (2015) Follow-up of children exposed to ionising radiation from cardiac catheterisation: the Coccinelle study. Radiation protection dosimetry 165:13–162.Breslow NE, Day NE (1987) Statistical Methods in Cancer Research Volume II: The Design and Analysis of Cohort Studies, IARC Scientific Publication. IARC Scientific Publication No. 82, Lyon, France: International Agency for Research on Cancer.NotesCOCCINELLE: French acronym for COhorte sur le risque de Cancer après Cardiologie INterventionnELLECC: Cardiac CatheterizationSIR: Standardized Incidence Ratios CI: Confidence IntervalsCNS: Central Nervous System

International audience; Purpose To evaluate the negative predictive value (NPV) of multiparametric magnetic resonance imaging (mpMRI), alone or combined with Prostate-Specific Antigen density (PSAd) to exclude clinically significant prostate cancer (csPCa). Patients and Methods We performed a retrospective chart review of all the patients who had transrectal ultrasound-guided biopsy (TRUSGB) in our center between January 2014 and March 2019. We included patients who had nonsuspicious prebiopsy mpMRI defined as Prostate Imaging-Reporting and Data System (PI-RADS)

Objective To report a contemporary series of Miami pouch (MP) enriched with a full technical description and step-by-step video to contribute to wider use. Patients and Methods A retrospective charts review of all patients who had a MP at our center between January 2016 and December 2017 was performed. The MP technique uses the terminal 15cm of ileum and the right colon to build an intestinal heterotopic pouch located in the right iliac fossa and connected to the skin by an efferent catheterizable tube. Primary outcome was continence defined as the absence of leakage between clean intermittent self-catheterization (CISC) with a maximal interval of 4 hours between each CISC. Results Fifteen patients had MP during the study period. Thirty-day postoperative Clavien III complications were observed in 2 (13.3%) patients. At 39 months of median follow-up, continence was obtained for all patients except for 2 patients whom reported intermittent night-time leakages due to long intervals (5 to 7 hours) between 2 CISC. No significant alteration of renal function was reported and no stenosis of the efferent tube neither difficulty to perform CISC was observed. Conclusions For patients who are candidates for radical cystectomy and not eligible for orthotopic neobladder, intestinal heterotopic pouch with a cutaneous continent urinary diversions as MP may be a reliable alternative. Patients should be informed of the existence of a valid alternative to ileal conduit since it may fit their expectations of a preserved body image without urine collecting appliances.

Background With the growing population of adults with congenital heart disease (ACHD), the number of catheter ablation procedures is expected to increase over time. Purpose We aimed to describe temporal trends in volume and outcomes of catheter ablation procedures in ACHD patients in a large tertiary center. Methods Retrospective observational study including all consecutive ACHD patients undergoing catheter ablation in a tertiary reference center over a 15-year period. Acute procedural success rate (including complete success in case of non-inducibility of any arrhythmia at the end of the procedure) as well as freedom from recurrence at 12 months were analyzed. Results From November 2004 to November 2019, 302 catheter ablations in 221 ACHD patients (43.6±15.0 years, 58.9% males) were performed. The annual number of catheter ablation increased progressively from 4 to 60 by year (p Conclusions The number of catheter ablation procedures in ACHD patients has considerably increased over the last 15 years. Advances in ablative technologies appear to be associated with a low rate of complications and a significant improvement in acute and midterm outcomes. Evolution of acute procedural success Funding Acknowledgement Type of funding source: None

Objective To describe, based on the French National Health Insurance (NHI) data, time trends in diabetes medications after treatment initiation in two consecutive cohorts of people newly treated for type 2 diabetes (T2D) in 2008 (1st cohort) and 2013 (2nd cohort). Materials and methods People, aged 45 years and older, newly treated for T2D in 2008 and 2013 were identified in the French NHI Data System. Treatment changes were collected for each year of follow-up. Logistic regression was performed to identify factors associated with metformin discontinuation. Results Respectively, 157 940 and 160 670 beneficiaries (mean age: 63 and 64 years; men proportion: 53 and 52 %) of the French NHI general scheme initiated a diabetes treatment in 2008 and 2013. Metformin was the first monotherapy and increased in use: 67% of monotherapies in 2008 versus 77% in 2013. Monotherapy percentage decreased from the second year onwards in both cohorts. A marked increase of metformin-DPP4i combination therapy was observed (14% of dual therapies in 2008 versus 46% in 2015 in the first cohort), replacing the metformin-sulfonylureas combination as a second-line treatment. Metformin discontinuation was statistically associated with female gender, social deprivation, age, and anti-diabetic polypharmacy. Discontinuation of diabetes treatment was observed after 5-years for, respectively, 10% and 13% in the first and second cohorts. Conclusion Descriptive analysis of 2 consecutive national cohorts showed an evolution in the prescription patterns of anti-diabetic treatments over a short period. With early treatment intensification, increasing rate of metformin monotherapy, and changes in dual-therapy strategy.

Background The classical functions of the skeleton encompass locomotion, protection and mineral homeostasis. However, cell-specific gene deletions in the mouse and human genetic studies have identified the skeleton as a key endocrine regulator of metabolism. The bone-specific phosphatase, Phosphatase, Orphan 1 (PHOSPHO1), which is indispensable for bone mineralisation, has been recently implicated in the regulation of energy metabolism in humans, but its role in systemic metabolism remains unclear. Here, we probe the mechanism underlying metabolic regulation by analysing Phospho1 mutant mice. Results Phospho1−/− mice exhibited improved basal glucose homeostasis and resisted high-fat-diet-induced weight gain and diabetes. The metabolic protection in Phospho1−/− mice was manifested in the absence of altered levels of osteocalcin. Osteoblasts isolated from Phospho1−/− mice were enriched for genes associated with energy metabolism and diabetes; Phospho1 both directly and indirectly interacted with genes associated with glucose transport and insulin receptor signalling. Canonical thermogenesis via brown adipose tissue did not underlie the metabolic protection observed in adult Phospho1−/− mice. However, the decreased serum choline levels in Phospho1−/− mice were normalised by feeding a 2% choline rich diet resulting in a normalisation in insulin sensitivity and fat mass. Conclusion We show that mice lacking the bone mineralisation enzyme PHOSPHO1 exhibit improved basal glucose homeostasis and resist high-fat-diet-induced weight gain and diabetes. This study identifies PHOSPHO1 as a potential bone-derived therapeutic target for the treatment of obesity and diabetes.

Summary Objectives To evaluate the efficacy of Continuous Saline Bladder Irrigation (CSBI) after blue light transurethral resection of bladder tumor (TURBT) to prevent recurrence of low- to intermediate-risk Non-Muscle Invasive Bladder Cancer (NMIBC). Patients and methods We conducted a retrospective study including patients with low- to intermediate-risk NMIBC who underwent TURBT in two urological centers between January 2017 and December 2018. Each TURBT was performed using blue light after intravesical instillation of hexaminolaevulinic acid. The experimental group included patients who received CSBI while the control group included patients without CSBI. When practice, CSBI was started immediately after the surgery and was interrupted 24 hours thereafter. Low-risk NMIBC had a surveillance while intermediate NMIBC had 8 adjuvant endovesical instillations of Mitomycin. The primary endpoint was bladder tumor recurrence free-survival which was defined as the time between the initial TURBT and the date of TURBT for bladder recurrence. Results A total of 167 patients (median age: 71 years) were included: 20% female, 15% low-risk, 85% intermediate-risk NMIBC. CSBI was performed in 95 cases (57%). No complication related to irrigation was reported. Bladder recurrence was observed in 55 cases (32.9%): 22 (23.1%) in the CSBI group vs. 33 (45.8%) in the control group (P = 0.002). Multivariate stepwise logistic regression analysis with backward selection revealed that CSBI (HR 0.47 [0.27–0.81]; P = 0.006) and MMC (HR 0.55 [0.31–0.95]; P = 0.034) were significantly associated with reduced risk of bladder recurrence. Conclusions Continuous saline bladder irrigation reduced the risk of bladder recurrence after blue light TURBT in patients with low- to intermediate-risk NMIBC while being safe. Prospective randomized study is needed to confirm these results. Level of evidence 3.

International audience; BackgroundReal-world data that support the use of sacral neuromodulation (SNM) for lower urinary tract dysfunctions are of continued interest.ObjectiveTo evaluate the effectiveness, quality of life (QoL), patient-reported outcomes (PROs), and safety of SNM with the InterStim™ system in real life during 1-yr postimplant.Design, setting, and participantsThis is a prospective, multicenter, observational study at 25 representative public and private French sites. Eligible patients received SNM therapy for overactive bladder (OAB) and non-obstructive urinary retention based on local standard of care. Overall, 320 patients were enrolled; 247 received permanent implant or replacement; 204 implanted patients completed second follow-up after mean of 10.0 ± 3.8 mo.Outcome measurements and statistical analysisEffectiveness outcomes were change in voids, leaks, and catheterizations/day. Other outcomes included validated QoL and disease severity scores as well as PROs and adverse event data. Outcomes at follow-ups were compared with baseline using the Wilcoxon signed-rank test.Results and limitationsVoids in urinary frequency (UF) and leaks/day in urinary urge incontinence (UI) patients were significantly reduced after 10 mo in both de novo (mean baseline voids/day UF de novo: 12.7 vs 8.6 after 10 mo; p < 0.001; mean baseline leaks/day UI de novo: 4.3 vs 1.1 after 10 mo; p < 0.001) and replacement patients (mean baseline voids/day UF replacement: 11.5 vs 7.9 after 10 mo; p < 0.001; mean baseline leaks/day UI replacement: 5.4 vs 1.0 after 10 mo; p < 0.001). Disease bother, Urinary Symptom Profile score, and Ditrovie questionnaire score were also significantly improved. Revisions postimplant occurred in 20% of patients including in 9% due to permanent explantation during a mean exposure time of 24.3 mo.ConclusionsThrough a real-life study, SOUNDS (Sacral neuromOdUlation with InterStim™ therapy for intractable lower uriNary tract DySfunctions) confirms the clinical effectiveness, safety, and positive effect of SNM on QoL and PROs for the treatment of OAB patients.Patient summaryThese analyses on French patients who received sacral neuromodulation (SNM) for retention or OAB during a 10-mo period showed that SNM improved OAB symptoms, quality of life, and reduced disease bother.Trial registrationClinicalTrials.gov: NCT02186041

Background There are limited published data focused on outcomes of transcatheter pulmonary valve replacement (TPVR) with either a Sapien XT or Sapien 3 (S3) valve. Objectives This study sought to report short-term outcomes in a large cohort of patients who underwent TPVR with either a Sapien XT or S3 valve. Methods Data were entered retrospectively into a multicenter registry for patients who underwent attempted TPVR with a Sapien XT or S3 valve. Patient-related, procedural, and short-term outcomes data were characterized overall and according to type of right ventricular outflow tract (RVOT) anatomy. Results Twenty-three centers enrolled a total of 774 patients: 397 (51%) with a native/patched RVOT; 183 (24%) with a conduit; and 194 (25%) with a bioprosthetic valve. The S3 was used in 78% of patients, and the XT was used in 22%, with most patients receiving a 29-mm (39%) or 26-mm (34%) valve. The implant was technically successful in 754 (97.4%) patients. Serious adverse events were reported in 67 patients (10%), with no difference between RVOT anatomy groups. Fourteen patients underwent urgent surgery. Nine patients had a second valve implanted. Among patients with available data, tricuspid valve injury was documented in 11 (1.7%), and 9 others (1.3%) had new moderate or severe regurgitation 2 grades higher than pre-implantation, for 20 (3.0%) total patients with tricuspid valve complications. Valve function at discharge was excellent in most patients, but 58 (8.5%) had moderate or greater pulmonary regurgitation or maximum Doppler gradients >40 mm Hg. During limited follow-up (n = 349; median: 12 months), 9 patients were diagnosed with endocarditis, and 17 additional patients underwent surgical valve replacement or valve-in-valve TPVR. Conclusions Acute outcomes after TPVR with balloon-expandable valves were generally excellent in all types of RVOT. Additional data and longer follow-up will be necessary to gain insight into these issues.

We evaluated the feasibility and outcomes of immediate preoperative renal artery embolization (IPRAE) before complex nephrectomy for locally advanced RCC ± inferior vena cava thrombus (IVCT). A comparative retrospective (2007–2017) multicenter study which included 145 patients with locally advanced RCC ± IVCT: 99 radical nephrectomies vs. 46 radical nephrectomies with IPRAE identified in the prospective UroCCR national database (CNIL DR 2013–206; NCT03293563). IPRAE was performed under local anesthesia the day of nephrectomy (