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Graph Neural Networks (GNNs) are a popular approach for predicting graph structured data. As GNNs tightly entangle the input graph into the neural network structure, common explainable AI approaches are not applicable. To a large extent, GNNs have remained black-boxes for the user so far. In this paper, we show that GNNs can in fact be naturally explained using higher-order expansions, i.e. by identifying groups of edges that jointly contribute to the prediction. Practically, we find that such explanations can be extracted using a nested attribution scheme, where existing techniques such as layer-wise relevance propagation (LRP) can be applied at each step. The output is a collection of walks into the input graph that are relevant for the prediction. Our novel explanation method, which we denote by GNN-LRP, is applicable to a broad range of graph neural networks and lets us extract practically relevant insights on sentiment analysis of text data, structure-property relationships in quantum chemistry, and image classification., Comment: 14 pages + 6 pages supplement

International audience; Objectives: Our aim was to assess if switching from a protease inhibitors (PI)-based regimen to a PI-free one is associated with an increased risk of Kaposi Sarcoma (KS) relapse among patients living with HIV (PLHIV) with history of KS and controlled HIV replication.Methods: In a retrospective analysis of the prospectively collected Dat'AIDS database we selected patients who both had a past KS history and a HIV-1 viral load below 200 copies/mL while being PI-treated. We searched for KS relapses while persistent virological success was maintained for at least 6 months, whether patients kept taking the PI, or switched to PI-free regimen.Results: Among the 216 patients with past KS event and a history of HIV-1 infection efficiently treated by a PI-based regimen, 148 patients (68.5%) later switched to a PI-sparing regimen. Their baseline characteristics were not different from non-switching patients. We described 7 cases of relapse (3.2% of the 216 patients). Five cases of relapse occurred in switching patients (3.4%). The remaining two relapses occurred in PI-treated patients (2.9%). At KS relapse, CD4 cell count was 459 cells/μL (range 225-560) for switching patients, compared with 362 and 136 cells/μL for the other two patients.Conclusions: In this large cohort of PLHIV with a history of KS and ART-controlled HIV replication, KS relapses were described in 3.2% of the patients, and were not more frequent when a PI-containing ART regimen has been switched to a PI-free regimen. Our results do not support a specific effect of PI on KS.

Resume Introduction La pose d’implants UroLift® peut etre preferee a la chirurgie endoscopique classique pour les patients qui souhaitent preserver leur sexualite ou pour ceux qui privilegient une recuperation postoperatoire rapide. L’absence de recours systematique a une anesthesie generale est un element important renforcant l’aspect mini-invasif de la procedure et ameliorant la vitesse de recuperation. L’objectif de ce travail etait de rapporter notre experience preliminaire du traitement par UroLift® sous anesthesie locale. Materiels et methodes Une analyse retrospective a ete conduite en incluant tous les patients traites par UroLift® entre 2017 et 2021 dans notre centre. L’anesthesie locale reposait en l’instillation de 2 gels de Xylocaine a 4°C dans l’uretre 15 minutes avant l’intervention. Le critere de jugement principal etait le bon deroulement de l’intervention sans interruption pour cause de douleur ni necessite de recours a tout autre mode d’anesthesie ou d’analgesie. Resultats Vingt-sept patients ont ete inclus dont l’âge median etait de 65 ans avec un volume prostatique de 46 mL. L’International Prostate Score Symptom (IPSS) etait de 23. Les 3 premiers patients ont ete operes sous anesthesie generale. L’anesthesie locale etait introduite a partir du 4e patient. Il n’y a eu aucun recours a d’autres modalites d’analgesie ou d’anesthesie ou interruption de la procedure. La duree operatoire etait de 10 minutes et la douleur etait evaluee a 1 sur une echelle visuelle analogique. A 3 mois, le score IPSS etait de 9 (p = 0,001). Conclusion Cette experience preliminaire confirme la faisabilite de la mise place de l’implant UroLift® sous anesthesie locale sans aucun echec de la prise en charge proposee. L’amelioration du score IPSS etait conforme a celle des essais cliniques deja publies. Niveau de preuve 3.

BACKGROUND AND PURPOSE In patients with acute ischemic stroke (AIS) and a large vessel occlusion (LVO), thrombus migration (T-Mig) is a common phenomenon before mechanical thrombectomy (MT), revealed by pre-treatment imaging. Previous works have used qualitative scales to define T-Mig. The aim of this study was to evaluate the determinants and impact of quantitatively assessed T-Mig on procedural characteristics and clinical outcome. METHODS Consecutive patients with AIS due to LVO treated by MT at a reference academic hospital were analysed. Distance between vessel origin and beginning of the thrombus on MRI (3D-time-of-flight and/or contrast-enhanced magnetic-resonance-angiography) and digital-substracted-angiography (DSA) were measured in millimeters using a curve tool. Thrombus migration was defined quantitatively as ∆TD calculated as the difference between pre-MT-DSA and MRI thrombus location. ∆TD was rated as significant if above 5mm. RESULTS A total of 267 patients were included (mean age 70±12 years; 46% females) were analyzed. Amongst them, 65 (24.3%) experienced any degree of T-Mig. T-Mig was found to be associated with iv-tPA administration prior to thrombectomy (β-estimate 2.52; 95% CI [1.25-3.79]; p

Summary Background Patients with COVID-19 pneumonia can have increased inflammation and elevated cytokines, including interleukin (IL)-6, which might be deleterious. Thus, sarilumab, a high-affinity anti-IL-6 receptor antibody, might improve the outcome of patients with moderate-to-severe COVID-19 pneumonia. Methods We did a multicentric, open-label, Bayesian randomised, adaptive, phase 2/3 clinical trial, nested within the CORIMUNO-19 cohort, to test a superiority hypothesis. Patients 18 years or older hospitalised with COVID-19 in six French centres, requiring at least 3L/min of oxygen but without ventilation assistance and a WHO Clinical Progression Scale [CPS] score of 5 were enrolled. Patients were randomly assigned (1:1) via a web-based system, according to a randomisation list stratified on centre and with blocks randomly selected among 2 and 4, to receive usual care plus 400 mg of sarilumab intravenously on day 1 and on day 3 if clinically indicated (sarilumab group) or usual care alone (usual care group). Primary outcomes were the proportion of patients with WHO-CPS scores greater than 5 on the 10-point scale on day 4 and survival without invasive or non-invasive ventilation at day 14. This completed trial is closed to new participants and is registered with ClinicalTrials.gov , NCT04324073 . Findings 165 patients were recruited from March 27 to April 6, 2020, and 148 patients were randomised (68 patients to the sarilumab group and 80 to the usual care group) and followed up for 90 days. Median age was 61·7 years [IQR 53·0–71·1] in the sarilumab group and 62·8 years [56·0–71·7] in the usual care group. In the sarilumab group 49 (72%) of 68 were men and in the usual care group 59 (78%) of 76 were men. Four patients in the usual care group withdrew consent and were not analysed. 18 (26%) of 68 patients in the sarilumab group had a WHO-CPS score greater than 5 at day 4 versus 20 (26%) of 76 in the usual care group (median posterior absolute risk difference 0·2%; 90% credible interval [CrI] −11·7 to 12·2), with a posterior probability of absolute risk difference greater than 0 of 48·9%. At day 14, 25 (37%) patients in the sarilumab and 26 (34%) patients in the usual care group needed ventilation or died, (median posterior hazard ratio [HR] 1·10; 90% CrI 0·69–1·74) with a posterior probability HR greater than 1 of 37·4%. Serious adverse events occurred in 27 (40%) patients in the sarilumab group and 28 (37%) patients in the usual care group (p=0·73). Interpretation Sarilumab treatment did not improve early outcomes in patients with moderate-to-severe COVID-19 pneumonia. Further studies are warranted to evaluate the effect of sarilumab on long-term survival. Funding Assistance publique—Hopitaux de Paris

Calcaneus's Ewing sarcoma is a rare location with a poor prognosis and remains challenging for tumor surgery. We present 3 cases of calcaneus resection for Ewing sarcoma in children and its reconstruction managed by induced-membrane technique. To our knowledge, this technique has never been published for hindfoot's tumor management. Three children (aged from 9 to 14 years) had partial or total resection of calcaneus initially replaced by a cement spacer. The second step consisted of removing the cement and filling the membrane cavity with autograft taken from the ipsilateral iliac crest, potentially combined with bone substitute. In the meantime, children received chemotherapy and possibly radiotherapy according to the Euro E.W.I.N.G. 99 protocol. It was possible to optimize bone formation as we carried out the bone grafting procedure sometime after the treatments. In one case, the evolution was marked by local septic complication, 9 months after resection, and by tumor recurrence in presacral soft tissues treated with radiotherapy and chemotherapy. Partial weightbearing was allowed after 6 weeks of cast, under the protection of a splint. Graft consolidation was achieved at a median of 3.2 months (3-3.5) for all. After a median follow-up of 9 years (5-13), all preserved their limb and were considered in remission. The 3 children reached adulthood, with a median age of 21 years (19-24.8). At last follow-up, median Musculoskeletal Tumor Score was 73% (63-87), and median American Orthopaedic Foot and Ankle Society hind foot score was 78 (72-87).

Background: Pathological Q waves are correlated with infarct size, and Q-wave regression is associated with left ventricular ejection fraction improvement. There are limited data regarding the association of Q-wave regression and clinical outcomes. Our main objective was to assess the association of pathological Q wave evolution after re-perfusion with clinical outcomes after anterior STEMI.Methods: Standard 12-lead electrocardiograms (ECGs) were recorded in 780 anterior STEMI patients treated with primary percutaneous coronary intervention (PCI) from the CIRCUS trial. ECGs were recorded before and 90 min following PCI, as well as at hospitalization discharge and 12 months of follow-up. The number of classic ECG criteria Q waves was scored for each ECG. Patients were classified in the Q wave regression group if they had re-gression of at least one Q wave between the post-PCI, the discharge and/or one year ECGs. Patients were classified in the Q wave persistent group if they had the same number or greater between the post-PCI, the discharge and/ or 1 and one year ECGs. All-cause death and heart failure events were assessed for all patients at one year.Results: There were 323(43%) patients with persistent Q waves (PQ group), 378(49%) patients with Q wave re-gression (RQ group) and 60(8%) patients with non-Q wave MI (NQ group). Infarct size as measured by the peak creatine kinase was significantly greater in the PQ group compared to the RQ and NQ groups (4633 +/- 2784 IU/l vs. 3814 +/- 2595 IU/l vs. 1733 +/- 1583 IU/l respectively, p b 0.0001). At one year, there were 22 deaths (7%) in the PQ-group, 15 (4%) in the RQ-group and none in the NQ-group (p = 0.04). There was a 4-fold increase in the risk of death or heart failure in the PQ compared to the NQ group (HR 4.7 [1.1; 19.3]; p = 0.03), but there was no significant difference between NQ and RQ groups (HR 3.3 [0.8; 13.8]; p = 0.09).Conclusion: Ina population of anterior STEMI patients, persistent Q waves defined according to the classic ECG criteria after reperfusion was associated with a 4-fold increase in the risk of heart failure or death compared to non-Q-wave MI, while Q-wave regression was associated with significantly lower risk of events.(c) 2019 Elsevier Inc. All rights reserved.

Post-transplant lymphoproliferative disorder is a growing complication of kidney transplantation and is associated with a poor prognosis. Anti-CD19 chimeric antigen receptor (CAR) T-cell therapy is an important new treatment option modifying the outcome of refractory hematological cancers. Here, we report the case of a 40-year-old kidney transplant recipient who developed a Burkitt-like lymphoma with 11q aberration 5 years after transplantation. After 3 unsuccessful lines of chemotherapy, it was decided to treat the patient with anti-CD19 CAR T cells as a salvage therapy. Three months after CAR T-cell infusion, she experienced a grade IIB T cell-mediated rejection with severe tubulitis (T3), slight interstitial inflammation (I1), and severe intimal arteritis (V2) with blood suffusion. Among T cells infiltrating the graft, some of them expressed the anti-CD19 CAR. CAR T cells within the graft and in blood samples were also detected by droplet digital polymerase chain reaction. Function of the kidney transplant improved after corticosteroid treatment and remained stable. However, lymphoma progressed, with a massive pulmonary mass leading to the patient's death 10 months after CAR T-cell infusion.

Pulmonary CTA is a ubiquitous study interpreted by radiologists with different levels of experience in a variety of practice settings. Pulmonary embolism (PE) can range from an incidental and clinically insignificant finding to a clinically significant thrombus that can be managed on an outpatient basis to a potentially fatal condition requiring immediate medical or invasive management. Accordingly, a clear and concise pulmonary CTA report should effectively communicate the most pertinent findings to help the treating medical team diagnose or exclude the diagnosis of PE and provide information to guide appropriate management. In this expert panel narrative review, we discuss the purpose of the radiology report for pulmonary CTA, the optimal report format, the relevant findings that need to be addressed and their clinical significance.

Screening for silent coronary artery disease in asymptomatic patients with diabetes mellitus (DM) is challenging and controversial. In this context, it seems crucial to identify early markers of coronary artery disease.The aim of this study was to investigate the incremental value of resting left ventricular (LV) global longitudinal strain (GLS) for the prediction of positive results on stress (exercise or dobutamine) transthoracic echocardiography in 273 consecutive asymptomatic high-risk patients with DM. Positive results on stress transthoracic echocardiography were defined as stress-induced LV wall motion abnormalities (new or worsening preexisting abnormalities).Compared with patients with negative stress results, those with positive stress results (n = 28 [10%]) more frequently had cardiovascular risk factors, complications of DM, vascular disease, moderate and severe calcification of the aortic valve and mitral annulus, and worse resting LV GLS (-16.7 ± 2.9% vs -19.0 ± 1.9%, P .001). On multivariable logistic regression analysis, DM duration10 years, diabetic retinopathy, LV hypertrophy, and impaired LV GLS (odds ratio, 1.39 [95% CI, 1.14-1.70] per percentage increase; odds ratio, 5.16 [95% CI, 1.96-13.59] for LV GLS worse than -18%) were independently associated with positive results on stress transthoracic echocardiography. The area under the curve to predict positive results was 0.74 for LV GLS with a cutoff of -18.0% (sensitivity 68%, specificity 78%). The area under the curve of the multivariable model to predict test results was improved by the addition of LV GLS (P .001), with a bias-corrected area under the curve after bootstrapping of 0.842 [95% CI, 0.753-0.893].The present findings show that resting LV GLS is associated with the presence of silent ischemia and could be useful to better identify asymptomatic patients with DM who might benefit from coronary artery disease screening.

Optoelectronic systems can exert precise control over targeted neurons and pathways throughout the brain in untethered animals, but similar technologies for the spinal cord are not well established. In the present study, we describe a system for ultrafast, wireless, closed-loop manipulation of targeted neurons and pathways across the entire dorsoventral spinal cord in untethered mice. We developed a soft stretchable carrier, integrating microscale light-emitting diodes (micro-LEDs), that conforms to the dura mater of the spinal cord. A coating of silicone-phosphor matrix over the micro-LEDs provides mechanical protection and light conversion for compatibility with a large library of opsins. A lightweight, head-mounted, wireless platform powers the micro-LEDs and performs low-latency, on-chip processing of sensed physiological signals to control photostimulation in a closed loop. We use the device to reveal the role of various neuronal subtypes, sensory pathways and supraspinal projections in the control of locomotion in healthy and spinal-cord injured mice., Optogenetics is applied to the entire mouse spinal cord.

Summary Introduction Holmium laser enucleation of the prostate (HoLEP) is a validated alternative to transurethral resection of the prostate (TURP) and open prostatectomy (OP) for surgical treatment of bladder outlet obstruction (BOO) due to benign prostatic hyperplasia (BPH). The surgical technique may vary considerably from one surgeon to another. The three-lobe technique remains the reference procedure, but some surgeons claim “en bloc” enucleation could help to shorten enucleation time. Our objective was to prospectively assess the clinical results of “en bloc” HoLEP. Methods Consecutive 109 patients presenting with lower urinary tract symptoms (LUTS) related to BPH and selected for surgical treatment were prospectively included in an observational clinical study. There were no exclusion criteria as long as the patient was operated on by one of the two participating surgeons. The surgeons involved had previous experience of more than 200 HoLEP cases, including more than 50 “en bloc” procedures, before starting the clinical study. Clinical data were prospectively collected in a common computerized database and analysed once the 3-month follow-up data were collected including complications, maximum urinary flow rate (Qmax), post-void residual urine volume (PVR), the International Prostate Symptom Score (IPSS) and the Quality of life score (QoL). Results Overall, 109 consecutive patients were included with median IPSS and QoL score of 20/35 and 5/6 respectively. At inclusion median prostatic size was 70 mL, Qmax was 8 mL/s, and PVR was160 mL. The median length of the complete procedure, the enucleation and the morcellation were, respectively, 41 min, 30 min and 10 min. The mean enucleation efficiency was 1.5 g/min, and the mean morcellation efficiency was 4.5 g/min. The median bladder catheterization and hospitalization length were of 18 hours and 1 day respectively and 41% of patients had day-case procedure. Early post-operative complications were reported in 17 cases (16%) including 3 Clavien IIIb (bladder clot removal in the operating room). At 3-month, the IPSS and QoL decreased to 3/35 and 1/6 while Qmax and PVR improved to 26 mL/s and 40 mL. Conclusion In this bi-centric study evaluating short-term outcomes of the “en bloc” technique, the operating time was very short (41 min) with excellent functional outcomes. A prospective clinical trial is necessary to confirm these results are due to the surgical technique itself and not only to the skills of the surgeons.

International audience; In this paper we enhance the EasyCrypt proof assistant to reason about computational complexity of adversaries. The key technical tool is a Hoare logic for reasoning about computational complexity (execution time and oracle calls) of adversarial computations. Our Hoare logic is built on top of the module system used by EasyCrypt for modeling adversaries. We prove that our logic is sound w.r.t. the semantics of EasyCrypt programs-we also provide full semantics for the EasyCrypt module system, which was previously lacking. We showcase (for the first time in EasyCrypt and in other computer-aided cryptographic tools) how our approach can express precise relationships between the probability of adversarial success and their execution time. In particular, we can quantify existentially over adversaries in a complexity class, and express general composition statements in simulation-based frameworks. Moreover, such statements can be composed to derive standard concrete security bounds for cryptographic constructions whose security is proved in a modular way. As a main benefit of our approach, we revisit security proofs of some well-known cryptographic constructions and we present a new formalization of Universal Composability (UC).

Robot-assisted partial nephrectomy (RAPN) is a difficult procedure with risk of significant perioperative complications. The objective was to evaluate the impact of preoperative planning and intraoperative guidance with 3D model reconstructions on perioperative outcomes of RAPN. We conducted a retrospective analysis of all patients who underwent RAPN for kidney tumor by three high-volume expert surgeons from academic centers. Clinical data were collected prospectively after written consent into the French kidney cancer network database UroCCR (CNIL-DR 2013-206; NCT03293563). Our cohort was divided into two groups: 3D-Image guided RAPN group (3D-IGRAPN) and control group. A propensity score according to age, pre-operative renal function and RENAL tumor complexity score was used. Both surgical techniques were compared in terms of perioperative outcomes. The initial study cohort included 230 3D-IGRAPN and 415 control RAPN. Before propensity-score matching, patients in the 3D-IGRAPN group had a larger tumor (4.3 cm vs. 3.5 cm, P

Objectives: To describe the evolution of day-case success rate over the years and to identify predictive factors for prolonged hospitalization or readmissions. Methods: Retrospective review of all ...

Detailed effects of electrode size on electrograms (EGMs) have not been systematically examined.We aimed to elucidate the effect of electrode size on EGMs and investigate an optimal configuration of electrode size and interelectrode spacing for gap detection and far-field reduction.This study included 8 sheep in which probes with different electrode size and interelectrode spacing were epicardially placed on healthy, fatty, and lesion tissues for measurements. Between 3 electrode sizes (0.1 mm/0.2 mm/0.5 mm) with 3 mm spacing. As indices of capability in gap detection and far-field reduction, in different electrode sizes (0.1 mm/0.2 mm/0.5 mm) and interelectrode spacing (0.1 mm/0.2 mm/0.3 mm/0.5 mm/3 mm) and the optimized electrode size and interelectrode spacing were determined. Compared between PentaRay and the optimal probe determined in study 2.Study 1 demonstrated that unipolar voltage and the duration of EGMs increased as the electrode size increased in any tissue (P.001). Bipolar EGMs had the same tendency in healthy/fat tissues, but not in lesions. Study 2 showed that significantly higher gap to lesion volume ratio and healthy to fat tissue voltage ratio were provided by a smaller electrode (0.2 mm or 0.3 mm electrode) and smaller spacing (0.1 mm spacing), but 0.3 mm electrode/0.1 mm spacing provided a larger bipolar voltage (P.05). Study 3 demonstrated that 0.3 mm electrode/0.1 mm spacing provided less deflection with more discrete EGMs (P .0001) with longer and more reproducible AF cycle length (P .0001) compared to PentaRay.Electrode size affects both unipolar and bipolar EGMs. Catheters with microelectrodes and very small interelectrode spacing may be superior in gap detection and far-field reduction. Importantly, this electrode configuration could dramatically reduce artifactual complex fractionated atrial electrograms and may open a new era for AF mapping.

Inhibitor of apoptosis proteins (IAPs) regulate apoptosis and modulate NF‐κB signaling thereby driving expression of genes involved in immune/inflammatory responses. The orally available IAP antagonist Debio 1143 has potential to enhance tumor response to chemoradiotherapy and/or immunotherapy. Patients with pre‐operative squamous cell carcinomas of the head and neck (SCCHN) received: Debio 1143 monotherapy (200 mg/day [D]1–15 +/‐ 2); Debio 1143 (200 mg/day D1–15 +/‐ 2) plus cisplatin (40 mg/m2 D 1 and 8); cisplatin alone (40 mg/m2 D 1 and 8; EudraCT: 2014‐004655‐31). Pharmacokinetic/pharmacodynamic effects were assessed in plasma and resected tumors. Primary end point; effect of Debio 1143 on cellular IAP‐1 (cIAP‐1). Levels of cIAP‐1/‐2, X‐linked inhibitor of apoptosis protein (XIAP), tumor infiltrating lymphocytes (TILs), including CD8+ T cells, programmed cell death protein 1 (PD‐1), PD‐ligand 1 (PD‐L1), and gene expression were also analyzed. Twenty‐three of 26 patients completed treatment. In the Debio 1143 monotherapy cohort (n = 13), mean tumor concentrations of Debio 1143 were 18‐fold (maximum 55.2‐fold) greater than in plasma, exceeding the half‐maximal inhibitory concentration for cIAPs and XIAP by 100 to 1000‐fold, with significant engagement/degradation of cIAP‐1 (p

BACKGROUND The impact of estrogen and testosterone on atherosclerotic cardiovascular disease is well known, but the role of the gonadotropins follicle-stimulating hormone (FSH), luteinizing hormone (LH), and prolactin (PRL) to some extent remain less studied. OBJECTIVES To explore the angiogenic potential of gonadotropins on endothelial colony-forming cells (ECFCs). METHODS We examined the effects of various doses of gonadotropins on ECFCs obtained from cord blood by assessing colony number, proliferation, migration, and sprouting ability. Moreover, we studied thrombin generation in ECFCs exposed to gonadotropins by performing a thrombin generation assay. Finally, we determined the levels of circulating gonadotropins in 30 men, to exclude the effect of estrogen, with lower extremity arterial disease (LEAD), in comparison with age- and sex-matched controls. RESULTS Exposure to FSH, LH, or PRL resulted in an increase in ECFC migration but showed no effect on proliferation or ECFC commitment from cord blood mononuclear cells. Using a three-dimensional fibrin gel assay, we showed that ECFC sprouting was significantly enhanced by gonadotropins. Exposure to FSH also increased the thrombin generation of ECFCs exposed to FSH. Finally, FSH and LH levels in men with LEAD were higher than those in controls. CONCLUSION Gonadotropins increase ECFC-related angiogenesis and may be involved in thrombin generation in cardiovascular disease. Gonadotropins may act as biomarkers; moreover, we hypothesize that gonadotropin-blocking strategies may be a novel interesting therapeutic approach in atherosclerotic cardiovascular disease.

Summary Background The use of cyclophosphamide in patients with acute exacerbation of idiopathic pulmonary fibrosis (IPF) is unknown. Our study was designed to evaluate the efficacy and safety of four cyclophosphamide pulses in addition to high-dose methylprednisolone in this population. Methods In this double-blind, placebo-controlled trial done in 35 departments across 31 hospitals in France, adult patients (≥18 years) with acute exacerbation of IPF and those with suspected acute exacerbation of IPF were randomly assigned in a 1:1 ratio using a web-based system to receive either intravenous pulses of cyclophosphamide (600 mg/m2) plus uromitexan as haemorrhagic cystitis prophylaxis (200 mg/m2) at the time of cyclophosphamide administration and then again, 4 h later, or placebo at days 0, 15, 30, and 60. Random assignment was stratified according to the severity of IPF and was block-balanced with variable block sizes of four or six patients. Patients receiving mechanical ventilation, with active infection, with active cancer, or who were registered on the lung transplant waiting list were excluded. All patients received standardised high-dose glucocorticoids. The investigators, patients, and the sponsor were masked to the treatment assignments. The primary endpoint was 3-month all-cause mortality, analysed by a χ2 test adhering to an intention-to-treat principle. The trial is now complete and registered with ClinicalTrials.gov , NCT02460588 . Findings Between Jan 22, 2016, and July 19, 2018, 183 patients were assessed for eligibility, of whom 120 patients were randomly assigned and 119 patients (62 [52%] with severe IPF) received at least one dose of cyclophosphamide (n=60) or placebo (n=59), all of whom were included in the intention-to-treat analysis. The 3-month all-cause mortality was 45% (27/60) in patients given cyclophosphamide compared with 31% (18/59) in the placebo group (difference 14·5% [95% CI −3·1 to 31·6]; p=0·10). Similar results were found after adjustment by IPF severity (odds ratio [OR] 1·89 [95% CI 0·89–4·04]). The risk of death at 3 months, independent of the treatment received, was higher with severe than non-severe IPF (OR 2·62 [1·12–6·12]) and was lower with the use of antifibrotic therapy (OR 0·33 [0·13–0·82]). Adverse events were similar between groups by 6 months (25 [42%] in the cyclophosphamide group vs 30 [51%] in the placebo group) and their proportion, including infections, did not differ. Overall infection was the main adverse event and occurred in 20 (33%) of 60 patients in the cyclophosphamide group versus 21 (36%) of 59 patients in the placebo group. Interpretation In patients with acute exacerbation of IPF, adding intravenous cyclophosphamide pulses to glucocorticoids increased 3-month mortality. These findings provide evidence against the use of intravenous cyclophosphamide in such patients. Funding Programme Hospitalier de Recherche Clinique of the French Ministry of Health (PHRC 2014–502), Roche Pharmaceuticals.

Background: In patients with atrial fibrillation (AF) undergoing percutaneous coronary intervention (PCI), selecting an antithrombotic regimen requires balancing risks of ischemic cardiac events, stroke, and bleeding. Methods: We studied 467 patients with AF undergoing PCI in the time period from December 2015 to July 2018 identified via a chart audit by 47 Canadian cardiologists in the CONNECT AF+PCI (the Coordinated National Network to Engage Interventional Cardiologists in the Antithrombotic Treatment of Patients With Atrial Fibrillation Undergoing Percutaneous Coronary Intervention) study, to determine patterns of initial antithrombotic therapy selection. Results: The median (25th, 75th percentile) CHADS2 score was 2 (1, 3), and PCI was performed in the setting of acute coronary syndrome in 62.1%. Triple antithrombotic therapy (TAT) was the initial treatment in 62.7%, dual-pathway therapy in 25.7%, and dual antiplatelet therapy in 11.6%, with a temporal increase in use of dual-pathway therapy during the course of the study; median intended TAT duration was 1 (1, 3) month. Compared with patients selected for TAT, patients selected for dual-pathway therapy were less likely to have prior myocardial infarction (35.8% vs 25.8%, P = 0.045) and prior PCI (33.8% vs 23.3%, P = 0.03), and they received shorter total length of stents (38 [23, 56] vs 30 [20, 46] mm, P = 0.03). Patients selected for dual-pathway therapy had a higher prevalence of prior stroke/transient ischemic attack (13.0% vs 23.3%, P = 0.01). There was no difference in prevalence of anemia (21.5% vs 25.8%, P = 0.30). Use of dual-pathway therapy was similar among patients with acute coronary syndrome and those with stable disease (24.1% vs 28.2%, P = 0.32). Conclusions: Approximately one-quarter of AF patients undergoing PCI are treated with dual-pathway therapy in Canadian practice, with its use increasing during the studied period. Patients selected for dual-pathway therapy have less-complex coronary disease history and intervention. Résumé: Introduction: Les patients atteints de fibrillation auriculaire (FA) qui subissent une intervention coronarienne percutanée (ICP) et choisissent un schéma posologique antithrombotique ont besoin de peser les risques d’événements cardiaques d’origine ischémique, d’accidents vasculaires cérébraux et d’hémorragies. Méthodes: Les 467 patients atteints de FA ayant subi une ICP de décembre 2015 à juillet 2018 qui ont fait l’objet de notre étude ont été trouvés lors de la vérification des dossiers par 47 cardiologues canadiens de l’étude CONNECT AF+PCI (Coordinated National Network to Engage Interventional Cardiologists in the Antithrombotic Treatment of Patients With Atrial Fibrillation Undergoing Percutaneous Coronary Intervention) pour déterminer les schémas de sélection du traitement antithrombotique initial. Résultats: Le score CHADS2 médian (25e, 75e percentile) était de 2 (1, 3), et l’ICP avait été réalisée dans le cadre du syndrome coronarien aigu chez 62,1 % des patients. La trithérapie antithrombotique (TTA) était le traitement initial chez 62,7 % des patients, la bithérapie, chez 25,7 % des patients, et la bithérapie antiplaquettaire, chez 11,6 % des patients, mais il y avait une augmentation temporelle dans l’utilisation de la bithérapie durant l’étude; la durée médiane prévue de la TTA était de 1 (1, 3) mois. Comparativement aux patients sélectionnés pour la TTA, les patients sélectionnés pour la bithérapie étaient moins susceptibles d’avoir eu un infarctus du myocarde précédent (35,8 % vs 25,8 %, P = 0,045) et une ICP précédente (33,8 % vs 23,3 %, P = 0,03), et recevaient des endoprothèses de longueur totale plus courte (38 [23, 56] vs 30 [20, 46] mm, P = 0,03). Les patients sélectionnés pour la bithérapie montraient une prévalence plus élevée d’accidents vasculaires cérébraux/accidents ischémiques transitoires (13,0 % vs 23,3 %, P = 0,01). Il n’existait aucune différence dans la prévalence de l’anémie (21,5 % vs 25,8 %, P = 0,30). L’utilisation de la bithérapie était similaire chez les patients atteints d’un syndrome coronarien aigu et chez les patients dont la maladie était stable (24,1 % vs 28,2 %, P = 0,32). Conclusions: Dans la pratique canadienne, environ le quart des patients atteints de FA qui subissent une ICP sont traités par bithérapie, mais durant la période étudiée, son utilisation avait augmenté. Les patients sélectionnés pour la bithérapie ont des antécédents et des interventions liées aux maladies coronariennes moins complexes.

Although indispensable, radiation exposure during cardiac catheterization procedures can cause specific radiation-induced diseases. These affect the patient but also the interventional cardiologist. Exposure to high or repeated radiation doses causes deterministic effects. Moreover, even low-dose exposure, especially when repeated, produces a risk of stochastic effets. In that respect, it is crucial to improve the radiation safety of cardiac angiography and interventions, to promote radiation protection and to maintain this exposure « As Low As Reasonably Achievable ». Thus, there is a necessity to spread knowledge about safety standards and recommandations to reduces the dose among interventionalists. Data collection and comparaison of practices are precious to this quality improvement process. For the year 2020, France-PCI registry had collected dosimetric datas related to 55 783 coronary angiographic and interventional procedures from 30 centers in France. Mean fluoroscopy time was 4,4 minutes for diagnostic procedures. Mean PDS was 1 767cGy.Cm2 and mean Air Kerma de 257Gy. Coronary percutaneous angioplasty procedures were related to approximately two to three times higher mean exposures. Mean exposure related to chronic coronary total occlusion treatment procedures was also two times higher than exposure related to non-CTO interventions. These data also highlighted wide disparities between centers.

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 (

Forearm sarcoma is rare in children. Here, we report three cases. One child presented undifferentiated soft-tissue sarcoma involving the ulna, another had Ewing's sarcoma of the ulna, and the third had Ewing's sarcoma of the proximal radius. In the first case, there were episodes of iterative aseptic nonunion, treated surgically. At last follow-up (respectively 11, 9 and 8 years postoperatively), the mean Musculoskeletal Tumor Society (MSTS) score was 80%, 90% and 77% respectively, and all cases were in remission. The induced membrane technique to reconstruct bone defect after sarcoma resection in children is a possible limb-salvage strategy.

Developed in the late 1980s, rotational atherectomy has raised a lot of hope for its innovative principle of selective ablation, allowing volume reduction (instead of redistribution) of atherosclerotic plaque, while sparing healthy tissue. Long shunned for its disappointing results on restenosis, the Rotablator finally reasserted itself in the 2000s; era of drug eluting stents and coronary angioplasty boom, thus generating emergence of complex lesions. Indeed, the Rotablator has demonstrated an undeniable benefit in complex (type C) and calcified lesions preparation (before stenting), with a procedural success rate of 95%. Although these lesions only represent a small amount (2-3%) of percutaneous coronary interventions (PCI), they remain a technical impasse for plain-old balloon angioplasty strategy, making the Rotablator more suitable for these resistant lesions' treatment. Registry data attest the safety of this therapy, with a rate of peri-procedural complications and in-hospital mortality comparable to conventional angioplasty (France PCI register). However, certain specific, rare but serious complications (burr entrapment, broken Rotawire, coronary perforation) justify trained teams, perfect knowledge of the equipment, and strict compliance with good practice guidelines. In 2018, the rise of a new method of atherectomy by intra-vascular lithotripsy (Shockwave) has coincided with Rotablator decreasing activity (this finding being biased by a general decrease in PCI activity due to Covid pandemic). This therapeutic range's enhancement revolutionizes calcified lesions treatment, tending towards precise targeting of each indication, depending in particular on calcium distribution's anatomy in the plaque.

Background Systemic sclerosis (SSc) is associated with a variability of mortality rates in the literature. Objective To determine the mortality and its predictors in a long-term follow-up of a bi-centric cohort of SSc patients. Methods A retrospective observational study by systematically analyzing the medical records of patients diagnosed with SSc in Toulouse University Hospital and Ducuing Hospital. Standardized Mortality Ratio (SMR), mortality at 1, 3, 5, 10, and 15 years of disease and causes of death were described. Predictors of mortality using Cox regression were assessed. Results Three hundred seventy-five patients were included: 63 with diffuse cutaneous SSc, 279 with limited cutaneous SSc, and 33 with sine scleroderma. The SMR ratio was 1.88 (95% CI 1.46–1.97). The overall survival rates were 97.6% at 1 year, 93.4% at 3 years, 87.1% at 5 years, 77.9% at 10 years, and 61.3% at 15 years. Sixty-nine deaths were recorded. 46.4% were SSc related deaths secondary to interstitial lung disease (ILD) (34.4%), pulmonary hypertension (31.2%), and digestive tract involvement (18.8%). 53.6% were non-related to SSc: cardiovascular disorders (37.8%) and various infections (35.1%) largely distanced those from cancer (13.5%). Four significant independent predictive factors were identified: carbon monoxide diffusing capacity (DLCO) < 70% (HR=3.01; p=0.0053), C-reactive protein (CRP) >5 mg/l (HR=2.13; p=0.0174), cardiac involvement (HR=2.86; p=0.0012), and the fact of being male (HR=3.25; p=0.0004). Conclusion Long-term data confirmed high mortality of SSc. Male sex, DLCO 5mg/l were identified as independent predictors of mortality. Supplementary Information The online version contains supplementary material available at 10.1186/s13075-021-02672-y., • Male sex, cardiac involvement, DLCO 5 mg/l are strong predictors of mortality in systemic sclerosis. • This study shows the survival of subtypes and in particular sine scleroderma. • Sine scleroderma subtype has better survival than diffuse or limited cutaneous subtypes. • Non-systemic sclerosis-related deaths are more frequent than systemic sclerosis-related deaths. • Cardiovascular events non-systemic sclerosis-related are the main deaths. Supplementary Information The online version contains supplementary material available at 10.1186/s13075-021-02672-y.

Goal The aim of the study is to assess the incidence, risk factors and prognosis of definite stent thrombosis (ST) at 1 year in the France PCI multicenter prospective registry. Patients and methods Only patients who underwent coronary angioplasty with at least one stent implantation between 1st January 2014 and 31 December 2019 were included. The population was separated into 2 groups: the "ST" group with stent thrombosis and the "control" group without stent thrombosis. Results 35,435 patients were included. 256 patients (0.72%) presented a ST at 1 year. The rate of ST decreased significantly in acute coronary syndrome (1.5% in 2014 vs. 0.73% in 2019; p = 0.05) but not in chronic coronary syndrome (0.46% in 2014 vs 0.40%; p = 0.98). The risk factors are young age (65.8 years vs 68.2; p = 0.002), clinical context (35.27% vs 16.68%; p = 0.0001), diabetes (35.2 % vs 26.4%; p = 0.002), renal failure (11.7% vs 8%; p = 0.009) and history of coronary angioplasty (28.63% vs 21.86%; p = 0.009) and peripheral arterial disease (14.5% vs 10.1%; p = 0.021), LV dysfunction (37% vs 27.5%; p = 0.003), mean length (39.6 mm vs 31, 7mm; p Conclusion Since 2014, the incidence of ST at 1 year has been decreasing but remains stuck at a floor level of 0.54% in 2019. The battle for ST seems to have been partly won and its risk factors well identified, but its mortality is still high.

Purpose: To investigate the predictive value of pretherapeutic metabolic tumor imaging using 18-fluorodeoxyglucose positron emission tomography (FDG-PET) for regional response in oropharyngeal cancer patients undergoing primary (chemo)radiation. Methods: Retrospective analysis of oropharyngeal cancer patients treated with primary (chemo)radiation at the University Hospital Zurich from 2010 to 2019 with available FDG-PET. The SUVmax of the largest lymph node metastases was recorded. Regional response was assessed using posttherapeutic FDG-PET at 12 weeks and regional recurrence-free survival. Results: 95 patients with a mean age of 68.5 years (SD 10.3) were included. The median pretherapeutic nodal SUVmax was 8.3 (interquartile range 4.4–13.3). A pretherapeutic nodal SUVmax above 6 significantly predicted poorer regional recurrence-free survival (log-rank test, P = 0.009) in univariate analysis. However, in multivariate analysis SUVmax above 6 was not significant in predicting regional recurrence-free survival (Cox regression P = 0.189). Clinical N category showed a trend in which a more severe stage had a poorer regional survival (Cox regression P = 0.073). Conclusion: The SUVmax of the largest lymph node metastasis seems to play a role in predicting regional response in oropharyngeal cancer patients, after stratifying for N category. More research is needed to investigate whether highly metabolically active disease is less likely to respond to chemoradiation.

OBJECTIVES: We aimed to assess patterns of care delivered to older patients with locally advanced head and neck squamous cell carcinoma (LA-HNSCC), and to analyze the use of geriatric assessment (GA) and assessment of quality of life (QoL).MATERIALS AND METHODS: Members of the head and neck cancer group and the older task force of the European Organisation for Research and Treatment of Cancer (EORTC), members the European Head and Neck Society and members of national groups in Europe were asked to complete a questionnaire about treatment delivered, use of GA, and QoL assessment in older patients with LA-HNSCC.RESULTS: Investigators from 111 centers replied, including 90 (81.1%) academic centers, 16 (14.4%) community hospitals, and 5 (4.5%) private clinics. Large differences in treatment patterns were found. For instance, for oropharyngeal carcinoma, one third of the centers indicated that they treat 40% of older patients with chemoradiation. Fourteen centers (12.6%) routinely perform GA, while 43 centers (38.7%) never do, and 39 centers (35.1%) sometimes do. QoL is assessed on a routine basis in one fifth of the centers.CONCLUSIONS: Large differences exist across institutions in the patterns of care delivered to older patients with LA-HNSCC. Prospective studies are required to learn how GA can guide treatment decisions, and how QoL and treatment outcome can be improved. For that, consensus on standard of care is essential.

OBJECTIVE Angiopoietins (Angs) regulate endothelial permeability. Ang-1 and 2 (Ang-1 and Ang-2) are implied in endothelial stability through an antagonism effect. The objectives of the present study were to describe and compare changes in Ang levels after transcatheter aortic valve replacement (TAVR) and surgical aortic valve replacement (SAVR). DESIGN A prospective, single-center study. PARTICIPANTS Adult patients with aortic stenosis scheduled for SAVR or TAVR. INTERVENTIONS None. MEASUREMENTS AND MAIN RESULTS Ang-1 and Ang-2 were measured using an enzyme-linked immunosorbent assay right before surgery (T0), at the end of surgery (T1), and at day one (T2). Sixty consecutive patients (SAVR group [n = 30] and TAVR group [n = 30]) were included between January and June 2017. Ang-1 decreased significantly after both TAVR (T0: 3,663 [2,602-4,262]; T1: 1,611 [981-2,409]; T2: 1,082 [652-1,589] ng/mL; p < 0.0001) and SAVR (T0: 1,603 [975-2,849]; T1: 783 [547-1,024]; T2: 828 [460-1,227] ng/mL; p = 0.0001). Ang-2 increased significantly after SAVR (T0: 2,472 [1,502-3,622]; T1: 2,997 [1,759-3,839]; T2: 5,421 [3,557-7,087] ng/mL; p < 0.0001) but did not change markedly after TAVR (T0: 3,343 [2,661-6,272]; T1: 3,788 [2,574-5,016]; T2: 3,446 [3,029-6,313] ng/mL; p = 0.066). Among patients with paravalvular leakage, the changes in the plasma Ang-2 level and the Ang-2/Ang-1 ratio were greater. CONCLUSION SAVR induces greater alterations of Ang homeostasis than TAVR, confirming a role for the use of cardiopulmonary bypass. Paravalvular leakage after TAVR is associated with Ang changes similar to those observed with SAVR.

A better understanding of the central role of inflammation in the development of coronary artery disease (CAD) has been the impetus for the evaluation of therapeutic strategies targeting the interleukin-1s/interleukin-6 cytokine signaling pathway, involved in both chronic atherogenesis and in triggering of atherosclerotic plaque rupture. As an inexpensive pharmacologic agent with relatively few adverse effects that tend to be mild and tolerable, the role of colchicine in secondary prevention of atherothrombotic events has been the focus of multiple recent large-scale randomized controlled trials involving patients with stable CAD (Low-Dose Colchicine [LoDoCo] and LoDoCo2 trials), a recent myocardial infarction (Colchicine Cardiovascular Outcome Trial [COLCOT], Colchicine in Patients With Acute Coronary Syndrome [COPS], and Colchicine and Spironolactone in Patients With Myocardial Infarction/Synergy Stent Registry [CLEAR SYNERGY] trials), and undergoing percutaneous coronary interventions (Colchicine in Percutaneous Coronary Intervention [COLCHICINE-PCI] trial). Based on this evidence, low-dose colchicine (0.5 mg once daily) should be considered in patients with recent myocardial infarctions—within 30 days and, ideally, within 3 days—or with stable CAD to improve cardiovascular outcomes. Colchicine should not be used in patients with severe renal or hepatic disease because of the risk of severe toxicity. No serious adverse effect was associated with the combined use of colchicine and high-intensity statin therapy in large trials. The impact of colchicine in high-risk populations of patients with peripheral arterial disease and in those with diabetes for the primary prevention of CAD remains to be established.

International audience; Background and objectives Kidney impairment of ANCA-associated vasculitides can lead to kidney failure. Patients with kidney failure may suffer from vasculitis relapses but are also at high risk of infections and cardiovascular events, which questions the maintenance of immunosuppressive therapy. Design, setting, participants, & measurements Patients with ANCA-associated vasculitides initiating long-term dialysis between 2008 and 2012 in France registered in the national Renal Epidemiology and Information Network registry and paired with the National Health System database were included. We analyzed the proportion of patients in remission off immunosuppression over time and overall and event-free survival on dialysis (considering transplantation as a competing risk). We compared the incidence of vasculitis relapses, serious infections, cardiovascular events, and cancers before and after dialysis initiation. Results In total, 229 patients were included: 142 with granulomatous polyangiitis and 87 with microscopic polyangiitis. Mean follow-up after dialysis initiation was 4.6±2.7 years; 82 patients received a kidney transplant. The proportion of patients in remission off immunosuppression increased from 23% at dialysis initiation to 62% after 5 years. Overall survival rates on dialysis were 86%, 69%, and 62% at 1, 3, and 5 years, respectively. Main causes of death were infections (35%) and cardiovascular events (26%) but not vasculitis flares (6%). The incidence of vasculitis relapses decreased from 57 to seven episodes per 100 person-years before and after dialysis initiation ( P =0.05). Overall, during follow-up, 45% of patients experienced a serious infection and 45% had a cardiovascular event, whereas 13% experienced a vasculitis relapse. Conclusions The proportion of patients with ANCA-associated vasculitis in remission off immunosuppression increases with time spent on dialysis. In this cohort, patients were far less likely to relapse from their vasculitis than to display serious infectious or cardiovascular events. Podcast This article contains a podcast at https://www.asn-online.org/media/podcast/CJASN/2021_11_08_CJN03190321.mp3

Purpose To develop a genotype assay to assess associations with common and rare age-related macular degeneration (AMD) risk variants, to calculate an overall genetic risk score (GRS), and to identify potential misdiagnoses with inherited macular dystrophies that mimic AMD. Design Case-control study. Participants Individuals (n = 4740) from 5 European cohorts. Methods We designed single-molecule molecular inversion probes for target selection and used next generation sequencing to sequence 87 single nucleotide polymorphisms (SNPs), coding and splice-site regions of 10 AMD-(related) genes (ARMS2, C3, C9, CD46, CFB, CFH, CFI, HTRA1, TIMP3, and SLC16A8), and 3 genes that cause inherited macular dystrophies (ABCA4, CTNNA1, and PRPH2). Genetic risk scores for common AMD risk variants were calculated based on effect size and genotype of 52 AMD-associated variants. Frequency of rare variants was compared between late AMD patients and control individuals with logistic regression analysis. Main Outcome Measures Genetic risk score, association of genetic variants with AMD, and genotype–phenotype correlations. Results We observed high concordance rates between our platform and other genotyping platforms for the 69 successfully genotyped SNPs (>96%) and for the rare variants (>99%). We observed a higher GRS for patients with late AMD compared with patients with early/intermediate AMD (P Conclusions This study reports a genotype assay for common and rare AMD genetic variants, which can identify individuals at intermediate to high genetic risk of late AMD and enables differential diagnosis of AMD-mimicking dystrophies. Our study supports sequencing of CFH, CFI, and C3 genes because they harbor rare high-risk variants. Carriers of these variants could be amendable for new treatments for AMD that currently are under development.

Background The arrival of highly effective, well-tolerated, direct-acting antiviral agents (DAA) led to a dramatic decrease in hepatitis C virus (HCV) prevalence. Human immunodeficiency virus (HIV)-HCV–coinfected patients are deemed a priority population for HCV elimination, while a rise in recently acquired HCV infections in men who have sex with men (MSM) has been described. We describe the variations in HIV-HCV epidemiology in the French Dat’AIDS cohort. Methods This was a retrospective analysis of a prospective cohort of persons living with HIV (PLWH) from 2012 to 2018. We determined HCV prevalence, HCV incidence, proportion of viremic patients, treatment uptake, and mortality rate in the full cohort and by HIV risk factors. Results From 2012 to 2018, 50 861 PLWH with a known HCV status were followed up. During the period, HCV prevalence decreased from 15.4% to 13.5%. HCV prevalence among new HIV cases increased from 1.9% to 3.5% in MSM but remained stable in other groups. Recently acquired HCV incidence increased from 0.36/100 person-years to 1.25/100 person-years in MSM. The proportion of viremic patients decreased from 67.0% to 8.9%. MSM became the first group of viremic patients in 2018 (37.9%). Recently acquired hepatitis represented 59.2% of viremic MSM in 2018. DAA treatment uptake increased from 11.4% to 61.5%. More treatments were initiated in MSM in 2018 (41.2%) than in intravenous drug users (35.6%). In MSM, treatment at the acute phase represented 30.0% of treatments in 2018. Conclusions A major shift in HCV epidemiology was observed in PLWH in France from 2012 to 2018, leading to a unique situation in which the major group of HCV transmission in 2018 was MSM. Clinical Trials Registration. NCT02898987.

18-flurodesoxyglucose position emission tomography (FDG-PET) with computed tomography (CT) or magnetic resonance imaging (MRI) is a broadly accepted tool for pretherapeutic staging and post-therapeutic assessment of response. The prognostic value of sequential post-therapeutic FDG-PETs and the impact of change in metabolic activity has been scarcely reported so far. We hypothesized that an increase in metabolic activity (as measured by maximum standardized uptake value, SUVmax) would be predictive for recurrence. We retrospectively assessed all oral, oropharyngeal, laryngeal, and hypopharyngeal squamous cell carcinoma patients treated at the Department of Otorhinolaryngology—Head and Neck Surgery, University Hospital Zurich between April 1st, 2010 and September 30th, 2018 (N = 337). After a negative post-treatment FDG-PET at 3 months, we measured the SUVmax of the local tumor area and the regional lymph nodes on follow-up FDG-PET at 9 months. We then correlated SUVmax difference between 9 and 3 months with tumor recurrence using Kaplan Meier analysis. During follow-up, 68 patients (20.2%) had local recurrence and 53 had regional recurrence (15.7%) at a median time of 9.0 (IQR 4.25–14) and 7.0 (IQR 5.25–23) months, respectively. An increase in local and/or regional SUVmax from the 3 months to the 9 months post-therapeutic FDG-PET resulted in a poorer recurrence-free survival (Log rank, P = 0.001, for both). An increase in local SUVmax between 3 and 9 months was associated with a hazard ratio of 4.17 for recurrence (95%CI 1.89–9.2, P = 0.0003). In conclusion, an increase in metabolic activity/SUVmax between two post-therapeutic FDG-PETs requires a histological examination as it is associated with tumor recurrence.

Resume Introduction La surveillance active (SA) est la principale option therapeutique pour les cancers de prostate (CaP) a faible risque evolutif. L’objectif de ce travail etait d’identifier des facteurs de risque (FDR) de sortie de SA. Materiel et methode Une cohorte historique a ete constituee entre janvier 2011 et octobre 2019 avec tous les patients en SA de notre service. Les caracteristiques initiales des patients qui poursuivaient une SA au terme du suivi ont ete comparees a celles des patients sortis de SA. Une autre analyse a compare les caracteristiques initiales des patients sortis precocement de SA (dans les 3 annees suivant le diagnostic) a celles des autres patients. Resultats Deux cent deux patients ont ete inclus avec une duree moyenne de suivi de 54,54 ± 32 mois. Au moment de l’analyse, 72 patients (36 %) etaient sortis de SA, 118 (58 %) etaient toujours en SA et 12 (6 %) etaient perdus de vue. Soixante-six patients (92 %) etaient sortis de SA en raison d’une progression du CaP, 4 (5 %) par choix personnel et 2 (3 %) pour passage en surveillance simple. Seul le temps de doublement du PSA Conclusion La cinetique d’evolution du PSA etait le principal FDR identifie de sortie de SA au sein de notre cohorte. Niveau de preuve 3.

Sodium fluorescein (NaFL) has been used to aid in the resection of primary and secondary lesions within the brain. Comparatively, there is limited research on clinical applications for lesions within the spinal cord. Fluorescein-guided microsurgery may increase the ability to localize and safely surgically treat spinal lesions. Twelve patients with spinal cord lesions received fluorescein sodium 10% (Alcon Laboratories INC, Fort Worth, TX, USA) at 3 mg/kg prior to surgical resection. Intraoperative visualization of fluorescence was performed using a Zeiss Pentero (Carl Zeiss AG, Oberkochen, Germany) microscope equipped with a Yellow560 filter or a Leica OH6 (Leica Microsystems, Wetzlar, Germany) equipped with a FL560 filter. Administration of NaFL resulted in lesional fluorescent contrast extravasation and facilitated surgical resection and localization in all twelve patients. In patients with a goal of complete resection, NaFL aided in complete resection of the spinal lesions in seven patients. In surgical resection patients, pathology was consistent with WHO grade I myxopapillary ependymoma in one patient, WHO grade II ependymoma in five patients, and nerve sheath tumor in one patient. In the other five patients, NaFL allowed for intraoperative tissue identification and successful tissue biopsy. In patients undergoing biopsy, tissue samples were positive for an intramedullary abscess, EBV-driven lymphoproliferative disease, and primary glial neoplasms. Fluorescein is a helpful microsurgical tool in guiding surgical resection and in the localization of intramedullary spinal lesions. Further research is necessary to explore fluorescein sodium applications in the resection of spinal cord lesions.

Since the law of March 4, 2002, several modifications have impacted medical practices and their medico-legal implications. In case of an infectious complication not related to a fault of the practitioners (surgeons, anesthetists), the patient has the right to compensation assumed by the care structures. Moreover, the lack of preoperative information is no longer just a failing of the ethical standards but a breach of medical and legal obligations. Then, aims of this study were: (1) to describe the reasons for a lawsuit in France following total primary hip (THA) and total knee (TKA) arthroplasties and (2) to compare litigation characteristics of private and public practices. Civil (private practice) and administrative (public practice) court decisions in France between 1990 and 2020 were collected using the two main legal data sources (Legifrance, Doctrine). Eighty-three TKA and 173 THA cases were identified. Reasons for complaint in primary THA were mainly infection (29%), prosthetic failures (18%), nerves injuries (17%), and leg length discrepancies (11%). The main grounds for complaint in favor of the plaintiff were diagnostic or indication mistakes (100%), infections (80%), especially if a lack of information was recognized (88%). Reasons for complaint following primary TKA were mainly infections (65%) and persistent pain or stiffness (12%). Whatever the reason, the verdict was in favor of the plaintiff in about 2/3 of the cases. THAs were more at risk of appeal in administrative procedures than in civil (p = 0.008). There were more cases of implant failure in civil proceedings (p = 0.008). Indemnities after primary THA was higher in public activity litigation (p = 0.04). There were no differences in verdicts, grounds for complaints, and compensation between public and private practices for primary TKA. The main complaint about all the arthroplasties in France was a septic complication. The lack of information could be an added pejorative element for the final verdict.

BACKGROUND: Adolescent Idiopathic Scoliosis (AIS) requires complex medical care because of multiple consequences especially on daily activities. Muscular involvement is part of the problem and may be treatable. OBJECTIVE: To analyze trunk muscle strength using an isokinetic dynamometer in female adolescents with AIS one year after orthopedic treatment by brace and compare the findings to a matched group of an asymptomatic cohort. METHODS: The trunk flexors and extensors strength was measured using an isokinetic dynamometer at 60, 90 and 120∘/s. Peak Moment (PM), Mean Power (MP) and the flexor/extensor ratio in 100 patients aged 14 to 18 years old were compared to a control group (N= 32) of asymptomatic age-matched females. In the AIS group, correlation analyses were computed to search for contributing factors to isokinetic performances, including morphological characteristics of patients, as well as clinical and radiological characteristics of the scoliosis. RESULTS: The trunk flexors in the AIS group were significantly but moderately (15%) weaker across speeds compared to their control counterparts at all speeds. No parallel weakness was noted for the extensors. While the MP of AIS patients was significantly weaker than that of the controls, 33% for flexors and by 31% for extensors, no significant differences were observed for the F/E ratios. The correlational analyses has indicated that weight and BMI were contributing factors at all speeds. CONCLUSION: Adolescents with AIS had weaker trunk extensors and mostly flexors compared to healthy females. Within this AIS population, weight and BMI seem to have a negative impact on muscular performances, whereas clinical and radiological characteristics of the scoliosis do not seem to contribute.

Objective Contrast-enhanced computed tomography angiography (CTA) is commonly used to investigate acute abdominal conditions, but the risk of contrast-induced acute kidney injury (CI-AKI) has been poorly investigated in patients with acute mesenteric ischemia. The aim of the present study was to evaluate the incidence of CI-AKI in these patients and identify potential predictive factors. Methods Patients admitted for acute mesenteric ischemia who had a diagnostic CTA with contrast medium and a follow-up of creatinine concentration were retrospectively included. Results Among 53 patients included, 9 (16.9%) developed CI-AKI. The prevalence of chronic kidney disease did not differ significantly between those who developed CI-AKI and those who did not (33.3 vs 18.2%, p=.372). Plasma total bilirubin and conjugated bilirubin levels were significantly higher in patients who developed CI-AKI (17.5 vs 8.0 μmol/L, p=.013 and 8.0 vs 3.0 μmol/L, p=.031, respectively). The proportion of patients who had revascularization was similar between patients who developed CI-AKI and those who did not (11.1 vs 20.5%, p>.999). No significant difference was observed for 30-day mortality and all-cause mortality for a median follow-up of 168 days (22.2 vs 13.6%, p=.611; and 33.3 vs 61.4%, p=.153, respectively). Conclusion This study reports the incidence of CI-AKI in patients with acute mesenteric ischemia after diagnostic CTA with contrast medium. Plasma bilirubin levels were a predictive factor of CI-AKI in these patients. The administration of contrast media during revascularization was not associated with an increased risk of CI-AKI.

The prevalence of non-linear viewing habits calls for new regulation practices that extend beyond the current scope of traditional audiovisual regulators. Yet content quotas expressed as shares of ...

AIMS To compare efficacy and safety between neurogenic and non-neurogenic women after adjustable continence therapy (ACT®) balloons implantation to treat stress urinary incontinence (SUI) due to intrinsic sphincter deficiency. METHODS In the present retrospective multicentric study, all neurogenic and non-neurogenic women implanted with ACT® balloons between 2000 and 2018 were considered for inclusion. Efficacy was compared 1 year after implantation, and women were allocated in three different groups as follows. Success: maximum 1 pad per day and patient's impression of improvement assessed using a numeral rating scale (NRS) ≥8/10. Improvement: decrease of daily pad use and/or NRS ≥5/10. Failure: increase or stability of daily pad use or NRS

The Aeson® total artificial heart (A-TAH) has been developed as a total heart replacement for patients at risk of death from biventricular failure. We previously described endothelialization of the hybrid membrane inside A-TAH probably at the origin of acquired hemocompatibility. We aimed to quantify vasculogenic stem cells in peripheral blood of patients with long-term A-TAH implantation. Four male adult patients were included in this study. Peripheral blood mononuclear cells were collected before A-TAH implantation (T0) and after implantation at one month (T1), between two and five months (T2), and then between six and twelve months (T3). Supervised analysis of flow cytometry data confirmed the presence of the previously identified Lin-CD133+CD45- and Lin-CD34+ with different CD45 level intensities. Lin-CD133+CD45-, Lin-CD34+CD45- and Lin-CD34+CD45+ were not modulated after A-TAH implantation. However, we demonstrated a significant mobilization of Lin-CD34+CD45dim (p = 0.01) one month after A-TAH implantation regardless of the expression of CD133 or c-Kit. We then visualized data for the resulting clusters on a uniform manifold approximation and projection (UMAP) plot showing all single cells of the live Lin- and CD34+ events selected from down sampled files concatenated at T0 and T1. The three clusters upregulated at T1 are CD45dim clusters, confirming our results. In conclusion, using a flow cytometry approach, we demonstrated in A-TAH-transplanted patients a significant mobilization of Lin-CD34+CD45dim in peripheral blood one month after A-TAH implantation. Using a flow cytometry approach, we demonstrated in A-TAH transplanted patients a significant mobilization of Lin-CD34+CD45dim in peripheral blood one month after A-TAH implantation. This cell population could be at the origin of newly formed endothelial cells on top of hybrid membrane in Carmat bioprosthetic total artificial heart.

Background The usefulness of D-dimer measurement to rule out venous thromboembolism (VTE) during pregnancy is debated. Objectives We performed a systematic review and meta-analysis to investigate the safety of D-dimer to rule out acute VTE in pregnant women with suspected pulmonary embolism and/or deep vein thrombosis. Methods Two reviewers independently identified studies through PubMed and Embase until June 2021, week 1. We supplemented our search by manually reviewing reference lists of all retrieved articles, clinicalTrials.gov, and reference literature. Prospective or retrospective studies in which a formal diagnostic algorithm was used to evaluate the ability of D-dimer to rule out VTE during pregnancy were eligible. Results We identified 665 references through systematic database and additional search strategies; 45 studies were retrieved in full, of which four were included, after applying exclusion criteria. Three studies were prospective, and one had a retrospective design. The 3-month thromboembolic rate in pregnant women left untreated after a negative D-dimer was 1/312 (0.32%; 95% CI, 0.06-1.83). The pooled estimate values were 99.5% for sensitivity (95% CI, 95.0-100.0; I², 0%) and 100% for negative predictive value (95% CI, 99.19-100.0; I², 0%). The prevalence of VTE and the yield of D-dimer were 7.4% (95% CI, 3.8-12; I², 83%) and 34.2% (95% CI, 15.9-55.23; I², 89%) respectively. Conclusion Our results suggest that D-dimer allows to safely rule out VTE in pregnant women with suspected VTE and a disease prevalence consistent with a low/intermediate or unlikely pretest probability.