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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.

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.

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

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

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.

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.

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.

Resume L’osteotomie femorale distale de valgisation voit ses indications s’elargir par une meilleure comprehension des deformations segmentaires du membre inferieur. Historiquement, une deformation globale en varus etait corrigee dans le tibia et une deformation en valgus dans le femur. Cette approche consistant a realiser une correction « tout dans le tibia » pour un varus global peut neanmoins conduire a une morphologie postoperatoire anormale car non-anatomique avec creation d’un interligne oblique et potentiellement de contraintes de cisaillement cartilagineuses. Une technique originale d’osteotomie femorale de valgisation par fermeture laterale est decrite, celle-ci permet la correction d’un genu varum d’origine femorale ou mixte en cas d’osteotomie tibiale de valgisation associee. La technique detaillee permet de limiter le risque de fracture de charniere tout en ameliorant les suites postoperatoires.

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.

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.

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.

Aim This review article summarizes the current clinical practice guidelines around disease definitions and risk stratifications, and the treatment of non-muscle-invasive bladder cancer (NMIBC). Recently completed and ongoing clinical trials of novel and investigational therapies in Bacillus Calmette-Guerin (BCG)-naive, BCG-recurrent, and BCG-unresponsive patient populations are also described, e.g., those involving immune checkpoint inhibitors, targeted therapies, other chemotherapy regimens, vaccines, and viral- or bacterial-based treatments. Finally, a brief overview of enhanced cystoscopy and drug delivery systems for the diagnosis and treatment of NMIBC is provided. Background A global shortage of access to BCG is affecting the management of BCG-naive and BCG-recurrent/unresponsive NMIBC; hence, there is an urgent need to assist patients and urologists to enhance the treatment of this disease. Methods Searches of ClinicalTrials.gov, PubMed, and Google Scholar were conducted. Published guidance and conference proceedings from major congresses were reviewed. Conclusion Treatment strategies for NMIBC are generally consistent across guidelines. Several novel therapies have demonstrated promising antitumor activity in clinical trials, including in high-risk or BCG-unresponsive disease. The detection, diagnosis, surveillance, and treatment of NMIBC have also been improved through enhanced disease detection.

Purpose To evaluate the impact of COVID-19 pandemic on functional urology procedures in France. Methods A prospective study was conducted within 11 secondary and tertiary referral centers in France. Patients aged > 18 years who were diagnosed with a functional urology disease before the national lockdown (March 17th, 2020) and who required a surgery were included. Study period went from March 17th to September 30th 2020. The included interventions were listed according to the guidelines for functional urology enacted by the French Association of Urology and delay of reoperation was compared to the guidelines’ delay. The primary outcome was the number of procedures left unscheduled at the end of the study period. Descriptive statistics were performed. Results From March 17th 2020 to September 3 rd 2020, 1246 patients with a previous diagnosis of a functional urological disease requiring a surgery were included. The mean follow-up was 140.4 days (± 53.4). Overall, 316 interventions (25.4%) were maintained whereas 74 (5.9%) were canceled, 848 (68.1%) postponed and 8 patients (0.6%) died. At the end of the follow-up, 184 patients (21.7%) were still not rescheduled. If the intervention was postponed, the mean delay between the initial and final date was 85.7 days (± 64.4). Conclusion Overall, more than two thirds of interventions had to be postponed and the mean delay between the initial and final date was about three months.

Summary Aim Secondary uretero-arterial fistulas (SUAF) are uncommon, underrated and threatening for any patient. Gross hematuria is a clinical symptom of this pathology for patients with history of pelvic radiotherapy, complex pelvic surgery or long-term ureteral stenting. The purpose of this work is to assess risk factors, diagnosis and treatment of SUAF. Methods Monocentric and retrospective series of 6 new cases illustrated by a literature review through MedLine and Pubmed using the keywords “arterio-ureteral fistula”, “arterio iliac fistula” and “ilio-ureteral fistula”. We excluded uretero-arterial fistula following vascular surgery. Results Our series included 4 men and 2 women. All patients had a history of complex pelvic surgery and long-term ureteral stenting. Three patients had history of pelvic radiotherapy. They all had inaugural macroscopic haematuria episode. Two fistula cases were diagnosed on 5 repeated CT-scans. In 2 out of 5 cases, arteriography highlighted the fistula. Fistulas were generally located at the left common iliac artery. An endovascular stent was placed in 5 out of 6 cases. One patient needed open surgery. After treatment, 3 patients remained alive, 3 patients died either by a fistula relapse or by complications late in the treatment. Conclusion SUAF are uncommon, but serious. Today, there is no specific recommendation regarding complex treatment of these fistulas. Endovascular stents seem to be a good therapeutic option. Level of proof 3.

Background The prevalence of pressure injuries (PIs) in critically ill patients has been extensively studied, but there is uncertainty regarding the risk factors. The main objective of this study was to describe the prevalence of PIs in critically ill patients. Secondary objectives were to describe PI, use of preventive measures for PI, and factors associated with occurrence of PI in the intensive care unit (ICU). Material and methods This was a 1-day point-prevalence study performed on a weekday in June 2017 in ICUs in France. On the same day, we noted the presence or absence of PI in all hospitalised patients of the participating ICUs, data on the ICUs, and the characteristics of patients and of PI. Results Eighty-six participating ICUs allowed the inclusion of 1228 patients. The prevalence of PI on the study day was 18.7% (95% confidence interval: 16.6–21.0). PIs acquired in the ICU were observed in 12.5% (95% confidence interval: 10.6–14.3) of critically ill patients on the study day. The most frequent locations of PI were the sacrum (57.4%), heel (35.2%), and face (8.7%). Severe forms of PI accounted for 40.8% of all PIs. Antiulcer mattresses were used in 91.5% of the patients, and active and/or passive mobilisation was performed for all the patients. Multiple logistic regression analysis identified longer length of stay in the ICU, a higher Simplified Acute Physiology Score, higher body weight, motor neurological disorder, high-dose steroids, and absence of oral nutrition on the study day as factors independently associated with occurrence of PI in the ICU. Conclusion This large point-prevalence study shows that PIs are found in about one of five critically ill patients despite extensive use of devices for preventing PI. Acquisition of PI in the ICU is strongly related to the patient's severity of illness on admission to the ICU and length of stay in the ICU.

Aims: It has been hypothesized that altitude training may alter running mechanics due to several factors such as the slower training velocity with associated alteration in muscle activation and coordination. This would lead to an altered running mechanics attested by an increase in mechanical work for a given intensity and to the need to “re-establish” the neuromuscular coordination and running biomechanics postaltitude. Therefore, the present study aimed to test the hypothesis that “live high—train high” would induce alteration in the running biomechanics (ie, longer contact time, higher vertical oscillations, decreased stiffness, higher external work). Methods: Before and 2 to 3 days after 3 weeks of altitude training (1850–2200 m), 9 national-level middle-distance (800–5000 m) male runners performed 2 successive 5-minute bouts of running at moderate intensity on an instrumented treadmill with measured ground reaction forces and gas exchanges. Immediately after the running trials, peak knee extensor torque was assessed during isometric maximal voluntary contraction. Results: Except for a slight (−3.0%; P = .04) decrease in vertical stiffness, no mechanical parameters (stride frequency and length, contact and flight times, ground reaction forces, and kinetic and potential work) were modified from prealtitude to postaltitude camp. Running oxygen cost was also unchanged. Discussion: The present study is the first one to report that “live high—train high” did not change the main running mechanical parameters, even when measured immediately after the altitude camp. This result has an important practical implication: there is no need for a corrective period at sea level for “normalizing” the running mechanics after an altitude camp.

Background A small proportion of patients with chronic obstructive pulmonary disease (COPD) patients present severe pulmonary hypertension (PH), defined by mean pulmonary artery pressure (mPAP) ≥35 mm Hg measured by right heart catheterization. Little is known about the characteristics of severe PH-COPD. The aim of the study based on a national registry was to describe this phenotype. Methods We prospectively included and followed patients with incident PH-COPD. Clinical, functional, hemodynamic data at inclusion and follow-up were retrieved. Survival assessed by Kaplan-Meier analysis was the primary end-point. Results From 2012 to 2016, 99 patients from 13 French centers were included in the study (82 males; median age 66.0 years [interquartile range 62.0-72.0]). At inclusion, most patients had marked dyspnea (55.6% and 22.2% New York Heart Association class III and IV, respectively). During 12 months before inclusion, 42.9% had an exacerbation requiring a hospitalization. Pulmonary function tests showed a moderate obstructive pattern with median (interquartile range) FEV1 50.0 [35.0-63.0] % predicted and low diffusing capacity for carbon monoxide, median 20.0 [16.5-30.6] % predicted. The median values for PaO2 and PaCO2 on room air were 50.0 [44.8-62.0] and 36.0 [31.1-43.0] mm Hg. Median values of mPAP, pulmonary artery occlusion pressure, cardiac index and pulmonary vascular resistance were 42.0 [37.0-48.0] mm Hg, 11.0 [9.0-14.0] mm Hg, 3.0 [2.4-3.6] L/min/m2, and 6.3 [4.2-7.9] WU, respectively. Mean restricted survival was 15.0 [13.9-16.0] months. Conclusions Severe PH-COPD is characterized by moderate airway obstruction but marked dyspnea and marked hypoxemia, low DLCO and high mPAP. This phenotype is associated with poor prognosis.

Aims Whether obesity is associated with a higher risk of cardiovascular events in the absence of metabolic risk factors is a matter of debate. We evaluated the associations among metabolically healthy obesity (MHO) and different types of incident cardiovascular events in a contemporary population. Methods All patients discharged from French hospitals in 2013 with at least 5 years of follow-up and without a history of major adverse cardiovascular event (myocardial infarction, heart failure [HF], ischemic stroke or cardiovascular death, MACE-HF) or underweight/malnutrition were identified. They were categorized by phenotypes defined by obesity and 3 metabolic abnormalities (diabetes mellitus, hypertension, and hyperlipidemia). Hazard ratios for cardiovascular events during follow-up were adjusted on age, sex and smoking status at baseline. Results In total, 2,873,039 individuals were included in the analysis, among whom 272,838 (9.5%) had obesity. During a mean follow-up of 4.9 years, when pooling men and women, individuals with MHO had a higher risk of MACE-HF (multivariate-adjusted hazard ratio [HR] 1.22, 95% confidence interval [CI]: 1.19-1.24), new-onset HF (HR 1.34, 95%CI 1.31-1.37), and AF (HR 1.33, 95%CI 1.30-1.37) compared with individuals with no obesity and 0 metabolic abnormalities. By contrast, risks were not higher for myocardial infarction (HR 0.92, 95%CI 0.87-0.98), ischemic stroke (HR 0.93, 95%CI 0.88-0.98) and cardiovascular death (HR 0.99, 95%CI 0.93-1.04). MHO in men was associated with higher risk of clinical events compared to MH men with normal weight (HR 1.12 to 1.80) while women with MHO had lower risk for most events than MH women with normal weight (HR 0.49 to 0.99). Conclusions In a large and contemporary analysis of patients seen in French hospitals, individuals with MHO did not have a higher risk of myocardial infarction, ischemic stroke or cardiovascular death than metabolically healthy individuals with no obesity. By contrast they had a higher risk of new-onset HF and new onset AF. Notable differences were however observed in men and women in the sex-stratified analysis. This article is protected by copyright. All rights reserved.

Aims Venoarterial extracorporeal membrane oxygenation (VA‐ECMO) is increasingly being used in circulatory failure. The main indications are cardiogenic shock, post‐cardiotomy cardiac failure, and refractory cardiac arrest. However, VA‐ECMO weaning is particularly challenging, and weaning failure is reported to be as high as 50%, with increased related mortality. Levosimendan is a novel long acting effect inodilator used in cardiogenic shock and terminal heart failure decompensation. Levosimendan use in VA‐ECMO patients seems to reduce weaning failure regardless of the initial aetiology and to reduce mortality when administrated early after VA‐ECMO initiation. However, studies are limited to retrospective analyses and reported case series. The aim of the WEANILEVO trial is to evaluate whether administration of levosimendan before VA‐ECMO weaning is associated with a reduced rates of weaning failure and recourse to other temporary circulatory support. Methods and results WEANILEVO is a randomized, prospective, multicentre, double‐blind, parallel‐group, controlled trial. One hundred eighty patients will be enrolled if they had acute circulatory heart failure treated with VA‐ECMO and for whom weaning is expected within 48 h. The study drugs are either levosimendan (0.2 μg/kg/min for 24 h) or a placebo. The primary endpoint of the trial is the absence of VA‐ECMO weaning, recourse to another VA‐ECMO, or other temporary circulatory assistance or death within 7 days of VA‐ECMO weaning. Conclusions Levosimendan use in VA‐ECMO appears to be beneficial for reducing weaning failure and mortality. The results of WEANILEVO should significantly influence decisions regarding the use of levosimendan for VA‐ECMO weaning.

International audience; Background Diagnosis of heparin-induced thrombocytopenia (HIT) requires pretest probability assessment and dedicated laboratory assays.Objective To develop a pretest score for HIT.Design Observational; analysis of prospectively collected data of hospitalized patients suspected with HIT (ClinicalTrials.gov NCT00748839).Setting Thirty-one tertiary hospitals in France, Switzerland, and Belgium.Patients Patients tested for HIT antibodies (2280 evaluable), randomly allocated to derivation and validation cohorts.Measurements Independent adjudicators diagnosed HIT based on the prospectively collected data and serotonin release assay results.Results Heparin-induced thrombocytopenia was diagnosed in 234 (14.7%) and 99 (14.5%) patients in the two cohorts. Eight features were associated with HIT (in brackets, points assigned for score calculation of the score): unfractionated heparin (1); therapeutic-dose heparin (1); cardiopulmonary bypass (cardiac surgery) (2); major trauma (3); 5- to 21-day interval from anticoagulation initiation to suspicion of HIT (4); >= 40% decrease in platelet count over

Background No current guidelines are available for managing septic bursitis (SB). Objectives To describe the clinical characteristics and management of olecranon and prepatellar SB in five French tertiary care centres. Methods This is a retrospective observational multicentre study. SB was diagnosed on the basis of positive cultures of bursal aspirate. In the absence of positive bursal fluid, the diagnosis came from typical clinical presentation, exclusion of other causes of bursitis and favourable response to antibiotic therapy. Results We included 272 patients (median age of 53 years, 85.3% male and 22.8% with at least one comorbidity). A microorganism was identified in 184 patients (67.6%), from bursal fluids in all but 4. We identified staphylococci in 135 samples (73.4%), streptococci in 35 (19%) and 10 (5.5%) were polymicrobial, while 43/223 bursal samples remained sterile (19.3%). Forty-nine patients (18%) were managed without bursal fluid analysis. Antibiotic treatment was initially administered IV in 41% and this route was preferred in case of fever (P = 0.003) or extensive cellulitis (P = 0.002). Seventy-one (26%) patients were treated surgically. A low failure rate was observed (n = 16/272, 5.9%) and failures were more frequent when the antibiotic therapy lasted Conclusions Despite variable treatments, SB resolved in the majority of cases even when the treatment was exclusively medical. The success rate was equivalent in the non-surgical and the surgical management groups. However, a treatment duration of

To compare transcorporal vs bulbar artificial urinary sphincter (AUS) implantation in men with fragile urethra and to investigate the risk factors of AUS explantation in this population. The charts of all male patients who had an AUS implantation between 2004 and 2020 in 16 centers were reviewed retrospectively. The primary endpoint was device explantation-free survival. Only patients with a fragile urethra were included in the present analysis. Fragile urethra was defined as a urethra carrying a high risk of cuff erosion because of prior radiotherapy and/or history of AUS explantation and/or history of urethral stricture surgery. The patients were divided in two groups according to the implantation site: bulbar vs transcorporal. 464 patients were included for analysis. 88 patients underwent a transcorporal AUS implantation and 376 underwent a bulbar AUS implantation. Explantation-free survival was similar in both groups (estimated 5-year explantation free survival rates 55.3% vs. 58.4%; p=0.98). In the subgroup of patients with a history of previous AUS explantation, transcorporal approach tended to bring longer explantation-free survival (2-year explantation-free survival: 61.9% vs. 58.2%; p=0.096). In multivariate analysis, the only risk factor of shorter explantation-free survival was the history of previous AUS explantation (HR=2.65; p=0.01). Transcorporal AUS implantation was not associated with longer explantation-free survival. History of previous AUS explantation was the only risk factor associated with shorter explantation-free survival and this subgroup of patients may be the only one to draw benefits of transcorporal AUS implantation.

Background and objectives In Canada, men having sex with men (MSM) are deferred for 3 months from last sexual contact to reduce human immunodeficiency virus (HIV) risk to recipients. The aim of this paper was to model the Canadian residual risk of HIV-positive source plasma incorporating pathogen inactivation (PI) under no MSM deferral scenarios for apheresis plasma donations. Materials and methods A combined Bayesian network (BN) and Monte Carlo approach were implemented to estimate the HIV residual risk under 3-month deferral compared with no deferral without quarantine scenarios for MSM donors. Models involve the stochastic generation of donation and its infection status based on its corresponding simulated donor profile. Viral load reduction conferred by PI used by source plasma fractionators was simulated. Model parameters were derived from Hema-Quebec and Canadian Blood Services data, viral loads in a large sample of HIV-positive US blood donors, CSL Behring documentation and from published data. Results In the most likely scenario for the 3-month deferral model, there were 2.71 positive donations per 1,000,000 donations (95% confidence interval [CI] 2.63-2.78). For the no-deferral model, there were 3.01 positive donations per 1,000,000 donations (95% CI 2.94-3.09). For both scenarios, the risk of having an infectious pool was 0 in 300,000 pools (95% CI 0-0.0000123) after consideration of PI. Conclusion Based on simulation results, there would be a negligible HIV residual risk associated with the removal of a time-based MSM deferral without quarantine for source plasma incorporating PI.

Purpose Automated planning techniques aim to reduce manual planning time and inter-operator variability without compromising the plan quality which is particularly challenging for head-and-neck (HN) cancer radiotherapy. The objective of this study was to evaluate the performance of an a priori-multicriteria plan optimization algorithm on a cohort of HN patients. Methods A total of 14 nasopharyngeal carcinoma (upper-HN) and 14 “middle-lower indications” (lower-HN) previously treated in our institution were enrolled in this study. Automatically generated plans (autoVMAT) were compared to manual VMAT or Helical Tomotherapy planning (manVMAT-HT) by assessing differences in dose delivered to targets and organs at risk (OARs), calculating plan quality indexes (PQIs) and performing blinded comparisons by clinicians. Quality control of the plans and measurements of the delivery times were also performed. Results For the 14 lower-HN patients, with equivalent planning target volume (PTV) dosimetric criteria and dose homogeneity, significant decrease in the mean doses to the oral cavity, esophagus, trachea and larynx were observed for autoVMAT compared to manVMAT-HT. Regarding the 14 upper-HN cases, the PTV coverage was generally significantly superior for autoVMAT which was also confirmed with higher calculated PQIs on PTVs for 13 out of 14 patients, whereas PQIs calculated on OARs were generally equivalent. Number of MUs and total delivery time were significantly higher for autoVMAT compared to manVMAT. All plans were considered clinically acceptable by clinicians. Conclusions Overall superiority of autoVMAT compared to manVMAT-HT plans was demonstrated for HN cancer. The obtained plans were operator-independent and required no post-optimization or manual intervention.

Introduction Head and neck reconstructive surgery using a flap is increasingly common. Best practices and outcomes for postoperative radiotherapy (poRT) with flaps have not been specified. We aimed to provide consensus recommendations to assist clinical decision-making highlighting areas of uncertainty in the presence of flaps. Material and methods Radiation, medical, and surgical oncologists were assembled from GORTEC and internationally with the Head and Neck Cancer International Group (HNCIG). The consensus-building approach covered 59 topics across four domains: (1) identification of postoperative tissue changes on imaging for flap delineation, (2) understanding of tumor relapse risks and target volume definitions, (3) functional radiation-induced deterioration, (4) feasibility of flap avoidance. Results Across the 4 domains, international consensus (median score ≥ 7/9) was achieved only for functional deterioration (73.3%); other consensus rates were 55.6% for poRT avoidance of flap structures, 41.2% for flap definition and 11.1% for tumor spread patterns. Radiation-induced flap fibrosis or atrophy and their functional impact was well recognized while flap necrosis was not, suggesting dose-volume adaptation for the former. Flap avoidance was recommended to minimize bone flap osteoradionecrosis but not soft-tissue toxicity. The need for identification (CT planning, fiducials, accurate operative report) and targeting of the junction area at risk between native tissues and flap was well recognized. Experts variably considered flaps as prone to tumor dissemination or not. Discrepancies in rating of 11 items among international reviewing participants are shown. Conclusion International GORTEC and HNCIG-endorsed recommendations were generated for the management of flaps in head and neck radiotherapy. Considerable knowledge gaps hinder further consensus, in particular with respect to tumor spread patterns.

International audience; Aim: To compare methods of quantifying serum hepcidin (based on MS and ELISA) and their ability to diagnose true iron deficiency anemia in critically ill patients. Materials & methods: Serum hepcidin was measured in 119 critically ill patients included in the HEPCIDANE clinical trial, using either an ultra-sensitive ELISA kit (from DRG) or two different MS methods. Results: The results show a good correlation between the different methods studied. The Bland–Altman analysis and the Kappa test for clinical groups show a good or very good agreement between the different tests. Conclusion: ELISA or MS show a satisfactory commutability to quantify serum hepcidin. This is of great importance for the determination of therapeutic strategies in iron deficiency.

To test the hypothesis that interval-training (IHT) would be impaired by hypoxia to a larger extent than repeated-sprint training (RSH) and that dietary nitrate (NO3−) would mitigate the detrimental effect of hypoxia to a larger extent during IHT than RSH. Thirty endurance-trained male participants performed IHT (6 × 1 min at 90%∆ with 1 min active recovery) and RSH (2 sets of 6 × 10 s “all-out” efforts with 20 s active recovery) on a cycle ergometer, allocated in one of three groups: normobaric hypoxia (~ 13% FiO2) + NO3− − HNO, n = 10; normobaric hypoxia + placebo − HPL, n = 10; normoxia (20.9% FiO2) + placebo − CON, n = 10. Submaximal oxygen uptake ( $$\dot{V}$$ O2), time spent above 90% of maximal $$\dot{V}$$ O2 (≥ 90 $$\dot{V}$$ O2max) and heart rate (≥ 90 HRmax) were compared between IHT and RSH sessions and groups. Additionally, mean power output (MPO), decrement score and % of power associated with $$\dot{V}$$ O2max (%p $$\dot{V}$$ O2max) in RSH sessions were analyzed. $$\dot{V}$$ O2 at sub-maximal intensities did not differ between training protocols and groups (~ 27 ml kg−1 min−1). ≥ 90 HRmax was significantly higher in IHT compared to RSH session (39 ± 8 vs. 30 ± 8%, p = 0.03) but only in HNO group. MPO (range 360–490 W) and decrement score (10–13%) were similar between groups although %p $$\dot{V}$$ O2max was significantly higher (p = 0.04) in CON (166 ± 16 W) compared with both HPL (147 ± 15 W) and HNO (144 ± 10 W) groups. IHT responses were neither more impaired by hypoxia than RSH ones. Moreover, dietary NO3− supplementation impacted equally IHT and RSH training responses’ differences between hypoxia and normoxia.

International audience; Background & aims: Sarcopenia is a multifactorial syndrome resulting in a decrease in both muscle mass and function. Little is known about the prevalence and prognostic impact of sarcopenia in patients with acutely decompensated chronic heart failure (ADHF). We aimed to evaluate the prevalence (main endpoint) and impact of sarcopenia on ADHF patients.Methods: 140 ADHF patients were enrolled between November 2014 and September 2018 in a multi-center prospective longitudinal study. A similar, independent multi-departmental cross-sectional study in 165 ADHF patients was used for external validation of prevalence data. All subjects were assessed on the European Working Group on Sarcopenia criteria.Results: Ninety-one patients (65%) had sarcopenia (vs. 53.6% in the external replication regional cohort). Patients with sarcopenia were older and more likely to have eGFR

Resume Introduction Lorsque la deformation tibiale ou femorale n’est pas analysee avec precision, les osteotomies de correction peuvent aboutir a une interligne articulaire oblique. L’objectif de cette etude etait d’evaluer la deformation preoperatoire des patients planifies pour une osteotomie de correction et d’analyser les taux d’anomalies morphologiques du tibia et du femur obtenus apres le planning virtuel de correction realise a l’aide d’un logiciel de mesures 3D. Materiel et methode Les scanners de 327 patients programmes pour une osteotomie ont ete retrospectivement analyses. Chaque patient etait planifie a l’aide d’un logiciel et la correction virtuelle simulee etait validee par le chirurgien. Apres realisation de l’osteotomie virtuelle, les valeurs angulaires du tibia et du femur dans le plan coronal etaient considerees comme anormales si elles se trouvaient en dehors de l’intervalle de confiance a 97,5 % retrouvees pour des genoux non arthrosiques. Apres l’osteotomie virtuelle, les anomalies morphologiques etaient classees en deux groupes. Une erreur de type 1 correspondait a une sous- ou sur-correction au niveau du site de l’osteotomie aboutissant a une morphologie osseuse anormale. Une erreur de type 2 correspondait a une erreur au niveau du site de correction aboutissant a une morphologie osseuse non corrigee liee a une valeur angulaire en dehors de son intervalle de confiance. Resultats Le taux global d’anomalies planifiees apres osteotomie tibiale etait de 50,8 % (166/327) avec des erreurs de type 1 dans 44 % et de type 2 dans 6,7 %. Apres osteotomie femorale virtuelle, le taux global d’erreurs etait de 6,7 % (22/327) avec uniquement des anomalies de type 1. Un faible angle HKA preoperatoire etait significativement associee a une correction non anatomique (R2 = 0,12, p Conclusion Une correction non anatomique etait retrouvee dans plus de la moitie des cas analyses et plus frequemment en cas d’alignement global preoperatoire en varus. Ces resultats suggerent que les chirurgiens doivent considerer les valeurs angulaires normales afin d’eviter la creation d’une interligne oblique. Niveau de preuve III ; etude de cohorte retrospective.

Background Patients with obesity are at higher risk for community-acquired and nosocomial infections. However, no study has specifically evaluated the relationship between obesity and ventilator-associated pneumonia (VAP). Research Question Is obesity associated with an increased incidence of VAP? Study Design and Methods This study was a post hoc analysis of the Impact of Early Enteral vs Parenteral Nutrition on Mortality in Patients Requiring Mechanical Ventilation and Catecholamines (NUTRIREA2) open-label, randomized controlled trial performed in 44 French ICUs. Adults receiving invasive mechanical ventilation and vasopressor support for shock and parenteral nutrition or enteral nutrition were included. Obesity was defined as BMI ≥ 30 kg/m2 at ICU admission. VAP diagnosis was adjudicated by an independent blinded committee, based on all available clinical, radiologic, and microbiologic data. Only first VAP episodes were taken into account. Incidence of VAP was analyzed by using the Fine and Gray model, with extubation and death as competing risks. Results A total of 699 (30%) of the 2,325 included patients had obesity; 224 first VAP episodes were diagnosed (60 and 164 in obese and nonobese groups, respectively). The incidence of VAP at day 28 was 8.6% vs 10.1% in the two groups (hazard ratio, 0.85; 95% CI 0.63-1.14; P = .26). After adjustment on sex, McCabe score, age, antiulcer treatment, and Sequential Organ Failure Assessment at randomization, the incidence of VAP remained nonsignificant between obese and nonobese patients (hazard ratio, 0.893; 95% CI, 0.66-1.2; P = .46). Although no significant difference was found in duration of mechanical ventilation and ICU length of stay, 90-day mortality was significantly lower in obese than in nonobese patients (272 of 692 [39.3%] patients vs 718 of 1,605 [44.7%]; P = .02). In a subgroup of patients (n = 123) with available pepsin and alpha-amylase measurements, no significant difference was found in rate of abundant microaspiration of gastric contents, or oropharyngeal secretions between obese and nonobese patients. Interpretation Our results suggest that obesity has no significant impact on the incidence of VAP.

Globally, about 400 million people reside at terrestrial altitudes above 1500 m, and more than 100 million lowlanders visit mountainous areas above 2500 m annually. The interactions between the low barometric pressure and partial pressure of O2, climate, individual genetic, lifestyle and socio-economic factors, as well as adaptation and acclimatization processes at high elevations are extremely complex. It is challenging to decipher the effects of these myriad factors on the cardiovascular health in high altitude residents, and even more so in those ascending to high altitudes with or without preexisting diseases. This review aims to interpret epidemiological observations in high-altitude populations; present and discuss cardiovascular responses to acute and subacute high-altitude exposure in general and more specifically in people with preexisting cardiovascular diseases; the relations between cardiovascular pathologies and neurodegenerative diseases at altitude; the effects of high-altitude exercise; and the putative cardioprotective mechanisms of hypobaric hypoxia.

Purpose: To report the changes in the training characteristics, performance, and heart-rate variability (HRV) of the world’s most successful male biathlete of the last decade. Method: During the analyzed 11-year (2009–2019) period, the participant won 7 big crystal globes, corresponding to the winner of the International Biathlon Union World Cup. The training characteristics are reported as yearly volume (in hours) of low-intensity training (LIT), moderate- and high-intensity training, and speed and strength training. Performance was quantified by the number of World Cup top-3 positions per season. HRV was expressed as low- and high-frequency spectral power (in milliseconds squared), root-mean-square difference of successive R–R interval (in milliseconds), and heart rate (in beats per minute). Results: The training volume increased from 530 to ∼700 hours per year in 2009–2019, with a large polarization in training intensity distribution (ie, LIT 86.3% [2.9%]; moderate-intensity training 3.4% [1.5%]; high-intensity training 4.0% [0.7%]; strength 6.3% [1.6%]). The number of top-3 positions increased from 2 to 24–26 in 2009–2018 but decreased to 6 in 2019. The mean supine values in the root-mean-square difference of successive R–R interval and high-frequency spectral power divided by heart rate increased until 2015, which were stable over 2016–2018 but decreased in 2019. The number of top-3 positions was related to the total (r = .66, P = .02) and LIT (r = .92, P Conclusion: The improvement in performance of the participant was mainly determined by the progressive increase in training volume, especially performed at low intensity, and was correlated to parasympathetic activity markers. This case study confirms the effectiveness of the training method, with a large amount of LIT in an elite endurance athlete, and of regular HRV monitoring.

Marathon running involves complex mechanisms that cannot be measured with objective metrics or laboratory equipment. The emergence of wearable sensors introduced new opportunities, allowing the continuous recording of relevant parameters. The present study aimed to assess the evolution of stride-by-stride spatio-temporal parameters, stiffness, and foot strike angle during a marathon and determine possible abrupt changes in running patterns. Twelve recreational runners were equipped with a Global Navigation Satellite System watch, and two inertial measurement units clamped on each foot during a marathon race. Data were split into eight 5-km sections and only level parts were analyzed. We observed gradual increases in contact time and duty factor as well as decreases in flight time, swing time, stride length, speed, maximal vertical force and stiffness during the race. Surprisingly, the average foot strike angle decreased during the race, but each participant maintained a rearfoot strike until the end. Two abrupt changes were also detected around km 25 and km 35. These two breaks are possibly due to the alteration of the stretch-shortening cycle combined with physiological limits. This study highlights new measurable phenomena that can only be analyzed through continuous monitoring of runners over a long period of time.

BACKGROUND The institutionalization of a patient with Alzheimer's disease or other dementia (ADOD) is the last resort for the latter's family and/or caregivers. We hypothesized that the degree of kinship between the patient and his/her caregiver would influence the likelihood of institutionalization. OBJECTIVE To assess the association between institutionalization of patients with ADOD and the degree of kinship with the family caregiver. METHODS A cross-sectional study of patients with ADOD aged 75 or over attending a memory center in France for the first time between 2011 and 2014, as recorded in the French National Alzheimer Database. Multivariable logistic regression was used to assess factors associated with institutionalization after adjustment for age, sex, the Mini-Mental State Examination score, educational level, and type of dementia. RESULTS A total of 52,874 patients were included. The primary caregiver was most often a child (54.8%) or the spouse (36.7%). Compared with the "spouse" reference category, all the other caregiver categories were associated with a significantly greater likelihood of institutionalization; the odds ratio [95% confidence interval] was 4.68 [3.67-5.92] when the carer was a grandchild, 5.48 [4.93-6.09] for a child, 4.93 [4.11-5.91] for a daughter-/son-in-law, 8.76 [7.15-10.70] for a sibling, and 8.93 [7.48-10.65] for a niece/nephew. CONCLUSION The likelihood of institutionalization of older patients with ADOD varied with the degree of kinship. Compared with the "spouse" reference category, the likelihood was higher for all other types of caregivers but was especially high when the caregiver was not a direct descendant of the patient.

Like in other neurodegenerative diseases, protein aggregation, mitochondrial dysfunction, oxidative stress and neuroinflammation are hallmarks of Parkinson’s disease (PD). Differentiating characteristics of PD include the central role of α-synuclein in the aggregation pathology, a distinct vulnerability of the striato-nigral system with the related motor symptoms, as well as specific mitochondrial deficits. Which molecular alterations cause neurodegeneration and drive PD pathogenesis is poorly understood. Here, we summarize evidence of the involvement of three interdependent factors in PD and suggest that their interplay is likely a trigger and/or aggravator of PD-related neurodegeneration: hypoxia, acidification and inflammation. We aim to integrate the existing knowledge on the well-established role of inflammation and immunity, the emerging interest in the contribution of hypoxic insults and the rather neglected effects of brain acidification in PD pathogenesis. Their tight association as an important aspect of the disease merits detailed investigation. Consequences of related injuries are discussed in the context of aging and the interaction of different brain cell types, in particular with regard to potential consequences on the vulnerability of dopaminergic neurons in the substantia nigra. A special focus is put on the identification of current knowledge gaps and we emphasize the importance of related insights from other research fields, such as cancer research and immunometabolism, for neurodegeneration research. The highlighted interplay of hypoxia, acidification and inflammation is likely also of relevance for other neurodegenerative diseases, despite disease-specific biochemical and metabolic alterations.

Introduction Oral anticoagulant (OAC) intervention trials have typically included clinical event outcomes. However, there is no standard list of outcomes to be used in OAC research. This study aimed to describe and classify the outcomes used in recent prospective clinical studies involving OACs. Materials and methods We searched MEDLINE, EMBASE, and CINAHL databases from January 2009 to July 2019 for prospective studies with an intervention or control group that included one or more oral anticoagulants. We abstracted details about each included study and the outcomes used from the study report and its accompanying protocol. Using the Core Outcome Measures in Effectiveness Trials (COMET) Initiative recommendations, we categorised each outcome into one of five domains (mortality/survival, physiological/clinical, life impact, resource use, and adverse events). Our primary outcome was the prevalence of use of an outcome domain across studies. Results We included 70 prospective studies, including 52 randomized controlled trials and 18 prospective cohort studies. A total of 121 different outcomes were reported. The COMET domains were represented in the 70 studies as follows: mortality (63/70, 90.0%); physiological/clinical domain (70/70, 100%), life impact domain (43/70, 61.4%), resource use domain (26/70, 37.1%), and adverse events domain (55/70, 78.6%). Conclusion Outcome reporting in prospective studies of OACs more frequently concentrates on mortality, physiological/clinical domains, and adverse events compared to life impact and resource utilization domains, the latter uncommonly used. A priority for future research includes developing a core outcome set (COS) for OAC research that represents all domains.

COVID-19 pneumonia has specific features and outcomes that suggests a unique immunopathogenesis. Severe forms of COVID-19 appear to be more frequent in obese patients, but an association with metabolic disorders is not established. Here, we focused on lipoprotein metabolism in patients hospitalized for severe pneumonia, depending on COVID-19 status. Thirty-four non-COVID-19 and 27 COVID-19 patients with severe pneumonia were enrolled. Most of them required intensive care. Plasma lipid levels, lipoprotein metabolism, and clinical and biological (including plasma cytokines) features were assessed. Despite similar initial metabolic comorbidities and respiratory severity, COVID-19 patients displayed a lower acute phase response but higher plasmatic concentrations of non-esterified fatty acids (NEFAs). NEFA profiling was characterised by higher level of polyunsaturated NEFAs (mainly linoleic and arachidonic acids) in COVID-19 patients. Multivariable analysis showed that among severe pneumonia, COVID-19-associated pneumonia was associated with higher NEFAs, lower apolipoprotein E and lower high-density lipoprotein cholesterol concentrations, independently of body mass index, sequential organ failure (SOFA) score, and C-reactive protein levels. NEFAs and PUFAs concentrations were negatively correlated with the number of ventilator-free days. Among hospitalized patients with severe pneumonia, COVID-19 is independently associated with higher NEFAs (mainly linoleic and arachidonic acids) and lower apolipoprotein E and HDL concentrations. These features might act as mediators in COVID-19 pathogenesis and emerge as new therapeutic targets. Further investigations are required to define the role of NEFAs in the pathogenesis and the dysregulated immune response associated with COVID-19.Trial registration: NCT04435223.

Background In intensive care units (ICUs), patients experiencing post-extubation respiratory failure have poor outcomes. The use of noninvasive ventilation (NIV) to treat post-extubation respiratory failure may increase the risk of death. This study aims at comparing mortality between patients treated with NIV alternating with high-flow nasal oxygen or high-flow nasal oxygen alone. Methods Post-hoc analysis of a multicenter, randomized, controlled trial focusing on patients who experienced post-extubation respiratory failure within the 7 days following extubation. Patients were classified in the NIV group or the high-flow nasal oxygen group according to oxygenation strategy used after the onset of post-extubation respiratory failure. Patients reintubated within the first hour after extubation and those promptly reintubated without prior treatment were excluded. The primary outcome was mortality at day 28 after the onset of post-extubation respiratory failure. Results Among 651 extubated patients, 158 (25%) experienced respiratory failure and 146 were included in the analysis. Mortality at day 28 was 18% (15/84) using NIV alternating with high-flow nasal oxygen and 29% (18/62) with high flow nasal oxygen alone (difference, − 11% [95% CI, − 25 to 2]; p = 0.12). Among the 46 patients with hypercapnia at the onset of respiratory failure, mortality at day 28 was 3% (1/33) with NIV and 31% (4/13) with high-flow nasal oxygen alone (difference, − 28% [95% CI, − 54 to − 6]; p = 0.006). The proportion of patients reintubated 48 h after the onset of post-extubation respiratory failure was 44% (37/84) with NIV and 52% (32/62) with high-flow nasal oxygen alone (p = 0.21). Conclusions In patients with post-extubation respiratory failure, NIV alternating with high-flow nasal oxygen might not increase the risk of death. Trial registration number The trial was registered at http://www.clinicaltrials.gov with the registration number NCT03121482 the 20th April 2017.

Background Amiloride is a competitive blocker of the epithelial sodium (Na) channel in the renal collecting duct. It is a less potent diuretic than thiazides or loop diuretics, but is often used in association with its potassium (K)-sparing profile. Whether amiloride has a hypocalciuric effect similar to thiazides remains unclear. Animal studies and experiments on cell lines suggested that amiloride increases calcium (Ca) reabsorption in the distal nephron, but human studies are scarce. Methods We performed a post hoc analysis of a study with 48 healthy males (mean ± standard deviation age, 23.2 ± 3.9 years) who were assigned to a high-Na/low-K diet for 7 days before receiving 20 mg of amiloride orally. Urinary excretions of electrolytes were measured at 3 and 6 h afterwards; we calculated the relative changes in urinary excretion rates after amiloride administration. Results The high-Na/low-K diet led to an expected suppression of plasma renin and aldosterone. Amiloride showed a mild natriuretic effect associated with a decreased kaliuresis. Urinary Ca excretion dropped substantially (by 80%) 3 h after amiloride administration and remained low at the sixth hour. At the same time, fractional excretion of lithium decreased by a third, reflecting an increased proximal tubular reabsorption. Conclusions During a high-Na/low-K diet, amiloride had a strong acute hypocalciuric effect, most probably mediated by increased proximal Ca reabsorption, even though a distal effect cannot be excluded. Further studies should establish if chronic amiloride or combined amiloride/thiazide treatment may decrease calciuria more efficiently and be useful in preventing kidney stones.

The objective of this study was to determine the reasons for complaints and describe the judicial means upstream of France's courts following arthroscopy. This is a retrospective observational study including all compensation records related to arthroscopic surgery, collected from the two leading French insurance organizations: MACSF and Branchet companies, from 2014 to 2018. Three medical experts performed the protocol and analysis. Finally, 247 procedures were included. The most common motives were: the appearance or persistence of pain (43.7%), postoperative infection (29.1%), technical errors (10.5%), nerve damage (5.7%), arterial lesions (2.8%), side errors (2.4%). Knee arthroscopies were more at risk of legal action for infection (p = 0.0006), and for disappointing results or persistent pain (p = 0.001). The first recourse was the conciliation and compensation commission (CCI) in 136 cases (55.1%), the civil court (TGI) in 88 cases (35.6%) and amicable settlement in 23 cases (9.3%). The mean time between surgery and the complaint was 32.8 ± 25.7 months, and was shorter in the case of an amicable procedure (p

Resume Objectif L’objectif du Comite des Troubles Mictionnels de l’Homme (CTMH) de l’Association Francaise d’Urologie (AFU) etait de mettre a jour les recommandations francaises parues en 2012 et celles de l’EAU parues en 2019 concernant la prise en charge chirurgicale et interventionnelle de l’obstruction sous-vesicale (OSV) liee a une hyperplasie benigne de prostate (HBP). Methodes Une revue systematique de la litterature (PubMed®), concernant l’OSV liee a l'HBP, a ete conduite entre 2018 et 2020 afin de completer celle prise en compte par les recommandations precedentes. Ce travail a comporte une strategie bibliographique predefinie puis une analyse critique de la litterature avec attribution de niveaux de preuve et redaction de conclusions et de recommandations permettant de repondre aux questions cliniques posees. Resultats/recommandations Proposer une incision cervicoprostatique (ICP) pour traiter chirurgicalement les patients ayant des symptomes du bas appareil urinaire (SBAU) moderes a severes avec un volume prostatique 80 cm3. Les implants intra-prostatiques sont une alternative pour traiter les SBAU chez les patients souhaitant conserver leur fonction ejaculatoire et ayant un volume prostatique Conclusion Les evolutions notables des techniques de prise en charge chirurgicales de l’OSV liee a l’HBP s’orientent vers une diminution de la morbidite des gestes et une amelioration de la qualite de vie au-dela du simple traitement des SBAU.

Although value-based actions are often associated with improved mental health outcomes, few studies have explored this relationship on a daily level. The aim of this diary study was to explore how value-based actions change over time and assess how these fluctuations are associated to psychological distress and well-being both within- and between-day. Ninety-seven Canadian post-secondary students (n = 1581 observations) took part in this study. For 21 consecutive days, they were invited to complete end-of-day diaries (EOD) querying their daily level of distress, well-being and value-based actions. The questionnaires were sent to each student's mobile phone at a random time between 18:00 p.m. and 22:30 p.m. Data were analysed using multilevel modeling and time-lagged analysis. The results show that 1) daily value-based actions were negatively associated with daily distress and positively associated with daily well-being, 2) well-being reported in a given daily diary predicted next-day value-based actions, and 3) greater variability in daily value-based actions was associated with marginally lower daily well-being and steepened increases in daily distress over time.

Resume Introduction De nombreuses techniques dites mini-invasives ont emerge ces dernieres annees dans le traitement chirurgical de l’obstruction due a l’hyperplasie benigne de la prostate (HBP). L’objectif de cet article etait de faire le point sur leurs evolutions et leurs resultats respectifs. Materiel et methode Une revue coherente de la litterature entre 2013 et 2020 a ete realisee par un panel d’experts nationaux de la chirurgie de l’HBP. Les donnees ont ensuite ete discutees par l’ensemble des co-auteurs afin d’obtenir un consensus vis-a-vis des articles selectionnes et de leur analyse. Un etat des lieux a enfin ete redige pour proposer une vue d’ensemble de ces avancees technologiques et de leur disponibilite en France. Resultats Le traitement de l’obstruction sous-vesicale liee a l’HBP s’est beaucoup diversifie ces 5 dernieres annees. L’inventaire comporte 5 nouvelles technologies permettant aujourd’hui une desobstruction transuretrale non ablative (UROLIFT®, ITIND®), transuretrale ablative (REZUM®), transuretrale ablative avec assistance robotique (AQUABEAM®) ou endovasculaire par embolisation des arteres prostatiques. Seul l’UROLIFT® est consideree comme une technologie etablie dans les dernieres recommandations de l’EAU. Les quatre autres sont en cours d’evaluation et des recommandations europeennes n’ont ete emises uniquement pour deux d’entre eux, l’AQUABEAM® et l’embolisation des arteres prostatiques. Conclusion Ces nouvelles techniques mini-invasives ont pour but d’augmenter les options therapeutiques pour la prise en charge de l’HBP afin de proposer une prise en charge plus adaptee aux souhaits du patient. Certaines se positionnent en alternative au traitement chirurgical, d’autres a la place du traitement medical ou entre le traitement medical et chirurgical. Ces technologies ne sont pas toutes au meme niveau de developpement, d’evaluation et de niveau de preuve mais ont en commun une diffusion restreinte en France, compte tenu notamment de leur cout. Leur utilisation au sein d’etudes validees permettra de positionner leur utilisation ulterieure de facon plus precise.

Resume But Etude medico-economique comparative des couts entre resection transuretrale monopolaire de la prostate (RTUP) en hospitalisation complete avec 3 nuits et photovaporisation prostatique (PVP) au laser Greenlight en ambulatoire. Materiel et methodes Une analyse retrospective par minimisation des couts sur la periode 2017-2019 a ete realisee dans un centre hospitalier prive francais pour les sejours associes aux actes de RTUP et de PVP en rapport avec une hypertrophie benigne de la prostate. L’estimation de la balance couts-benefices peri-operatoire liee aux deux techniques a ete realisee du point de vue de l’etablissement par la methode du micro-costing. Resultats 871 resections d’adenome de prostate ont ete realisees sur la periode de l’etude, dont 743 photovaporisations prostatiques (soit 85 %). La duree de sejour moyenne des patients operes d’une RTUP etait de 3,7 jours versus 0,9 jours pour la PVP dont 64,7 % etaient realisees en ambulatoire. La balance couts/recettes est en faveur de la PVP en ambulatoire par rapport a la RTUP en hospitalisation conventionnelle de 3 nuits, avec une difference de plus de 500€ par patient pour des sejours de niveau de severite 1. Conclusion Dans le centre hospitalier prive de notre etude, la PVP en ambulatoire apparaissait financierement plus interessante qu’une RTUP avec trois nuits d’hospitalisation complete pour un patient de niveau de severite 1. Le gain financier pour l’etablissement se trouve principalement dans la reduction de la duree moyenne de sejour et la prise en charge ambulatoire. Niveau de preuve 3.

Several international guidelines concerning lower extremity arterial disease (LEAD) have been published recently, in particular, by the American Heart Association the European Society of Cardiology/European Society for Vascular Surgery, the European Society for Vascular Medicine and the Society for Vascular Surgery. These guidelines differ in some respects and certain issues are not addressed. The objective of this consensus driven by the French Societies of vascular Medicine and surgery was to analyze the disparities between the different guidelines, as well as certain issues not covered, and develop proposals with regard to these points. The following fields of LEAD have been explored: 1) classifications, 2) clinical evaluation, 3) diagnostic criteria, 4) quantification of arterial stenosis using duplex ultrasound, 5) detection of asymptomatic multisite lesions, 6) screening for LEAD in the context of cardiac disease, 7) medical treatment, 8) supervised exercise therapy, 9) revascularization and revascularization of the internal artery stenosis, 10) management of chronic limb ischemia, 11) longitudinal follow-up, and 12) diet.

The present study aimed to propose and assess the physiological responses of a novel graded karate test. Ten male national-level karate athletes (age 26 ± 5 yrs; body mass 69.5 ± 11.6 kg; height 1.70 ± 0.09 m) performed two exercise tests (separated by 2-7 days): 1) a running-based cardiopulmonary exercise test; 2) a graded karate test. The cardiopulmonary exercise test was comprised of an individualized ramp protocol for treadmill running, and the graded karate test was comprised of a sequence of ‘kisami-gyaku-zuki” punching at a fixed frequency of a stationary target that becomes progressively distant. Cardiorespiratory responses, blood lactate concentration, and perceived exertion were measured. A verification phase was also performed in both tests to confirm the maximal physiological outcomes. The graded karate test evoked similar maximal responses to the running protocol: V̇O2 (57.4 ± 5.1 vs 58.3 ± 3.5 mL·kg-1·min-1; p = 0.53), heart rate (192 ± 6 vs 193 ± 10]beats.min-1; p = 0.62) and blood lactate (14.6 ± 3.4 vs 13.1 ± 3.0 mmol·L-1; p = 0.14) with a shorter duration (351 ± 71 vs 640 ± 9 s; p < 0.001). Additionally, the graded karate test evoked higher V̇O2 (72.6 ± 6.5 vs 64.4 ± 4.3 %V̇O2MAX; p = 0.005) and heart rate (89.4 ± 4.6 vs 77.3 ± 7.2 %HRMAX p < 0.001) at the ventilatory threshold and a higher heart rate (97.0 ± 2.4 vs 92.9 ± 2.2 %HRMAX; p = 0.02) at the respiratory compensation point. Incremental and verification phases evoked similar responses in V̇O2 and minute-ventilation during both tests. This novel displacement-based sport-specific test evoked similar maximal and higher submaximal responses, indicating a superior pathway to assess karate athletes.

Objectives The aim of this study is to describe determinants of quality of life (QOL) quoted by vulnerable older patients with cancer and compare them with domains included in cancer-specific QOL questionnaires. Material and methods This prospective, monocenter, observational study was performed in a French university hospital. Cancer patients Patients with cancer aged over 74 years were recruited when referred for an out-patient geriatric evaluation (n = 102). After geriatric assessment, they were invited to respond to open-ended questions, Q1: “For you, what is most important to have a good QOL?” Q2: “What could improve your QOL?” Q3: “What could worsen your QOL?” A Delphi process was conducted to categorize patient responses according to content analysis. Results The most frequently patient-reported determinants for high quality of life were maintaining close ties with family/friends or social relations, autonomy for decision and mobility without depending on others, being in good health, not suffering from pain and the absence of problems concerning relatives. Global health status, physical functioning/mobility, social functioning and worries about others were the more frequently mentioned QOL domains related to the EORTC QLQ-C30 and ELD14 questionnaires. Some determinants of QOL were not linked to pre-defined domains, some others without a 100% consensus after the Delphi process, illustrating the subjectivity of QOL analysis by a single practitioner. Conclusion Patient interview with open-ended questions provides valuable supplementary information to QOL questionnaires, in order to personalize health related (cancer treatment, pain management…) and global (maintenance of autonomy and family/social relations…) assessment and intervention.