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Muscle injuries of the hamstrings are among the most frequent in football and a main cause for significant time away from training and competition. The purpose of this study was to prospectively evaluate the loss of muscle volume in recreational football players three and six weeks after initial trauma. We hypothesized that significant muscle volume loss occurs within 6 weeks after the initial injury event. Twenty recreational football players (mean-age=25 ± 4years; mean-height=181 ± 8cm; mean-weight=81 ± 10kg) with type3a (minor partial muscle tear) and type3b (moderate partial muscle tear) injuries were included. Muscle volume was determined using established methods for the hamstrings and the quadriceps femoris muscle within 3 days and after 3 and 6 weeks following the initial injury. The injured hamstrings lost 6.5% (mean=64 cm3(95%CI=31-98 cm3), p

Introduction. Le service sanitaire des étudiants en santé (SSeS) est une formation obligatoire introduisant de nouvelles approches pédagogiques en premier cycle des études de médecine comme la démarche-projet et l’éducation pour la santé. Un tutorat des étudiants de 3e année préparant leur SSeS, par 42 étudiants de troisième cycle volontaires, a été instauré à Rennes. Les étudiants sont ainsi formés au rôle de tuteur et à l’éducation pour la santé. Objectif. Explorer le vécu des étudiants-tuteurs du SSeS. Méthode. Entre février et juin 2019, une étude qualitative exploratoire par entretiens individuels semi-directifs a été conduite auprès d’un échantillon raisonné d’étudiants de troisième cycle. Trois entretiens d’experts ont enrichi le guide d’entretien. Les données ont été double codées avec triangulation des données et analysées pour aboutir à un modèle selon la méthode par théorisation ancrée. Résultats. Quatorze étudiants ont été inclus. Tous se déclaraient novices en éducation pour la santé. Leurs attentes étaient fortes. L’accompagnement de chaque groupe était singulier. La proximité d’âge et les réseaux sociaux facilitaient les échanges. Les étudiants se sont initiés au rôle de supervision et ont enrichi leur compétence en éducation pour la santé. La qualité des apprentissages était variable : du questionnement autonome à un recours passif aux expériences antérieures. Elle était influencée par le degré d’interactions tuteur-tutorés et la disponibilité de l’étudiant de troisième cycle. Discussion. L’intérêt pédagogique pour les étudiants est double par l’acquisition de compétences en tutorat et éducation pour la santé en lien avec les objectifs pédagogiques du 3e cycle. Différents facteurs influencent la qualité des apprentissages. Les apprentissages réciproques se réfèrent au socioconstructivisme.

Cardiac sarcoidosis (CS) is a complex disease that can manifest as a diverse array of arrhythmias. CS patients may be at higher risk for sudden cardiac death (SCD), and, in some cases, SCD may be the first presenting symptom of the underlying disease. As such, identification, risk stratification, and management of CS-related arrhythmia are crucial in the care of these patients. Left untreated, CS carries significant arrhythmogenic morbidity and mortality. Cardiac manifestations of CS are a consequence of an inflammatory process resulting in the myocardial deposition of noncaseating granulomas. Endomyocardial biopsy remains the gold standard for diagnosis; however, biopsy yield is limited by the patchy distribution of the granulomas. As such, recent guidelines have improved clinical diagnostic pathways relying on advanced cardiac imaging to help in the diagnosis of CS. To date, corticosteroids are the best studied agent to treat CS but are associated with significant risks and limited benefits. Implantable cardioverter-defibrillators have an important role in SCD risk reduction. Catheter ablation in conjunction with antiarrhythmics seems to reduce ventricular arrhythmia burden. However, the appropriate selection of these patients is crucial as ablation is likely more helpful in the setting of a myocardial scar substrate versus arrhythmia driven by active inflammation. Further studies investigating CS pathophysiology, the pathway to diagnosis, arrhythmogenic manifestations, and SCD risk stratification will be crucial to reduce the high morbidity and mortality of this disease.

The regulation of cell-cholesterol efflux is not completely understood. Our aim was to assess the role of HDL- and non-HDL-related parameters in ATP-binding cassette transporter-A1 (ABCA1) and scavenger receptor class B-type-I (SRBI) cell-cholesterol efflux capacity (CEC) in coronary heart disease (CHD) cases and controls.Lipids and apoA-I-containing HDL particles (by 2D gel-electrophoresis and immunodetection) were measured in 534 statin-treated CHD patients and in 1076 age-, gender-, and BMI-matched controls. ABCA1-CEC and SRBI-CEC were measured in apoB-depleted serum of 100 cases and 100 controls.Cases had significantly higher concentrations of preβ-1 particles (88%) and ABCA1-CEC (34%) compared to controls. ABCA1-CEC was positively correlated with the concentrations of preβ-1 particles, triglycerides, small-dense (sd) LDL-C, and LDL-C in both cases and controls. Moreover, both the concentration and the functionality of preβ-1 particles (ABCA1-CEC/mg preβ-1) were positively associated with the concentrations of sdLDL-C and triglycerides. Cases had 27% lower levels of large HDL particles but similar SRBI-CEC compared to controls. SRBI-CEC was correlated positively with HDL-C, apoA-I, and large-HDL particle levels. However, the functionality of large-HDL particles (SRBI-CEC/mg large particles) was significantly and positively correlated with the preβ-1/α-1 ratio, sdLDL-C, and triglycerides.CHD patients have significantly higher concentration, but less functional preβ-1 particles in term of cholesterol efflux capacity compared to controls. Triglyceride-rich lipoproteins have significant influence on either the concentration or the functionality or both of HDL particles and consequently HDL-CEC.

Transthoracic echocardiography (TTE) is the primary clinical imaging modality for the assessment of patients with isolated aortic regurgitation (AR) in whom TTE’s linear left ventricular (LV) dimension is used to assess disease severity to guide aortic valve replacement (AVR), yet TTE is relatively limited with regards to its integrated semi-quantitative/qualitative approach. We therefore compared TTE and cardiovascular magnetic resonance (CMR) assessment of isolated AR and investigated each modality’s ability to predict LV remodeling after AVR. AR severity grading by CMR and TTE were compared in 101 consecutive patients referred for CMR assessment of chronic AR. LV end-diastolic diameter and end-systolic diameter measurements by both modalities were compared. Twenty-four patients subsequently had isolated AVR. The pre-AVR estimates of regurgitation severity by CMR and TTE were correlated with favorable post-AVR LV remodeling. AR severity grade agreement between CMR and TTE was moderate (ρ = 0.317, P = 0.001). TTE underestimated CMR LV end-diastolic and LV end-systolic diameter by 6.6 mm (P

Purpose: Ficolin-3 deficiency is caused by a mutation (+1637delC) in the FCN3 gene. It is a rare condition and has been associated with both infection and autoimmune disease including systemic lupus erythematosus (SLE). Here we investigated if ficolin-3 deficiency is more frequent in patients than in controls and tried to identify a common phenotype among ficolin-3 deficient individuals. Since a significant part of patients identified with ficolin-3 deficiency was diagnosed with SLE, we explored whether the heterozygous state of the FCN3+1637delC variant represents a risk factor in the development of SLE. Further, we examined other possible causes of ficolin-3 deficiency when the FCN3+1637delC is not present. Methods: A systematic literature search for studies measuring ficolin-3 was carried out. We examined 362 SLE patients and 596 controls for the presence of the variant FCN3+1637delC. We established assays for measurements of ficolin-3 and of auto-antibodies against ficolin-3. We sequenced the coding and non-coding regions of the FCN3 gene in an SLE patient with ficolin-3 deficiency not carrying the +1637delC. Results: Ficolin-3 deficiency leads to an 8-time increased odds of having a disease (p < 0.05). Three out of nine patients with deficiency had SLE. The heterozygous state of the deficiency variant is not associated with increased risk of developing SLE (p = 0.18). Conclusion: By systematically reviewing the literature for the described cases of ficolin-3 deficiency, an autoimmune phenotype is emerging. Thirty-three percent of the ficolin-3 deficient patients had SLE. Heterozygosity for the FCN3 gene deletion causing the deficiency does not seem to be associated with the development of SLE.

Background and Aims ANCA-associated vasculitis (AAV) is the most common cause of rapidly progressive glomerulonephritis globally and the most common finding in renal biopsies for those above 75 years of age. Patients with AAV have had an improved outcome after the introduction of immunosuppressive therapy. However, there is still an increased risk of end stage renal failure, complications to therapy, comorbidities and death. The European Vasculitis Society (EUVAS) has run several prospective randomized clinical trials (RCT) since late -90’ies as an attempt to improve the outcome for patients with a broad spectrum of AAV. The aim of the current study was to analyze results from a 10-year follow-up of patients who have participated in EUVAS’s randomized clinical trials to report on patient outcomes using current standard of care immunosuppressive treatment. Method Data on patient outcomes were collected from questionnaires to the principal investigators of the original RCTS (74 centers from 17 countries in Europe): MEPEX, NORAM, CYCAZAREM, CYCLOPS, IMPROVE, RITUXVAS and MYCYC. All patients were well characterized at inclusion in the trials respectively, as was the type and duration of induction therapy. Long-term follow-up data regarding cumulative duration and type of immunosuppressive therapy, end stage renal failure (ESRF), renal transplantation, patient survival and comorbidities as cardiovascular events, infections were recorded. Efforts have been made to control and validate the collected data. Results The current dataset comprises 858 patients, of whom 708 were eligible to include in this study. We received questionnaires regarding patient outcomes from 70% of the cohort. The median age was 60 years at time of the diagnosis of AAV; 487 patients had GPA (57%) and 371 MPA (43%). The median follow-up time was 8.0 years (IQR: 2.9-13.6). During the observation period, there were 305 deaths: 78 patients died within the first year of follow up, 69 during the following 5 years, and another 158 patients after 5 years. The main causes of death were infections (25%), cardiovascular disease (14%) and malignancies (13%), followed by pulmonary diseases, vasculitis, others, kidney disease and gastrointestinal disease. Vasculitis were a major contributor to the causes of death in 18% of the patients. Median survival time for the whole cohort was 17.8 years (95%CI: 15.6 – 20.1). Survival rate at 5 and 10 years was 81.6% and 66.5% respectively. Advanced age, low estimated glomerular filtration rate and male sex were negative prognostic factors for patient survival in the Cox model. When we categorized the deaths according to their initial CKD stage, the highest number of deaths was found in the group of patients with low eGFR i.e. an initial CKD stage V (40%). The initial CKD stage, as shown in the Kaplan-Meier curve, was found to have an important impact on the patient survival (LR: 144.4 p In our cohort, 159 patients (18.5%) reached ESRF, of whom 110 patients died (69%); the main cause of death in this group was infection. Conclusion In a series of over 800 patients with AAV, ten-year mortality was predominantly associated with impaired renal function at onset, older age and male gender, rather than subtype of disease. The main strength of this study is that we have a well-defined cohort of patients with AAV, all with well-defined induction treatments and a long period of follow-up with the possibility to analyze possible prognostic factors regarding outcomes. Further analyses are ongoing regarding comparative statistics, cumulative incidence of malignancies, renal transplantation and comorbidities. The data supports efforts to diagnose these patients at an earlier stage, when they have a higher eGFR and to tailor therapy for the individual patient. Although newer treatment modalities are available, there is still a considerable morbidity and mortality in the long-term.

BACKGROUND Literature reporting [18F]fluorodexoyglucose positron emission tomography (FDG-PET) of small bowel adenocarcinoma, a rare tumor, is sparse. To assess FDG uptake in small bowel adenocarcinoma, we retrospectively analyzed a large, single-center database and determined the expression of glucose-transporter type 1 (GLUT-1). METHODS Screening of PET datasets in the database (N.=28,961 scans) for untreated histologically-confirmed primary small bowel adenocarcinoma revealed evaluable PET datasets for eight patients. Maximum and peak standardized uptake values (SUV max and SUV peak , respectively) were calculated via volume-of-interest (VOI) analysis. Additionally, GLUT-1 expression on tumor specimens was prospectively immunohistochemically assessed. RESULTS All primary tumors showed high FDG uptake: mean SUVmax was 9.5±2.6 (range: 5.0-13.0) and SUVpeak, 8.1±2.3 (range: 3.9-10.7). Corresponding biopsy specimens (N.=7) demonstrated high GLUT-1 expression. CONCLUSIONS Primary small bowel adenocarcinomas have a high GLUT-1 expression. Tumor lesions consistently demonstrated high FDG uptake pre-treatment, suggesting FDG-PET utility in staging and follow-up of these tumors.

We developed a deep convolutional neural network (CNN) based method to remove streaking artefact from accelerated radial acquisitions of myocardial T

Introduction This study sought to assess ocular surface disease changes following cataract surgery combined with trabecular micro-bypass stent(s) implantation (iStent or iStent inject). Methods This prospective interventional single-arm clinical trial enrolled 47 eyes with mild-to-moderate open-angle glaucoma (OAG) on 1–4 glaucoma medications who underwent phacoemulsification and trabecular micro-bypass stent(s) implantation. Key glaucoma and ocular surface data through 3 months postoperatively included the Ocular Surface Disease Index score (OSDI), corneal/conjunctival staining (Oxford Schema), fluorescein tear break-up time (FTBUT), conjunctival hyperemia (Efron Scale), glaucoma medications, and intraocular pressure (IOP). Results Mean OSDI scores improved from 40.1 ± 21.6 (severe) preoperatively to 17.5 ± 15.3 (mild) at 3 months (p

Non-invasive imaging plays a pivotal role in modern-day medicine from diagnosis to management of disease. It is crucial to have a solid understanding of the various indications and limitations of these techniques to be able to best utilize the different modalities in risk assessment and clinical decision-making. Through this chapter, we will go through the fundamentals of the different modalities and selection of an image modality based on the disease being investigated and individual patient characteristics. A multimodality approach to patient evaluation is needed more times than not, and it is important to choose modalities that complement each other rather than repeating the same evaluation.

Purpose To develop and evaluate an imaging sequence to simultaneously quantify the epicardial fat volume and myocardial T1 relaxation time. Methods We introduced a novel simultaneous myocardial T1 mapping and fat/water separation sequence (joint T1 -fat/water separation). Dixon reconstruction is performed on a dual-echo data set to generate water/fat images. T1 maps are computed using the water images, whereas the epicardial fat volume is calculated from the fat images. A phantom experiment using vials with different T1 /T2 values and a bottle of oil was performed. Additional phantom experiment using vials of mixed fat/water was performed to show the potential of this sequence to mitigate the effect of intravoxel fat on estimated T1 maps. In vivo evaluation was performed in 17 subjects. Epicardial fat volume, native myocardial T1 measurements and precision were compared among slice-interleaved T1 mapping, Dixon, and the proposed sequence. Results In the first phantom, the proposed sequence separated oil from water vials and there were no differences in T1 of the fat-free vials (P = .1). In the second phantom, the T1 error decreased from 22%, 36%, 57%, and 73% to 8%, 9%, 16%, and 26%, respectively. In vivo there was no difference between myocardial T1 values (1067 ± 17 ms versus 1077 ± 24 ms, P = .6). The epicardial fat volume was similar for both sequences (54.3 ± 33 cm3 versus 52.4 ± 32 cm3 , P = .8). Conclusion The proposed sequence provides simultaneous quantification of native myocardial T1 and epicardial fat volume. This will eliminate the need for an additional sequence in the cardiac imaging protocol if both measurements are clinically indicated.

To assess long-term efficacy and safety of salsalate to improve glycemia in persons with diabetes risk, who are overweight with statin-treated, stable coronary heart disease.Glycemic status was assessed in 192 persons without diabetes at baseline in a pre-specified secondary analysis from Targeting INflammation Using SALsalate in CardioVascular Disease (TINSAL-CVD), a multi-center, double-masked, randomized (1:1), placebo-controlled, parallel clinical trial.Participants were mostly Caucasian males, age 60±7 years, BMI 31.4±3.0 kg/mSalsalate improves glycemia in obese persons at increased risk for diabetes, and hence may decrease risk of incident type 2 diabetes. Salsalate may inform new therapeutic approaches for diabetes prevention, but renal safety may limit clinical utility.

Background The European League Against Rheumatism (EULAR) Recommendation for primary and small vessel vasculitis were published in 2009. Objectives To update the 2009 recommendations with the focus being ANCA-Associated Vasculitis (AAV) using systematic literature review, as well as expert opinion where appropriate. Methods A combined taskforce from European League Against Rheumatism (EULAR), the European Renal Association (ERA-EDTA) and European Vasculitis Society (EUVAS) conducted a modified Delphi exercise to identify key areas of guideline for update. The identified themes were then used to generate keywords for literature searches. For the purpose of update a date period of 1st January 2007 to 1st February 2015 was chosen, to interrogate the main medical literature databases (MEDLINE, EMBASE, CENTRAL). From an initial 1,347 hits, 82 clinically relevant studies were identified. The evidence presented was discussed and summarized by the experts in the course of a consensus finding and voting process. Levels of evidence and grades of recommendations were derived and levels of agreement (strengths of recommendations) were determined. Results The 15 recommendations cover general aspects, such as attainment of remission and the need for shared decision-making between rheumatologists and patients. The more specific items relate to starting immunosuppressive therapy using a strategy in combination with glucocorticoids to induce remission, followed by a period of remission maintenance. For remission induction of life or organ-threatening AAV, cyclophosphamide and rituximab are considered to have similar efficacy. Azathioprine, rituximab and methotrexate are the preferred choices for remission maintenance. The recommendations address plasma exchange which is recommended, in the setting of rapidly progressive renal failure or severe diffuse pulmonary haemorrhage. To enable the recommendations to have maximum validity the voting process was also repeated amongst the members of EUVAS. Conclusions The recommendations have been updated and changes include; choice of drug therapy (both for induction, relapse and remission maintenance), monitoring for complications, the usefulness of repeated biopsy in those thought to having relapsing disease, monitoring for hypoimmunoglobulinaemia and recommendations on patient education. These recommendations are intended for use by healthcare professionals, doctors in specialist training, medical students, pharmaceutical industries and drug regulatory organisations. Disclosure of Interest None declared

The development of radiofrequency ablation for the treatment of atrial fibrillation has led to an increased interest in the accurate determination of pulmonary vein anatomy and left atrial fibrosis assessment to help plan the procedure and to monitor for postablation stenosis. Contrast-enhanced magnetic resonance angiography readily demonstrates the pulmonary veins and is the method of choice for these imaging studies. In this chapter, we review the methods used to image the pulmonary veins, normal and anomalous pulmonary venous anatomy. We describe how late gadolinium enhancement imaging is used to identify fibrosis and scar. The utility of cardiovascular magnetic resonance before and after atrial fibrillation ablation is described.

Objective We aimed to investigate the association of diffuse myocardial fibrosis by cardiac magnetic resonance (CMR) T 1 with complex ventricular arrhythmia (ComVA) in mitral valve prolapse (MVP). Methods A retrospective analysis was performed on 41 consecutive patients with MVP referred for CMR between 2006 and 2011, and 31 healthy controls. Arrhythmia analysis was available in 23 patients with MVP with Holter/event monitors. Left ventricular (LV) septal T 1 times were derived from Look-Locker sequences after administration of 0.2 mmol/kg gadopentetate dimeglumine. Late gadolinium enhancement (LGE) CMR images were available for all subjects. Results Patients with MVP had significantly shorter postcontrast T 1 times when compared with controls (334±52 vs 363±58 ms; p=0.03) despite similar LV ejection fraction (LVEF) (63±7 vs 60±6%, p=0.10). In a multivariable analysis, LV end-diastolic volume, LVEF and mitral regurgitation fraction were all correlates of T 1 times, with LVEF and LV end-diastolic volume being the strongest (p=0.005, p=0.008 and p=0.045, respectively; model adjusted R 2 =0.30). Patients with MVP with ComVA had significantly shorter postcontrast T 1 times when compared with patients with MVP without ComVA (324 (296, 348) vs 354 (327, 376) ms; p=0.03) and only 5/14 (36%) had evidence of papillary muscle LGE. Conclusions MVP may be associated with diffuse LV myocardial fibrosis as suggested by reduced postcontrast T 1 times. Diffuse interstitial derangement is linked to subclinical systolic dysfunction, and may contribute to ComVA in MVP-related mitral regurgitation, even in the absence of focal fibrosis.

We developed a deep convolutional neural network (CNN) based method to remove streaking artefact from accelerated radial acquisitions of myocardial T 1-mapping images. A deep CNN based on a modified U-Net architecture was developed and trained to remove the streaking artefacts from under-sampled T 1 mapping images. A total of 2090 T 1-weighted images for 33 patients (55 ± 15 years, 19 males) and five healthy subjects (30 ± 14 years, 2 males) were used for training and testing the network. The images were acquired using radial slice interleaved T 1 mapping sequence (STONE) and retrospectively under-sampled to achieve acceleration rate of 4 (corresponding to 48 spokes). The dataset was split into training and testing subsets with 23 subjects (60%) and 15 subjects (40%), respectively. For generating voxel-wise T 1 maps, a two-parameter fitting model was used. Network performance was evaluated using normalized mean square error (NMSE), structural similarity index (SSIM) and peak signal-to-noise ratio (PSNR) metrics. The proposed network allowed fast (T 1-weighted testing images and the corresponding T 1 maps with PSNR = 64.3 ± 1.02, NMSE = 0.2 ± 0.09 and SSIM = 0.9 ± 0.3 × 10−4. There was no statistically significant difference between the measured T 1 maps for both per-subject (reference: 1085 ± 37 ms, CNN: 1088 ± 37 ms, p = 0.4) and per-segment (reference: 1084 ± 48 ms, CNN: 1083 ± 58 ms, p = 0.9) analyses. In summary, deep CNN allows fast and reliable removal of streaking artefact from under-sampled radial T 1 mapping images. Our results show that the highly non-linear operations of deep CNN processing of T 1 mapping images do not impact accurate reconstruction of myocardial T 1 maps.

Podeu consultar la correcció d'errades a: http://dx.doi.org/10.1136/annrheumdis-2016-209133corr1, In this article, the 2009 European League Against Rheumatism (EULAR) recommendations for the management of antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) have been updated. The 2009 recommendations were on the management of primary small and medium vessel vasculitis. The 2015 update has been developed by an international task force representing EULAR, the European Renal Association and the European Vasculitis Society (EUVAS). The recommendations are based upon evidence from systematic literature reviews, as well as expert opinion where appropriate. The evidence presented was discussed and summarised by the experts in the course of a consensus-finding and voting process. Levels of evidence and grades of recommendations were derived and levels of agreement (strengths of recommendations) determined. In addition to the voting by the task force members, the relevance of the recommendations was assessed by an online voting survey among members of EUVAS. Fifteen recommendations were developed, covering general aspects, such as attaining remission and the need for shared decision making between clinicians and patients. More specific items relate to starting immunosuppressive therapy in combination with glucocorticoids to induce remission, followed by a period of remission maintenance; for remission induction in life-threatening or organ-threatening AAV, cyclophosphamide and rituximab are considered to have similar efficacy; plasma exchange which is recommended, where licensed, in the setting of rapidly progressive renal failure or severe diffuse pulmonary haemorrhage. These recommendations are intended for use by healthcare professionals, doctors in specialist training, medical students, pharmaceutical industries and drug regulatory organisations.

Attention to resource utilization has led to increased scrutiny of the appropriateness of initial diagnostic imaging studies on the basis of current guidelines. Far less attention has been paid to examining the lack of appropriate follow-up studies.A retrospective cross-sectional analysis was performed of 3,781 consecutive outpatients referred for transthoracic echocardiography (TTE) from July to December 2008. Data from the electronic medical records were extracted to see if patients with at least moderate left-sided valvular stenosis or regurgitation underwent subsequent echocardiographic studies within 60 days of the period recommended by the 2006 American College of Cardiology and American Heart Association valve guidelines document.Of 342 outpatients with at least moderate valve dysfunction, 38 (11%) were excluded for reasons that precluded the need for a follow-up study (e.g. death, surgery). Of the remaining 304 patients, only 179 (59%) underwent follow-up echocardiography within the recommended period. Rates of timely follow-up TTE were higher when ordering physicians were cardiologists or cardiovascular surgeons (65%) compared with primary care physicians or internal medicine specialists (45%) (P.01). Follow-up rates were significantly different for aortic stenosis (77%), mitral stenosis (67%), aortic regurgitation (49%), and mitral regurgitation (49%) (P.01). Patients receiving timely follow-up TTE were younger (66 ± 15 vs 71 ± 15 years, P = .002) and more likely to be male (odds ratio, 1.79; 95% CI, 1.12-2.85; P = .01).To the authors' knowledge, this is the first study demonstrating low rates of compliance with guideline-recommended monitoring TTE in patients with at least moderate valve dysfunction. Cardiac practitioners have significantly better compliance. Strategies are needed to improve timely follow-up care in this population.

ObjectivesThe RITUXVAS trial reported similar remission induction rates and safety between rituximab and cyclophosphamide based regimens for antineutrophil cytoplasm antibody (ANCA)-associated vasculitis at 12 months; however, immunosuppression maintenance requirements and longer-term outcomes after rituximab in ANCA-associated renal vasculitis are unknown.MethodsForty-four patients with newly diagnosed ANCA-associated vasculitis and renal involvement were randomised, 3:1, to glucocorticoids plus either rituximab (375 mg/m2/week×4) with two intravenous cyclophosphamide pulses (n=33, rituximab group), or intravenous cyclophosphamide for 3–6 months followed by azathioprine (n=11, control group).ResultsThe primary end point at 24 months was a composite of death, end-stage renal disease and relapse, which occurred in 14/33 in the rituximab group (42%) and 4/11 in the control group (36%) (p=1.00). After remission induction treatment all patients in the rituximab group achieved complete B cell depletion and during subsequent follow-up, 23/33 (70%) had B cell return. Relapses occurred in seven in the rituximab group (21%) and two in the control group (18%) (p=1.00). All relapses in the rituximab group occurred after B cell return.ConclusionsAt 24 months, rates of the composite outcome of death, end-stage renal disease and relapse did not differ between groups. In the rituximab group, B cell return was associated with relapse.Trial registration numberISRCTN28528813.

The HAWAI registry evaluated the role of heart rate variability in predicting the occurrence of ventricular tachycardia and fibrillation (VT/VF) and sinus tachycardia in patients with an implantable cardioverter-defibrillator (45 patients with 155 RR recordings). A significant decrease of the mean value of all RR intervals (MeanNN) was observed in the period starting 20 and 40 min prior to VT/VF and sinus tachycardia, respectively. The standard deviation of RR intervals (SDNN) and the power at low frequency (LF) were the only parameters with significant changes prior to VT/VF. For sinus tachycardia, the root mean square of successive differences of all successive RR intervals (r-MSSD) and the power at low and high frequency (HF) decreased, whereas SDNN and the power at very low frequency increased. Comparison of RR recordings preceding VT/VF and sinus tachycardia revealed significant differences of the MeanNN, SDNN, r-MSSD, LF and HF. Based on a classification and regression tree analysis, MeanNN, SDNN and r-MSSD showed a sensitivity of 94.4% and a specificity of 50.6% as predictors of VT/VF. Our results suggest that the temporal changes in heart rate before an arrhythmic event can be used to predict the occurrence of VT/VF. These parameters may be used to optimize pacing therapies designed to prevent VT/VF recurrences as well as for improving device-based discriminators for VT/VF and sinus tachycardia.

Until recently, standard of care for patients with generalized or severe antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) has consisted of an induction regimen with cyclophosphamide (CYC) and corticosteroids followed by maintenance treatment with azathioprine. This regimen is associated with significant toxicity resulting in considerable morbidity and mortality whereas relapses are still not infrequent. In two controlled trials, the Rituximab in ANCA-associated Vasculitis study (RAVE) and the RITUXVAS trial of the European Vasculitis Study Group (EUVAS), rituximab (RTX) proved non-inferior to CYC for induction of remission. In addition, outcome at 18 months for the RAVE trial and 12 months for the RITUXVAS trial showed that RTX without maintenance treatment was as efficacious as CYC followed by azathioprine maintenance. To prevent relapses, which occur particularly in patients positive for PR3-ANCA, 500 mg RTX given every 6 months was shown to be superior to azathioprine in a French study. Thus, RTX is a new and promising therapeutic armamentarium for AAV although long-term safety has still to be established.

Higher hemoglobin A1c (HbA1c) is associated with lower cognitive function in type 2 diabetes. To determine whether associations persist at lower levels of dysglycemia in patients who have established cardiovascular disease, cognitive performance was assessed in the Targeting INflammation Using SALsalate in CardioVascular Disease (TINSAL-CVD) trial.The age-adjusted relationships between HbA1c and cognitive performance measured by the Mini-Mental State Examination, Digit Symbol Substitution Test, Rey Auditory Verbal Learning Test, Trail Making Test, and Categorical Verbal Fluency were assessed in 226 men with metabolic syndrome and established stable coronary artery disease.Of the participants, 61.5% had normoglycemia, 20.8% had impaired fasting glucose, and 17.7% had type 2 diabetes. HbA1c was associated with cognitive function tests of Digit Symbol Substitution Test, Rey Auditory Verbal Learning Test, Trail Making Test, and Categorical Verbal Fluency (all P.02), but not the Mini-Mental State Examination. In an age-adjusted model, a 1% (11 mmol/mol) higher HbA1c value was associated with a 5.9 lower Digit Symbol Substitution Test score (95% confidence interval [CI], -9.58 to -2.21; P.0001); a 2.44 lower Rey Auditory Verbal Learning Test score (95% CI, -4.00 to -0.87; P.0001); a 15.6 higher Trail Making Test score (95% CI, 5.73 to 25.6; P.0001); and a 3.71 lower Categorical Verbal Fluency score (95% CI, -6.41 to -1.01; P.02). In a multivariate model adjusting for age, education, and cardiovascular covariates, HbA1c remained associated with cognitive function tests of Rey Auditory Verbal Learning Test (R(2) = 0.27, P.0001), Trail Making Test (R(2) = 0.18, P.0001), and Categorical Verbal Fluency (R(2) = 0.20, P.0001), although association with the Digit Symbol Substitution Test was reduced.Higher HbA1c is associated with lower cognitive function performance scores across multiple domain tests in men with metabolic syndrome and coronary artery disease. Future studies may demonstrate whether glucose lowering within the normative range improves cognitive health.

© 2017 International Society of Nephrology. Published by Elsevier Inc. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/)., The 2016 European Vasculitis Society (EUVAS) meeting, held in Leiden, the Netherlands, was centered around phenotypic subtyping in antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV). There were parallel meetings of the EUVAS petals, which here report on disease assessment; database; and long-term follow-up, registries, genetics, histology, biomarker studies, and clinical trials. Studies currently conducted will improve our ability to discriminate between different forms of vasculitis. In a project that involves the 10-year follow-up of AAV patients, we are working on retrieving data on patient and renal survival, relapse rate, the cumulative incidence of malignancies, and comorbidities. Across Europe, several vasculitis registries were developed covering over 10,000 registered patients. In the near future, these registries will facilitate clinical research in AAV on a scale hitherto unknown. Current studies on the genetic background of AAV will explore the potential prognostic significance of genetic markers and further refine genetic associations with distinct disease subsets. The histopathological classification of ANCA-associated glomerulonephritis is currently evaluated in light of data coming out of a large international validation study. In our continuous search for biomarkers to predict clinical outcome, promising new markers are important subjects of current research. Over the last 2 decades, a host of clinical trials have provided evidence for refinement of therapeutic regimens. We give an overview of clinical trials currently under development, and consider refractory vasculitis in detail. The goal of EUVAS is to stimulate ongoing research in clinical, serological, and histological management and techniques for patients with systemic vasculitis, with an outlook on the applicability for clinical trials.

The European League Against Rheumatism recommendations for the management of antineutrophil cytoplasmic antibody-associated vasculitis have been recently published. Unique to recommendation development, they were also voted on by members of a learned society. This paper explores the wider validity of the recommendations among people who self-identify as clinicians caring for patients with vasculitis. In addition to the task force, a learned society (European Vasculitis Society-EUVAS) was invited, through online survey, to rate independently the strength of evidence of each recommendation to obtain an indication of the agreement among the final target audience and ultimate end-users of the recommendations. The survey took place in June 2015. Of the 158 EUVAS members surveyed, there were 88 responses (55.7%). There was a large degree of agreement in the voting patterns between EUVAS survey participants and task force members. Notable exceptions were lower grades for the recommendation of the use of rituximab for remission induction in patients with eosinophilic granulomatosis with polyangiitis and for methotrexate and mycophenolate mofetil as remission maintenance agents in patients with granulomatosis with polyangiitis/microscopic polyangiitis by EUVAS members. These results are encouraging and suggest that the voting patterns of the task force are representative of the wider vasculitis community. We recommend future recommendations adopt this approach for data/expert-based treatment guidelines, especially for multisystem diseases.

Objective To develop a simplified method to quantify liver fat using computed tomography (CT) fat % index (CT FPI ) compared to liver spleen method (CT L/S , CT L−S ). Methods Noncontrast CT of the liver was performed in 89 patients (overweight, obese, severely obese) to quantify fat, using the following: CT FPI =[(65−patient HU)/65]×100, normal live r =65 HU. Results There was a strong linear correlation between CT FPI and the standard method of assessing liver fat using CT L/S ( r =−0.901), CT L−S ( r =−0.911). Hepatic HU and CT FPI were significantly different in the severely obese group compared to other two groups ( P Conclusion Significant correlation indicates equal diagnostic accuracy of the two methods in appropriately calibrated scanners.

Purpose To develop and evaluate an image reconstruction technique for cardiac MRI (CMR) perfusion that uses localized spatio-temporal constraints. Methods CMR perfusion plays an important role in detecting myocardial ischemia in patients with coronary artery disease. Breath-hold k-t–based image acceleration techniques are typically used in CMR perfusion for superior spatial/temporal resolution and improved coverage. In this study, we propose a novel compressed sensing-based image reconstruction technique for CMR perfusion, with applicability to free-breathing examinations. This technique uses local spatio-temporal constraints by regularizing image patches across a small number of dynamics. The technique was compared with conventional dynamic-by-dynamic reconstruction, and sparsity regularization using a temporal principal-component (pc) basis, as well as zero-filled data in multislice two-dimensional (2D) and three-dimensional (3D) CMR perfusion. Qualitative image scores were used (1 = poor, 4 = excellent) to evaluate the technique in 3D perfusion in 10 patients and five healthy subjects. On four healthy subjects, the proposed technique was also compared with a breath-hold multislice 2D acquisition with parallel imaging in terms of signal intensity curves. Results The proposed technique produced images that were superior in terms of spatial and temporal blurring compared with the other techniques, even in free-breathing datasets. The image scores indicated a significant improvement compared with other techniques in 3D perfusion (x-pc regularization, 2.8 ± 0.5 versus 2.3 ± 0.5; dynamic-by-dynamic, 1.7 ± 0.5; zero-filled, 1.1 ± 0.2). Signal intensity curves indicate similar dynamics of uptake between the proposed method with 3D acquisition and the breath-hold multislice 2D acquisition with parallel imaging. Conclusion The proposed reconstruction uses sparsity regularization based on localized information in both spatial and temporal domains for highly accelerated CMR perfusion with potential use in free-breathing 3D acquisitions. Magn Reson Med 72:629–639, 2014. © 2013 Wiley Periodicals, Inc.

Bei allen Revisionseingriffen sowohl an der autologen wie an der PTFE-Interponat-Fistel gilt das Gebot des sparsamen Umgangs mit den Gefasen. Neben einem zu niedrigen Shuntfluss sind Intimahyperplasie und Stenose der protheto-venosen Anastomose haufige Grunde fur eine Shuntdysfunktion. Die Ergebnisse der duplexsonographischen Untersuchung geben den Weg der Revisionseingriffe vor. Ein fruhzeitiger Reeingriff vor Shuntverschluss und Shuntthrombose kann die Implantation zentralvenoser Katheter vermeiden. Die chirurgische Intervention sollte durch eine digitale Subtraktionsangiographie (DSA) kontrolliert werden, insbesondere wenn intraoperativ der Grund des Shuntverschlusses nicht ersichtlich wird und an eine zentralvenose Stenose gedacht werden muss, die mit der Duplexsonographie nur limitiert dargestellt werden kann. Chirurgisch kommen neben der offenen Revision auch perkutane und Hybridverfahren zum Einsatz. Stealsyndrome mit normalen und hohen Shuntflussen sollten chirurgisch unterschiedlich angegangen werden. Dabei stehen das DRIL-Verfahren und die Proximalisierung der Fistel zur Verfugung. Wahrend das DRIL-Verfahren bei hohen Shuntflussen einen Verschluss der distalen Arterie in Kauf nimmt, wird der Zufluss nach distal bei der Proximalisierung erhoht. Shuntinfektionen sind eine haufige und lebensbedrohliche Komplikation und sollten fruhestmoglich behandelt werden. Bei septischen Verlaufen einer PTFE-Infektion muss der Shunt ausgebaut werden. Shuntaneurysmen werden solange akzeptiert, wie der Shunt keine Dysfunktion aufweist. Neben einem chirurgischen Vorgehen steht zur Ausschaltung der Aneurysmen Stent und Thrombininjektion zur Verfugung. Perigraftreaktionen in Form einer Schwellneigung sind seltene Komplikationen, die bei Persistenz mit einem Austausch des Interponats behoben werden konnen. Sensible neurologische Ausfalle nach Shuntanlagen sind eine haufige Komplikation mit groser Ruckbildungstendenz. Motorische Ausfalle sind selten und sollten bei Persistenz neurochirurgisch versorgt werden.

Importance Inflammation may contribute to pathological associations among obesity, diabetes mellitus, and cardiovascular disease. Objective To determine whether targeting inflammation using salsalate compared with placebo reduces progression of noncalcified coronary artery plaque. Design, Setting, and Participants In the Targeting Inflammation Using Salsalate in Cardiovascular Disease (TINSAL-CVD) trial participants were randomly assigned between September 23, 2008, and July 5, 2012, to 30 months of salsalate or placebo in addition to standard, guideline-based therapies. Randomization was computerized and centrally allocated, with patients, health care professionals, and researchers masked to treatment assignment. Participants were overweight and obese statin-using patients with established, stable coronary heart disease. Interventions Salsalate (3.5 g/d) or placebo orally over 30 months. Main Outcomes and Measures The primary outcome was progression of noncalcified coronary artery plaque assessed by multidetector computed tomographic angiography. Secondary outcomes were other measures of safety and efficacy. Results Two hundred fifty-seven participants were randomized to salsalate (n = 129) or placebo (n = 128). Their mean (SD) age was 60.8 (7.0) years, and 94.0% (236 of 251) were male. One hundred ninety participants (89 in the salsalate group and 101 in the placebo group) completed the study. Compared with baseline, there was no increase in noncalcified plaque volume in the placebo-treated patients and no difference in change between the salsalate and placebo groups (mean difference, −1 mm3; 95% CI, −11 to 9 mm3;P = .87). Salsalate treatment decreased total white blood cell, lymphocyte, monocyte, and neutrophil counts and increased adiponectin levels without change in C-reactive protein levels. Fasting glucose, triglycerides, uric acid, and bilirubin levels were decreased in the salsalate group compared with the placebo group, while hemoglobin levels were increased. Urinary albumin levels increased, with tinnitus and atrial arrhythmias more common, in the salsalate group compared with the placebo group. Conclusions and Relevance Salsalate when added to current therapies that include a statin does not reduce progression of noncalcified coronary plaque volume assessed by multidetector computed tomographic angiography in statin-using patients with established, stable coronary heart disease. The absence of progression of noncalcified plaque volume in the placebo group may limit interpretation of the trial results. Trial Registration clinicaltrials.gov Identifier:NCT00624923