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To determine the predictive factors of mortality after hospitalization for acute heart failure (AHF) in an internal medicine department. Retrospective observational analysis conducted on 164 patients hospitalized for AHF in 2016-2017. Demographic, clinical and biological characteristics were assessed during hospitalization. The primary endpoint was the occurrence of all-cause death. Multivariate analysis was performed using the Cox model adjusted for age and renal function. The study population was mostly female (n = 106, 64.6%), elderly (82.9 years ± 10.0), with a preserved LVEF (86%). Mean Charlson comorbidity index was 6.5 ± 2.5. After a median follow-up of 17.5 months (IQR 6-38), 109 patients (65%) had died with a median time to death of 14 months (IQR 3-29). In univariate analysis, patients who died were significantly older, had lower BMI and renal function, and higher CCI and NT-proBNP levels (median of 4944 ng/l [2370-14403] versus 1740 ng/l [1119-3503], p 0.001). In multivariate analysis, risk factors for death were lower BMI (HR 0.69, CI [0.53-0.90], p = 0.005), lower albuminemia (HR 0.77 [0.63-0.94], p = 0.009), higher ferritinemia (HR 1.38 [1.08-1.76], p = 0.010), higher uricemia (HR 1.28 [1.02-1.59], p = 0.030), higher NT-proBNP (HR 2.46 [1.65-3.67], p 0.001) and longer hospital stay (HR 1.25 [1.05-1.49] p = 0.013). In elderly multimorbid patients, AHF prognosis appears to be influenced by nutritional criteria, including lower BMI, hypoalbuminemia, and hyperuricemia (independently of renal function). These results underline the importance of nutritional status, especially as therapeutic options are available. This consideration paves the way for further research in this field.

International audience; Background: Inflammation of unknown origin (IUO) is a challenging situation in internal medicine.Objectives: To describe the final diagnoses in IUO and assess the helpfulness of 18F-fluorodesoxyglucose positron emission tomography with computerized tomography (18F-FDG-PET/CT) in the diagnosis strategy.Results: A total of 317 IUO patients with 18F-FDG-PET/CT were enrolled. A diagnosis was reached in 228 patients: noninfectious inflammatory diseases (NIID) (37.5%), infectious diseases (18.6%), malignancies (7.9%), and non-systemic-inflammatory miscellaneous diseases (7.9%). The two leading causes of NIID were polymyalgia rheumatica and giant cell arteritis. 18F-FDG-PET/CT results were classified as true positive in 49.8% of patients and contributory in 75.1% of overall IUO patients (after the complete investigation set and a prolonged follow-up). In multivariate analysis, only C-reactive protein minimum level (≥50 mg/L) was associated with the contributory status of 18F-FDG-PET/CT.Conclusion: Within the wide spectrum of IUO underlying diseases, 18F-FDG-PET/CT is helpful to make a diagnosis and to eliminate inflammatory diseases. Obese patients constitute a specific group needing further studies

Giant cell arteritis (GCA) has a relapsing-remitting course and is associated with high burden of comorbidities, leading to repeated hospitalizations. We investigated the burden, risk factors, causes and outcomes of hospitalization and readmission in patients with GCA in a US national cohort.Using the 2017 US National Readmission Database, we identified adults ≥50-year- old hospitalized with GCA between January-June 2017, with at least a 6-month of follow-up. We estimated the burden of hospitalization including 6-month risk of readmission, total days spent in hospital and costs, annually. We examined patient-, hospital-, and index hospitalization-related factors for 6-month readmission and total days of hospitalization, through binomial logistic regression.We included 1,206 patients hospitalized with GCA (70% women, median age, 77y), with 13% patients experiencing GCA-related ophthalmological complications at index admission. On follow-up, 3% died, and 34% patients were readmitted within 6 months, primarily for infections (23%) and cardiovascular diseases (15%). Charlson's comorbidity index ≥1, smoking, and obesity were associated with readmission. Patients with GCA spent 5 [3-11] days in median in hospital per year, with those in top quartile spending 19 [14-26] days/year in hospital.Patients with GCA frequently experience unplanned healthcare utilization, with 1 in 3 experiencing readmission within 6 months, and 3% dying within the follow-up. Infection and cardiovascular diseases are common causes of readmission, and may be related to corticosteroid exposure. Population health management strategies are required for these vulnerable patients with GCA. This article is protected by copyright. All rights reserved.

In the early phase of the pandemic, we were among the first to postulate that neutrophil extracellular traps (NETs) play a key role in COVID-19 pathogenesis. This exploratory prospective study based on 279 individuals showed that plasma levels of neutrophil elastase, myeloperoxidase and circulating DNA of nuclear and mitochondrial origins in nonsevere (NS), severe (S) and postacute phase (PAP) COVID-19 patients were statistically different as compared to the levels in healthy individuals, and revealed the high diagnostic power of these NETs markers in respect to the disease severity. The diagnostic power of NE, MPO, and cir-nDNA as determined by the Area Under Receiver Operating Curves (AUROC) was 0.95, 097, and 0.64; 0.99, 1.0, and 0.82; and 0.94, 1.0, and 0.93, in NS, S, and PAP patient subgroups, respectively. In addition, a significant fraction of NS, S as well as of PAP patients exhibited aCL IgM/IgG and anti-B2GP IgM/IgG positivity. We first demonstrate persistence of these NETs markers in PAP patients and consequently of sustained innate immune response imbalance, and a prolonged low-level pro-thrombotic potential activity highlighting the need to monitor these markers in all COVID-19 PAP individuals, to investigate postacute COVID-19 pathogenesis following intensive care, and to better identify which medical resources will ensure complete patient recovery.

Objectives Aldosterone and renin determinations play an important role in the etiological diagnosis of secondary hypertension. The analytical performances of new aldosterone and renin immunoassays on the Lumipulse G600II® system (Fujierbio) were investigated and compared with those of the iSYS® system (IDS) on patients concerned by medical investigations in a context of suspected or proven Primary aldosteronism. Methods By using the Lumipulse® G Aldosterone and Renin assays we performed imprecision study, linearity and method comparison (n=107). Accuracy of this new renin assay was tested using the International Standard (WHO IS 68/356). We also assessed the equivalence of the different samples types (n=29). Results The imprecision evaluation showed all CVs ® G Aldosterone and Renin assays respectively. The linearity was excellent over the clinical range and the comparison with the iSYS® assays (n=79) showed a strong correlation (R2=1) despite a slight tendency to underestimation (bias of −17.53 pg/mL or 48.56 pmol/L for aldosterone and −15.395 pg/mL for renin). Moreover, the contingency studies based on diagnostic criteria showed that Lumipulse® G results lead to the same clinical diagnosis that iSYS® results. A clear correlation was obtained between EDTA and heparin plasma as well as with the serum for all range of measures. Conclusions The Lumipulse® G Aldosterone and Renin assays present performances compatible with a routine use in medical laboratories. The precise quantification in the low range can be of interest in some clinical contexts especially standing/laying tests. However, the standardisation against the WHO International Standard Renin would be advisable.

International audience; Aims: Biomarkers are not recommended until now to guide the management of patients with heart failure (HF). Soluble suppression of tumorigenicity 2 (sST2) appears as a promising biomarker. The current study considered pre-discharged sST2 values as a guide for medical management in patients admitted for acute HF decompensation, in an attempt to reduce hospital readmission.Methods and results: STADE-HF was a blinded prospective randomized controlled trial and included 123 patients admitted for acute HF. They were randomized into the usual treatment group (unknown sST2 level) or the interventional treatment group, for whom sST2 level was known and used on Day 4 of hospitalization to guide the treatment. The primary endpoint was the readmission rate for any cause at 1 month. It occurred in 10 patients (19%) in the usual group and 18 (32%) in the sST2 group without statistical difference (P = 0.11). Post hoc analysis in the whole group shows that the mean duration of hospitalization was lower in patients with low sST2 (

Objectives: Giant cell arteritis (GCA) is associated with severe outcomes such as infections and cardiovascular diseases. We describe here the impact of GCA patients’ characteristics and treatment exposure on the occurrence of severe outcomes. Methods: Data were collected retrospectively from real-world GCA patients with a minimum of six-months follow-up. We recorded severe outcomes and treatment exposure. In the survival analysis, we studied the predictive factors of severe outcomes occurrence, including treatment exposure (major glucocorticoids (GCs) exposure (>10 g of the cumulative dose) and tocilizumab (TCZ) exposure), as time-dependent covariates. Results: Among the 77 included patients, 26% were overweight (BMI ≥ 25 kg/m2). The mean cumulative dose of GCs was 7977 ± 4585 mg, 18 patients (23%) had a major GCs exposure, and 40 (52%) received TCZ. Over the 48-month mean follow-up period, 114 severe outcomes occurred in 77% of the patients: infections—29%, cardiovascular diseases—18%, hypertension—15%, fractural osteoporosis—8%, and deaths—6%. Baseline diabetes and overweight were predictive factors of severe outcomes onset (HR, 2.41 [1.05–5.55], p = 0.039; HR, 2.08 [1.14–3.81], p = 0.018, respectively) independently of age, sex, hypertension, and treatment exposure. Conclusion: Diabetic and overweight GCA patients constitute an at-risk group requiring tailored treatment, including vaccination. The effect of TCZ exposure on the reduction of severe outcomes was not proved here.

Primary Sjögren’s syndrome (pSS) can be associated with neurological and cognitive involvement, negatively affecting patients’ quality of life. The aim of this study was to assess whether pSS patients are at higher risk of hospitalization for neurological diseases. Through a nationwide retrospective study using the French Health insurance database (based on International Classification for Disease codes, ICD-10), we selected patients hospitalized with new-onset pSS between 2011 and 2018. We compared the incidence of hospitalization for dementia, multiple sclerosis (MS), encephalitis, and peripheral neuropathy with an age- and sex-matched (1:10) hospitalized control group. Adjusted Hazard Ratios (aHR) considered confounding factors, particularly socio-economic status and cardiovascular diseases. We analyzed 25,661 patients hospitalized for pSS, compared with 252,543 matched patients. The incidence of hospitalization for dementia was significantly higher in pSS patients (aHR = 1.27 (1.04–1.55); p = 0.018), as well as the incidence of hospitalization for MS, encephalitis, and inflammatory polyneuropathies (aHR = 3.66 (2.35–5.68), p < 0.001; aHR = 2.66 (1.22–5.80), p = 0.014; and aHR = 23.2 (12.2–44.5), p < 0.001, respectively). According to ICD-10 codes, pSS patients exhibited a higher incidence of hospitalization for dementia, encephalitis, MS, and peripheral neuropathies than controls. Physicians must be aware of these neurological risks to choose the most appropriate diagnostic work-up.

Inflammation of unknown origin (IUO) is a challenging situation in internal medicine.To describe the final diagnoses in IUO and assess the helpfulness ofA total of 317 IUO patients withWithin the wide spectrum of IUO underlying diseases

Obesity is associated with increased cardiovascular risk. Bariatric surgery (BS) improves the clinical and metabolic profile. Retinal caliber changes could precede cardiovascular events. Different studies have shown an improvement in retinal caliber after BS. The aim of this study was to examine retinal caliber and other cardiovascular target organ damage before and after BS.Monocentric, prospective cohort study at the Montpellier University Hospital. Biologic features, vessel stiffness, echocardiograph variables, and retinal caliber at baseline and 6 and 12 months were assessed in consecutive patients with class 2 or 3 obesity undergoing BS. A mixed linear model adjusted for age and sex was used.We included 88 patients (75 women). The mean (SD) age was 43 years (11) and mean (SD) baseline weight 117 (21) Kg. Mean changes in the first year after BS were - 5.1 µm in central retinal vein equivalent (CRVE) (p 0.0001), + 0.02 in arteriole-to-venule ratio (AVR) (p 0.0001), - 1.4 mmol/L in glycemia (p 0.0001), - 1.0 mg/L in natural logarithm of C-reactive protein (p 0.0001), and - 54.0 g in left ventricular mass (p = 0.0005). We observed no significant improvement in arterial stiffness markers. Predictors of improvement in CRVE were high baseline weight (p = 0.030), male sex (p = 0.025), and no diabetes history (p Dynamic links between variations = 0.047).The retinal microvascular phenotype improved during the first year after bariatric surgery, with decreased CRVE and increased AVR. Factors associated with retinal microvascular plasticity were male sex, high baseline weight, and absence of diabetes. Longitudinal assessment of retinal vascular calibers may offer new insights into the pathophysiology of subclinical vascular processes.

Objectives: The objective of this prospective, single-center study was to explore the mid-term outcomes 6 to 9 months after hospitalization in an Intensive Care Unit (ICU) for severe COVID-19 infection. Methods: Patients systematically underwent biological tests, pulmonary function tests, chest computed tomography (CT) scan, and psychological tests. Results: Among 86 patients, including 71 (82.6%) men, median age of 65.8 years (56.7; 72.4), 57 (71.3%) patients presented post-COVID-19 asthenia, 39 (48.1%) muscle weakness, and 30 (36.6%) arthralgia. Fifty-two (64.2%) patients had a decreased diffusion capacity for carbon monoxide (DLCO)

International audience; Obstructive sleep apnea is a potentially dangerous condition with significant risks of comorbidities if left untreated. It represents a cardiovascular risk factor in the general population, and a higher prevalence is observed in patients already suffering from cardiovascular diseases. The gold standard treatment, continuous positive airway pressure, is not always accepted or tolerated. The mandibular advancement device represents an alternative treatment that we propose to implement in our study. The objective here is to first present a brief review of the topic. Due to poor evidence in the field, we propose a pilot study to evaluate the effect of a mandibular advancement device in patients with cardiovascular disease who are not treated for their sleep pathology in order to improve their therapeutic management.

Objective: To explore the diagnostic contribution of the 18F-FDG-PET/CT in a population of patients with classical fever of unknown origin (FUO), to pinpoint its place in the diagnostic decision tree in a real-life setting, and to identify the factors associated with a diagnostic 18F-FDG-PET/CT. Method: All adult patients (aged ≥ 18 years) with a diagnosis of classical FUO who underwent an 18F-FDG-PET/CT in the University Hospital of Montpellier (France) between April 2012 and December 2017 were included. True positive 18F-FDG-PET/CT, which evidenced a specific disease causing FUO, were considered to be contributive. Results: Forty-four patients with FUO have been included (20 males, 24 females, mean age 57.5 ± 17.1 years). Diagnoses were obtained in 31 patients (70.5%), of whom 17 (38.6%) had non-infectious inflammatory diseases, 9 had infections (20.5%), and 3 had malignancies (6.8%). 18F-FDG-PET/CT was helpful for making a final diagnosis (true positive) in 43.6% of all patients. Sensitivity and specificity levels were 85% and 37%, respectively. A total of 135 investigations were performed before 18F-FDG-PET/CT, mostly CT scans (93.2%) and echocardiography (59.1%), and 108 after 18F-FDG-PET/CT, mostly biopsies (including the biopsy of a temporal artery) (25%) and MRIs (34%). In multivariate analysis, the hemoglobin level was significantly associated with a helpful 18F-FDG-PET/CT (p = 0.019, OR 0.41, 95% CI (0.20–0.87)), while the CRP level was not associated with a contributive 18F-FDG-PET/CT. Conclusion: 18F-FDG-PET/CT may be proposed as a routine initial non-invasive procedure in the diagnostic workup of FUO, especially in anemic patients who could be more likely to benefit from 18F-FDG-PET/CT.

Introduction We aimed to evaluate the impact of an immersive simulation session on the experience of the beginning of residency. Methods The interventional group consisted of newly recruited residents in 2019, who participated in the workshop presenting four emergency scenarios frequently encountered during night shifts; the control group comprised residents who had begun their internship in 2018, without having participated in the simulation workshop. The level of psychological stress and self-confidence were self-estimated in the simulation group before and immediately after the workshop. During the second semester of residency, stress, self-efficacy and anxiety were evaluated in both groups with the Perceived Stress Scale (PSS), General Self-efficacy Scale (GSES), and Generalized Anxiety Disorder-7 (GAD-7) scale. Results In the second semester 2020, the PSS, GSES and GAD-7 were 20.71 ± 8.15 and 22.44 ± 5.68 (P = 0.40); 26.88 ± 6.30 and 27.11 ± 3.95 (P = 0.87); 6.94 ± 5.25 and 8.89 ± 4.78 (P = 0.22) for the simulation (n = 17, 89.5% of participation) and control (n = 9, 75%) groups, respectively. In the simulation group, the level of self-confidence had significantly improved from 1.82 ± 0.95 before the session to 2.29 ± 1.16 after the session (P = 0.05). Interestingly, this improvement in self-confidence was significantly correlated with GAD-7 (P = 0.014) and PSS (P = 0.05), and tended to be correlated with GSES (P = 0.09). Conclusion Our study showed a significant improvement in self-confidence between before and after the simulation session. Residents who experienced an improvement in self-confidence saw their stress and anxiety levels decrease during the second semester reevaluation, in favor of a prolonged benefit from the session.

We aimed to explore the relationship between comorbidities and the structural progression in symptomatic knee and/or hip osteoarthritis (OA) patients. We analyzed the 5-year outcome of non-obese participants (body mass index (BMI) &lt, 30 kg/m2) from the KHOALA cohort having symptomatic hip and/or knee OA (Kellgren and Lawrence (KL) ≥ 2). The primary endpoint was radiological progression, defined as ΔKL ≥ 1 of the target joint at 5 years. The secondary outcome was the incidence of total knee or hip replacement over 5 years. Dichotomous logistic regression models assessed the relationship of comorbidities with KL progression and joint replacement while controlling for gender, age and BMI. Data from 384 non-obese participants were analyzed, 151 with hip OA and 254 with knee OA. At 5 years, cardiovascular diseases (CVD) were significantly associated with the 5-year KL change in both knee (OR = 2.56 (1.14–5.78), p = 0.02) and hip OA (OR = 3.45 (1.06–11.17), p = 0.04). No significant relationship was found between any type of comorbidities and knee or hip arthroplasty. This 5-year association between CVD and radiological progression of knee and hip OA in non-obese participants argue for an integrated management of CVD in knee and hip OA non-obese patients.

Despite improvement in the prognosis of ANCA-associated vasculitides (AAVs), increased mortality, mainly from a cardiovascular origin, persists. We aimed to determine the role of cardiovascular risk factors (CVRFs) on the occurrence of major cardiovascular events (MACEs) in AAVs. Patients with AAVs were successively included in a prospective cohort study, which assessed CVRFs (defined by age &gt, 50 years in men and &gt, 60 years in women, personal history of cardiovascular disease, smoking status, obesity, diabetes, dyslipidemia, hypertension, and sedentary lifestyle), the use of glucocorticoids and immunosuppressive agents at baseline and during follow-up, and the occurrence of MACEs. One hundred and three patients were included, with a median follow-up time of 3.5 years. In the glucocorticoids and cyclophosphamide adjusted multivariate analysis, the occurrence of MACEs was associated with older age (p = 0.001, OR = 14.71, 95% CI (confidence interval) = 2.98–72.68), cardiovascular history (p = 0.007, OR (odds ratio) = 6.54, 95% CI = 1.66–25.71), sedentary lifestyle (p = 0.011, OR = 4.50, 95% CI = 1.42–14.29), hypertension (p = 0.017, OR = 5.04, 95% CI = 1.33–19.12), and dyslipidemia (p = 0.03, OR = 3.86, 95% CI = 1.14–13.09). The occurrence of MACEs was associated with the number of CVRFs (p &lt, 0.001), but not with the use of glucocorticoids or cyclophosphamide (p = 0.733 and p = 0.339, respectively). The implementation of a screening and management program for modifiable CVRFs, particularly hypertension, sedentary lifestyle, and dyslipidemia, may be beneficial for AAV patients in order to reduce their cardiovascular risk.

Background and objective Cardiovascular diseases (CVD) are the leading causes of death in chronic inflammatory rheumatic diseases and are not solely explained by the increased prevalence of cardiovascular (CV) risk factors in this population. Arterial stiffness, assessed primarily by pulse wave velocity (PWV) and more indirectly by augmentation index (AIx), is a surrogate marker of CVD that should be considered. The objective of this review was to investigate the relationship between arterial stiffness and chronic inflammatory and/or autoimmune diseases. Methods We performed a systemic literature review of articles published in Medline from January 2012 to April 2020 restricted to English languages and to human adults. We selected relevant articles about the relationship between arterial stiffness and rheumatoid arthritis, systemic lupus erythematosus, psoriasis, Sjogren's syndrome and ankylosing spondylitis. For each selected article, data on PWV and AIx were extracted and factors that may have an impact on arterial stiffness were identified. Results A total of 214 references were identified through database searching and 82 of them were retained for analysis. Arterial stiffness is increased in chronic inflammatory and autoimmune diseases. Traditional CV risk factors such as hypertension and dyslipidemia accentuate this relationship. Current data are insufficient to determine whether disease activity significantly influences arterial stiffness, whereas disease duration seems rather critical. TNF-alpha inhibitors and cardiorespiratory fitness tend to decrease arterial stiffness. Finally, increased arterial stiffness leads to diastolic dysfunction, which is the main mechanism of heart failure in chronic inflammatory rheumatic diseases. Conclusion CV risk assessment in chronic inflammatory and autoimmune diseases should also rely on PWV and AIx.

International audience

International audience; Background: Medication errors (ME) can be reduced through preventive strategies such as medication reconciliation. Such strategies are often limited by human resources and need targeting high risk patients.Aims: To develop a score to identify patients at risk of ME detected during medication reconciliation in a specific population from internal medicine unit.Methods: Prospective observational study conducted in an internal medicine unit of a French University Hospital from 2012 to 2016. Adult hospitalised patients were eligible for inclusion. Medication reconciliation was conducted by a pharmacist and consisted in comparing medication history with admission prescription to identify MEs. Risk factors of MEs were analysed using multivariate stepwise logistic regression model. A risk score was constructed using the split-sample approach. The split was done at random (using a fixed seed) to define a development data set (N = 1256) and a validation sample (N = 628). A regression coefficient-base scoring system was used adopting the beta-Sullivan approach (Sullivan's scoring).Results: Pharmacists detected 740 MEs in 368/1884 (19.5%) patients related to medication reconciliation. Female gender, number of treatments >7, admission from emergency department and during night or weekend were significantly associated with a higher risk of MEs. Risk score was constructed by attributing 1 or 2 points to these variables. Patients with a score ≥3 (OR [95% CI] 3.10 [1.15-8.37]) out of 5 (OR [95% CI] 8.11 [2.89-22.78]) were considered at high risk of MEs.Conclusions: Risk factors identified in our study may help prioritising patients admitted in internal medicine units who may benefit the most from medication reconciliation (ClinicalTrials.gov number NCT03422484).

Primary Sjögren’s syndrome (pSS) is an autoimmune disease, associated with a high risk of lymphoma. Mounting evidence suggests that cardiovascular morbidity and mortality are higher in patients with pSS, although data are heterogeneous. The aim of this study was to assess whether pSS patients are at higher risk of hospitalisation for cardiovascular events (CVEs), venous thromboembolic events (VTEs), pulmonary hypertension (PH), and sleep apnoea syndrome (SAS). Through a nationwide population-based retrospective study using the French health insurance database, we selected new-onset pSS in-patients hospitalised between 2011 and 2018. We compared the incidence of CVEs (ischemic heart diseases (IHDs), strokes, and heart failure), SAS, VTEs, and PH with an age- and sex-matched (1:10) hospitalised control group. The calculations of adjusted hazard ratios (aHR) included available confounding factors. We studied 25,661 patients hospitalised for pSS compared with 252,543 matched patients. The incidence of hospitalisation for IHD, SAS, and PH was significantly higher in pSS patients (aHR: 1.20 (1.06–1.34), p = 0.003, aHR: 1.97 (1.70–2.28), p &lt, 0.001, and aHR: 3.32 (2.10–5.25), 0.001, respectively), whereas the incidence of stroke, heart failure, and VTE was the same between groups. Further prospective studies are needed to confirm these results and to explore the pathophysiological mechanisms involved.

Objectives To explore the 10-year tolerability profile of glucocorticoids (GC) use in patients with early RA. Methods Analysis of 10-year outcome from the early arthritis ESPOIR cohort. Patients were stratified in two groups, without or with GC treatment at least once during their follow-up. The primary outcome was a composite of deaths, cardiovascular diseases (CVD), severe infections and fractures. The weighted Cox time-dependent analysis model was used with inverse probability of treatment weighting (IPTW) propensity score method. Results Among the 608 patients [480 women, mean age of 47.5 (12.1) years], 397 (65%) received low-dose GC [median 1.9 mg/day (IQR 0.6–4.2), mean cumulative prednisone dose 8468 mg (8376), mean duration 44.6 months (40.1)]. In univariate analysis, over 95 total events (10 deaths, 18 CVDs, 32 fractures and 35 severe infections), patients taking GC experienced more events (n = 71) than those without GC (n = 24) (P =0.035). Highest cumulative exposure of GC (≥8.4 g) was associated with highest risk of occurrence of the primary outcome (24.3%, P =0.007), CVDs (7.9%, P =0.001) and severe infections (9.9%, P =0.024). The risk of events over time was significantly associated with GC, age, hypertension and ESR. The risk associated with GC treatment increased between the first follow-up visit [hazard ratio (HR) at 1 year = 0.46, 95% CI: 0.23, 0.90] and 10 years (HR = 6.83, 95% CI: 2.29, 20.35). Conclusion The 10-year analysis of this prospective early RA cohort supports a dose and time-dependent impact of low-dose GC treatment, with a long-term high risk of severe outcomes. Trial registration (ClinicalTrials.gov Identifier: NCT03666091).

Since Hippocrates, the cornerstone of medical practice has been the doctor-patient relationship. The question here is whether these basic principles are still compatible with this unusual COVID-period. This pandemic represents a serious threat to human health, leading to profound changes in behavior in daily life but also in health care. Because of limited resources, health-managers must choose well-balanced solutions able to protect patients and citizens on the one hand and to provide maximal benefit for the society on the other hand. We are going through a moment of rupture that we must acknowledge. Here, we discussed how the doctor-patient relationship could be compromised. Doctors are focused on cares whereas patients are focused on scare. Profound changes occur presently, from the way we present ourselves to each other (including the masks), the poor conditions for physical examination, the mental suffering of both patient and caregiver until sometimes terrible end-of-life conditions. The historical point-of-view helps us to keep in mind previous experiences, and the philosophical perspective helps to contextualize this unedited situation. We should stop briefly our daily rush to put these considerations into perspective to overcome these challenges. Nothing is as effective as trust: let's rebuild it.

International audience; We read with deep interest the report by Tepasse et al .1 concerning two cases of persisting viraemia in coronavirus disease 2019 (COVID‐19) with fatal outcome. Whilst severe acute respiratory syndrome coronavirus‐2 (SARS‐CoV‐2) infection in the early stages of infection has been well described, less is known about the development of antibodies to SARS‐CoV‐2, clearance of RNA shedding and clinical outcome of COVID‐19. In addition, the impact of immunosuppressive treatments on disease severity is not yet established, but several reports suggest a more prolonged disease in patients under rituximab, a B‐cell depleting drug.2-4 Here we report a case of persisting COVID‐19, following combined treatment with rituximab and bendamustine for lymphoma, which immediately recovered after convalescent plasma transfusion. We think that this case raises promising perspectives for immunocompromised patients with persisting COVID‐19.

Background. The new coronavirus SARS-CoV-2, responsible for the Covid-19 pandemic, uses the angiotensin converting enzyme type 2 (ACE2), a physiological inhibitor of the renin angiotensin aldosterone system (RAAS), as a cellular receptor to infect cells. Since the RAAS can induce and modulate pro-inflammatory responses, it could play a key role in the pathophysiology of Covid-19. Thus, we aimed to determine the levels of plasma renin and aldosterone as indicators of RAAS activation in a series of consecutively admitted patients for Covid-19 in our clinic. Methods. Plasma renin and aldosterone levels were measured, among the miscellaneous investigations needed for Covid-19 management, early after admission in our clinic. Disease severity was assessed using a seven-category ordinal scale. Primary outcome of interest was the severity of patients&rsquo, clinical courses. Results. Forty-four patients were included. At inclusion, 12 patients had mild clinical status, 25 moderate clinical status and 7 severe clinical status. In univariate analyses, aldosterone and C-reactive protein (CRP) levels at inclusion were significantly higher in patients with severe clinical course as compared to those with mild or moderate course (p &lt, 0.01 and p = 0.03, respectively). In multivariate analyses, only aldosterone and CRP levels remained positively associated with severity. We also observed a positive significant correlation between aldosterone and CRP levels among patients with an aldosterone level greater than 102.5 pmol/L. Conclusions. Both plasmatic aldosterone and CRP levels at inclusion are associated with the clinical course of Covid-19. Our findings may open new perspectives in the understanding of the possible role of RAAS for Covid-19 outcome.

It has been well documented that patients with rheumatoid arthritis (RA) are at higher risk for many comorbidities1, even in early RA2. The concept of comorbidity refers to chronic conditions that coexist with the index disease, such as RA, with potential interactions between RA and comorbidities that may worsen patient global well-being. In fact, this concept does not seem so recent, because a global healthcare approach has always been the gold standard in the management of many chronic diseases. However, specifically regarding RA management, the innovative aspect lies in involving rheumatologists in addressing the field of comorbidities. Thanks to tight control of joint outcomes with targeted disease-modifying antirheumatic drugs (DMARD), the rheumatologists became involved in other dimensions of RA, such as quality of life or comorbidities. Evidenced-based and practical recommendations for screening and managing comorbidities in RA have been developed2,3,4,5,6. Such comorbidities in RA include various conditions such as cardiovascular diseases, hypertension (HTN), diabetes, pulmonary diseases, depression, osteoporosis, and malignancies. Comorbidities appear to be of utmost importance to consider, not only because of their high prevalence but also because of their potential involvement in RA outcome7. Comorbidities affect morbidity, increase mortality, impair quality of life, and affect response to treatment, while increasing the complexity of managing RA and its costs. This is also true in early RA. In the Canadian Early Arthritis cohort, comorbidities were associated with higher disease activity and worse functional status8. Indeed, comorbidities have been reported to be a negative predictor of achieving the treatment target, … Address correspondence to Dr. C. Roubille, Department of Internal Medicine, 371 Avenue du Doyen Gaston Giraud, CHU Montpellier, University of Montpellier, 34295 Montpellier, France. E-mail: c-roubille{at}chu-monpellier.fr

Introduction L’internat, et en particulier son debut, associe aux premieres gardes, est une periode source de stress et d’anxiete importante. La simulation en sante est un outil pedagogique reconnu comme efficace pour l’amelioration des competences techniques mais egalement non techniques dans de nombreux domaines. Cependant, elle est encore peu utilisee dans le co- Diplome d’Etudes Specialisees (DES) de Medecine Interne Immunologie Clinique, Maladies Infectieuses et Tropicales, et Allergologie (MIIC-MIT-A). Son utilisation a par ailleurs montre un benefice sur le stress, l’anxiete et le sentiment d’auto-efficacite chez les etudiants infirmiers. L’objectif de cette etude etait d’evaluer le benefice d’une seance de simulation immersive sur le vecu des premieres gardes des internes du co-DES de MIIC-MIT-A. Materiels et methodes Nous avons realise une etude prospective, controlee, multicentrique, dans laquelle deux groupes d’internes ont ete constitues. Le groupe simulation comprenait les internes qui ont beneficie de la seance de simulation immersive pour la preparation aux premieres gardes lors du premier semestre d’internat, comportant 4 scenarios mettant en jeu des situations critiques (choc hypovolemique sur hemorragie digestive, detresse respiratoire aigue avec arret cardiorespiratoire, choc septique sur pyelonephrite obstructive, choc anaphylactique). Il etait constitue des internes des DES de MIIC-MIT-A de Montpellier, Bordeaux et Nice, qui ont passe les Epreuves Classantes Nationales Informatisees (ECNi) en 2019. Le groupe controle, qui n’a pas beneficie des seances de simulation, etait constitue des internes du meme co-DES de Montpellier et Nice, qui ont passe les ECNi en 2018. L’objectif principal etait d’explorer l’impact de la seance de simulation immersive realisee au premier semestre d’internat, sur le stress, l’anxiete, et le sentiment d’auto efficacite lors des premieres gardes, evalues au second semestre. Les objectifs secondaires etaient la comparaison du stress et de la confiance en soi auto estimes entre le debut et la fin de la seance, et leur association avec le stress, l’anxiete, et l’auto-efficacite au second semestre. Le niveau de stress et de confiance en soi etaient evalues par autoquestionnaire anonymise en debut et fin de seance (echelles de Likert de 0 a 5). Au cours du second semestre, les niveaux de stress, d’anxiete et de sentiment d’auto-efficacite ont ete evalues dans les deux groupes d’internes, a l’aide d’echelles validees : Perceived Stress Scale (PSS), Generalized Anxiety Disorder -7 (GAD-7) scale et General Self-efficacy Scale (GSES). Nous avons enfin evalue la satisfaction des apprenants et leur avis concernant la pertinence de cet outil dans leur formation dans le cadre du co-DES de MIIC-MIT-A. Resultats Les groupes simulation et controle comprenaient respectivement 19 et 9 internes. Au second semestre, les scores PSS, GSES et GAD-7 etaient de 20.71 ± 8,15 et 22,44 ± 5,68 (p = 0,40) ; 26,88 ± 6,30 et 27,11 ± 3,95 (p = 0,87) ; 6,94 ± 5,25 et 8,89 ± 4,78 (p = 0,22) dans les groupes simulation et controle, respectivement. A noter qu’en utilisant le seuil de 8 pour le GAD-7, a partir duquel on considere que l’interroge est anxieux, on retrouve 35,3 % d’internes anxieux dans le groupe simulation contre 55,6 % dans le groupe controle (p = 0,32). Dans le groupe simulation, le niveau de confiance en soi s’est significativement ameliore apres la seance (1,82/5 avant versus 2,29/5 apres, p = 0,05). De maniere interessante, cette amelioration de la confiance en soi est significativement correlee au niveau d’anxiete (GAD-7 ; p = 0,014) et de stress (PSS ; p = 0,05) au second semestre, et tendait a l’etre avec le GSES (p = 0,09). Le niveau de satisfaction des internes concernant la seance etait excellent, ainsi que leur volonte d’integration de la simulation dans le co-DES (4,8/5 ± 0,5). Conclusion Notre etude a mis en evidence une amelioration significative de la confiance en soi entre avant et apres la seance de simulation. Les internes qui tirent un benefice immediat de la seance de simulation, avec une amelioration de leur confiance en eux, voient leur niveau de stress et d’anxiete diminuer a moyen terme au second semestre. A notre connaissance, il s’agit de la premiere etude controlee montrant l’interet de la simulation immersive sur le vecu du debut d’internat et des premieres gardes en MIIC-MIT-A. La simulation semble etre une methode d’interet pour l’amelioration des competences et du vecu des internes dans le co-DES de MIIC-MIT-A.

Introduction L’amelioration du pronostic a court terme des patients atteints de vascularites, grâce aux strategies combinant la corticotherapie et les traitements immunosuppresseurs, a vu emerger l’interet de mieux caracteriser les comorbidites des patients. Les comorbidites s’ajoutent aux atteintes d’organes secondaires a la vascularite et pourraient en modifier le pronostic. Peu de donnees sont disponibles sur l’impact des comorbidites sur l’evolution de la vascularite et la qualite de vie. L’objectif de ce travail etait de determiner l’association entre les comorbidites a l’inclusion et le pronostic des patients. Patients et methodes Les patients suivis pour vascularites associees aux ANCA, dont la granulomatose avec polyangeite (GPA), la granulomatose eosinophilique avec polyangeite (GEPA) et la polyangeite microscopique (PAM), ont ete inclus prospectivement dans une etude de soins courant evaluant les comorbidites et les sequelles (cohorte OSTEOVAS). La mesure de la densite minerale osseuse, la composition corporelle et le contenu en tissu adipeux visceral (VAT) et sous-cutane (SAT) ont ete calcules par absorptiometrie biphotonique a rayons-X. Les scores du VDI, le HAQ et le SF36 ont ete calcules a l’inclusion. Le critere de jugement principal (CJP) etait un critere composite defini par la survenue de deces, d’evenements indesirables graves (EIG) attribuables au traitement ou d’une rechute majeure de la vascularite a 3 ans. Le CJP a ete analyse par un modele de Cox, et l’association aux scores par des modeles lineaires. En criteres secondaires, nous avons etudie l’association entre les comorbidites et les scores de qualite de vie et de sequelles. Resultats Un total de 103 patients (57 femmes, âge moyen 52,4 ± 17,4 ans, duree moyenne de la maladie 6 ans ± 6,4) a ete suivi au moins 3 ans, incluant 62 patients avec GPA, 29 GEPA, et 12 PAM. A 3 ans de suivi, 37 patients (36 %) ont atteint le CJP: EIG attribuable au traitement (n = 26), rechute majeure (n = 10) ou deces (n = 6). En analyse univariee, comparativement a un taux de pre albumine inferieur a 0,2 g/l, un taux de pre-albumine superieur a 0,4 g/l a l’inclusion etait significativement associe a une moindre survenue d’un evenement a 3 ans (HR = 0,18 [0,08–0,31]; p = 0,007), alors qu’un taux normal ne l’etait pas. L’osteoporose (presente chez 27 %) (HR 1,73 [0,69–4,12]; p = 0,11) et la sedentarite (presente chez 21 %) (HR 1,78 [0,71–4,53]; p = 0,12) tendaient a etre associees au CJP. Parmi les criteres de jugement secondaires, l’hypertension arterielle (HTA), la sedentarite et le tertile superieur du ratio VAT/SAT etaient significativement associes au retentissement fonctionnel de la vascularite (HAQ eleve a l’inclusion, p Conclusion L’etat nutritionnel evalue par la prealbumine, l’osteoporose et la sedentarite semblent avoir un impact important sur la qualite de vie et le devenir des patients atteints de vascularite systemique, en termes de complications et de sequelles. Le contenu en tissu adipeux visceral et l’HTA pourraient avoir un impact sur le handicap fonctionnel et les capacites physiques des patients.

Introduction L’erytheme noueux et la dermatose neutrophilique sont des entites cliniques associees a de nombreuses etiologies infectieuses, inflammatoires, medicamenteuses ou neoplasiques, bien qu’elles puissent etre aussi idiopathiques. Nous rapportons le cas d’une patiente ayant developpe un erytheme noueux et une dermatose neutrophilique lors d’une primo-infection EBV, etiologie rarement rapportee dans la litterature. Observation Une patiente de 19 ans, sans antecedent en dehors d’un tabagisme actif consulte aux urgences pour un tableau de lesions erythemateuses douloureuses des membres inferieurs, non febriles. L’interrogatoire retrouve une notion d’angine deux mois auparavant avec un test diagnostique rapide pour le streptocoque negatif. Elle ne rapporte pas de symptomes evocateurs d’une maladie inflammatoire chronique de l’intestin, d’une infection digestive ou d’une sarcoidose. L’examen physique retrouve des lesions d’erytheme noueux des membres inferieurs et une splenomegalie moderee sans autre anomalie clinique, notamment sans adenopathie ni synovite. Quelques jours plus tard apparaissent des lesions erythemato-papuleuses du decollete, du visage, et un erytheme douloureux du nez associees a des ulcerations de la bouche et du voile du palais, sans ulceration genitale. Le bilan biologique retrouve un syndrome inflammatoire avec une CRP a 124 mg/L. L’enzyme de conversion de l’angiotensine est normale de meme que le bilan calcique. Le quantiferon et les ASLO sont negatifs. La radiographie thoracique ne revele ni anomalie parenchymateuse ni adenopathie. La biopsie d’une lesion papuleuse pre-sternale met en evidence une necrose epidermique massive avec infiltrat inflammatoire dermique superficiel et profond a polynucleaires neutrophiles associes a des images de poussieres nucleaires, compatibles avec une dermatose neutrophilique, sans argument pour une sarcoidose. Le FDG-TEP scanner ne retrouve pas d’argument pour une maladie inflammatoire ou neoplasique. La serologie EBV est en faveur d’une primo-infection avec des IgG anti-EBNA negatifs, anti-VCA positifs a 74 U/mL, des IgM anti-VCA positifs > 160 U/mL. La PCR EBV est positive, avec une charge virale a 16 092 UI/mL. Le diagnostic d’erytheme noueux et de dermatose neutrophilique secondaire a une primo-infection EBV est alors retenu. Un traitement par anti-inflammatoires non steroidiens est introduit principalement a visee antalgique. L’evolution est favorable avec disparition progressive des lesions en un mois, negativation du syndrome inflammatoire biologique et diminution de la charge virale EBV a 6935 UI/mL. Discussion Bien que l’erytheme noueux soit une situation frequente en medecine interne, la litterature rapporte seulement quelques cas d’erytheme noueux associe a une primo-infection EBV, tous pediatriques [1] excepte un cas recent decrivant cette association chez une jeune fille de 19 ans [2] . En revanche, a notre connaissance, l’association d’une primo-infection EBV et d’une dermatose neutrophilique n’a pas ete rapportee et la survenue concomitante d’un erytheme noueux et d’une dermatose neutrophilique reste peu decrite [3] . Conclusion L’erytheme noueux est une porte d’entree frequente dans de nombreuses maladies. Apres elimination des causes classiques, ce cas illustre le fait que l’infection a EBV est une etiologie a rechercher, notamment chez les patients jeunes. Son association a une dermatose neutrophilique demeure exceptionnelle.

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Background and objectives The optimization of immunosuppressive therapies has led to a marked improvement in the survival of ANCA-associated vasculitides (AAV). The main issue now appears to be the management of comorbidities and the improvement of quality of life. The objective of this review was to investigate the incidence and the impact of AAV-associated comorbidities, as well as the determinants of health-related quality of life (HRQoL). Methods We performed a systematic literature review of articles published in Medline from 2001 to 04/28/2020. We selected relevant articles about AAV-associated comorbidities as well as HRQoL and fatigue. For each selected article, data on the incidence of comorbidity were extracted, and factors associated with the Mental component score (MCS) and the Physical component score (PCS) were identified. Results Among the 10,993 references identified, 103 were retained for the final analysis. A significant increase in cardiovascular risk was evidenced, particularly for coronary artery disease and thromboembolic events, especially during the active phase of the disease. AAV was also associated with bronchiectasis, thyroid diseases and osteoporosis. A marked decrease in HRQoL and an increase in fatigue and anxiety were reported. Decrease in PCS and MCS was associated with fatigue, mood disorders, sleep disturbance, and/or unemployment. Conclusion The excess mortality of AAV is still a concern, partly in connection with cardiovascular and thromboembolic comorbidities. AAV patients also experiment a reduction in their HRQoL that requires integrated management. Patients with AAV need comorbidity management strategies to improve their quality of life and outcomes.

Background The long-term effect of comorbidities on progression of structural changes in osteoarthritis (OA) remains poorly understood. Patients with knee OA have been reported to be at increased risk of several comorbidities including cardiovascular diseases (CVD). Nevertheless, the impact of all comorbidities on structural progression and on arthroplasty, not only in knee but also in hip OA, should be further defined. Objectives The objective of our study was to explore the relationship between comorbidities and the progression of structural changes in symptomatic knee and/or hip OA patients over 5 years. Methods The KHOALA (Knee and Hip OsteoArthritis Long-term Assessment) cohort is a French prospective multicenter observational cohort that included 878 subjects, aged 40 to 75 years, with symptomatic hip and/or knee OA at baseline (Kellgren and Lawrence (KL) ≥2). The structural progression was defined by the increase of one point of KL (ΔKL ≥1) or incidence of total knee or hip replacement at 5 years. Various comorbidities were analyzed: cardiovascular diseases excluding hypertension (coronary artery disease, heart failure, stroke, lower limb arteriopathy), hypertension, diabetes, smoking, dyslipidemia, metabolic syndrome, osteoporosis, neurological (e.g. Parkinson’s disease, dementia), digestive (e.g. gastroesophageal reflux disease, ulcer), pulmonary (e.g. asthma, COPD), and psychiatric (depression, anxiety) diseases. Multivariate analysis was performed separately in hip and knee OA adjusted on age, sex and body mass index (BMI). Subjects with a BMI> 30 kg/m² were excluded from the analysis given the close relationship between obesity and the different comorbidities analyzed. Subjects with KL = 4 at the time of inclusion were also excluded from the analysis. Results Data from 631 non-obese subjects (BMI Conclusion This 5-year data analysis of the KHOALA cohort revealed a significant association between cardiovascular comorbidities and structural progression of knee OA in subjects without obesity (BMI Disclosure of Interests Camille Roubille Grant/research support from: expanscience, Joel Coste: None declared, Jeremie Sellam: None declared, Anne-Christine Rat: None declared, Francis Guillemin Grant/research support from: Expanscience, Christian Roux: None declared

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Introduction Les vascularites sont des maladies rares pouvant avoir des consequences graves en cas de retard de prise en charge. Il est rare chez une meme personne de developper deux vascularites differentes. Peu de cas de patients ayant a la fois une granulomatose avec polyangeite et une arterite a cellules geantes sont rapportes dans la litterature. Nous rapportons le cas d’une patiente, ayant initialement developpe une granulomatose avec polyangeite qui, un an apres la fin des traitements, a declare une arterite a cellules geantes objectivee au FDG TEP-scanner et a la biopsie de l’artere temporale. Observation Une patiente de 75 ans a ete hospitalisee en mars 2017 pour une alteration de l’etat general evoluant depuis 6 mois. Sur le plan biologique, outre un syndrome inflammatoire (CRP a 247 mg/L), une insuffisance renale aigue avec une creatininemie a 300 μmol/L, une hematurie microscopique et une proteinurie a 7 g/g avaient ete mises en evidence. Le bilan immunologique retrouvait des c-ANCA positifs a 1/400 avec des anticorps anti-PR3 a 1026 UI/mL. Un scanner thoraco-abdomino-pelvien montrait un aspect de sinusite chronique maxillaire gauche. La ponction-biopsie renale retrouvait une glomerulonephrite extra-capillaire avec des lesions essentiellement actives. Le diagnostic de granulomatose avec polyangeite a donc ete retenu. La patiente est traitee par plasmapherese, corticoides et cyclophosphamide suivant le protocole CORTAGE. Un traitement d’entretien par rituximab est debute en juillet 2017, la derniere perfusion ayant lieu en janvier 2019. La patiente est revue en consultation en juillet 2019, la creatininemie est a 86 μmol/L et les ANCA sont negatifs. Elle est consideree en remission de sa maladie 6 mois apres l’arret des traitements. En decembre 2019, la patiente est hospitalisee pour des cephalees. L’examen clinique ne retrouve pas d’anomalie en dehors d’une hyperthermie autour de 38,5 ° C, avec une anorexie sans amaigrissement. La CRP est a 200 mg/L, la fonction renale est normale avec une creatininemie a 70 μmol/L, sans proteinurie ni hematurie. Les ANCA sont negatifs. Un scanner corps total ne retrouve pas d’anomalie intra-cerebrale, pas de foyer infectieux profond, ni de lesion suspecte de neoplasie mais un aspect de sinusite maxillaire gauche. Un traitement par augmentin est debute dans l’hypothese infectieuse de la sinusite, sans amelioration clinicobiologique. Le FDG TEP-scanner met en evidence une fixation franche de l’aorte et de ses branches, en faveur d’une vascularite des gros vaisseaux. Un traitement par corticoides est debute a la dose de 0,7 mg/kg. Une biopsie de l’artere temporale rapporte un aspect d’arterite a cellules geantes. La symptomatologie de la patiente s’ameliore sous corticotherapie et le syndrome inflammatoire regresse avec une CRP a 18 mg/L a la sortie d’hospitalisation. Discussion Il n’existe que peu de cas dans la litterature de patients presentant, de maniere simultanee ou differee, une arterite a cellules geantes et une granulomatose avec polyangeite. Une recente revue de la litterature rapporte [1] 15 cas decrits. Parmi ces 15 cas, il y en a 12 ou l’arterite a cellules geantes precedait la granulomatose avec polyangeite, et 3 ou il s’agissait de la situation inverse. Dans 4 de ces cas [2] , [3] , la presentation etait simultanee. Elle etait cependant plus frequemment espacee de plusieurs mois, voire de plusieurs annees. Neanmoins, parmi ces differents cas decrits, un prelevement histologique confirmant le diagnostic pour l’une ou l’autre des pathologies n’etait pas systematiquement disponible. Il parait pourtant important, dans ce genre de situations, d’apporter le maximum d’arguments possibles pour etayer le diagnostic. Dans la majorite des cas, le traitement de ces vascularites repose en tout ou partie sur les corticoides. Il faut rappeler ici que ceux-ci presentent des effets secondaires non negligeables qu’il convient de surveiller attentivement chez ces patients cortisones au long cours pour deux maladies differentes. L’essor de nouvelles therapeutiques permettant d’eviter l’utilisation prolongee ou a trop fortes doses des corticoides prend ici tout son sens. Conclusion Bien que la probabilite de developper deux vascularites differentes est faible, notre observation rappelle qu’il ne faut pas negliger cette possibilite et encourage a mettre tous les moyens en œuvre pour eviter un retard diagnostique pouvant etre deletere pour le patient.

Introduction Les donnees actuelles suggerent un sur-risque de morbi-mortalite cardiovasculaire (CV) chez les patients atteints d’arthrose. Cependant, il reste a determiner si l’arthrose et les comorbidites CV ne font que coexister chez des patients partageant des facteurs de risque communs ou si des mecanismes physiopathologiques partages sous-tendent une interconnexion entre ces pathologies. Nous avons realise une meta-analyse explorant le role des comorbidites CV dans la progression structurale de l’arthrose. Materiels et methodes Nous avons realise une revue systematique de la litterature puis une meta-analyse sur l’association avec la progression structurale de l’arthrose peripherique, definie par une aggravation du score de Kellgren et Lawrence (KL) avec un KL ≥ 2 initialement, ou la pose d’une prothese articulaire au cours du suivi, avec ajustement sur l’index de masse corporel. Ainsi a partir des bases de donnees de Pubmed, Cochrane, Embase et les resumes des principaux congres de rhumatologie, nous avons selectionne les etudes ayant evalue l’association avec les comorbidites CV et leurs facteurs de risque, incluant les maladies CV, l’atherosclerose, le syndrome metabolique, le diabete, les dyslipidemies, et l’hypertension arterielle (HTA). Resultats Neuf etudes ont pu etre incluses. Le risque de progression radiographique de l’arthrose n’etait pas significativement associe a l’HTA. Le diabete apparaissait comme protecteur avec un OR a 0,81, IC 95 % [0,66–1,00]. Les resultats etaient similaires lors de la stratification par sexe, avec pour les hommes un OR a 0,73, IC 95 % [0,57–0,92], et pour les femmes, un OR a 0,75, IC 95 % [0,63–0,90]. Il n’y avait pas d’association significative avec le HDL bas. Le risque de pose de prothese de genou etait augmente avec l’HTA (OR = 1,22, IC 95 % [1,08–1,37]), tandis que le HDL bas etait inversement associe (OR = 0,77, IC 95 % [0,61–0,97]). Il n’etait pas retrouve d’association significative avec l’hypertriglyceridemie, le syndrome metabolique ou le diabete. L’analyse du risque de pose de prothese de hanche ne retrouvait pas de lien significatif avec l’HTA ou le syndrome metabolique tandis que l’hypertriglyceridemie etait inversement associee avec un OR a 0,88, IC 95 % [0,80–0,97], comme le HDL bas (OR = 0,86, IC 95 % [0,77–0,96]). Il en va de meme pour le diabete (OR = 0,72, IC 95 % [0,54–0,96]). Le risque de pose de prothese de hanche ou de genou, retrouvait aussi le diabete comme facteur inversement associe (OR = 0,75, IC 95 % [0,71–0,79]). Conclusion Notre meta-analyse met en evidence l’HTA comme facteur de risque associe a la pose de prothese du genou, tandis que le diabete est associe a une reduction du risque de progression radiographique, et de recours a la prothese de hanche. De meme, le HDL bas est associe a une reduction de pose de prothese de genou et de hanche, et l’hypertriglyceridemie a une reduction du risque de prothese de hanche. Nos resultats plaident en faveur d’une prise en charge integree des facteurs de risque CV chez les patients atteints d’arthrose.

Introduction Les donnees actuelles suggerent un sur-risque de morbi-mortalite cardiovasculaire chez les patients atteints d’arthrose. Il reste a determiner si l’arthrose et les comorbidites cardiovasculaires (CV) ne font que coexister chez des patients partageant des facteurs de risque communs ou si des mecanismes physiopathologiques partages sous-tendent une interconnexion entre ces pathologies. Nous avons ainsi realise une meta-analyse explorant le role des comorbidites CV dans le developpement de l’arthrose. Materiels et methodes Nous avons realise une revue systematique de la litterature, puis une meta-analyse sur l’association des comorbidites CV et leurs facteurs de risque avec l’incidence structurale de l’arthrose peripherique, definie par un score de Kellgren et Lawrence (KL) ≥ 2 au cours du suivi. A partir des bases de donnees de Pubmed, Cochrane, Embase et des resumes des principaux congres de rhumatologie, nous avons selectionne les etudes ayant evalue au cours du temps l’association avec les comorbidites CV et leurs facteurs de risque, incluant les maladies CV, l’atherosclerose, le syndrome metabolique, le diabete, les dyslipidemies, et l’hypertension arterielle (HTA). Resultats Huit etudes ont pu etre incluses. Le risque d’incidence de l’arthrose etait significativement associe a l’HTA (OR = 1,47, IC 95 % [1,09, 1,98]) et au syndrome metabolique (OR = 2,96, IC 95 % [1,00, 8,77]). Il n’y avait pas d’association significative avec le diabete (5 etudes dont une portait sur la hanche et les autres, le genou). Il n’etait pas retrouve d’association entre le HDL bas et la survenue d’une gonarthrose, et il en etait de meme pour l’hypertriglyceridemie et les maladies CV. Conclusion Notre meta-analyse met en evidence l’HTA et le syndrome metabolique comme facteurs de risque potentiels d’incidence radiographique de l’arthrose. Nos resultats plaident en faveur d’une prise en charge integree des facteurs de risque CV, non seulement pour prevenir les evenements CV mais aussi possiblement pour reduire la survenue d’arthrose.

Introduction Les recommandations nationales et internationales de prise charge de la polyarthrite rhumatoide (PR) proposent de prescrire des glucocorticoides (GC) a faibles doses et sur des durees courtes, si possible moins de 6 mois. Si la toxicite a court terme est bien documentee et parait faible, une controverse existe toujours sur le risque des GC a moyen et long termes. L’objectif de ce travail etait de determiner la tolerance de la corticotherapie a long terme chez les patients atteints de PR incidente dans le cadre de la cohorte ESPOIR. Patients et methodes Nous avons analyse les patients atteints de PR precoce (criteres ACR/EULAR 2010) dans la cohorte ESPOIR. Ils ont ete stratifies en deux groupes, avec ou sans traitement par GC, au moins une fois au cours de leur suivi (mediane de suivi de 10 ans IQR [9-10]). Le critere de jugement principal etait un critere composite defini par la survenue de deces, d’evenements cardiovasculaires (incluant ischemie myocardique, accident vasculaire cerebral, insuffisance cardiaque), d’infection severe, ou de fracture. Afin de reduire l’impact du biais de selection des traitements et des facteurs de confusion potentiels, un modele de Cox pondere par score de propension, methode IPTW (inverse probability of treatment weighting), a ete utilise. Resultats Parmi les 608 patients atteints de PR (480 femmes, âge moyen de 47,5 ± 12,1 ans), 397 patients (65 %) ont recu de faibles doses de prednisone (mediane 1,9 mg/jour [IQR 0,6-4,2]), principalement pendant les 6 premiers mois (70 %). La duree moyenne du traitement par GC etait de 44,6 ± 40,1 mois. Au total, 95 evenements ont ete identifies au cours du suivi : 10 deces, 18 evenements cardiovasculaires, 32 fractures et 35 infections severes. En analyse univariee a 10 ans, les patients prenant des GC ont connu significativement plus d’evenements (n = 71) que ceux sans GC (n = 24) (p = 0,035), en particulier des infections severes (n = 30 avec GC contre 5 sans GC, p = 0,009) ( Tableau 1 a), avec un effet dose cumulee (p = 0,007). En analyse multivariee (methode IPTW), le risque de survenue d’evenements est significativement associe au traitement par GC (p Tableau 2 ). Conclusion Cette analyse de la cohorte ESPOIR sur 10 ans met en evidence un risque eleve dose et temps-dependant de survenue d’evenements severes d’un traitement par GC a faible dose dans la PR incidente.

Background:We previously failed to find any significant difference with regard to severe outcomes (death, severe infections, fractures, cardiovascular diseases [CVD]) between recent-onset RA patients taking or not low-dose GC treatment in a 7-year analysis of the ESPOIR cohort (1).Objectives:To explore the 10-year tolerability profile of GC use in patients with early RA.Methods:We analysed data from the early arthritis (less than 6 months disease duration) ESPOIR cohort. Patients were stratified in two groups, with or without GC treatment at least once during their follow-up (median 10 years IQR [9-10]). The primary outcome was a composite of death, CVD (including myocardial ischemia, cerebrovascular accident and heart failure), severe infection and fracture. In order to reduce the impact of treatment selection bias and potential confounding factors, the weighted Cox time-dependent analysis model was used with inverse probability of treatment weighting (IPTW) propensity score method.Results:Among the 608 RA patients (480 women, mean age of 47.5 ± 12.1 years), 397 patients (65%) received low-dose prednisone (median 1.9 mg/day [IQR 0.6-4.2], mainly during the first 6 months (70%). The mean duration of GC treatment was 44.6 months ± 40.1. Overall, 95 events were identified during follow-up: 10 deaths, 18 CVD, 32 fractures and 35 severe infections. Based on univariate analysis at 10 years, patients taking GC experienced significantly more events (n=71) than those without GC (n=24) (p=0.035), especially severe infections (n=30 with GC versus 5 without GC, p=0.009) (table 1), with a cumulative dose effect (p=0.007).On weighted Cox time-dependent analysis, using the IPTW propensity score method, the risk of events over time was significantly associated with GC treatment (p ) (figure 1 and table 2).Table 1.Primary outcome and events at 10 years: univariate analysisTotal study population (n=608)Without GCWith CGP ValuePrimary outcome95 (15.6%)24 (11.4%)71 (17.9%)0.035Death10 (1.6%)1 (0.5%)9 (2.3%)0.103Cardiovascular diseases18 (3%)3 (1.4%)15 (3.8%)0.177Severe infections35 (5.8%)5 (2.4%)30 (7.6%)0.009Fractures32 (5.3%)15 (7.1%)17 (4.3%)0.137Table 2.Time-dependent relationship between glucocorticoids treatment and risk of eventsestimated by hazard ratioTime (Months)Hazard Ratio (95% CI)120.46 (0.23 - 0.90)240.62 (0.36 - 1.08)360.83 (0.52 - 1.33)481.12 (0.73 - 1.72)601.52 (0.96 - 2.40)722.05 (1.19 - 3.52)842.77 (1.44 - 5.34)963.74 (1.69 - 8.26)1085.05 (1.98 - 12.91)1206.83 (2.29 - 20.35)Figure 1.Time-dependent relationship between glucocorticoids treatment and risk of eventsestimated by hazard ratio (HR)Conclusion:This 10-year analysis of the ESPOIR cohort supports a dose and time-dependent impact of very low-dose GC treatment in early RA, with a long-term high risk of severe outcomes.Disclosure of Interests:Camille Roubille Consultant of: Servier, Pfizer, Novartis, Amandine Coffy: None declared, Nathalie Rincheval: None declared, Maxime Dougados Grant/research support from: AbbVie, Eli Lilly, Merck, Novartis, Pfizer and UCB Pharma, Consultant of: AbbVie, Eli Lilly, Merck, Novartis, Pfizer and UCB Pharma, Speakers bureau: AbbVie, Eli Lilly, Merck, Novartis, Pfizer and UCB Pharma, Rene-Marc Flipo Speakers bureau: Novartis, Janssen, Lilly, Jean-Pierre Daures: None declared, Bernard Combe Grant/research support from: Novartis, Pfizer, Roche-Chugai, Consultant of: AbbVie; Gilead Sciences, Inc.; Janssen; Eli Lilly and Company; Pfizer; Roche-Chugai; Sanofi, Speakers bureau: Bristol-Myers Squibb; Gilead Sciences, Inc.; Eli Lilly and Company; Merck Sharp & Dohme; Pfizer; Roche-Chugai; UCB

International audience; Purpose of review: Hypertriglyceridemia occurs mainly because of metabolic disorders secondary to diabetes, alcohol intake, and/or overweight. Genetic factors have also been clearly identified in most severe cases. Triglycerides are generally considered as ‘bystanders’ for cardiovascular diseases. However, biological and basic research provides strong data suggesting that triglyceride-rich lipoproteins could be involved in the pathophysiology of cardiovascular diseases.Recent findings: The REDUCE-IT trial recently showed that icosapent ethyl reduces major cardiovascular events and related death.Summary: For many years, low-density lipoproteins (LDLs) have been considered the Holy Grail for atherosclerotic cardiovascular disease management. New data from basic research in biology, epidemiology, genetics, and preliminary clinical trials support the hypothesis that triglyceride-rich lipoproteins could be the causal factors for atherosclerotic cardiovascular disease; hence, triglyceride should be taken into consideration in the management of these patients. Omega-3-fatty acids used in the REDUCE-IT trial reduced the residual cardiovascular risk efficiently beyond statins. However, its effect has to be completely understood as it seems to be unrelated to LDLc or triglyceride reduction, but linked to pleiotropic effects involving inflammation, platelet adhesion, and plaque instability reduction, paving the way for trials that will target more specific potential pathophysiologic pathways.

Angiotensin-converting enzyme inhibitors and angiotensin receptor blockers have been the cornerstone for the treatment of heart failure (HF) with reduced ejection fraction for decades. According to recent and promising studies, sacubitril/valsartan (SV) might be efficient in alternative indications in the area of HF with preserved left ventricular ejection fraction, chronic kidney disease, and so on. This review briefly summarizes these promising therapeutic options regarding SV and the potential limits and pitfalls for its use in routine practice (due to cognitive uncertainties).

Key points ASCVD reduction is based on LDL reduction, especially by statins. Highly elevated TG could be harmful, especially because of the risk of pancreatitis. Elevation of TG is mainly due to metabolic disorders and diabetes, alcohol intake and overweight. Genetic factors have been clearly identified in the most severe cases. TG have been generally considered as bystanders for cardiovascular diseases (CVD). Both biological and basic research provide strong data suggesting that TG-rich lipoproteins could be involved in the pathophysiology of CVD. Recent epidemiological and genetics studies strongly corroborate the causal role of TG in CVD. This paves the way for new approaches in the management of patients both for primary and secondary prevention.

International audience

Objective In the perspective of personalized management of osteoarthritis (OA), a clinically relevant concern is the impact of meniscal extrusion (Ext) on response to treatment. This study aimed at determining the effects of conventional OA pharmacological treatments and those of the combination of glucosamine and chondroitin sulfate (Glu/CS) on knee structural changes in the presence or absence of Ext, using data from the progression cohort of the Osteoarthritis Initiative. Methods In this longitudinal study, knee OA participants were stratified based on whether (+) or not (−) they received analgesics/NSAIDs (+ and −analgesics/NSAIDs) and/or Glu/CS (+ and −Glu/CS) for 24 consecutive months and on the presence (Ext+) or absence (Ext−) of medial meniscal extrusion at baseline. The main outcomes were knee structural changes including the loss of joint space width (JSW) and cartilage volume loss measured by quantitative MRI. Results In both − and +analgesics/NSAIDs groups ( n = 300 each), the Ext+ participants had more-advanced disease at baseline (T0) and more JSW loss and cartilage volume loss in the medial compartment ( p ≤ 0.003, univariate; p ≤ 0.049, multivariate analyses) at both 12 (T12) and 24 (T24) months compared to Ext− participants. In the −analgesics/NSAIDs group, Ext+ participants taking Glu/CS had significantly less cartilage volume loss in the medial plateau at T24 ( p ≤ 0.010, univariate and multivariate analyses). In the +analgesics/NSAIDs group at T24, Ext− participants taking Glu/CS had less cartilage volume loss in the global ( p ≤ 0.002, univariate and multivariate analyses) and medial and lateral plateaus ( p = 0.034 and p = 0.013, respectively, multivariate analysis). No significant difference in JSW loss was found between the groups. Conclusion This study is the first to demonstrate, using qMRI, that meniscal extrusion can modify the response to Glu/CS treatment in knee OA patients, depending on the severity of the disease.

Background: Smoking has been associated with psoriasis prevalence and severity. Objective: To evaluate prevalence of smoking in patients with psoriasis and to examine the relationship between smoking and psoriasis severity. Methods: MEDLINE, EMBASE, and Cochrane databases (1960-2012) and conference proceedings (2010-2012) were systematically searched using keywords relevant to psoriasis and smoking. Controlled studies addressing psoriasis and smoking status were included. A meta-analysis for the relative risk of smoking in psoriasis patients was performed. Results: Meta-analysis identified a significant association between smoking and psoriasis with a relative risk of 1.88 (95% CI, 1.66-2.13) for smoking in patients with psoriasis versus patients without psoriasis. Eight articles of 11 with data on smoking and psoriasis severity suggested that severity increases with smoking status. Conclusions: This literature review is in favor of a positive association between the prevalence of smoking and psoriasis as well as an association between smoking and severity of psoriasis.

Objective Studies have proposed vastus medialis (VM) muscle cross-sectional area change as a variable associated with cartilage volume loss in knee osteoarthritis (OA). However, the VM also includes fat (%Fat), which may influence knee function. This study analyzed the VM area and %Fat data, separately and in combination, to predict symptoms, cartilage volume loss, and bone marrow lesion (BML) change in knee OA. Methods This study included the according-to-protocol population (n = 143) of a 2-year knee OA randomized clinical trial having magnetic resonance imaging at baseline and 2 years. Correlations used multivariate analyses. Results Greater baseline value for VM area and %Fat were significantly associated with sex (male, area; female, %Fat), higher body mass index (BMI), and Western Ontario and McMaster Universities Osteoarthritis Index stiffness, function, and total scores (better, high area; worse, high %Fat). Moreover, a VM %Fat increase of 1% at 2 years was associated with worsening of cartilage volume loss in the global knee (P = 0.015) and some subregions (P ≤ 0.030), and with an increment of BML global score change (P < 0.001). A 1% decrease in VM area at 2 years was associated with worsening of knee pain score (P = 0.048). Importantly, the concurrent presence of low VM area, high VM %Fat, and high BMI identified a subgroup of patients with greater cartilage volume loss in the medial femur (P = 0.028) than the rest of the cohort. Conclusion These data demonstrated, for the first time, that VM fat content is a strong predictor of cartilage volume loss and the occurrence and progression of BML. Importantly, the combined data of VM area, VM %Fat, and BMI identified patients at higher risk for OA progression.