DHU FIRE

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Potier L.,DHU FIRE | Potier L.,University Paris Diderot | Potier L.,French Institute of Health and Medical Research | Roussel R.,DHU FIRE | And 15 more authors.
Heart | Year: 2017

Objective ACE inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) are widely prescribed in patients with high cardiovascular (CV) risk. However, whether both classes have equivalent effectiveness to prevent CV events remains unclear. The aim of this study was to compare the incidence of major CV events between ACEI and ARB users. Methods The Reduction of Atherothrombosis for Continued Health registry is an observational study who enrolled 69 055 individuals with high CV risk. Among them, 40 625 patients (ACEIs 67.9% and ARBs 32.1%) were included. Main outcome was rates of CV mortality, non-fatal myocardial infarction, non-fatal stroke or hospitalisation for CV disease at 4 years. Results In a propensity score-adjusted cohort, the incidence of the primary outcome was lower in patients on ARBs compared with ACEIs (29.2% vs 33.4%; adjusted HR 0.90; 95% CI 0.86 to 0.95; p<0.001). Similar results were observed for CV (6.9% vs 8.2%; HR 0.83; 95% CI 0.75 to 0.93; p=0.001) and all-cause mortality (11.6% vs 12.6%; HR 0.89; 95% CI 0.82 to 0.97; p=0.005). Analyses using propensity score matching yielded similar results. History of diabetes or estimated glomerular filtration rate did not affect the results. ARB use was associated with lower rates of all-cause mortality in secondary prevention but not in primary prevention patients (p-value for interaction=0.03). Conclusion ARB use appears to be associated with 10% lower rates of CV events compared with ACEIs, especially in patients with established CV disease. Our results suggest that ARBs may provide superior protection against CV events than ACEIs in high-risk patients in real-world practice. © 2017 Article author(s).


Vidal-Petiot E.,DHU Fire | Vidal-Petiot E.,University Paris Diderot | Bens M.,University Paris Diderot | Choudat L.,Hopital Bichat | And 8 more authors.
Journal of Hypertension | Year: 2015

Case report: A 20-year-old woman presented with malignant hypertension associated with hypokalemia, metabolic alkalosis and elevated plasma renin and aldosterone levels. Computed tomography angiography (CTA) evidenced a 22mm tissular mass in the posterior cortex of the left kidney, and 18F-flurodeoxyglucose PET (18-FDG PET) imaging showed no hypermetabolism of the tumour. Following nephron-sparing surgery, blood pressure and potassium levels rapidly normalized, allowing interruption of all treatments within 2 weeks. Discussion: Reninoma is a rare juxtaglomerular cell tumour (JGCT) producing excessive amounts of renin resulting in severe hypertension. Pathological studies revealed that tumoural cells highly expressed renin and contained electron-dense structures, typical of renin-containing granules. Tumoural cells also exhibited the vascular cell surface marker CD34, but, in contrast with previous reports, did not express the tyrosine-protein kinase Kit (cKit or CD117). Dissociation of the tumour allowed to obtain confluent cultures of elongated smooth muscle actin (SMA)-positive cells producing high amounts of renin. However, after the first passage, subcultured human juxtaglomerular cells rapidly lost renin and CD34 expressions and their ability to produce renin. Conclusion: The present case of reninoma emphasizes the need for CTA in the etiologic work up of otherwise unexplained severe hypertension. 18-FDG PET imaging showed no hypermetabolism of the tumour, in accordance with its reported benignity. Pathological studies further emphasized that high expressions of renin and CD34 are typical hallmarks of reninoma. Although CD117 has been proposed to represent a reliable marker of JGCT, the present findings indicate that reninomas may not always express this marker. © 2015 Wolters Kluwer Health, Inc.


Hurabielle C.,Hopital Saint Louis | Pillebout E.,Hopital Saint Louis | Stehle T.,DHU Fire | Pages C.,Hopital Saint Louis | And 14 more authors.
PLoS ONE | Year: 2016

Context Serum creatinine has been reported to increase in patients receiving Vemurafenib, yet neither the prevalence nor the mechanism of this adverse event are known. Objective We aimed to evaluate the frequency and the mechanisms of increases in plasma creatinine level in patients receiving Vemurafenib for advanced melanoma. Methods We performed a retrospective monocentric study including consecutive patients treated with Vemurafenib for an advanced melanoma. We collected clinical and biological data concerning renal function before introduction of Vemurafenib and in the course of monthly follow- up visits from March 2013 to December 2014. Cystatin C-derived glomerular filtration rate was evaluated before and after Vemurafenib initiation, as increase in serum cystatin C is specific to a decrease in the glomerular filtration rate. We also performed thorough renal explorations in 3 patients, with measurement of tubular secretion of creatinine before and after Vemurafenib initiation and a renal biopsy in 2 patients. Results 70 patients were included: 97% of them displayed an immediate, and thereafter stable, increase in creatinine (+22.8%) after Vemurafenib initiation. In 44/52 patients in whom Vemurafenib was discontinued, creatinine levels returned to baseline. Serum cystatin C increased, although proportionally less than serum creatinine, showing that creatinine increase under vemurafenib was indeed partly due to a renal function impairment. In addition, renal explorations demonstrated that Vemurafenib induced an inhibition of creatinine tubular secretion. Conclusion Thus, Vemurafenib induces a dual mechanism of increase in plasma creatinine with both an inhibition of creatinine tubular secretion and slight renal function impairment. However, this side effect is mostly reversible when Vemurafenib is discontinued, and should not lead physicians to discontinue the treatment if it is effective. © 2016 Hurabielle et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.


Vecchierini M.-F.,Center Du Sommeil Et Of La Vigilance | Vecchierini M.-F.,University of Paris Descartes | Attali V.,Groupe Hospitalier Pitie Salpetriere Charles Foix | Attali V.,Paris-Sorbonne University | And 14 more authors.
Sleep Medicine | Year: 2015

Background: Mandibular repositioning devices (MRDs) are usually recommended as the first therapy option in patients with mild-to-moderate obstructive sleep apnoea (OSA). However, data on the long-term efficacy of MRDs are limited, not only in OSA patients who are noncompliant with continuous positive airway pressure (CPAP) but also in those with more severe OSA. The ORCADES study aimed to prospectively determine the long-term efficacy and tolerability of two custom-made Narval™ MRDs for obstructive sleep apnoea-hypopnoea syndrome (OSAHS) patients. The interim 3- to 6-month data are reported. Methods: Eligible patients had OSAHS and had refused or were noncompliant with prescribed CPAP. Outcome measurements after gradual mandibular advancement titration included: apnoea-hypopnoea index (AHI), oxygen saturation, sleepiness, symptoms, quality of life, side effects and compliance. Results: A total of 369 patients were included. Overall, MRD treatment was successful (≥50% decrease in AHI) in 76.2% of the participants; complete response (AHI <10/h) was achieved in 63.5%. Severe OSAHS was effectively treated (AHI <15/h) in about 60% of the participants; 38% had complete symptom resolution. Mandibular repositioning devices significantly decreased subjective sleepiness, eliminated symptoms and improved quality of life. They were well tolerated and compliance was excellent. Only 8% of the participants stopped MRD treatment due to side effects. Conclusion: Custom-made Narval™ MRDs are effective for mild to severe OSA in patients who refuse or are noncompliant with CPAP. They are well tolerated and have excellent compliance. © 2015 Elsevier B.V.


Matteau A.,Brigham and Women's Hospital | Yeh R.W.,Massachusetts General Hospital | Camenzind E.,University of Geneva | Steg P.G.,DHU FIRE | And 10 more authors.
American Journal of Cardiology | Year: 2015

Although trials comparing antiplatelet strategies after percutaneous coronary intervention report average risks of bleeding and ischemia in a population, there is limited information to guide choices based on individual patient risks, particularly beyond 1 year after treatment. Patient-level data from Patient Related Outcomes With Endeavor vs Cypher Stenting Trial (PROTECT), a broadly inclusive trial enrolling 8,709 subjects treated with drug-eluting stents (sirolimus vs zotarolimus-eluting stent), and PROTECT US, a single-arm study including 1,018 subjects treated with a zotarolimus-eluting stent, were combined. The risk of ischemic events, cardiovascular death/non-periprocedural myocardial infarction (MI)/definite or probable stent thrombosis, and bleeding events, Global Use of Strategies to Open Occluded Arteries moderate or severe bleed, were predicted using logistic regression. At median follow-up of 4.1 years, major bleeding occurred in 260 subjects (2.8%) and ischemic events in 595 (6.3%). Multivariate predictors of bleeding were older age, smoking, diabetes mellitus, congestive heart failure, and chronic kidney disease (all p <0.05). Ischemic events shared all the same predictors with bleeding events and gender, body mass index, previous MI, previous coronary artery bypass graft surgery, ST-segment elevation MI on presentation, stent length, and sirolimus-eluting stent use (all p <0.05). Within individual subjects, bleeding and ischemic risks were strongly correlated; 97% of subjects had a greater risk of ischemic events than bleeding. In conclusion, individual patient risks of ischemia and bleeding are related to many common risk factors, yet the predicted risks of ischemic events are greater than those of major bleeding in the large majority of patients in long-term follow-up. © 2015 Elsevier Inc.


Feldman L.,DHU FIRE | Feldman L.,University Paris Diderot | Feldman L.,French Institute of Health and Medical Research | Tubach F.,University Paris Diderot | And 19 more authors.
American Heart Journal | Year: 2014

Background: Previous studies, which compared the prevalence of high on-clopidogrel platelet reactivity (HCPR) in type 2 diabetes mellitus (T2DM) versus non-T2DM and obese versus nonobese patients provided conflicting results. Methods: We compared the prevalence of HCPR in patients with T2DM, metabolic syndrome (MS), or neither T2DM nor MS undergoing drug-eluting stent implantation for stable coronary artery disease. Platelet functions were measured after a 600-mg clopidogrel loading dose and after 4 months on clopidogrel 75 mg/d. Results: The prevalence of HCPR was significantly higher in 63 T2DM and 50 MS patients than in 43 patients with neither T2DM nor MS (46.0% and 52.0% vs 20.9%) after clopidogrel loading dose, whereas, at 4 months, only T2DM patients had a significantly higher prevalence of HCPR (50.8% and 31.3% vs 23.8%). By multivariable analysis, T2DM (odds ratio [OR] 3.62, 95% CI, 1.34-9.80, P = .011), MS (OR 4.00, 95% CI 1.39-11.46, P = .010), and previous chronic treatment with clopidogrel (OR 0.22, 95% CI 0.09-0.49; P b .001) were the main independent predictors of HCPR after clopidogrel loading dose, whereas only T2DM (OR 2.98, 95% CI 1.20-7.41, P = .017) was an important independent predictor of HCPR at 4 months. Conclusions: Both MS and T2DM were independent predictors of HCPR after clopidogrel loading dose. On clopidogrel maintenance therapy, only T2DM remained an independent predictor. This observation may be clinically relevant in the current era of antiplatelet therapy. © 2014 Elsevier Inc. All rights reserved.


Jamin A.,French Institute of Health and Medical Research | Jamin A.,University of Paris Pantheon Sorbonne | Jamin A.,Robert Debre Hospital | Dehoux L.,French Institute of Health and Medical Research | And 14 more authors.
Clinical and Experimental Immunology | Year: 2015

Summary: The efficacy of steroids and immunosuppressive treatments in idiopathic nephrotic syndrome (INS) hints at the implication of immune cells in the pathophysiology of the disease. Toll-like receptor (TLR) dysfunctions are involved in many kidney diseases of immune origin, but remain little described in INS. We investigated the expression and function of TLRs in peripheral blood mononuclear cells (PBMC) of INS children, including 28 in relapse, 23 in remission and 40 controls. No child had any sign of infection, but a higher Epstein-Barr virus viral load was measured in the PBMC of relapsing patients. TLR-3 expression was increased in B cells only during INS remission. There was a negative correlation between proteinuria and TLR-3 expression in total and the main subsets of PBMC from INS patients. The expression of TLR-8 was also increased in both CD4+ T cells and B cells in INS remission. There was a negative correlation between proteinuria and TLR-8 expression in total PBMC, CD4+ T cells and B cells of INS patients. Nevertheless, TLR-3 and TLR-8 expression was normalized in all PBMC subsets in an additional group of 15 INS patients in remission with B cell repletion after rituximab therapy. Paradoxically, interferon (IFN) regulatory factor 3 transactivation was increased in PBMC of all INS patients. In-vitro secretion of IFN-α and interleukin 6 were increased spontaneously in PBMC of INS remission patients, whereas PBMC from all INS patients displayed an impaired IFN-α secretion after TLR-3 stimulation. Thus, TLR-3 pathway dysfunctions may be closely involved in INS pathogenesis. © 2015 British Society for Immunology.

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