Showing papers by "Frédéric Charlotte published in 2018"
TL;DR: These recommendations include guidelines for clinical, laboratory, pathologic, and radiographic evaluation of patients with RDD together with treatment recommendations based on clinical experience and review of the literature.
295 citations
TL;DR: An update of the 2010 ESC guidelines for the management of atrial fibrillation and a novel risk factor-based approach for predicting stroke and thromboembolism in atrial Fibrillation are presented.
Abstract: REFERENCES [1] Go A, Hylek E, Phillips K, et al. Prevalence of diagnosed atrial fibrillation in adults national implications for rhythm management and stroke prevention: the AnTicoagulation and Risk Factors In Atrial Fibrillation (ATRIA) study. JAMA. 2001;285(18):2370–2375. [2] Camm AJ, Lip GYH, De Caterina R, et al. 2012 focused update of the ESC guidelines for the management of atrial fibrillation: an update of the 2010 ESC guidelines for the management of atrial fibrillation developed with the special contribution of the European Heart Rhythm Association. Eur Heart J. 2012;33(21):2719–2747. [3] Hart RG, Pearce LA, Aguilar MI. Meta-analysis: antithrombotic therapy to prevent stroke in patients who have nonvalvular atrial fibrillation. Ann Intern Med. 2007;146(12):857–867. [4] Lip GYH, Nieuwlaat R, Pisters R, Lane DA, Crijns HJGM. Refining clinical risk stratification for predicting stroke and thromboembolism in atrial fibrillation using a novel risk factor-based approach: the Euro Heart Survey on Atrial Fibrillation. Chest. 2010;137(2):263–272. [5] Go AS, Hylek EM, Chang Y, et al. Anticoagulation therapy for stroke prevention in atrial fibrillation: how well do randomized trials translate into clinical practice? JAMA. 2003;290(20):2685–2692. [6] Hughes M, Lip GY. Risk factors for anticoagulation-related bleeding complications in patients with atrial fibrillation: a systematic review. QJM. 2007;100(10):599–607.
71 citations
TL;DR: To determine risk factors for primary Sjögren's syndrome (SS)–associated lymphoma in a multicenter cohort of patients, with analysis of the predictive power of previously reported risk factors, including the presence of ectopic germinal center (GC)–like structures in minor salivary gland (MSG) biopsy tissue.
Abstract: Objective To determine risk factors for primary Sjogren's syndrome (SS)-associated lymphoma in a multicenter cohort of patients, with analysis of the predictive power of previously reported risk factors, including the presence of ectopic germinal center (GC)-like structures in minor salivary gland (MSG) biopsy tissue. Methods One hundred fifteen patients with primary SS were included, and MSG biopsy tissue from these patients was retrospectively examined, focusing on the presence of ectopic GC-like structures. Epidemiologic, clinical, biologic, immunologic, and histologic data were collected at the time of diagnosis of primary SS. Patients with non-Hodgkin's lymphoma (NHL) were compared with those without NHL during the follow-up period, using a Cox proportional hazards multiple regression model. Results NHL was diagnosed in 8 patients (6.96%), and ectopic GC-like structures in 19 patients (16.5%). The presence of ectopic GC-like structures was associated with a 7.8-fold increased risk of lymphoma occurrence (95% confidence interval [95% CI] 1.73-34.86 [P = 0.0075]). Other independent predictors included a positive cryoglobulin test result (hazard ratio [HR] 7.10, 95% CI 1.74-28.92 [P = 0.006]), male sex (HR 28.73, 95% CI 4.46-144.87 [P = 0.0004]), sensorimotor neuropathy (HR 35.48, 95% CI 5.79-217.39 [P = 0.0001]), and splenomegaly (HR 19.9, 95% CI 4.4-90 [P = 0.0001]). Conclusion The presence of ectopic GC-like structures in MSG biopsy tissue is associated with the risk of lymphoma in patients with primary SS. These data reinforce the major role of MSG biopsy tissue in primary SS, for the identification a priori of a subgroup of patients with the highest risk of lymphoma.
50 citations
TL;DR: A simple scoring system of aGVHD relying on the binary (yes or no) evaluation of five important visual parameters that reflect the complexity of the disease without the need to sacrifice the mice is proposed.
Abstract: Acute graft-versus-host disease (aGVHD) represents a challenging complication after allogeneic hematopoietic stem cell transplantation. Despite the intensive preclinical research in the field of prevention and treatment of aGVHD, and the presence of a well-established clinical grading system to evaluate human aGVHD, such a valid tool is still lacking for the evaluation of murine aGVHD. Indeed, several scoring systems have been reported, but none of them has been properly evaluated and they all share some limitations: they incompletely reflect the disease, rely on severity stages that are distinguished by subjective assessment of clinical criteria and are not easy to discriminate, which could render evaluation more time consuming, and their reproducibility among different experimenters is uncertain. Consequently, clinical murine aGVHD description is often based merely on animal weight loss and mortality. Here, we propose a simple scoring system of aGVHD relying on the binary (yes or no) evaluation of five important visual parameters that reflect the complexity of the disease without the need to sacrifice the mice. We show that this scoring system is consistent with the gold standard histological staging of aGVHD across several donor/recipient mice combinations. This system is also a strong predictor of survival of recipient mice when used early after transplant and is highly reproducible between experimenters.
47 citations
TL;DR: Rosai-Dorfman Disease (RDD), also known as sinus histiocytosis with massive lymphadenopathy, is a rare, nonmalignant Histiocytic proliferation of unknown etiology and belongs to the R group of histiocytes.
Abstract: Rosai-Dorfman Disease (RDD), also known as sinus histiocytosis with massive lymphadenopathy, is a rare, nonmalignant histiocytic proliferation of unknown etiology. According to the new classification, it belongs to the R group of histiocytoses.[1][1] The clinical course of this disease is quite
38 citations
TL;DR: The FibroTest has been validated as a biomarker to determine the stage of fibrosis in non‐alcoholic fatty liver disease (NAFLD) with results similar to those in chronic hepatitis C, CHC, B, and alcoholic liver disease.
Abstract: Background Although the FibroTest has been validated as a biomarker to determine the stage of fibrosis in non-alcoholic fatty liver disease (NAFLD) with results similar to those in chronic hepatitis C (CHC), B (CHB), and alcoholic liver disease (ALD), it has not yet been confirmed for the prediction of liver-related death. Aim To validate the 10-year prognostic value of FibroTest in NAFLD for the prediction of liver-related death. Method Patients in the prospective FibroFrance cohort who underwent a FibroTest between 1997 and 2012 were pre-included. Mortality status was obtained from physicians, hospitals or the national register. Survival analyses were based on univariate (Kaplan-Meier, log rank, AUROC) and multivariate Cox risk ratio taking into account age, sex and response to anti-viral treatment as covariates. The comparator was the performance of the FibroTest in CHC, the most validated population. Results 7082 patients were included; 1079, 3449, 2051, and 503 with NAFLD, CHC, CHB, and ALD, respectively. Median (range) follow-up was 6.0 years (0.1-19.3). Ten year survival (95% CI) without liver-related death in patients with NAFLD was 0.956 (0.940-0.971; 38 events) and 0.832 (0.818-0.847; 226 events; P = 0.004) in CHC. The prognostic value (AUROC / Cox risk ratio) of FibroTest in patients with NAFLD was 0.941 (0.905-0.978)/1638 (342-7839) and even higher than in patients with CHC 0.875 (0.849-0.901; P = 0.01)/2657 (993-6586). Conclusions The FibroTest has a high prognostic value in NAFLD for the prediction of liver-related death. (ClinicalTrials.gov number, NCT01927133).
21 citations
TL;DR: Two ECD patients with cardiovascular involvement were successfully treated with infliximab, a TNF-α monoclonal chimeric antibody, achieving an improvement of symptoms, cardiac involvement and function, and there is an unmet need for improving treatments in many patients with ECD, particularly in countries where access to targeted therapies is complicated or impossible.
Abstract: Erdheim-Chester disease (ECD) is a rare non-Langerhans cell histiocytosis characterised by long bones and various other organs’ involvements.1 Tissues are infiltrated by CD68+ CD1a− foamy histiocytes.2 Therapeutic options are pegylated interferon-α,3 cladribine,4 mTOR inhibitors5 and anakinra in mild forms of ECD.6 7 Conversely, targeted BRAF or MEK inhibitor therapies are used for refractory or life-threatening ECD manifestations.8 9 All these therapies have frequent side effects. Interferon-α leads to fatigue, cytopenias and autoimmune diseases. Anakinra needs subcutaneous daily injections, with frequent local intolerance. Targeted therapies cause skin cancers, QT allongement, rhabdomyolysis and haemorrhage,10 and we lack long-term safety data with these drugs. Moreover, targeted therapies are not available in all countries. Thus, there is an unmet need for improving treatments in many patients with ECD, particularly in countries where access to targeted therapies is complicated or impossible.
Although our comprehension of this disease has recently moved from inflammatory to clonal myeloproliferative disease,11 the accumulation of pathological histiocytes leads to an increase of several cytokines in blood and affected tissues. Cytokine/chemokine network has been described in ECD lesions, and most of these factors are regulated by tumour necrosis factor alpha (TNF-α), which is also expressed in ECD lesions and serous fluids like pericardial effusion12–14 and has been implicated in ECD pathogenesis in in vitro models.15 Two ECD patients with cardiovascular involvement were successfully treated with infliximab, a TNF-α monoclonal chimeric antibody, achieving an improvement of symptoms, cardiac involvement and function.14 We aim to determine the efficacy of infliximab in a larger series of patients with ECD.
We retrospectively reviewed …
18 citations
TL;DR: Almost 90% of the patients with RDD have cervical lymph nodes involvement although all the organs may virtually be involved, and the main therapeutic strategies rely on surgery, radiotherapy, steroids, immunosuppressive drugs or interferon-alpha and cladribine.
Abstract: Rosai-Dorfman disease (RDD) was first described by the French pathologist Paul Destombes in 1965. It frequently affects children or young adults and is characterized by the presence of large histiocytes with emperipolesis. More than 50 years after this first description, the pathogenesis of this rare disease is still poorly understood. The revised classification of histiocytoses published in 2016 identified various forms of RDD, from familial RDD to IgG4-associated RDD. Almost 90% of the patients with RDD have cervical lymph nodes involvement although all the organs may virtually be involved. Outcomes are typically favorable. Treatments may be necessary in case of compression or obstruction, and are not well codified. The main therapeutic strategies rely on surgery, radiotherapy, steroids, immunosuppressive drugs or interferon-alpha and cladribine.
15 citations
TL;DR: A new quantitative test for the diagnosis of nonalcoholic steatohepatitis (NASH) using a simplified histological definition derived from the FLIP-CRN-definition is constructed, and when associated with the FibroTest, identifies cases with clinically significant MLD.
Abstract: BACKGROUND One of the unmet needs in patients with metabolic risks is the prediction of metabolic liver disease (MLD) by noninvasive tests (NITs). OBJECTIVE The primary aim of this study was to construct a new quantitative test for the diagnosis of nonalcoholic steatohepatitis (NASH) using a simplified histological definition. PATIENTS AND METHODS As a reference, we used a simplified histological definition of NASH derived from the FLIP-CRN-definition that does not require the presence of steatosis and the presence of both lobular inflammation and ballooning. We analyzed 1081 patients from two prospective cohorts at risk of MLD who had biopsies and contemporaneous blood samples. These patients were divided randomly into a training group (n=541) and a control group (n=540) for internal validation. The new test was compared with standard tests, and applied in two large populations at risk of MLD. RESULTS Out of 1081 patients with biopsy, 39 (3.6%) cases with significant inflammatory activity or fibrosis (A2orF2) were missed by the current histological definitions. The combination of 11 parameters permitted to construct a test (NIT-NASHs) predicting NASH with an area under the receiver operating characteristic curve (AUROC) of 0.773 (95% confidence interval: 0.730-0.810), confirmed in the control group 0.814 (0.774-0.847). The AUROCs of NIT-NASHs were higher (all P<0.001) than those of ActiTest, FIB4, BARD, and nonalcoholic fatty liver disease scores. A combination of NIT-NASHs with FibroTest (AUROC=0.800; 0.759-0.835) enabled a better prediction (P<0.0001) of significant MLD, A2orF2, than the ActiTest-FibroTest combination. CONCLUSION These results suggested that this new test enables a quantitative assessment of NASH, and when associated with the FibroTest, identifies cases with clinically significant MLD. An external validation is needed.
14 citations
TL;DR: The findings indicate that hypoalphalipoproteinemia in male ECD patients carrying the BRAFV600E mutation favors the formation of lipid-laden histiocytes, which is an independent determinant of aortic infiltration in ECD.
Abstract: Objective- Erdheim-Chester disease (ECD) is a rare non-Langerhans cell histiocytosis characterized by the infiltration of multiple tissues with lipid-laden histiocytes. Cardiovascular involvement is frequent in ECD and leads to a severe prognosis. The objective of this study was to determine whether an alteration of lipid metabolism participates in the lipid accumulation in histiocytes and the cardiovascular involvement in ECD. Approach and Results- An analysis of plasma lipid levels indicated that male ECD patients carrying the BRAFV600E (B-Raf proto-oncogene, serine/threonine kinase) mutation exhibited hypoalphalipoproteinemia, as demonstrated by low plasma HDL-C (high-density lipoprotein cholesterol) levels. Capacity of sera from male BRAFV600E ECD patients to mediate free cholesterol efflux from human macrophages was reduced compared with control individuals. Cardiovascular involvement was detected in 84% of the ECD patients, and we reported that the presence of the BRAFV600E mutation and hypoalphalipoproteinemia is an independent determinant of aortic infiltration in ECD. Phenotyping of blood CD14+ cells, the precursors of histiocytes, enabled the identification of a specific inflammatory signature associated with aortic infiltration which was partially affected by the HDL phenotype. Finally, the treatment with vemurafenib, an inhibitor of the BRAFV600E mutation, restored the defective sera cholesterol efflux capacity and reduced the aortic infiltration. Conclusions- Our findings indicate that hypoalphalipoproteinemia in male ECD patients carrying the BRAFV600E mutation favors the formation of lipid-laden histiocytes. In addition, we identified the BRAF status and the HDL phenotype as independent determinants of the aortic involvement in ECD with a potential role of HDL in modulating the infiltration of blood CD14+ cells into the aorta.
13 citations
TL;DR: The cellular infiltrate of colorectal cancer (CRC) was assessed using computer-aided analysis of whole slide digital image derived from tissue microarray (TMA) and the proportion of IDO+ tissue areas in the lamina propria or in the non-epithelial area of the lymph node and in epithelial cells in each site was analysed.
TL;DR: A 18-year-old lady admitted in the authors' hospital for a 3 month-history of lower back pain, weight loss and severe fatigue has a massive infiltration by a morphologically heterogeneous MCs population, which could not be biologically confirmed because the patient refused additional blood tests.
Abstract: A 18-year-old lady was admitted in our hospital for a 3 month-history of lower back pain, weight loss and severe fatigue. Clinical examination showed hepatosplenomegaly and mild ecchymosis. Her laboratory investigations revealed anemia (hemoglobin 6.6 g/dL), thrombocytopenia (82 3 10/L), and eosinophilia (4.5 3 10/L). Meticulous blood smear examination showed the presence of few circulating atypical mast cells (MCs) (not appearing on the final leukocyte count). Bone marrow aspiration revealed a massive infiltration (>70% of all nucleated cells) by a morphologically heterogeneous MCs population (Figure 1A). Indeed, while some MCs were heavily granulated with a unique nucleus, others presented with major atypia (bior multi-nucleated cells and/or abnormal distribution of cytoplasmic granulations). Of note, numerous hemophagocytic mast cells (a finding frequently reported in mast cell leukemia [MCL]) were observed (Figure 1B). The hemophagocytic syndrome could not be biologically confirmed because the patient refused additional blood tests. Flow cytometric analysis on bone marrow revealed that the neoplastic cells expressed CD203c, CD117, CD30, CD25 but not CD2 (Figure 2). immunohistochemical staining confirmed positivity for tryptase, CD30 and CD117 in the malignant MCs (Figure 3). These findings were
TL;DR: This data indicates that Tournais-Dorfman disease is a central nervous system disorder associated with central giant cell granuloma and not necessarily a Mayer-Dejerine disease.
Abstract: e24180Background: Diagnosis of Rosai-Dorfman disease (RDD) is based on histology which is characterized by infiltration by CD68+ CD1a- S100+ histiocytes with large nuclei and abundant lesions of em...
TL;DR: L’objectif de l’etude etait de decrire les manifestations ophtalmiques de the maladie de DRD a partir des donnees du registre francais, a la fosse pachymeningite diffuse, which confirmait the nature histiocytaire.
Abstract: Introduction La maladie de Destombes-Rosai-Dorfman (DRD) est une histiocytose non-Langerhansienne rare du groupe R dont les manifestations cliniques sont dominees par l’atteinte ganglionnaire, en particulier cervicale, associee a une fievre et un syndrome inflammatoire biologique [1] . La mise en evidence d’un infiltrat histiocytaire CD68+ PS100+ CD1a- accompagne d’images d’emperipolese permet de confirmer le diagnostic. Les atteintes ophtalmiques de la maladie de DRD sont heterogenes et peu decrites [2] . Les atteintes des glandes lacrymales sont les plus frequentes mais des cas d’inflammation intra-oculaire ont ete decrits. L’objectif de l’etude etait de decrire les manifestations ophtalmiques de la maladie de DRD a partir des donnees du registre francais. Patients et methodes Les patients ont ete inclus a partir des donnees du registre francais des histiocytoses. Les criteres d’inclusion etaient une maladie de DRD definie par une presentation clinique et radiologique compatible, une documentation histologique et l’absence de pathologie associee tumorale ou hematologique (dont une histiocytose du groupe L). La recherche d’une mutation BRAFV600E a ete faite par pyrosequencage et PCR droplet. Resultats Neuf patients sur les 65 du registre ont ete inclus (13,8 %) : 6 hommes (66 %), d’âge median au diagnostic de DRD de 30,8 ans (6–64). Le delai moyen entre l’apparition des symptomes et le diagnostic definitif etait de 20 mois (0–60). Un patient (11 %) presentait un nodule conjonctival limbique dont la biopsie confirmait la nature histiocytaire. Deux patients (22 %) presentaient une infiltration histiocytaire des glandes lacrymales, un patient une sclerite (11 %), un patient une panuveite granulomateuse bilaterale avec œdeme papillaire bilateral sans autre cause retrouvee (11 %) et un patient un decollement de retine avec atteinte choroidienne bilaterale de la maladie de DRD confirmee histologiquement (11 %). Quatre patients (44 %) presentaient une tumeur intra-orbitaire avec retentissement sur l’acuite visuelle par compression du nerf optique. Un patient presentait un scotome central secondaire a une neuropathie optique bilaterale avec atrophie des nerfs optiques (11 %). Certains patients presentaient plusieurs types differents d’atteinte oculaire. Les deux patients presentant une atteinte retinienne et choroidienne et le patient presentant la neuropathie optique avaient egalement une atteinte meningee sous la forme d’une pachymeningite diffuse (33 %). Huit patients (89 %) avaient une atteinte ganglionnaire, 5 patients (62 %) presentaient une atteinte ORL avec des lesions localisees au cavum (n = 2), a la fosse nasale (n = 1) et a la fosse pterygopalatine (n = 2). Un patient presentait une surdite de perception. Seuls 3 patients avaient une atteinte osseuse et 1 une atteinte cutanee. L’histologie etait typique de DRD chez tous les patients, 1 remplissait egalement les criteres histologiques de maladie associee aux IgG4. Aucun patient ne presentait la mutation BRAFV600E. Sept patients ont recu une corticotherapie orale toujours en association a un autre traitement : 4 patients ont recu des traitements immunomodulateurs (methotrexate pour 4 patients, interferon chez 2 patients), 1 patient de la vinblastine et 4 patients de la cladribine. L’evolution etait favorable chez tous les patients traites avec une recuperation partielle de l’acuite visuelle et une regression de la taille des lesions sous traitement. Aucun patient parmi ceux traites ne presentait de remission complete. Conclusion Les atteintes ophtalmiques de la maladie de DRD sont heterogenes et semblent s’associer davantage aux atteintes meningees, en particulier pour les atteintes retiniennes, et ORL de la maladie. Cette proximite anatomique est en faveur d’un mecanisme d’extension des lesions par contiguite dans l’atteinte oculaire de la maladie de DRD.
TL;DR: Some patients with ECD may also present the iconic histological lesions described by Rosai and Dorfman, and overlap forms of such distinct histiocytoses between ECD and RDD is mainly driven by MAP2K1 but not by BRAF.
Abstract: Background Diagnosis of Erdheim-Chester disease (ECD) is based on characteristic imaging of bone, retroperitoneal and/or cardiovascular involvement.1 Biopsy is mandatory to exclude other diagnoses and confirm infiltration of histiocytes, but histology is not specific.2 By contrast diagnosis of Rosai-Dorfman disease (RDD), a rare histiocytosis, is based on histology, which is characterised by infiltration by CD68 +CD1 a- S100+ histiocytes with large nuclei and abundant lesions of emperipolesis.2 Up to 70% of ECD have BRAF or MAP2K1 mutations,3 which are rare in RDD. Objectives We investigated patients harbouring an ECD phenotype but RDD histology. Methods We reviewed records of ECD patients followed in Pitie-Salpetriere hospital (Paris, France) and Memorial Sloan Kettering Cancer Centre (New-York, NY, USA) between 2007 and 2018. Biopsy samples of the patients were systematically investigated for mutations of genes of MAP kinase pathway. Results Among 209 patients with ECD, we found 10 (4.7%) patients who had RDD histology. These 10 patients had typical ECD clinical and radiological presentation, in particular bones (n=7), vascular (n=5) and peritoneal (n=6) involvements. Patients also had typical neurological involvement of ECD (n=6). All patients except one had at least one biopsy with a compatible histology of ECD at diagnosis. ECD biopsies showed non-specific fibrosis (n=5), foamy CD 68+CD1 a- histiocytes (n=3) and/or Touton cells (n=1). Biopsies disclosing RDD histology were performed during the course of the disease involving testes (n=5), stomach (n=1), tibia (n=2), cheek (n=1) and omentum (n=1). All tissues showed lympho-plasmocytic infiltrate with large histiocytes infiltration. Histiocytes were CD68 +CD1 a- S100 +with large nuclei and abundant lesions of emperipolesis. Five patient harboured MAP2K1 mutation and one patient had PIK3CA mutation. None of the patients had BRAF mutation. Conclusions Some patients with ECD may also present the iconic histological lesions described by Rosai and Dorfman. Overlap forms of such distinct histiocytoses between ECD and RDD is mainly driven by MAP2K1 but not by BRAF. References [1] Diamond EL, Dagna L, Hyman DM, Cavalli G, Janku F, Estrada-Veras J, et al. Consensus guidelines for the diagnosis and clinical management of Erdheim-Chester disease. Blood. 2014;124:483–92. [2] Emile J-F, Abla O, Fraitag S, Horne A, Haroche J, Donadieu J, et al. Revised classification of histiocytoses and neoplasms of the macrophage-dendritic cell lineages. Blood. 2016;127:2672–81. [3] Haroche J, Charlotte F, Arnaud L, von Deimling A, Helias-Rodzewicz Z, Hervier B, et al. High prevalence of BRAF V600E mutations in Erdheim-Chester disease but not in other non-Langerhans cell histiocytoses. Blood. 2012;120:2700–3. Disclosure of Interest None declared