Service dImmunologie Clinique
Service dImmunologie Clinique
De Fontbrune F.S.,Service dHematologie Greffe |
Moignet A.,Hopital University Of Rennes |
Moignet A.,French Institute of Health and Medical Research |
Beaupain B.,Service dHematologie P Ediatrique |
And 22 more authors.
Blood | Year: 2015
Severe chronic primary neutropenia (CPN) is a rare entity, and long-term outcome and risk factors for infections in severe CPN adults have not been described to date.We report the characteristics and outcomes of 108 severe adult CPN patients enrolled in a multiinstitutional observational study. SevereCPNadultsweremostly female (78%), andmedian age at diagnosis was 28.3 years. Diagnosis was fortuitous in 62% of cases. The median absolute neutrophil count (ANC) at diagnosis was 0.4 × 109/L, and median ANC without granulocyte colony-stimulating factor (G-CSF) during follow-up was 0.5 × 109/L. Twentythree of 66 (34.8%) evaluable patients had neutrophil autoantibodies, and 6 of 47 (12.8%) a T-cell clone. The presence of neutrophil autoantibodies orT-cell clonewas not associated with any specific clinical or biological characteristics. No death or hematologic malignancies occurred, and 44 severe bacterial infectionswere reported in 27 patients with amedian follow-up of 8.3 years. Fifty patients received G-CSF either sporadically (n = 24) or continuously (n = 26) and responded (96%). Nineteen patients received immunosuppressive therapies: overall response (OR) was 41%, and median duration of response was 3 months. At diagnosis, the only predictive factor for the occurrence of severe bacterial infections was an ANC count below 0.2 × 109/L (OR, 0.76). Severe CPN in adults is characterized by a female predominance and a benign outcome with a low rate of severe bacterial infections and no secondary malignancies. G-CSF is efficient and well tolerated but is not required in a majority of patients. © 2015 by The American Society of Hemetology.
Audard V.,University Paris Est Creteil |
Audard V.,French Institute of Health and Medical Research |
Moutereau S.,Hopital Henri Mondor |
Vandemelebrouck G.,French Institute of Health and Medical Research |
And 11 more authors.
Orphanet Journal of Rare Diseases | Year: 2014
Background: The pathophysiologic mechanisms classically involved in sickle-cell nephropathy include endothelial dysfunction and vascular occlusion. Arguments demonstrating that ischemia-reperfusion injury-related kidney damage might coincide with vaso-occlusive crisis (VOC) are lacking. Methods. In this prospective study, we sought to determine whether tubular cells and glomerular permeability might be altered during VOC. Urine neutrophil gelatinase-associated lipocalin (NGAL) levels and albumin-excretion rates (AER) of 25 patients were evaluated prospectively during 25 VOC episodes and compared to their steady state (ST) values. Results: During VOC, white blood-cell counts (WBC) and C-reactive protein (CRP) were significantly higher than at ST but creatinine levels were comparable. Urine NGAL levels were significantly increased during VOC vs ST (P = 0.007) and remained significant when normalized to urine creatinine (P = 0.004), while AER did not change significantly. The higher urine NGAL concentration was not associated with subsequent (24-48 hour) acute kidney injury. Univariate analysis identified no significant correlations between urine NGAL levels and laboratory parameters during VOC. Conclusions: These results demonstrated that subclinical ischemia-reperfusion tubular injury is common during VOC and highlight the importance of hydroelectrolyte monitoring and correction during VOC. © 2014 Audard et al.; licensee BioMed Central Ltd.
PubMed | Laboratoire dImmunologie Leuco plaquettaire et dHistocompatibilite, Service dHematologie Greffe, University of Nantes, University of Angers and 11 more.
Type: Journal Article | Journal: Blood | Year: 2015
Severe chronic primary neutropenia (CPN) is a rare entity, and long-term outcome and risk factors for infections in severe CPN adults have not been described to date. We report the characteristics and outcomes of 108 severe adult CPN patients enrolled in a multi-institutional observational study. Severe CPN adults were mostly female (78%), and median age at diagnosis was 28.3 years. Diagnosis was fortuitous in 62% of cases. The median absolute neutrophil count (ANC) at diagnosis was 0.4 10(9)/L, and median ANC without granulocyte colony-stimulating factor (G-CSF) during follow-up was 0.5 10(9)/L. Twenty-three of 66 (34.8%) evaluable patients had neutrophil autoantibodies, and 6 of 47 (12.8%) a T-cell clone. The presence of neutrophil autoantibodies or T-cell clone was not associated with any specific clinical or biological characteristics. No death or hematologic malignancies occurred, and 44 severe bacterial infections were reported in 27 patients with a median follow-up of 8.3 years. Fifty patients received G-CSF either sporadically (n = 24) or continuously (n = 26) and responded (96%). Nineteen patients received immunosuppressive therapies: overall response (OR) was 41%, and median duration of response was 3 months. At diagnosis, the only predictive factor for the occurrence of severe bacterial infections was an ANC count below 0.2 10(9)/L (OR, 0.76). Severe CPN in adults is characterized by a female predominance and a benign outcome with a low rate of severe bacterial infections and no secondary malignancies. G-CSF is efficient and well tolerated but is not required in a majority of patients.
PubMed | Service de medecine interne et immunologie clinique, Nancy University Hospital Center, groupe hospitalier Cochin, Service de medecine interne 5D and 20 more.
Type: Journal Article | Journal: La Revue de medecine interne | Year: 2015
To develop French recommendations about screening and management of cardiovascular risk factors in systemic lupus erythematosus (SLE).Thirty-nine experts qualified in internal medicine, rheumatology and nephrology have selected recommendations from a list developed based on evidence from the literature. For each recommendation, the level of evidence and the level of agreement among the experts were specified.Experts recommended an annual screening of cardiovascular risk factors in SLE. Statins should be prescribed for primary prevention in SLE patients based on the level of LDL-cholesterol and the number of cardiovascular risk factors, considering SLE as an additional risk factor. For secondary prevention, experts have agreed on an LDL-cholesterol target of <0.7 g/L. Hypertension should be managed according to the 2013 European guidelines, using renin-angiotensin system blockers as first line agents in case of renal involvement. Aspirin can be prescribed in patients with high cardiovascular risk or with antiphospholipid antibodies.These recommendations about the screening and management of cardiovascular risk factors in SLE can be expected to improve clinical practice uniformity and, in the longer term, to optimize the management of SLE patients.
Bouillet L.,University Hospital |
Launay D.,University of Lille Nord de France |
Fain O.,University of Paris 13 |
Boccon-Gibod I.,University Hospital |
And 7 more authors.
Annals of Allergy, Asthma and Immunology | Year: 2013
Background Hereditary angioedema (HAE) is a rare and potentially life-threatening disease. New specific treatments are available. Objective To identify patients' features and patients' best therapeutic option. Methods A 1-year, multicenter, retrospective study was performed. The primary objective was to examine the clinical presentation of HAE. Secondary objectives included patient characteristics, management of HAE over 12 months, and health-related quality of life using the SF-36v2 questionnaire. Results One hundred ninety-three patients were included, and 69.4% were women. In the 12-month period, the mean number of HAE attacks was 7.6. Among the 568 reported attacks, localizations were the abdomen (57.1%), peripheral limbs (42.5%), upper airway (7.9%), and face (6.9%); 31.6% of attacks were severe and occurred statistically more often in women (P <.02). Compared with a population of allergic patients, all age- and sex-adjusted scores were significantly lower in patients with HAE (P <.05) except for the physical component summary. Health-related quality of life negatively correlated with the annual number of attacks and was markedly altered for patients having more than 5 attacks per year (P <.05 for all dimensions). Conclusion HAE is a severe disease that places a heavy burden on quality of life. © 2013 American College of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.
Dessap A.M.,Service de Reanimation Medicale |
Dessap A.M.,University Paris Est Creteil |
Dessap A.M.,French Institute of Health and Medical Research |
Deux J.-F.,Service dImagerie Medicale |
And 23 more authors.
American Journal of Respiratory and Critical Care Medicine | Year: 2011
Rationale: The pathophysiology of acute chest syndrome (ACS) in patients with sickle cell disease is complex, and pulmonary artery thrombosis (PT) may contribute to this complication. Objectives: To evaluate the prevalence of PT during ACS using multidetector computed tomography (MDCT). Methods: We screened 125 consecutive patients during 144 ACS episodes. One hundred twenty-one MDCTs (in 103 consecutive patients) were included in the study. Measurements and Main Results: Twenty MDCTs were positive for PT, determining a prevalence of 17% (95% confidence interval, 10-23%). Revised Geneva clinical probability score was similar between patients with PT and those without. D-dimer testing was very often positive (95%) during ACS. A precipitating factor for ACS was less frequently found in patients with PT as compared with those without. Patients with PT exhibited significantly higher platelet counts (517 [273-729] vs. 307 [228-412] 10 9/L, P < 0.01) and lower bilirubin (28 [19-43] vs. 44 [31-71] mmol/L, P < 0.01) levels at the onset of ACS as compared with others. In addition, patients with PT had a higher platelet count peak (537 [345-785] vs. 417 [330-555] 10 9/L, P = 0.048) and smaller bilirubin peak (36[18-51] vs. 46 [32-83] μmol/L, P = 0.048) and lactate dehydrogenase peak (357 [320-704] vs. 604 [442-788] IU/L, P = 0.01) during hospital stay as compared with others. Conclusions: PT is not a rare event in the context of ACS and seems more likely in patients with higher platelet counts and lower hemolytic rate during ACS. Patients with sickle cell disease presenting with respiratory symptoms suggestive of ACS may benefit from evaluation for PT.
Angelakis E.,French National Center for Scientific Research |
Botelho E.,French National Center for Scientific Research |
Socolovschi C.,French National Center for Scientific Research |
Sobas C.R.,Service Bacteriologue |
And 3 more authors.
Journal of Travel Medicine | Year: 2010
Background. Travelers are exposed to a variety of health risks in unfamiliar environments and fever is a common problem in patients returning from travel abroad. Rickettsial diseases are increasingly frequently being reported among international travelers. Here we present cases of Rickettsia typhi infection, the agent of murine typhus, that were identified in our laboratory the last year, in travelers from Tunisia. Methods. For each patient we tested an acute-phase serum sample and for one patient we tested a convalescent-phase serum sample. IgG and IgM antibody titers were estimated with use of the microimmunofluorescence (MIF) assay. Western blot (WB) assay was performed for all the patients. Results. We identified three cases of murine typhus after a travel in Tunisia. All cases were observed during late summer and early autumn and patients were suffering by persistent fever. None of them presented rash or inoculation eschar. MIF was positive for Rickettsia sp. in the acute-phase serum samples of two patients. In one patient, two acute-phase serum samples were Rickettsia sp. negative whereas a third convalescent-phase serum sample that was obtained 2 weeks after was Rickettsia sp. positive. By WB assay we identified infection by R typhi. A treatment was immediately started and patients became apyretic. Conclusions. In the countries of North Europe, although autochthones cases of murine typhus have not been described, sporadic cases of R typhi infection are identified in travelers who visited murine typhus endemic areas. Murine typhus should be considered in the diagnosis of febrile illness without rash in travelers returning from disease endemic areas, like the south Mediterranean area. © 2010 International Society of Travel Medicine. © 2010 International Society of Travel Medicine.
Goutell S.,Service Pharmaceutique Groupement Hospitalier Of Geriatrie |
Goutell S.,University Claude Bernard Lyon 1 |
Goutell S.,CNRS Biometry and Evolutionary Biology Laboratory |
Baudry T.,Service de Maladies Infectieuses et Tropicales |
And 14 more authors.
Antimicrobial Agents and Chemotherapy | Year: 2013
Limited data on the pharmacokinetics and pharmacodynamics (PK/PD) of unboosted atazanavir (uATV) in treatment-experienced patients are available. The aim of this work was to study the PK/PD of unboosted atazanavir in a cohort of HIV-infected patients. Data were available for 58 HIV-infected patients (69 uATV-based regimens). Atazanavir concentrations were analyzed by using a population approach, and the relationship between atazanavir PK and clinical outcome was examined using logistic regression. The final PK model was a linear one-compartment model with a mixture absorption model to account for two subgroups of absorbers. The mean (interindividual variability) of population PK parameters were as follows: clearance, 13.4 liters/h (40.7%), volume of distribution, 71.1 liters (29.7%), and fraction of regular absorbers, 0.49. Seven subjects experienced virological failure after switch to uATV. All of them were identified as low absorbers in the PK modeling. The absorption rate constant (0.38 ± 0.20 versus 0.75 ± 0.28 h-1; P = 0.002) and ATV exposure (area under the concentration-time curve from 0 to 24 h [AUC0-24], 10.3 ± 2.1 versus 22.4 ± 11.2mg·h·liter-1; P = 0.001) were significantly lower in patients with virological failure than in patients without failure. In the logistic regression analysis, both the absorption rate constant and ATV trough concentration significantly influenced the probability of virological failure. A significant relationship between ATV pharmacokinetics and virological response was observed in a cohort of HIV patients who were administered unboosted atazanavir. This study also suggests that twice-daily administration of uATV may optimize drug therapy. Copyright © 2013, American Society for Microbiology. All Rights Reserved.
Gasnault J.,Hopital University Of Bicetre Assistance Publique Hopitaux Of Paris Aphp |
Gasnault J.,French Institute of Health and Medical Research |
Costagliola D.,Groupe hospitalier Pitie Salpetriere APHP |
Costagliola D.,French Institute of Health and Medical Research |
And 16 more authors.
PLoS ONE | Year: 2011
Background: Progressive multifocal leukoencephalopathy (PML), a rare devastating demyelinating disease caused by the polyomavirus JC (JCV), occurs in severely immunocompromised patients, most of whom have advanced-stage HIV infection. Despite combination antiretroviral therapy (cART), 50% of patients die within 6 months of PML onset. We conducted a multicenter, open-label pilot trial evaluating the survival benefit of a five-drug cART designed to accelerate HIV replication decay and JCV-specific immune recovery. Methods and Findings: All the patients received an optimized cART with three or more drugs for 12 months, plus the fusion inhibitor enfuvirtide during the first 6 months. The main endpoint was the one-year survival rate. A total of 28 patients were enrolled. At entry, median CD4+ T-cell count was 53 per microliter and 86% of patients had detectable plasma HIV RNA and CSF JCV DNA levels. Seven patients died, all before month 4. The one-year survival estimate was 0.75 (95% confidence interval, 0.61 to 0.93). At month 6, JCV DNA was undetectable in the CSF of 81% of survivors. At month 12, 81% of patients had undetectable plasma HIV RNA, and the median CD4+ T-cell increment was 105 per microliter. In univariate analysis, higher total and naive CD4+ T-cell counts and lower CSF JCV DNA level at baseline were associated with better survival. JCV-specific functional memory CD4+ T-cell responses, based on a proliferation assay, were detected in 4% of patients at baseline and 43% at M12 (P = 0.008). Conclusions: The early use of five-drug cART after PML diagnosis appears to improve survival. This is associated with recovery of anti-JCV T-cell responses and JCV clearance from CSF. A low CD4+ T-cell count (particularly naive subset) and high JCV DNA copies in CSF at PML diagnosis appear to be risk factors for death. Trial Registration: ClinicalTrials.gov NCT00120367. © 2011 Gasnault et al.
PubMed | University of Paris Pantheon Sorbonne, ViiV Healthcare, Service des Maladies Infectieuses et Tropicales, Service dImmunologie Clinique and 3 more.
Type: Journal Article | Journal: Clinical infectious diseases : an official publication of the Infectious Diseases Society of America | Year: 2015
Dolutegravir has shown in vitro activity against human immunodeficiency virus type 2 (HIV-2). We report safety and efficacy data of regimens containing dolutegravir (50 mg twice daily) in antiretroviral-experienced, HIV-2-infected patients.HIV-2-infected patients experiencing virological failure to raltegravir received dolutegravir with optimized background antiretroviral combinations within the French Named Patient Program (NPP). Plasma HIV-2 RNA (pVL) was assessed at time of dolutegravir initiation (baseline), month 3, and month 6. Antiretroviral trough plasma concentrations (C12h) were determined using liquid chromatography coupled with tandem mass spectrometry.Thirteen HIV-2-infected-patients, with a median duration of 15 years infection and given 16 previous antiretroviral regimens, were included in NPP. Median follow-up was 9 months (min-max, 3-15 months). Median baseline pVL and CD4 cell count were 9544 copies/mL (inter quartile range [IQR], 3096-23 120 copies/mL) and 100 cells/L (IQR, 77-171 cells/L), respectively. Available integrase genotypic resistance patterns were Y143C/G/H/R (n = 5), Q148R/K (n = 2), and N155H (n = 4). Optimized background antiretroviral regimens conferring a genotypic sensitivity score 2 in 10 patients included nucleoside reverse transcriptase inhibitors associated with darunavir/ritonavir (n = 12), saquinavir/ritonavir (n = 2), and maraviroc (n = 3). At months 3 and 6, pVL was undetectable in 6 of 13 and 4 of 12 patients, respectively, and median CD4 count was 161 (101-188) cells/L and 167 (135-1353) cells/L, respectively. Median dolutegravir C12h was 4086 (1756-5717 ng/mL) ng/mL in 9 patients. No serious events were notified except 1 death from progressive multifocal leukoencephalopathy at month 4.Optimized dolutegravir-containing antiretroviral regimens supported by good plasma exposure provide a substantial initial efficacy rate for salvage therapy in heavily antiretroviral-experienced HIV-2-infected patients with virus harboring resistance to first-generation integrase inhibitors. Larger numbers of patients and longer follow-up are needed to confirm these findings.