Search

Abstract Background The objective of the study was to describe the evolution of chronic non-AIDS related diseases and their risk factors, in patients living with HIV (PLHIV) in the French ANRS CO3 Aquitaine prospective cohort, observed both in 2004 and in 2014 in order to improve long-term healthcare management. Methods The ANRS CO3 Aquitaine cohort prospectively collects epidemiological, clinical, biological and therapeutic data on PLHIV in the French Aquitaine region. Two cross sectional analyses were performed in 2004 and 2014, to investigate the patient characteristics, HIV RNA, CD4 counts and prevalence of some common comorbidities and treatment. Results 2138 PLHIV (71% male, median age 52.2 years in 2014) were identified for inclusion in the study, including participants who were registered in the cohort with at least one hospital visit recorded in both 2004 and 2014. Significant increases in the prevalence of diagnosed chronic kidney disease (CKD), bone fractures, cardiovascular events (CVE), hypertension, diabetes and dyslipidaemia, as well as an increase in treatment or prevention for these conditions (statins, clopidogrel, aspirin) were observed. It was also reflected in the increase in the proportion of patients in the “high” or “very high” risk groups of the disease risk scores for CKD, CVE and bone fracture score. Conclusions Between 2004 and 2014, the aging PLHIV population identified in the French ANRS CO3 Aquitaine prospective cohort experienced an overall higher prevalence of non-HIV related comorbidities, including CKD and CVD. Long-term healthcare management and long-term health outcomes could be improved for PLHIV by: careful HIV management according to current recommendations with optimal selection of antiretrovirals, and early management of comorbidities through recommended lifestyle improvements and preventative measures.

Background: No specific description of monoclonal gammopathies of undetermined significance (MGUS)-associated angioedema due to acquired C1 inhibitor deficiency (AAE-C1-INH) has been reported yet., Objective: To describe the biological and clinical characteristics, evolution, and response to treatment of MGUS-associated AAE-C1-INH., Materials and Methods: We conducted a French national retrospective observational study on MGUS-associated acquired angioedema spanning a 30-year period., Results: Forty-one patients with MGUS-associated AAE-C1-INH at diagnosis were included; 68% displayed anti-C1-INH antibodies. The monoclonal component was an IgM in 24 patients, IgG in 11, and IgA in 6 patients. The mean age at first angioedema attack was 63 years (standard deviation [SD] = 13 years) and at diagnosis 66 years (SD = 11 years). A total of 88% patients benefited from acute attack treatments, and 77% from long-term prophylaxis, either danazol, tranexamic acid, or lanadelumab. Median follow-up was 7 years, during which 14 patients (33%) evolved into well-defined malignant hemopathies. Fifty percent of patients were given a hematological treatment, either rituximab alone, indicated by recurrent attacks of angioedema in patients with AAE-C1-INH with anti-C1-INH antibodies, or validated combinations of chemotherapies, indicated by evolution into a lymphoma in 7 patients and a myeloma in 3 patients. Fifteen patients (35%) were in clinical complete remission of angioedema at last visit, of whom 60% had an undetectable serum monoclonal immunoglobulin., Conclusions: Complete remission of AAE-C1-INH is correlated to complete remission of the underlying hematological malignancy, as defined by an undetectable serum monoclonal immunoglobulin. In our MGUS-associated acquired angioedema cohort, we recorded an incidence of evolution into hematological malignancy of 4% per patient-year. It is therefore crucial to conduct full hematological workup during follow-up at an annual rate, and earlier if AAE relapses or if acute attack frequency increases., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Determining the etiology of aortitis is often challenging, in particular to distinguish infectious aortitis (IA) and noninfectious aortitis (NIA). This study aims to describe and compare the clinical, biological, and radiological characteristics of IA and NIA and their outcomes., Methods: A multicenter retrospective study was performed in 10 French centers, including patients with aortitis between 1 January 2014 and 31 December 2019., Results: One hundred eighty-three patients were included. Of these, 66 had IA (36.1%); the causative organism was Enterobacterales and streptococci in 18.2% each, Staphylococcus aureus in 13.6%, and Coxiella burnetii in 10.6%. NIA was diagnosed in 117 patients (63.9%), mainly due to vasculitides (49.6%), followed by idiopathic aortitis (39.3%). IA was more frequently associated with aortic aneurysms compared with NIA (78.8% vs 17.6%, P < .001), especially located in the abdominal aorta (69.7% vs 23.1%, P < .001). Crude and adjusted survival were significantly lower in IA compared to NIA (P < .001 and P = .006, respectively). In the IA cohort, high American Society of Anesthesiologists score (hazard ratio [HR], 2.47 [95% confidence interval {CI}, 1.08-5.66]; P = .033) and free aneurysm rupture (HR, 9.54 [95% CI, 1.04-87.11]; P = .046) were significantly associated with mortality after adjusting for age, sex, and Charlson comorbidity score. Effective empiric antimicrobial therapy, initiated before any microbial documentation, was associated with a decreased mortality (HR, 0.23, 95% CI, .08-.71]; P = .01)., Conclusions: IA was complicated by significantly higher mortality rates compared with NIA. An appropriate initial antibiotic therapy appeared as a protective factor in IA., Competing Interests: Potential conflicts of interest. P. R. reports payment or honoraria from Celgene, Novartis, and AdLiva and support for attending meetings and/or travel from Janssen-Cilag, Amgen, Roche, Takeda, Mylan, and Celgene. All other authors report no potential conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2022. Published by Oxford University Press on behalf of Infectious Diseases Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Purpose: To describe a procedure allowing early assessment of treatment response in Takayasu arteritis (TA) patients by averaging the standard uptake value obtained from N hottest voxels irrespective of their location within the F-FDG-positive vessel walls (SUVmax-N)., Methods: The procedure is illustrated in a score-V TA patient before and after 1 and 3 months of glucocorticoid treatment (scans 0-1-3, respectively). Comparison between scans was made by using SUVmax-N repeatability percentages with 95-99-99.9% reliability., Results: No significant difference in SUVmax (ie, N = 1) was found between scan 0 and 1, and between scan 1 and 3, with 95% reliability. A significant difference in SUVmax-N was found with 99.9% reliability for each scan pair by averaging N = 4100-515 hottest voxels (total hottest volume of 100.0-12.6 mL), respectively., Conclusions: The proposed SUVmax-N procedure may be an efficient tool to early assess treatment response in TA patients. Further studies involving series of patients with large vessel vasculitis are warranted to investigate its usefulness in their management.

Introduction: The incidence of cardiovascular implantable electronic device (CIED) infection is steadily increasing. However, no consensus has been reached with respect to the type and duration of antimicrobial therapy in this specific population of patients. The role played by new anti-Staphylococcus agents has not been defined. The aims of this study were to describe the microbiological characteristics of a large population of patients with CIED infections and to test the in vitro susceptibility of the various strains to different antimicrobials., Methods: Two hundred eighty-six patients with CIED infection were included. The minimal inhibitory concentrations of 9 antimicrobials, including linezolid, tigecycline, and daptomycin were measured against all strains of staphylococci isolated., Results: Microbiologic confirmation was obtained in 252 (88%) patients, the vast majority were from Staphylococcus species (86%), 90% of these were coagulase negative strains and 10% were Staphylococcus aureus; 30.5% were methicillin-resistant. All strains were susceptible to vancomycin, nearly 15% of coagulase negative strains were nonsusceptible to teicoplanin, and nearly 100% of the strains were susceptible to the 3 new antimicrobials., Conclusions: In this large contemporary study, we show that Staphylococcus is by far the most common cause of CIED infections, with the majority due to coagulase negative strains. Methicillin-resistance is common in this population. Currently, we would recommend vancomycin as first-line empirical therapy. However, given that not all patients tolerate vancomycin, we believe that newer antimicrobial therapies should now be tested in clinical trials to establish their clinical effectiveness in treating patients with device infections., (© 2012 Wiley Periodicals, Inc.)

Objectives: Delineation of mechanisms underlying neuropsychiatric systemic lupus erythematosus (NPSLE) and determination of biological markers could guide treatment choice. A study was undertaken to analyse the potential role of activated CD8+ T cells in NPSLE as previously reported in SLE nephritis., Methods: Flow cytometric immunophenotyping of blood lymphocytes was performed in 30 patients with NPSLE and 36 healthy individuals. The antigenic specificity of CD8+ T cells was studied using HLA-A0201 tetramers loaded with several myelin-derived peptides. The intracellular level of interferon γ (IFNγ) produced by activated CD8+ T cells was determined by flow cytometry., Results: A large increase in circulating activated CD8+ T lymphocytes expressing surface HLA-DR was found in patients with NPSLE without antiphospholipid syndrome (APS) (n=18) compared with patients with APS (n=12) or healthy controls (n=36). IFNγ-secreting myelin-specific CD8+ T cells were detected exclusively in the blood of patients with NPSLE without APS but with white matter lesions., Conclusions: These data strongly support the existence of a new immune effector mechanism responsible for CNS involvement in patients with NPSLE and suggest that analysing HLA-DR expression combined with myelin-specific tetramer staining on CD8+ T lymphocytes may be a valuable additional tool for the monitoring of these patients.

Introduction: The aim of this study was to determine whether mycophenolate mofetil (MMF) pharmacokinetics (PK) under combined MMF and prednisone remission-maintenance therapy can predict systemic lupus erythematosus (SLE) clinical flares., Methods: At inclusion, steady-state PK parameters of the MMF active form, mycophenolic acid (MPA), and its glucuronide metabolite (MPAG) were determined for 25 stable SLE patients without renal manifestations. Disease activity was assessed during 6 months of follow-up. Potential relationships between those entry MMF-PK variables and clinical outcome were analyzed., Results: MMF controlled disease activity in 17 patients (successes) and failed to do so for 8 others (failures). For failures and successes, respectively, entry MPA areas under the time-concentration curve between 0 and 12 hours (AUC(0-12 h)) (medians: 37.7 vs 73.1 mg/h/L, P = 0.003) and MPA 12-hour trough concentrations (C(12 h)) (medians: 1.5 vs 3.7 mg/L, P = 0.008) were significantly lower, and inclusion MPAG/MPA C(12 h) ratios (medians: 18.7 vs 10.2, P = 0.02) were significantly higher. According to our receiver operating characteristics curve analysis, MPA C(12 h) was best able to discriminate a flare during follow-up (93% sensitivity, 85% specificity). A 3-mg/L cut-off had 92% negative-predictive value for developing a flare during follow-up., Conclusions: For our SLE patients without renal manifestations, clinical flares developing under maintenance therapy were associated with steady-state inclusion MPA C(12 h) < 3 mg/L.

Kikuchi-Fujimoto disease (KFD), first described independently by Kikuchi and Fujimoto in 1972, is a subacute necrotizing lymphadenitis of unknown cause. Although most frequent in young Asian women, KFD has a worldwide distribution. Clinically, KFD is characterized by lymphadenitis of one or more lymph nodes, predominantly in the posterior cervical region, fever, and leukopenia in up to 50% of cases. Extranodal manifestations can occur, especially skin lesions and aseptic meningitides. Diagnosis is usually confirmed by analysis of samples from an excisional biopsy of the affected nodes. Histologically, the lesions affect the cortical and paracortical areas of the node. Characteristic features include focal necrosis predominantly in the paracortical region with abundant karyorrhectic debris and atypical mononuclear cells around the necrotic zone (crescent-shaped histiocytes, plasmacytoid monocytes, and small lymphocytes and immunoblasts, mostly CD3(+)/CD8(+)), most often with an intact lymph node capsule, an absence of neutrophils, and a paucity of plasma cells. KFD has been classified into three histological subtypes and is thought to progress from the proliferative type (> 50%) to the necrotizing type (30%) and finally resolve into the xanthomatous type (< 20%). Differential diagnoses should include malignant lymphoma, infectious diseases such as toxoplasmatic lymphadenitis, tuberculous lymphadenitis and cat scratch disease, and systemic lupus erythematosus (SLE). The cause of KFD is unknown: a viral infection has been suggested, but not demonstrated, possibly involving human herpes virus 8 or Epstein-Barr virus. Apoptotic cell death plays a role: proliferating CD8(+) T-lymphocytes act as both killers and victims in the apoptotic process via Fas and perforin pathways. The course is usually benign with resolution in a few months with the use of antiinflammatory drugs. Regular follow-up is required because SLE may develop several years after the onset of Kikuchi-Fujimoto disease.

Large granular lymphocyte (LGL) leukemia is a clonal proliferation of cytotoxic cells, either CD3(+) (T-cell) or CD3(-) (natural killer, or NK). Both subtypes can manifest as indolent or aggressive disorders. T-LGL leukemia is associated with cytopenias and autoimmune diseases and most often has an indolent course and good prognosis. Rheumatoid arthritis and Felty syndrome are frequent. NK-LGL leukemias can be more aggressive. LGL expansion is currently hypothesized to be a virus (Ebstein Barr or human T-cell leukemia viruses) antigen-driven T-cell response that involves disruption of apoptosis. The diagnosis of T-LGL is suggested by flow cytometry and confirmed by T-cell receptor gene rearrangement studies. Clonality is difficult to determine in NK-LGL but use of monoclonal antibodies specific for killer cell immunoglobulin-like receptor (KIR) has improved this process. Treatment is required when T-LGL leukemia is associated with recurrent infections secondary to chronic neutropenia. Long-lasting remission can be obtained with immunosuppressive treatments such as methotrexate, cyclophosphamide, and cyclosporine A. NK-LGL leukemias may be more aggressive and refractory to conventional therapy.

Objectives: To assess intracellular and plasma efavirenz concentrations in HIV-infected patients who switched to efavirenz-based highly active antiretroviral therapy (HAART) from successful protease inhibitor-based HAART., Patients and Methods: A total of 49 patients were included in this observational cohort study. At inclusion, all patients had plasma HIV-RNA levels<50 copies/mL and switched to efavirenz combined with two nucleoside reverse transcriptase inhibitors. Intracellular and plasma concentrations were measured 12 h post-dose, 1 month (M1) and 6 months (M6) after starting efavirenz. Virological success (VS) was defined as plasma HIV-RNA level<50 copies/mL within the first 12 months and remaining undetectable at the end of the follow-up., Results: VS was documented in 48 patients for at least 12 months (range 12-78 months). High inter-patient variabilities of intracellular and plasma efavirenz concentrations were observed (coefficients of variation>40%). At M1 and M6, respectively, median [Q1; Q3] intracellular efavirenz concentrations were 5300 [2830; 11 530] and 6790 [3870; 8790] ng/mL, median plasma efavirenz concentrations were 2050 [1600; 3100] and 2100 [1410; 2500] ng/mL. No correlation was found between intracellular and plasma concentrations. Plasma efavirenz levels exceeded the proposed threshold of 1000 ng/mL in 96% of patients from M1., Conclusions: For moderately pre-treated HIV-infected patients with few mutations who switched to efavirenz from previous successful HAART, the proposed plasma efficacy-threshold was reached without any dosage adaptation. VS was maintained beyond 12 months, despite high inter-patient and intra-patient variabilities of intracellular and plasma efavirenz concentrations.

Introduction: Thrombocytosis induced by heparin is rarely reported in the literature., Case: We report here four cases of thrombocytosis, three in patients under treatment for a stable myeloproliferative disorder. Thrombocytosis always regressed when heparin treatment was discontinued, and no thrombotic events occurred., Discussion: Following several reports suggesting an association between heparin and thrombocytosis, the French adverse drug reporting (pharmacovigilance) network identified 51 cases. Thrombocytosis associated with heparin is probably explained by the latter's potentiation of megakaryocytopoiesis, in particular, by inhibition of platelet factor 4 (PF4). Thrombocytosis is a further reason to monitor platelet counts during heparin treatment.

Common variable immunodeficiency (CVID) is a heterogeneous group of immunodeficiency syndromes that involves defective production of specific antibodies and decreased serum concentrations of > or =1 immunoglobulin isotype. We describe a patient with an atypical case of CVID who had extensive granulomatous lesions that were partially attributable to mycobacterial infection. In the peripheral blood, there was a massive increase in the number of double-negative CD3+ T cells that expressed the gammadelta T cell receptor.

Background: Bilateral adrenal hematoma is an uncommon cause of acute adrenal insufficiency. An association with thrombopenia induced by low-molecular-weight heparin even more so. Diagnosis is difficult as the clinical manifestations mimic septic shock., Case Report: A 63-year-old woman developed acute adrenal insufficiency due to bilateral adrenal hematoma following severe thrombopenia induced by low-molecular-weight heparin prescribed after an orthopedic operation. Outcome was favorable., Conclusion: Acute adrenal insufficiency must be entertained as a possible diagnosis in patients with heparin-induced thrombopenia.