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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.

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:2,138 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.

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.

Liquid chromatography coupled with mass spectrometry for the determination of total and unbound mycophenolic acid and its major metabolite in human plasma has been developed. Sample preparations were based on a fully automated solid-phase extraction process and ultrafiltration. Mass spectrometric data were acquired in a single-ion monitoring method. The analytes and nevirapine (internal standard) were well separated in an isocratic mode over 8 min. Validation study exhibited excellent linearity, with intra- and inter-day precision and accuracy of less than 12%. The assay was successfully applied to the pharmacokinetic study of mycophenolic acid in patients with autoimmune diseases.

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.

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.A total of 49 patients were included in this observational cohort study. At inclusion, all patients had plasma HIV-RNA levels50 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 level50 copies/mL within the first 12 months and remaining undetectable at the end of the follow-up.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 variation40%). 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.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.

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.

Resume Introduction Les thrombocytoses induites par l’heparine sont exceptionnellement decrites dans la litterature. Nous en rapportons quatre observations. Observations Il s’agissait 3 fois sur 4 de patients suivis pour un syndrome myeloproliferatif stable. L’hyperplaquettose etait toujours regressive a l’arret de l’heparine et n’etait jamais associee a un evenement thrombotique. Discussion Faisant suite a diverses publications suggerant une association entre heparine et thrombocytose, une recente enquete de pharmacovigilance francaise en rapporte 51 cas. Les thrombocytoses induites par l’heparine s’expliquent probablement par le role potentialisateur de la megacaryocytopoiese joue, notamment par inhibition du facteur 4 plaquettaire (PF4). Les thrombocytoses induites constituent une raison supplementaire pour surveiller les plaquettes au cours de l’heparinotherapie.

Microbiologic Characteristics and In Vitro Susceptibility to Antimicrobials. 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.

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.

Thrombocytosis induced by heparin is rarely reported in the literature.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.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.

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 (AUC0-12 h) (medians: 37.7 vs 73.1 mg/h/L, P = 0.003) and MPA 12-hour trough concentrations (C12 h) (medians: 1.5 vs 3.7 mg/L, P = 0.008) were significantly lower, and inclusion MPAG/MPA C12 h ratios (medians: 18.7 vs 10.2, P = 0.02) were significantly higher. According to our receiver operating characteristics curve analysis, MPA C12 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 C12 h < 3 mg/L.