Vancomycin-induced Henoch-Schönlein purpura: a case report

<p>Abstract</p> <p>Introduction</p> <p>Henoch-Schönlein purpura is a small-vessel systemic vasculitis. Although its exact pathophysiology remains unknown, Henoch-Schönlein purpura has been reported in association with various medical conditions including hypersensitivity. We report the case of a patient with vancomycin-induced Henoch-Schönlein purpura.</p> <p>Case presentation</p> <p>A 42-year-old Caucasian man who had previously undergone a heart transplant was diagnosed as having an intra-abdominal abscess after he underwent a Hartmann procedure. At 15 days after initiation of antibiotic therapy including vancomycin, he developed a purpuric rash of the lower limbs, arthralgia, and macroscopic hematuria. At that time, our patient was already on hemodialysis for end-stage renal disease. Henoch-Schönlein purpura was diagnosed. After a second 15-day course of vancomycin, a second flare of Henoch-Schönlein purpura occurred. Skin biopsies showed leucocytoclastic vasculitis with IgA deposits and eosinophils in the peri-capillary inflammatory infiltrate, suggesting an allergic mechanism. After vancomycin was stopped, we did not observe any further flares. Only five cases of isolated cutaneous vasculitis, one case of lupus-like syndrome and one case of Henoch-Schönlein purpura after vancomycin treatment have been described to date in the literature.</p> <p>Conclusions</p> <p>Clinicians should be aware that systemic vasculitis can be induced by some treatments. Vancomycin is a widely prescribed antibiotic. Occurrence of rare but serious Henoch-Schönlein purpura associated with vancomycin requires its prompt discontinuation.</p

Acute tubulointerstitial nephritis complicating Legionnaires' disease: a case report

<p>Abstract</p> <p>Introduction</p> <p>Legionnaires' disease is recognized as a multi-systemic illness. Afflicted patients may have pulmonary, renal, gastrointestinal tract and central nervous system complications. However, renal insufficiency is uncommon. The spectrum of renal involvement may range from a mild and transient elevation of serum creatinine levels to anuric renal failure requiring dialysis and may be linked to several causes. In our present case report, we would like to draw attention to the importance of the pathological documentation of acute renal failure by reporting a case of a patient with acute tubulointerstitial nephritis complicating Legionnaires' disease.</p> <p>Case presentation</p> <p>A 55-year-old Caucasian man was admitted to our hospital for community-acquired pneumonia complicated by acute renal failure. <it>Legionella pneumophila </it>serogroup type 1 was diagnosed. Although the patient's respiratory illness responded to intravenous erythromycin and ofloxacin therapy, his renal failure worsened, he became anuric, and hemodialysis was started. A renal biopsy was performed, which revealed severe tubulointerstitial nephritis. After initiation of steroid therapy, his renal function improved dramatically.</p> <p>Conclusions</p> <p>This case highlights the importance of kidney biopsies in cases where acute renal failure is a complicating factor in Legionnaires' disease. If the presence of acute tubulointerstitial nephritis can be confirmed, it will likely respond favorably to steroidal treatment and thus irreversible renal damage and chronic renal failure will be avoided.</p

Clinical Relevance of Tumor Cells with Stem-Like Properties in Pediatric Brain Tumors

BACKGROUND: Primitive brain tumors are the leading cause of cancer-related death in children. Tumor cells with stem-like properties (TSCs), thought to account for tumorigenesis and therapeutic resistance, have been isolated from high-grade gliomas in adults. Whether TSCs are a common component of pediatric brain tumors and are of clinical relevance remains to be determined. METHODOLOGY/PRINCIPAL FINDINGS: Tumor cells with self-renewal properties were isolated with cell biology techniques from a majority of 55 pediatric brain tumors samples, regardless of their histopathologies and grades of malignancy (57% of embryonal tumors, 57% of low-grade gliomas and neuro-glial tumors, 70% of ependymomas, 91% of high-grade gliomas). Most high-grade glioma-derived oncospheres (10/12) sustained long-term self-renewal akin to neural stem cells (>7 self-renewals), whereas cells with limited renewing abilities akin to neural progenitors dominated in all other tumors. Regardless of tumor entities, the young age group was associated with self-renewal properties akin to neural stem cells (P = 0.05, chi-square test). Survival analysis of the cohort showed an association between isolation of cells with long-term self-renewal abilities and a higher patient mortality rate (P = 0.013, log-rank test). Sampling of low- and high-grade glioma cultures showed that self-renewing cells forming oncospheres shared a molecular profile comprising embryonic and neural stem cell markers. Further characterization performed on subsets of high-grade gliomas and one low-grade glioma culture showed combination of this profile with mesenchymal markers, the radio-chemoresistance of the cells and the formation of aggressive tumors after intracerebral grafting. CONCLUSIONS/SIGNIFICANCE: In brain tumors affecting adult patients, TSCs have been isolated only from high-grade gliomas. In contrast, our data show that tumor cells with stem cell-like or progenitor-like properties can be isolated from a wide range of histological sub-types and grades of pediatric brain tumors. They suggest that cellular mechanisms fueling tumor development differ between adult and pediatric brain tumors

Host response exploration through different global approaches

Le diagnostic précoce et l’identification de la gravité du sepsis sont les 2 principaux éléments nécessaires pour une prise en charge optimale. Patients et méthodes: Nous avons utilisé la spectrométrie de masse MALDI-TOF pour identifier un profil de réponse spécifique des PBMCs et la formation in vitro de granulomes, comme moyen d’exploration de l’immunodépression du patient en sepsis sévère et âgé infecté. Résultats: Nous avons identifié des signatures spécifiques des PBMCs stimulées par des agonistes M1, des cytokines M2 ou différentes bactéries. La comparaison de spectres de patients en sepsis sévère avec les spectres des PBMCs stimulés a montré une signature spectrale de type Interleukine IL-10 et Interféron IFN-γ ainsi que CpG ODN. La formation des granulomes a mis en évidence un défaut de formation de granulomes chez les patients septiques. Les patients en sepsis sévère ne formant pas de granulome avaient des taux de monocytes et de lymphocytes diminués. Chez la personne âgée, une dénutrition était retrouvée. Un déficit en TNF sans augmentation de l’IL-10 associé à un défaut de différenciation des macrophages en cellules épithélioides et en cellules géantes multinucléées sont retrouvés en cas de défaut de formation. Conclusion: Le MALDI-TOF par son approche de caractérisation cellulaire par « profiling » à partir de l’analyse directe des cellules entières pourrait permettre de distinguer un SIRS inflammatoire ou infectieux ou encore aider le clinicien à dépister une complication infectieuse avant même la clinique et l’identification d’un micro-organisme. La formation des granulomes pourrait quant à elle servir à monitorer la réponse immune.Early diagnosis and identification of the severity of the picture are crucial to ensuring optimal management. Patients/methods: We used MALDI-TOF mass spectrometry to identify a specific response profile of PBMCs to infectious aggression and investigated the in vitro formation of granulomas to explore immunodepression in patients with severe sepsis and infected elderly subjects. Results: We identified specific signatures in PBMCs stimulated in vitro by M1 agonists, M2 cytokines or various bacteria. The comparison of the spectra of patients with severe sepsis with the spectra of PBMCs stimulated highlighted an Interleukin IL-10 and Interferon IFN-γ-type spectral signature in all the patients as well as a CpG-ODN signature. The granuloma formation highlighted the absence of granuloma formation in patients with sepsis. The lower monocyte and leukocyte counts in patients with severe sepsis not forming granulomas could explain this defect. In elderly subjects, malnutrition was observed. A TNF deficiency without an increase in IL-10 associated with defective differentiation of macrophages into epithelioid cells and multinuclear giant cells was observed in cases of defective granuloma formation. Conclusion: The direct analysis of whole cells using MALDI-TOF profiling requires little sample preparation and no prior extraction of the biomolecules. Mass spectrometry could help distinguish SIRS associated with an inflammatory or infectious condition or help the clinician to detect the onset of an infectious complication even before any clinical signs or the identification of the microorganism. The assessment of granuloma formation could be used to monitor the immune response

Prise en charge de l'hyperkaliémie par le médecin généraliste (enquête aurpès des médecins généralistes du département du Var)

L'objectif de notre étude était de décrire les principales causes de l'hyperkaliémie rencontrées en médecine générale et d'analyser les différentes stratégies de prise en charge en fonction de la cause et de la sévérité de celle-ci. Il s'agit d'une enquête descriptive et rétrospective portant sur 70 patients, présentés par 61 médecins de la région Toulonnaise par le biais d'un questionnaire. Les principales causes étaient la iatrogénie, l'insuffisance rénale chronique, les pseudohyperkaliémies et l'insuffisance rénale aiguë. Parmi les médicaments, les ARA II, les IEC et les diurétiques épargneurs de potassium étaient le plus souvent en cause. L'insuffisance rénale ou l'association de médicaments hyperkaliémiants augmentaient le risque d'hyperkaliémie sévère. La prise en charge des médecins semblait hétérogène. En effet, aucun facteur n'était indépendamment associé à la réalisation de l'ECG. Certaines étiologies comme l'insuffisance rénale et les psuedohyperkaliémies semblaient fortment influencer l'attitude thérapeutique. En effet, l'altération de la fonction rénale était associée à une prise en charge plus rapide et l'insuffisance rénale aiguë augmentait le nombre d'hospitalisations. De plus, si les hyperkaliémies légères étaient l'objet d'une attitude thérapeutique consensuelle, aucune différence n'était constatée entre les hyperkaliémies modérées et sévères. Ainsi, nous n'avons pas mis en évidence d'attitude thérapeutique spécifique de l'hyperkaliémie sévère ni de facteurs guidant la réalisation de l'ECG. Ceci peut être expliqué par l'absence de recommandations officielles guidant la pratique clinique.The aim of our study was to describe the main causes of hyperkalemia met in general practice and analyze different management strategies depending on the cause and severity of it. It was a descriptive and retrospective study of 70 outpatients, presented by 61 general practitioner of the area of Toulon through a questionnary. The main causes were drugs, chronic renal failure, pseudohyperkalemia and acute rela failure. Among the grugs, ARBs, ACE inhibitors and potassium-sparing diuretics were most often involved. Renal failureor drug combinaison increased the risk of severe hyperkalemia. The physicians management appeared heterogeneous. Indeed, no factor was independently associated with the implantation of the ECG. Some causes such as kidney failure and pseudohyperkalemia appeared to strongly influence the therapeutic approach. Indeed, imparied renal function was associated with faster treatment and acute renal failure increased the number of hospitalizations. In addition, if low hyperkalemia was subjected to a therapeutic consensus, non difference was found between moderate and severe hyperkalemia. Thus, we did no notice any specific therapeutic approach of severe hyperkalemia or any factors guiding the implementation of the ECG. This could be explained by the absence of official recommendations to guide clinical practice.AIX-MARSEILLE2-BU Méd/Odontol. (130552103) / SudocSudocFranceF

Caractéristiques cliniques, paracliniques et profil évolutif de l'atteinte aortique de la maladie de Horton (à propos de 26 cas d'aortite parmi 63 cas de maladie de Horton)

AIX-MARSEILLE2-BU Méd/Odontol. (130552103) / SudocSudocFranceF

Glycosylated Hemoglobin as a Surrogate for the Prevention of Cardiovascular Events in Cardiovascular Outcome Trials Comparing New Antidiabetic Drugs to Placebo

International audienceBackground and Objectives: The value of glycosylated hemoglobin (HbA1c) as a surrogate marker for the prevention of cardiovascular outcomes on antidiabetic drugs is debated. The 2008 FDA guidance led to multiple large clinical trials to evaluate the effect of new antidiabetic drugs versus placebo on major adverse cardiac events (MACE). The aim of this study was to evaluate the relation between MACE and HbA1c decrease between antidiabetic drug and placebo across the spectrum of cardiovascular outcome trials (CVOT). Methods: In this systematic review, we included randomized controlled trials that compared an antidiabetic drug to placebo in addition to current standard of care with the primary intention of demonstrating cardiovascular safety. We investigated the relationship between MACE decrease on antidiabetic drug and HbA1c reduction on antidiabetic drug using the coefficient correlation. We also studied the effects of potential confounders on MACE decrease. Results: Fourteen eligible trials including 128,149 patients were included, 12,114 of whom experienced MACE. Mean achieved HbA1c absolute reductions on antidiabetic treatment versus placebo varied from 0.29 to 1%. The decrease of MACE on antidiabetic drug was significantly correlated with mean HbA1c reduction (r = 0.88, 95% CI: 0.67-0.96, p < 0.001) and weight loss (r = 0.81, 95% CI: 0.46-0.94, p < 0.001). In a bivariate model including weight loss, only HbA1c reduction remained significantly correlated with the decrease of MACE on antidiabetic drug (p = 0.019). Conclusion: Across CVOT, the decrease in MACE incidence on various antidiabetic drugs is significantly correlated with HbA1c reduction. This metaanalysis supports HbA1c as an appropriate surrogate endpoint for cardiovascular events. Our analysis supports that changes in HbA1c should be taken into account while interpreting effects of new antidiabetic drugs on cardiovascular outcomes

Authors’ Reply to the Letter by Shoar et al. on “Glycosylated Hemoglobin as a Surrogate for the Prevention of Cardiovascular Events in Cardiovascular Outcome Trials Comparing New Antidiabetic Drugs to Placebo”

International audienceNo abstract availabl

Télémédecine et iatrogénie médicamenteuse en Ehpad

International audienc

Phenotypic diversity and emerging new tools to study macrophage activation in bacterial infectious diseases

International audienceMacrophage polarization is a concept that has been useful to describe the different features of macrophage activation related to specific functions. Macrophage polarization is responsible for a dichotomic approach (killing vs. repair) of the host response to bacteria; M1-type conditions are protective, whereas M2-type conditions are associated with bacterial persistence. The use of the polarization concept to classify the features of macrophage activation in infected patients using transcriptional and/or molecular data and to provide biomarkers for diagnosis and prognosis has most often been unsuccessful. The confrontation of polarization with different clinical situations in which monocytes/macrophages encounter bacteria obliged us to reappraise this concept. With the exception of M2-type infectious diseases, such as leprosy and Whipple's disease, most acute (sepsis) or chronic (Q fever, tuberculosis) infectious diseases do not exhibit polarized monocytes/macrophages. This is also the case for commensals that shape the immune response and for probiotics that alter the immune response independent of macrophage polarization. We propose that the type of myeloid cells (monocytes vs. macrophages) and the kinetics of the immune response (early vs. late responses) are critical variables for understanding macrophage activation in human infectious diseases. Explorating the role of these new markers will provide important tools to better understand complex macrophage physiology