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1.
Rev Med Interne ; 43(12): 703-712, 2022 Dec.
Article in French | MEDLINE | ID: mdl-36460439

ABSTRACT

Innate immunity, and more specifically the complement system, has arised renewed interest in the medical field in recent years. Many innovative complement-inhibiting drugs have appeared, acting at various levels of the complement cascade. These drugs have made it possible to transform poor prognosis of certain diseases. Many of them are currently being tested in clinical trials for various indications. Many questions appear about their optimal use and their future indications. This article recalls the fundamental role of the complement system in the human organism. It then discusses the diseases in which the complement is involved on the pathophysiological level. The third part details the different classes of complement inhibitors and briefly recalls the indications for which these treatments seem the most promising. Finally, we end with a discussion that highlights the different aspects and questions induced by these new treatments.


Subject(s)
Complement Inactivating Agents , Immunity, Innate , Humans , Complement Inactivating Agents/pharmacology , Complement Inactivating Agents/therapeutic use
3.
J Hosp Infect ; 112: 16-20, 2021 Jun.
Article in English | MEDLINE | ID: mdl-33636255

ABSTRACT

This study aimed to describe the contamination of sink drains (SDs) with carbapenemase-producing Enterobacterales (CPE) in three intensive care units (ICUs), and to assess the risk of transmission to hospitalized patients. All SDs were sampled monthly for CPE screening by culture. Rectal screening for CPE carriage was conducted weekly for hospitalized patients. CPE were isolated from 22% of SD samples. Some SDs remained colonized with the same strain for several months. No CPE acquisition occurred among hospitalized patients during the study. Certain strategies, such as systematic sampling of SDs in ICUs for screening for contamination by CPE, should be discouraged apart from during outbreaks.


Subject(s)
Enterobacteriaceae Infections , beta-Lactamases , Bacterial Proteins , Disease Outbreaks , Enterobacteriaceae Infections/diagnosis , Enterobacteriaceae Infections/epidemiology , Enterobacteriaceae Infections/prevention & control , Humans , Intensive Care Units
4.
Med Mal Infect ; 50(3): 305-307, 2020 May.
Article in English | MEDLINE | ID: mdl-32014291

ABSTRACT

OBJECTIVE: To compare the minimum inhibitory concentrations (MIC) of the ceftazidime-avibactam (CZA) combination versus ceftazidime alone (TZ) for Stenotrophomonas maltophilia. PATIENTS AND METHODS: MIC comparison was performed by E-tests. We assumed that CZA was more effective in vitro than TZ alone when CZA led to a category change from "Resistant" with TZ alone to "Susceptible" or "Intermediate" with CZA, or if the MIC of CZA was at least 4-fold lower than the MIC of TZ for TZ-susceptible isolates. RESULTS: For the 54 clinical isolates included in the study, CZA showed better results in terms of the proportion of susceptible isolates (66.7% vs. 38.9%, P<0.01), MIC50 (2µg/mL vs. 12µg/mL, P<0.05), and MIC distribution. According to our definition, CZA was also more effective in vitro than TZ alone for 50% of the isolates. CONCLUSION: Using CZA for empirical treatments in severe or polymicrobial infections with S. maltophilia seems appropriate.


Subject(s)
Azabicyclo Compounds/pharmacology , Ceftazidime/pharmacology , Gram-Negative Bacterial Infections/drug therapy , Stenotrophomonas maltophilia/drug effects , Clavulanic Acids/pharmacology , Cystic Fibrosis/complications , Drug Combinations , Drug Resistance, Multiple, Bacterial , Humans , Microbial Sensitivity Tests , Multicenter Studies as Topic , Ticarcillin/pharmacology
5.
J Hosp Infect ; 104(1): 53-56, 2020 Jan.
Article in English | MEDLINE | ID: mdl-31408692

ABSTRACT

Sink drains of six intensive care units (ICUs) were sampled for screening contamination with extended-spectrum ß-lactamase-producing Enterobacteriaceae (ESBLE). A high prevalence (59.4%) of sink drain contamination was observed. Analysing the data by ICU, the ratio 'number of ESBLE species isolated in sink drains/total number of sink drains sampled' was highly correlated (Spearman coefficient: 0.87; P = 0.02) with the ratio 'number of hospitalization days for patients with ESBLE carriage identified within the preceding year/total number of hospitalization days within the preceding year'. Concurrently, the distribution of ESBLE species differed significantly between patients and sink drains.


Subject(s)
Enterobacteriaceae Infections/microbiology , Enterobacteriaceae/enzymology , Intensive Care Units/statistics & numerical data , beta-Lactamases/genetics , Carbapenem-Resistant Enterobacteriaceae , Carrier State/epidemiology , Citrobacter/isolation & purification , Cross Infection/epidemiology , Drug Resistance, Multiple, Bacterial/drug effects , Enterobacteriaceae/isolation & purification , Enterobacteriaceae Infections/epidemiology , France/epidemiology , Humans , Klebsiella pneumoniae/isolation & purification , Surveys and Questionnaires , beta-Lactamases/drug effects
7.
Rev Med Interne ; 40(8): 545-552, 2019 Aug.
Article in French | MEDLINE | ID: mdl-30686549

ABSTRACT

CAR-T cells are genetically modified human lymphocytes and gene therapy medicinal products. They are developed to treat cancers that express a membrane antigen targeted by the CAR. The FDA approved the two first-in-class medicinal products in 2017 and EMA in August 2018; both are autologous CAR-T cells targeting CD19 that is expressed at the surface of normal B-cells throughout their differentiation, and on B-cell lymphoid malignancies. Clinical efficacy was demonstrated for B-cell acute lymphoblastic leukemias, non-Hodgkin's lymphoma and chronic lymphocytic leukemia, although the marketing authorizations are less liberal in terms of indications. Manufacturing of these personalized treatments necessitates that a novel organization and supply chain be set in place, to ensure product preservation, patient safety and compliance with complex regulatory requirements. Side effects are commensurate with clinical efficacy and can be life-threatening: proper management imposes tight coordination between various specialists, particularly between hematologists and intensive care practitioners. High pricing for these treatments is part of a long-term trend for increasing costs of innovations in hematology and oncology; it questions the ability of healthcare systems to sustain their reimbursement.


Subject(s)
Immunotherapy, Adoptive , Neoplasms/therapy , Receptors, Chimeric Antigen/immunology , Antigens, CD19/immunology , Humans , Receptors, Antigen, T-Cell/immunology , T-Lymphocytes/immunology
8.
J Thromb Haemost ; 17(2): 403-414, 2019 02.
Article in English | MEDLINE | ID: mdl-30456926

ABSTRACT

Essentials Neutrophil extracellular traps (NETs) are generated during deep vein thrombosis (DVT). The role of interferon γ (IFNγ) and natural killer (NK) cells in NET formation was studied. IFNγ promote venous thrombosis through NET formation. NK cell depletion reduces DVT. SUMMARY: Background Neutrophils contribute to venous thrombosis through the release of neutrophil extracellular traps (NETs), but the mechanism triggering their formation remains unclear. In vitro data show that interferon (IFN)-γ induces the formation of NETs. Objectives To determine whether IFN-γ and the transcription factor T-box expressed on T cells (Tbet) promote venous thrombosis through neutrophil activation. Methods Venous thrombosis was induced by flow restriction in the inferior vena cava in IFN-γ-/- , Tbet-/- or wild-type (WT) mice. After 48 h, thrombus size was measured by the use of high-frequency ultrasound. NET formation was determined by immunofluorescence. Results and Conclusions Thrombus formation was reduced in Tbet-/- and IFN-γ-/- mice, suggesting that Tbet/IFN-γ-expressing cells are required for venous thrombosis. The number of NETs formed during thrombosis was significantly lower in Tbet-/- and IFN-γ-/- mice. NET formation was also decreased in WT mice treated with an IFN-γ-blocking antibody. Injection of recombinant IFN-γ into IFN-γ-/- mice rescued the phenotype. Natural killer (NK) cells were specifically depleted prior to venous thrombosis induction. NK cell depletion results in decreased NET formation and smaller thrombi, suggesting that NK cells are required for thrombus development. In depleted mice, adoptive transfer of WT NK cells induced a similar thrombosis burden as in WT mice. In contrast, adoptive transfer of IFN-γ -/- NK cells resulted in thrombi similar in size to those in depleted mice. In vitro, we showed that WT neutrophils released fewer NETs when they were cocultured with IFN-γ-/- NK cells. This study demonstrates that NK cell-dependent IFN-γ production is crucial for thrombus development by promoting the formation of NETs by neutrophils.


Subject(s)
Blood Coagulation , Extracellular Traps/metabolism , Killer Cells, Natural/metabolism , Neutrophils/metabolism , Vena Cava, Inferior/metabolism , Venous Thrombosis/metabolism , Animals , Cells, Cultured , Coculture Techniques , Disease Models, Animal , Extracellular Traps/immunology , Interferon-gamma/genetics , Interferon-gamma/metabolism , Killer Cells, Natural/immunology , Male , Mice, Inbred C57BL , Mice, Knockout , Neutrophils/immunology , Signal Transduction , T-Box Domain Proteins/genetics , T-Box Domain Proteins/metabolism , Vena Cava, Inferior/immunology , Venous Thrombosis/genetics , Venous Thrombosis/immunology
10.
Clin Microbiol Infect ; 24(1): 83.e1-83.e6, 2018 Jan.
Article in English | MEDLINE | ID: mdl-28559002

ABSTRACT

OBJECTIVES: Prosthetic joint infections (PJI) are responsible for significant morbidity and mortality and their number continues to rise. Their management remains complex, especially the microbiological diagnosis. Besides 'homemade' tests developed by several teams, new molecular biology methods are now available with different analytical performance and usability. METHODS: We studied the performances of one of these tests: ITI® multiplex PCR (mPCR) by the Curetis® company and compared it to either 'optimized' culture or 16S rRNA PCR. We performed a retrospective multicentre study to assess the contributions of mPCR in the diagnosis of PJI. We randomly selected 484 intraoperative specimens among 1252 of various types (biopsy, bone, tissue around the prosthesis, synovial fluid) from 251 patients in seven different hospitals. Each sample was treated according to the recommendations of the manufacturer. RESULTS: In all, 154 out of 164 (93.9%) samples negative in culture were negative with the mPCR. Among the 276 positive samples in culture, 251 (90.9%) were monomicrobial, of which 119 (47.4%) were positive with the mPCR, and 25 (9.1%) were polymicrobial, of which 12 (48%) were positive with the mPCR. The concordance rate of mPCR with culture was 58.1% (53.6%-62.7%) and the concordance rate with 16S rRNA PCR was 70.1% (65.5%-74.6%). CONCLUSION: This new standardized molecular test showed a lack of detection when the bacterial inoculum was low (number of positive media per sample and number of colonies per media) but can be useful when patients have received antibiotic therapy previously.


Subject(s)
Joint Prosthesis/microbiology , Methicillin-Resistant Staphylococcus aureus/genetics , Multiplex Polymerase Chain Reaction/methods , Prosthesis-Related Infections/diagnosis , Prosthesis-Related Infections/microbiology , Staphylococcal Infections/diagnosis , Bacterial Proteins/genetics , Humans , Methicillin Resistance/genetics , Methicillin-Resistant Staphylococcus aureus/isolation & purification , Penicillin-Binding Proteins/genetics , Prosthesis-Related Infections/mortality , RNA, Ribosomal, 16S/genetics , Retrospective Studies , Staphylococcal Infections/microbiology
14.
Bone Marrow Transplant ; 51(8): 1082-6, 2016 08.
Article in English | MEDLINE | ID: mdl-27042835

ABSTRACT

Breast cancer carrying BRCA mutation may be highly sensitive to DNA-damaging agents. We hypothesized a better outcome for BRCA-mutated (BRCA(mut)) metastatic breast cancer (MBC) patients receiving high-dose chemotherapy and autologous hematopoietic stem cell transplantation (HDC AHSCT) versus unaffected BRCA (BRCA wild type; (BRCA(wt))) or patients without documented BRCA mutation (BRCA untested (BRCA(ut))). All female patients treated for MBC with AHSCT at Institut Paoli-Calmettes between 2003 and 2012 were included. BRCA(mut) and BRCA(wt) patients were identified from our institutional genetic database. Overall survival (OS) was the primary end point. A total of 235 patients were included. In all, 15 patients were BRCA(mut), 62 BRCA(wt) and 149 BRCA(ut). In multivariate analyses, the BRCA(mut) status was an independent prognostic factor for OS (hazard ratio (HR): 3.08, 95% confidence interval (CI): 1.10-8.64, P=0.0326) and PFS (HR: 2.52, 95% CI :1.29-4.91, P=0.0069). In this large series of MBC receiving HDC AHSCT, we report a highly favorable survival outcome in the subset of patients with documented germline BRCA mutations.


Subject(s)
BRCA1 Protein/genetics , BRCA2 Protein/genetics , Breast Neoplasms/mortality , Breast Neoplasms/therapy , Adult , Antineoplastic Agents/administration & dosage , Breast Neoplasms/genetics , Breast Neoplasms/pathology , Combined Modality Therapy , Female , Hematopoietic Stem Cell Transplantation/methods , Hematopoietic Stem Cell Transplantation/mortality , Humans , Mutation , Neoplasm Metastasis , Retrospective Studies , Survival Analysis , Treatment Outcome
16.
J Thromb Haemost ; 13(12): 2260-72, 2015 Dec.
Article in English | MEDLINE | ID: mdl-26414399

ABSTRACT

BACKGROUND: Growth arrest-specific 6 (Gas6)-deficient mice are protected against venous thromboembolism (VTE), suggesting a role for Gas6 in this disorder. We previously demonstrated that Gas6 induces forkhead box O1 (FoxO-1) phosphorylation through the phosphoinositide 3-kinase-Akt pathway. FoxO-1 regulates the expression of vascular cell adhesion molecule-1 (VCAM-1), a molecule that has been implicated in VTE. OBJECTIVES: To assess the role of FoxO-1 in Gas6-dependent VCAM-1 expression. METHODS: Thrombin was used to stimulate endothelial cells (ECs). Wild-type (WT) and Gas6(-/-) ECs were transfected with small interfering RNA targeting Axl or FoxO-1, a luciferase-coupled plasmid containing the FoxO-1 consensus sequence, and a phosphorylation-resistant FoxO-1 mutant, or treated with an Akt inhibitor. VCAM-1 mRNA expression was measured by real time-qPCR. VCAM-1 protein expression and FoxO-1 and Akt phosphorylation were assessed by western blot analysis. FoxO-1 localization was assessed by immunofluorescence. Adhesion of bone marrow mononuclear cells (BM-MCs) on ECs was assessed by fluorescence. RESULTS AND CONCLUSIONS: Thrombin induces both VCAM-1 expression and FoxO-1 phosphorylation and nuclear exclusion in WT ECs only. Silencing of FoxO-1 enhances VCAM-1 expression in both WT and Gas6(-/-) ECs. Inhibition of Akt or FoxO-1 phosphorylation prevents VCAM-1 expression in WT ECs. These data show that Gas6 induces FoxO-1 phosphorylation, leading to derepression of VCAM-1 expression. BM-MC-EC adhesion is increased by thrombin in WT ECs. BM-MC-EC adhesion is further increased when FoxO-1 is silenced, but decreased when FoxO-1 phosphorylation is inhibited. These results demonstrate that the Gas6-FoxO-1 signaling axis plays an important role in VCAM-1 expression in the context of VTE by promoting BM-MC-EC adhesion.


Subject(s)
Endothelial Cells/drug effects , Forkhead Transcription Factors/metabolism , Intercellular Signaling Peptides and Proteins/metabolism , Thrombin/pharmacology , Vascular Cell Adhesion Molecule-1/metabolism , Animals , Bone Marrow Cells/metabolism , Cell Adhesion , Cells, Cultured , Endothelial Cells/metabolism , Forkhead Box Protein O1 , Forkhead Transcription Factors/genetics , Gene Expression Regulation , Genotype , Intercellular Signaling Peptides and Proteins/deficiency , Intercellular Signaling Peptides and Proteins/genetics , Male , Mice, Inbred C57BL , Mice, Knockout , Mutation , Phenotype , Phosphorylation , Protein Kinase Inhibitors/pharmacology , Proto-Oncogene Proteins c-akt/antagonists & inhibitors , Proto-Oncogene Proteins c-akt/metabolism , RNA Interference , Signal Transduction , Time Factors , Transfection , Vascular Cell Adhesion Molecule-1/genetics , Venous Thromboembolism/genetics , Venous Thromboembolism/metabolism
18.
Int J Infect Dis ; 29: 166-8, 2014 Dec.
Article in English | MEDLINE | ID: mdl-25449252

ABSTRACT

We report the case of a 43-year-old man with a Mycoplasma hominis brain abscess occurring after a cranial trauma, which was identified by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS). The presence of colonies on classic blood agar plates and the use of MALDI-TOF MS, a valuable diagnostic tool that identified M. hominis due to its presence in the VITEK MS database, allowed the rapid diagnosis of this infection.


Subject(s)
Brain Abscess/diagnosis , Mycoplasma Infections/diagnosis , Mycoplasma hominis , Adult , Humans , Male , Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
19.
Pathol Biol (Paris) ; 62(4): 218-20, 2014 Aug.
Article in English | MEDLINE | ID: mdl-24996845

ABSTRACT

In the attempt to harmonize clinical practices between different French transplantation centers, the French Society of Bone Marrow Transplantation and Cell Therapies (SFGM-TC) set up its fourth annual series of workshops which brought together practitioners from all of its member centers. These workshops took place in September 2013 in Lille. Literature and intra-laboratories studies suggest that attached segment is representative of cord blood unit (CBU). Nevertheless, some discrepancies have been observed when analyzing large data registries. To address these issues, we have listed recommendations to increase the standardization of segment processing and quality control (QC), information on units of measurement and specifications and action to be taken in case of out of specifications QC results on segment.


Subject(s)
Cord Blood Stem Cell Transplantation/standards , Fetal Blood , Blood Preservation/methods , Blood Preservation/standards , Cryopreservation/methods , Cryopreservation/standards , France , Histocompatibility Testing , Humans , Quality Control , Stem Cells
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