Altered dendritic cell distribution in patients with common variable immunodeficiency

Recent data suggest a critical role for dendritic cells (DCs) in the generation of immunoglobulin-secreting plasma cells. In the work reported herein, we analyzed the frequency of peripheral blood plasmacytoid DCs (pDCs) and myeloid DCs (mDCs) in a cohort of 44 adults with common variable immunodeficiency (CVID) classified according to their CD27 membrane expression status on B cells. A deep alteration in the distribution of DC subsets, especially of pDCs, in the peripheral blood of CVID patients was found. Patients with a reduced number of class-switched CD27(+)IgD(-)IgM(- )memory B cells and patients with granulomatous disease had a dramatic decrease in pDCs (P = 0.00005 and 0.0003 vs controls, respectively) and, to a lesser extent, of mDCs (P = 0.001 and 0.01 vs controls, respectively). In contrast, patients with normal numbers of switched memory B cells had a DC distribution pattern similar to that in controls. Taken together, our results raise the possibility that innate immunity contributes to pathogenesis in CVID

Is Tocilizumab Plus Dexamethasone Associated with Superinfection in Critically Ill COVID-19 Patients?

BACKGROUND: Dexamethasone and tocilizumab are used to treat severely ill COVID-19 patients admitted to intensive care units (ICUs). We explored whether combination therapy increased the risk of superinfection compared to dexamethasone alone. METHODS: This observational, retrospective study included critically ill COVID-19 adult patients admitted to our ICU because of respiratory failure. Patients received dexamethasone with (Group 1) or without (Group 2) tocilizumab. Data were collected from electronic medical files. RESULTS: A total of 246 patients were included, of whom 150 received dexamethasone and tocilizumab, while 96 received dexamethasone alone. Acute respiratory distress syndrome was evident on admission in 226 patients, 56 of whom required mechanical ventilation (MV). Superinfections, mainly respiratory, were diagnosed in 59 patients, including 34/150 (23%) in Group 1 and 25/96 (26%) in Group 2 (p = 0.32). After multivariate analysis, the factors associated with a higher risk of superinfection included hematological malignancy (hazard ratio (HR): 2.47 (1.11-5.47), p = 0.03), MV (HR: 3.74 (1.92-7.26), p = 0.0001), and a higher SAPS-II score on admission (HR: 1.03 (1.01-1.06), p = 0.006). CONCLUSION: In critically ill COVID-19 patients, the addition of tocilizumab to dexamethasone was not associated with an increased risk of superinfection

A prospective, observational study of fidaxomicin use for Clostridioides difficile infection in France.

To describe the characteristics, management and outcomes of hospitalised patients with Clostridioides difficile infection (CDI) treated with and without fidaxomicin. This prospective, multicentre, observational study (DAFNE) enrolled hospitalised patients with CDI, including 294 patients treated with fidaxomicin (outcomes recorded over a 3-month period) and 150 patients treated with other CDI therapies during three 1-month periods. The primary endpoint was baseline and CDI characteristics of fidaxomicin-treated patients. At baseline, the fidaxomicin-treated population included immunocompromised patients (39.1%) and patients with severe (59.2%) and recurrent (36.4%) CDI. Fidaxomicin was associated with a high rate of clinical cure (92.2%) and low CDI recurrence (16.3% within 3 months). Clinical cure rates were ≥90% in patients aged ≥65 years, those receiving concomitant antibiotics and those with prior or severe CDI. There were 121/296 (40.9%) patients with adverse events (AEs), 5.4% with fidaxomicin-related AEs and 1.0% with serious fidaxomicin-related AEs. No fidaxomicin-related deaths were reported. Fidaxomicin is an effective and well-tolerated CDI treatment in a real-world setting in France, which included patients at high risk of adverse outcomes.Trial registration: Description of the use of fidaxomicin in hospitalised patients with documented Clostridium difficile infection and the management of these patients (DAFNE), NCT02214771, www.ClinicalTrials.gov

Diagnostic Value of (18)F-Fluorodeoxyglucose Positron Emission Tomography Computed Tomography in Prosthetic Pulmonary Valve Infective Endocarditis

OBJECTIVES: The aim of this study was to assess the diagnostic performances of (18)F-fluorodeoxyglucose ((18)F-FDG) positron emission tomography (PET)/computed tomography (CT) in congenital heart disease (CHD) patients with pulmonary prosthetic valve or conduit endocarditis (PPVE) suspicion. BACKGROUND: PPVE is a major issue in the growing CHD population. Diagnosis is challenging, and usual imaging tools are not always efficient or validated in this specific population. Particularly, the diagnostic yield of (18)F-FDG PET/CT remains poorly studied in PPVE. METHODS: A retrospective multicenter study was conducted in 8 French tertiary centers. Children and adult CHD patients who underwent (18)F-FDG PET/CT in the setting of PPVE suspicion between January 2010 and May 2020 were included. The cases were initially classified as definite, possible, or rejected PPVE regarding the modified Duke criteria and finally by the Endocarditis Team consensus. The result of (18)F-FDG PET/CT had been compared with final diagnosis consensus used as gold-standard in our study. RESULTS: A total of 66 cases of PPVE suspicion involving 59 patients (median age 23 years, 73% men) were included. Sensitivity, specificity, positive predictive value, and negative predictive value of (18)F-FDG PET/CT in PPVE suspicion were respectively: 79.1% (95% CI: 68.4%-91.4%), 72.7% (95% CI: 60.4%-85.0%), 91.9% (95% CI: 79.6%-100.0%), and 47.1% (95% CI: 34.8%-59.4%). (18)F-FDG PET/CT findings would help to correctly reclassify 57% (4 of 7) of possible PPVE to definite PPVE. CONCLUSIONS: Using (18)F-FDG PET/CT improves the diagnostic accuracy of the Duke criteria in CHD patients with suspected PPVE. Its high positive predictive value could be helpful in routine to shorten diagnosis and treatment delays and improve clinical outcomes.L'Institut de Rythmologie et modélisation Cardiaqu

Characterization of acute kidney injury in critically ill patients with severe coronavirus disease 2019

Abstract Background Coronavirus disease 2019 (COVID-19)-associated acute kidney injury (AKI) frequency, severity and characterization in critically ill patients has not been reported. Methods Single-centre cohort performed from 3 March 2020 to 14 April 2020 in four intensive care units in Bordeaux University Hospital, France. All patients with COVID-19 and pulmonary severity criteria were included. AKI was defined using Kidney Disease: Improving Global Outcomes (KDIGO) criteria. A systematic urinary analysis was performed. The incidence, severity, clinical presentation, biological characterization (transient versus persistent AKI; proteinuria, haematuria and glycosuria) and short-term outcomes were evaluated. Results Seventy-one patients were included, with basal serum creatinine (SCr) of 69 ± 21 µmol/L. At admission, AKI was present in 8/71 (11%) patients. Median [interquartile range (IQR)] follow-up was 17 (12–23) days. AKI developed in a total of 57/71 (80%) patients, with 35% Stage 1, 35% Stage 2 and 30% Stage 3 AKI; 10/57 (18%) required renal replacement therapy (RRT). Transient AKI was present in only 4/55 (7%) patients and persistent AKI was observed in 51/55 (93%). Patients with persistent AKI developed a median (IQR) urine protein/creatinine of 82 (54–140) (mg/mmol) with an albuminuria/proteinuria ratio of 0.23 ± 20, indicating predominant tubulointerstitial injury. Only two (4%) patients had glycosuria. At Day 7 after onset of AKI, six (11%) patients remained dependent on RRT, nine (16%) had SCr >200 µmol/L and four (7%) had died. Day 7 and Day 14 renal recovery occurred in 28% and 52%, respectively. Conclusion Severe COVID-19-associated AKI is frequent, persistent, severe and characterized by an almost exclusive tubulointerstitial injury without glycosuria

Mycobactérioses non aviaires chez le patient non infecté par le VIH

BORDEAUX2-BU Santé (330632101) / SudocPARIS-BIUM (751062103) / SudocSudocFranceF

Evaluation de la Neutrophil Gelatinase-Associated Lipocalin (NGAL) plasmatique comme marqueur de l'insuffisance rénale aiguë au cours du choc septique en réanimation médicale adulte

L'objectif principal de l'étude NESAKI est de déterminer la capacité de la pNGAL à prédire l'IRA pour des patients de réanimation médicale adulte admis pour un choc septique. Les objectifs secondaires sont de déterminer si la pNGAL es prédictive du caractère organique de l'IRA ou d'une hémofiltration, et d'étudier le comportement de la pNGAL qur les 48 premières heures du choc septique. Il s'agit d'une étude prospective observationnelle, non randomisée et sans double aveugle incluant 50 patients majeurs consécutifs admis en réanimation médicale pour un choc septique, entre le 1er juillet 2009 et le 31 avril 2010. La NGAL plasmatique a été dosée à l'entrée du patient, à J1 et à J2. Les patients étaient classés en deux groupes : non-IRA ou IRA (score RIFLE et/ou AKIN au moins égal à R ou 1 respectivement). Le groupe IRA a été divisé en fonction du caratère organique ou fonctionnel de l'atteinte rénale. Les 43 (86 %) patients en IRA ont eu une pNGAL moyenne significativement supérieure aux 7 patients non-IRA (471 +- 271 vs 134 +- 95 ng/ml, p < 0,001). L'ASC-ROC de la pNGAL pour le diagnostic d'IRA es à 0.898 pour un seuil à 337 ng/ml. La valeur de la pNGAL est stable sur les 3 premiers jours du sepsis. Les patients en IRA organique ont une pNGAL significativement supérieure aux patients en IRA fonctionnelle dès J1 (570 +- 322 VS 337 +- 246 ng/ml). Les 17 patients (34 %) qui ont été hémofiltrés ont une pNGAL significativement supérieure aux autres (636 +- 261 VS 314 +- 288 ng/ml, p < 0.001). Le seuil à partir duquel il faut envisager une hémofiltration est 348 ng/ml avec une ASC à 0.8. La pNGAL et un bon biomarqueur de l'IRA pour les patients en choc septique, mais le seuil utilisé doit être supérieur à celui proposé par le laboratoire. La créatininémie reste la référence pour le diagnostic d'IRA. La pNGAL présit le caractère organique de l'IRA ainsi que le recours à l'hémofiltration.BORDEAUX2-BU Santé (330632101) / SudocSudocFranceF

Les infections de matériel de stimulation cardiaque (aspects diagnostiques, microbiologiques et thérapeutiques)

INTRODUCTION : Les infections de matériel de strimulation cardiaque (IMS) sont des complications non rares, mal définies et peu décrites. L'objectif de notre travail était la description précise clinique, paraclinique, microbiologique et thérapeutique d'une série d'IMS afin d'en optimiser la prise en charge. MATERIELS ET METHODES : 286 patients ont été rétrospectivement inclus dans notre série entre janvier 2005 et décembre 2008. Parmi 252 IMS documentées (88 %), près de 3/4 des souches de cocci à Gram positif conservées au laboratoire de bactériologie ont été retestées in vitro, avec, pour chaque souche, la mesure des concenttrations minimales inhibitrices de nombreux antibiotiques, dont les plus récents : le linézolide, la daptomycine, la tigécycline et la dalbavancine. RESULTATS ET DISCUSSION : Colmpte tenu des implications thérapeutiques, nous proposons une classification des IMS distinguant les "IMS locales" des "endocardites sur sonde" dont plus de 30 % seraient classées comme "endocardites rejetées" d'après les critères de Duke. Bien que non spécifiques, les signes locaux sont plus fréquents en cas d'IMS locale et la fièvre, lus fréquente en cas d'endocardite sur sonde. L'exrériorisation oriente vers une origine poly microbienne. La biologie de routine n'est pas informative. La voie trans-œsophagienne accroît la sensibilité de l'échocardiographie. La culture du matériel de stimulation et des sondes permet le diagnostic microbiologique dans plus de 75 % des cas. Parmi les IMS documentées, les staphylocoques, principalement à coagulase négative, sont responsables de 85 % des cas. Ils sont résistants à la méticilline dans 35,5 % des IMS précoces et 24 % des IMS tardives. Aucun consensus n'est disponible quant à l'antibiothérapie prophylactique ou probabiliste. Colmpte tenu des bons résultats in vitro, le linézolide, la daptomycine et la ligécycline sont des alternatives thérapeutiques à considérer. CONCLUSION : L'optimisation de la prise en charge des IMS nécessite une classification, simple et spécifique, en IMS locales et endocardites sur sonde. La place de la microbiologie dans cette classification est primordiale. Les nouveaux antibiotiques dans le traitement des IMS sont prometteurs, à valider par des études cliniques prospectives.BORDEAUX2-BU Santé (330632101) / SudocSudocFranceF

Intérêt du rituximab dans la maladie des agglutinines froides (à propos de cinq observations)

BORDEAUX2-BU Santé (330632101) / SudocPARIS-BIUM (751062103) / SudocSudocFranceF