Reactivation of Epstein-Barr virus among intensive care patients: a prospective observational study.

PURPOSE: Herpesvirus reactivation has been documented among patients in the intensive care unit (ICU) and is associated with increased morbidity and mortality, particularly for cytomegalovirus (CMV). Epstein-Barr virus (EBV) has been poorly studied despite >95% of the population being seropositive. Our preliminary study suggested an association between EBV reactivation and increased morbidity and mortality. This study aimed to investigate this association among patients admitted to the ICU. METHODS: In this multicenter prospective study, polymerase chain reaction was performed to quantify EBV in patients upon ICU admission and then twice a week during their stay. Follow-up was 90 days. RESULTS: The study included 129 patients; 70 (54.3%) had EBV reactivation. On day 90, there was no difference in mortality rates between patients with and without reactivation (25.7% vs 15.3%, p = 0.22). Patients with EBV reactivation at admission had increased mortality compared with those without reactivation and those with later reactivation. EBV reactivation was associated with increased morbidity. Patients with EBV reactivation had fewer ventilator-free days at day 28 than those without reactivation (18 [1-22] vs. 21 days [5-26], p = 0.037) and a higher incidence of acute respiratory distress syndrome (34.3% vs. 17%, p = 0.04), infections (92.9% vs. 78%, p = 0.03), and septic shock (58.6% vs. 32.2%, p = 0.004). More patients with EBV reactivation required renal replacement therapy (30% vs. 11.9%, p = 0.02). EBV reactivation was also associated with a more inflammatory immune profile. CONCLUSION: While EBV reactivation was not associated with increased 90-day mortality, it was associated with significantly increased morbidity.

Effective use of intensive treatment against multiple myeloma of recipient origin after allogeneic transplantation for acute myeloid leukemia.

We describe here a 56-years -old woman cured in our institution for an acute myeloid leukemia (AML) and a monoclonal gammopathy of undetermined significance (MGUS). In order to treat AML, underwent allogeneic stem cell transplantation in second complete remission. Four years after transplant, MGUS evolved to multiple myeloma and was intensively treated with "autologous" transplant after successful mobilization. This report illustrates: (i) a lack of efficacy of graft versus myeloma effect in a patient probably cured of AML by graft versus leukaemia effect; (ii) the ability to mobilize peripheral blood stem cells in order to perform "autologous" transplantation after allogeneic transplantation.

Evaluation of hemostatic capacities among commando candidates: Would their blood suit a hemorrhagic war-injured patient in case of blood donation on the battlefield?

BACKGROUND: In case of a warm fresh whole blood transfusion on the battlefield, the blood donation usually occurs just after a combat phase and often after several days on the fields. To explore the hemostatic capacity of such blood, we analyzed the blood of volunteers attending the commando course of the French Navy, considering this course as an experimental model, placing them into the same physiological conditions as those faced by deployed fighters. METHODS: Venous blood was collected at the beginning of the course, mimicking their baseline status, and a second time 6 weeks later, from the remaining candidates, during the actual commando training, mimicking the stress conditions. For each candidate, we observed the differences between the two blood samples. RESULTS: Of the 112 men that attended the first day of the course, only 17 remained 6 weeks later. In the second blood samples, we noted significant increased leucocytes and platelets counts and significant decreased hematocrit and hemoglobin levels. Thrombin generation assays showed significantly lower normalized peak heights (-31%), lower normalized endogenous thrombin potential values (-29%), and lower velocity index (-35%). Normalized lag time and time to peak did not differ. Viscoelastometric testing revealed a significant increasing in clot firmness as assessed by maximum amplitude and amplitude at 6 minutes. The clot speed was significantly increased. CONCLUSION: This work brings new data on coagulation during prolonged and considerable physical exercise. No obvious deleterious modification of hemostatic properties was observed. The decrease of the endogenous thrombin potentials may reflect a better ability to control the thrombin generation once started. Altogether, these results suggest that this blood could suit well a hemorrhagic war-injured patient. LEVEL OF EVIDENCE: Prospective observational cohort study, Level III.

Direct oral anticoagulant plasma level measurement in clinical practice: A French single-institution retrospective study.

INTRODUCTION: To describe patient characteristics and clinical situations where DOAC assays were ordered and determine whether the assays indications and subsequent patient management were consistent with current guidelines. METHODS: Retrospective study of data from patients with prescriptions for three DOACs: dabigatran, rivaroxaban and apixaban treated at Percy Military Hospital (France) between 2016 and 2019. RESULTS: During the study period, 196 DOAC measurements were performed on 148 patients (median age: 82.5 years). The most frequently prescribed DOAC was rivaroxaban (57.5%) and the commonest indication was nonvalvular atrial fibrillation (77%). Measurements were performed on 3.5% of patients with an active prescription for DOAC, and DOAC prescriptions complied with the product's characteristic summary in 62.8% of cases. The number of assays performed increased 2.5-fold between 2017 and 2019. Most DOAC assays were ordered due to emergency surgery or procedures (46.9%), bleeding (19.9%) or a risk of drug accumulation (13.8%). Time from the last DOAC dose to sample collection was specified in the medical file in only 25.5% of cases. Reasons for ordering DOAC measurements were consistent with the guidelines in 87.2% of cases. Subsequent clinical decisions were consistent with the guidelines in 86.2% of cases. CONCLUSIONS: DOAC assays ordering frequency was rare but increased during study. Acute clinical situations were the most common source of test orders. A correct interpretation of the results and subsequent management occurred in most but not all cases, indicating the need for additional education for physicians to raise awareness about tests indications and results interpretation.

[Acute myeloid leukemia with t(8;21): unusual cytological presentation and immunophenotype]. / Leucémie aiguë myéloïde à t(8;21) : présentation cytologique et immunophénotype inhabituels.

We report the case of a 20 years old woman with unusual acute myeloid leukemia t(8;21). Cytological, phenotypic and cytogenetic investigations showed a divergence from those of the literature as well as data for the last 12 LA to t(8;21) supported in the service.

[Association between multiple myeloma and acute myeloid leukemia secondary to myelodysplastic syndrome]. / Association d'un myélome multiple et d'une leucémie aiguë myéloïde secondaire à un syndrome myélodysplasique.

We report a rare case of association of two distinct hematologic malignancies: refractory cytopenia with multilineage dysplasia associated with del(5q) and symptomatic multiple myeloma associated with del(17p) and del(13q). After 16 months, the patient presented an acute leukemic transformation of the myelodysplasic syndrome.

[Light-chain escape from plateau phase]. / Échappement des chaînes légères de la phase de plateau.

We report the first case of light-chain escape from plateau phase occurring after 7 years of evolution of multiple myeloma in a patient who had never received new molecules. A very good partial response was obtained.

[Signification of Epstein-Barr virus detection in the cerebrospinal fluid of a patient with human immunodeficiency virus related Burkitt lymphoma]. / Signification de la détection du virus d'Epstein-Barr dans le liquide céphalorachidien d'un patient suivi pour un lymphome de Burkitt lié au virus de l'immunodéficience humaine.

The significance of Epstein-Barr virus detection in the cerebrospinal fluid of patients with Burkitt lymphoma is poorly studied. We report the case of a patient with immunodeficiency associated Burkitt lymphoma in complete remission who presented 5 months after the end of treatment, an isolated optic neuritis. Lumbar puncture found lymphocytic meningitis and the viral load of Epstein-Barr virus was 234,000 copies per milliliter in the cerebrospinal fluid. These symptoms could be explained by Epstein-Barr virus meningoencephalitis but the detection of MYC rearrangements in the cerebrospinal fluid confirms the diagnosis of Burkitt lymphoma cerebral relapse. The detection of the Epstein-Barr virus DNA in the cerebrospinal fluid should be interpreted with caution.

[Plasmacytoïd dendritic cells acute leukemia: a case report]. / Leucémie aiguë dérivée des cellules dendritiques plasmacytoïdes : à propos d'un cas.

We describe a case of a patient hospitalized in haematology unit for treatment to blastic plasmacytoid dendritic cell neoplasm. Apart skin lesions found at diagnosis in 83% of patients, few elements suggest the diagnosis. Cytology is not characteristic and no cytogenetic abnormality is specific to the LpDC, the karyotype shows generally at least three cytogenetic abnormalities. Definitive diagnosis rests to identification of a blastic population with immunophenotype CD4+ CD56+. This leukemia is chemosensitive but the relapse rate is important and the survival time is 16 months.

Mechanisms of TRAIL-induced apoptosis in leukemic plasmacytoid dendritic cells.

OBJECTIVE: Dendritic cells play a central role in regulating the innate and adaptive immune responses. Plasmacytoid dendritic cells (PDC) represent a newly identified kind of DC with specialized functions aimed at fighting against viral infections. Recently, we have shown that CD4+CD56+ malignancies were leukemia arising from PDC, with a particularly aggressive clinical course. Hence, we asked whether these malignant PDC could be killed via TRAIL, a death-inducing ligand that belongs to a new class of anticancer drugs currently under development. MATERIALS AND METHODS: In this study we used a PDC line (GEN2.2) we recently developed from leukemic PDC as a model. RESULTS: We show that GEN2.2 PDC are sensitive to TRAIL-induced apoptosis and can be killed in vitro by TRAIL-expressing NK cells. Our results suggest that TRAIL binds to Death Receptor 5 (DR5) expressed by GEN2.2 and induces apoptosis mainly via caspases 10, 8, and 3. Interestingly, during infection with influenza, DR5 decreases on GEN2.2 cell surface, which consequently become resistant to TRAIL-induced apoptosis. Moreover, we confirmed the expression of DR5 or DR4 on half of LPDC tested, suggesting the possibility to kill these cells via TRAIL. Hopefully, normal PDC expressed neither DR4 nor DR5. CONCLUSION: These results suggest that TRAIL agonists represent a therapeutic alternative for the treatment of LPDC.