In vitro evaluation of a new viscoelastometry-based point-of-care analyzer.

INTRODUCTION: The VCM is a point-of-care analyzer using a new viscoelastometry technique for rapid assessment of hemostasis on fresh whole blood. Its characteristics would make it suitable for use in austere environments. The purpose of this study was to evaluate the VCM in terms of repeatability, reproducibility and interanalyzer correlation, reference values in our population, correlation with standard coagulation assays and platelet count, correlation with the TEG5000 analyzer and resistance to stress conditions mimicking an austere environment. METHODS: Repeatability, reproducibility, and interanalyzer correlation were performed on quality control samples (n = 10). Reference values were determined from blood donor samples (n = 60). Correlations with standard biological assays were assessed from ICU patients (n = 30) and blood donors (n = 60) samples. Correlation with the TEG5000 was assessed from blood donor samples. Evaluation of vibration resistance was performed on blood donor (n = 5) and quality control (n = 5) samples. RESULTS: The CVs for repeatability and reproducibility ranged from 0% to 11%. Interanalyzer correlation found correlation coefficients (r2) ranging from 0.927 to 0.997. Our reference values were consistent with those provided by the manufacturer. No robust correlation was found with conventional coagulation tests. The correlation with the TEG5000 was excellent with r2 ranging from 0.75 to 0.92. Resistance to stress conditions was excellent. CONCLUSION: The VCM analyzer is a reliable, easy-to-use instrument that correlates well with the TEG5000. Despite some logistical constraints, the results suggest that it can be used in austere environments. Further studies are required before its implementation.

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.

Performances, feasibility and acceptability of nasopharyngeal swab, saliva and oral-self sampling swab for the detection of severe acute respiratory syndrome coronavirus 2.

Molecular diagnosis on nasopharyngeal swabs (NPS) is the current standard for COVID-19 diagnosis, but saliva may be an alternative specimen to facilitate access to diagnosis. We compared analytic performances, feasibility and acceptability of NPS, saliva, and oral-self sampling swab for the detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). A prospective, multicenter study was conducted in military hospitals in France among adult outpatients attending COVID-19 diagnosis centers or hospitalized patients. For each patient, all samples were obtained and analyzed simultaneously with RT-PCR or transcription-mediated amplification method. Clinical signs, feasibility, and acceptability for each type of sample were collected. A total of 1220 patients were included, corresponding to 1205 NPS and saliva and 771 OS. Compared to NPS, the sensitivity, specificity, and kappa coefficient for tests performed on saliva were 87.8% (95% CI 83.3-92.3), 97.1% (95% CI 96.1-98.1), and 0.84 (95% CI 0.80-0.88). Analytical performances were better in symptomatic patients. Ct values were significantly lower in NPS than saliva. For OS, sensitivity was estimated to be 61.1% (95% CI 52.7-69.4) and Kappa coefficient to be 0.69 (95% CI 0.62-0.76). OS was the technique preferred by the patients (44.3%) before saliva (42.4%) and NPS (13.4%). Instructions were perceived as simple by patients (> 90%) for saliva and OS. Finally, the painful nature was estimated to be 0.9 for OS, on a scale from 0 to 10, and to be 5.3 for NPS. Performances of OS are not sufficient. Saliva is an acceptable alternative to NPS for symptomatic patient but the process required additional steps to fluidize the sample.

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.

Evaluation of the Quotient® MosaiQ™ COVID-19 antibody microarray for the detection of IgG and IgM antibodies to SARS-CoV-2 virus in humans.

The MosaiQ® COVID-19 Antibody test fulfills the minimal requirements for serological testing according to the French regulation.

Activated Clotting Time Monitoring during Atrial Fibrillation Catheter Ablation: Does the Anticoagulant Matter?

Atrial fibrillation (AF) catheter ablation is performed in patients receiving direct oral anticoagulants (DOACs) with intra-procedural unfractionated heparin (UFH) administration to achieve activated clotting time (ACT) at 300 s, as for vitamin K antagonist (VKA). We determined whether ACT monitoring might be transposed from VKA to DOAC-treated patients. Blood was taken from 124 patients receiving uninterrupted dabigatran, rivaroxaban, apixaban, or VKA or being untreated. DOAC concentration or INR (VKA) were measured. ACT was determined at baseline, and after spiking with UFH doses equivalent to 1000, 2500, 5000 and 10000 IU in vivo. At baseline, anticoagulants prolonged ACT differently, ACT was longer with dabigatran and shorter with apixaban despite similar concentrations. ACT strongly correlated with INR and dabigatran concentration, but not with apixaban or rivaroxaban concentrations. Moreover, UFH effects on ACT prolongation depended on the anticoagulant: dose-response curves in samples with VKA and dabigatran were parallel whereas ACT prolongation in response to UFH was significantly smaller with rivaroxaban and especially apixaban. Therefore, UFH to achieve ACT at 300 s might be transposed from VKA to uninterrupted dabigatran-treated patients but not to patients receiving FXa-inhibitors, especially apixaban. Targeting 300 s might expose to UFH overdosing and bleeding, questioning the current anticoagulation strategy.

Evaluation of Systematic Blood Testing at the Time of Recruitment to the Armed Forces: Retrospective Monocentric Study Among 726 French Army Soldiers.

INTRODUCTION: In the French armed forces, the biological checkup required during the recruitment process comprises a urinalysis (urinary dipstick), a complete blood count (CBC), and measurement of serum levels of aspartate aminotransferase, alanine aminotransferase, fasting blood glucose, and creatinine. This study aimed to evaluate the benefits of this biological checkup and to determine the most relevant parameters. MATERIALS AND METHODS: We conducted a monocentric retrospective study of all standardized and systematically conducted blood tests (CBC and measurement of aspartate aminotransferase, alanine aminotransferase, fasting blood glucose, and creatinine) over a 15-month period among 726 French Army recruits. RESULTS: The population included mainly young males (85.4%, mean age 21.6 years). More than half (54.1%) of the blood tests had at least one abnormal parameter, most often concerning the CBC. Anemia occurred in 5.3% of the population and was mostly normocytic. Microcytosis was mostly not associated with anemia (72.3% of cases). Lymphopenia occurred in 20.1% of the population and was mostly mild. Eosinophilia was present in 5.1% of the population and was never severe. Thrombocytopenia occurred in 0.7% of the population and was never severe. Serum levels of aminotransferases were elevated in 8.1% of the population. Fasting plasma glucose averaged 84 mg/dL (SD: 0.07) ranging from 64 to 123 mg/dL, was abnormal in 0.4% of the population, and one case of diabetes was diagnosed. Serum creatinine concentration was elevated in 0.7% of the population. CONCLUSION: CBCs gave useful information but iron deficiency was common and insufficiently detected by this single analysis. Assessing aminotransferase levels without screening for viral hepatitis and systematic measurement of fasting plasma glucose levels did not appear to be efficient. In addition, the only interest in systematic measurement of creatinine serum levels was to obtain a reference level for long-term follow-up. In addition to the urinary dipstick, the systematic biological checkup at recruitment could be limited to a CBC with measurement of plasma ferritin levels and Hepatitis B virus serology, providing that any CBC abnormalities, in particular cytopenia, eosinophilia, and microcytosis, are systematically investigated. For a public health approach, systematic screening for other sexually transmitted infections could be proposed.

Occupational Exposures to Ebola Virus in Ebola Treatment Center, Conakry, Guinea.

We report 77 cases of occupational exposures for 57 healthcare workers at the Ebola Treatment Center in Conakry, Guinea, during the Ebola virus disease outbreak in 2014-2015. Despite the high incidence of 3.5 occupational exposures/healthcare worker/year, only 18% of workers were at high risk for transmission, and no infections occurred.

Decontamination of a field laboratory dedicated to Ebola virus-infected patients.

In 2015, the French Armed Forces deployed a biosafety level 3 (BSL3) field laboratory as a part of an Ebola treatment center in Guinea. When closing the center, laboratory decontamination operations were necessary. We present the decontamination protocols applied for the BSL3 field laboratory, making the entire module ready for a future use.

Ebola Virus RNA Stability in Human Blood and Urine in West Africa's Environmental Conditions.

We evaluated RNA stability of Ebola virus in EDTA blood and urine samples collected from infected patients and stored in West Africa's environmental conditions. In blood, RNA was stable for at least 18 days when initial cycle threshold values were <30, but in urine, RNA degradation occurred more quickly.

Rhabdomyolysis in Ebola Virus Disease. Results of an Observational Study in a Treatment Center in Guinea.

BACKGROUND: The pathogenesis of Ebola virus disease (EVD) remains unclear. The sporadic nature of Ebola outbreaks and their occurrence in resource-limited settings have precluded the acquisition of extensive clinical and laboratory data. Rhabdomyolysis during EVD has been suggested to occur in previous studies showing increased aspartate aminotransferase-alanine aminotransferase ratios, but, to date, has not been confirmed with creatine kinase (CK) assays. METHODS: We performed an observational study of 38 patients admitted to an Ebola treatment center from January to April 2015. CK values from patients with confirmed EVD were compared with those in patients without confirmed EVD. A panel of other analyses were also performed. In patients with EVD, characteristics were compared between survivors and nonsurvivors. RESULTS: High levels of CK were more frequent in patients with EVD than in those without (P = .002), and rhabdomyolysis was more frequent (59% vs 19%, respectively; P = .03). CK levels >5000 U/L were observed in 36% of patients with EVD. Also in patients with EVD, fatal outcome was significantly associated with higher creatinine and bilirubin levels, international normalized ratio, and viral load. CONCLUSIONS: Rhabdomyolysis is a frequent disorder in EVD and seems to be more common than in other viral infections. It may contribute to the renal failure observed in nonsurviving patients. More studies are needed to determine the impact of rhabdomyolysis on EVD outcome.

Moderate Thermal Strain in Healthcare Workers Wearing Personal Protective Equipment During Treatment and Care Activities in the Context of the 2014 Ebola Virus Disease Outbreak.

The extent of thermal strain while wearing personal protective equipment (PPE) during care activities for Ebola virus disease patients has not yet been characterized. From January to March 2015, 25 French healthcare workers (HCWs) in Conakry, Guinea, volunteered to be monitored while wearing PPE using an ingestible thermal sensor. The mean (standard deviation) working ambient temperature and relative humidity were 29.6 °C (2.0 °C) and 65.4% (10.3%), respectively; the mean time wearing PPE was 65.7 (13.5) minutes; and the mean core body temperature increased by 0.46 °C (0.20 °C). Four HCWs reached or exceeded a mean core body temperature of ≥ 38.5 °C. HCWs wearing PPE for approximately 1 hour exhibited moderate but safe thermal strain.