COVID-19 Repeated Convalescent Plasma Collection: Analysis of 149 Donations from 88 French Military Health Workers.

BACKGROUND: Passive therapy with convalescent plasma (CP) could be an effective and safe treatment option in COVID-19 patients. Neutralizing antibodies present in CP generated in response to SARS-CoV-2 infection and directed against the receptor-binding domain of the spike protein are considered to play a major role in the viral clearance. CP infusion may also contribute to the modulation of the immune response through its immunomodulatory effect. We describe for the first time the effectiveness of a CP collection protocol from repeated donations in young patients. MATERIALS AND METHODS: We enrolled health service workers who experienced mild to moderate COVID-19 and from whom several donations have been collected. No minimal severity threshold and no biological cure criteria were required. Donors could return to a second plasma donation 14 days after the first donation. A minimal neutralizing antibody titer of 1:40 was considered for clinical use. RESULTS: Eighty-eight donors were included (median age 35 [28-48] years, 41 women), and 149 plasma products were collected. COVID-19 were mainly WHO stage 2 infections (96%). Among the 88 first donations, 76% had neutralizing antibody titers higher than or equal to 1:40. Eighty-eight percent of donors who came for a second donation had a neutralizing antibody titer of 1:40. Median durations were 15 (15-19) and 38 (33-46) days from the first to the second donation and from recovery to the second donation, respectively. Sixty-nine percent of donors who came for a third donation had a neutralizing antibody titer of 1:40. Median durations were 16 (13-37) and 54 (49-61) days from the second to the third donation and from recovery to the third donation, respectively. No significant difference was observed between the IgG ratio and the age of the donors or the time between recovery and donation. The average IgG ratio did not significantly vary between donations. When focused on repeated blood donors, no significant differences were observed either. CONCLUSION: The recruitment of young patients with a mild to moderate CO-VID-19 course is an efficient possibility to collect CP with a satisfactory level of neutralizing antibodies. Repeated donations are a well-tolerated and effective way of CP collection.

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.

Effect of Preconditioned Mesenchymal Stromal Cells on Early Microvascular Disturbance in a Mouse Sepsis Model.

Septic patients often die in a context of multiple organ dysfunction syndrome (MODS), despite the macro-hemodynamic parameters being normalized and after the onset of antibiotic therapy. Microcirculation injury during sepsis affects capillary permeability and leukocyte-endothelium interactions and is thought to be instrumental in organ injury. Several studies have demonstrated a beneficial effect of mesenchymal stromal cells (MSCs) injection on survival and organ dysfunctions in sepsis models. In vivo activity of MSCs also appears to be very much dependent on the information provided before injection. Indeed preconditioning by interferon γ (IFNγ; MSC-IFNγ) increases immunosuppressive capacity of MSCs in vitro and in vivo. Therefore, the objective was to evaluate the effect of MSC naive or IFNγ preconditioned on leukocyte-endothelium interactions in a polymicrobial sepsis model by intraperitoneal feces injection. Six hours (H6) after this induction, we used intravital microscopy in mice cremaster muscle venules to study the flow behavior of leukocytes. Plasmas were harvested to evaluate inflammation level and endothelial activation. We showed that MSC-IFNγ have a beneficial effect on microcirculation, by increasing the flow of white blood cells (WBCs) and the percentage of venules containing flowing WBCs, by significantly reducing the adhesion of WBCs and by increasing the average red blood cell velocity (VRBC). In conclusion, our results suggest that intravenous injection of preconditioned MSC-IFNγ improves microvascular hemodynamics in early phases of sepsis.

Clinical Features of Mycobacterium canettii Infection: A Retrospective Study of 20 Cases Among French Soldiers and Relatives.

BACKGROUND: Mycobacterium canettii forms part of the Mycobacterium tuberculosis complex. Mycobacterium canettii infections are mainly described in the Horn of Africa. The permanent presence of French soldiers in Djibouti raises the question of the risk of being infected with M. canettii. Here, we describe M. canettii infections among French military and their families between 1998 and 2015. METHODS: This retrospective study relied on 3 sources of data: the reference center for mycobacteria in the Biology Department at Percy Military Hospital in Paris, the French Military Center for Epidemiology and Public Health, and the scientific literature. After an exhaustive census of the strains, we studied the epidemiological data on 20 cases among French soldiers and their families. RESULTS: Twenty cases of M. canettii infections are reported, including 5 unpublished cases. Adenitis predominates (n = 15), especially in the cervico facial area and among children; 1 case was observed 1 month after dental care in Djibouti. The pulmonary forms were less frequent (n = 6), and 3 atypical forms are described. All patients had stayed in Djibouti. CONCLUSIONS: Cases of M. canettii infection among the French military consisted mainly of adenitis; disseminated forms were possible with immunodeficiency. Their evolution under specific treatments was comparable to that of tuberculosis. The presumed origin of the infection seemed to be environmental, possibly a water reservoir, and not due to human-to-human contagion.

Input of a Multi-Disciplinary Meeting in the Treatment of Osteoarticular Infections in French War Casualties.

INTRODUCTION: Extremity war-wounds present an elevated risk of infection and compromise reconstructive procedures. In a French military hospital, a multi-disciplinary meeting (MDM) was created to standardize the care given to soldiers with osteoarticular infection. The aim of this study was to evaluate the usefulness of MDM decisions. METHODS: An observational case study was performed including the French wounded at war treated for an osteoarticular infection between 2004 and 2016. They were separated into two groups according to their time of management: before (group A) or after (group B) the MDM creation in September 2010. Various operative and bacteriological parameters were analyzed retrospectively. A questionnaire was created to evaluate healthcare professionals' satisfaction toward the usefulness of the MDM on their practice. RESULTS: During the study period, 38 patients were included: 19 in group A and 19 in group B. Initial tests found an infection with one pathogen in 15 patients, an infection with 2 pathogens in 11 patients, and an infection with 3 or more pathogens in 12 patients. Enterobacter cloacae was the most common pathogen. Pseudomonas aeruginosa and Escherichia coli were also frequent. The mean number of samples taken to conduct the bacteriological tests per operating session was significantly higher for group B than for group A. Twelve of the 14 questioned healthcare professionals believed the MDM was very useful in their patient management. CONCLUSION: The MDM seems to have had a beneficial impact on orthopedic surgeon practices. A significant increase of the number of samples taken was the most obvious sign that the French recommended practices for osteoarticular infections were followed since the creation of MDM.

Mesenchymal Stromal Cells Based Therapy in Systemic Sclerosis: Rational and Challenges.

Systemic Sclerosis (SSc) is a rare chronic disease, related to autoimmune connective tissue diseases such as Systemic Lupus Erythematosus and Sjögren's Syndrome. Although its clinical heterogeneity, main features of the disease are: extensive tissue fibrosis with increase matrix deposition in skin and internal organ, microvascular alterations and activation of the immune system with autoantibodies against various cellular antigens. In the diffuse cutaneous scleroderma subtype, the disease is rapidly progressive with a poor prognosis, leading to failure of almost any internal organ, especially lung which is the leading cause of death. Primary trigger is unknown but may involve an immune process against mesenchymal cells in a genetically receptive host. Pathophysiology reveals a pivotal role of fibrosis and inflammation alterations implicating different cell subtypes, cytokines and growth factors, autoantibodies and reactive oxygen species. Despite improvement, the overall survival of SSc patients is still lower than that of other inflammatory diseases. Recommended drugs are agents capable of modulating fibrotic and inflammatory pathways. Cellular therapy has recently emerged as a credible option. Besides autologous hematopoietic stem cell transplantation which demonstrated remarkable improvement, mesenchymal stromal cells (MSCs) represent promising therapeutic candidates. Indeed, these cells possess anti-inflammatory, antiproliferative, antifibrotic, and immunomodulary properties especially by secreting a large panel of bioactive molecules, addressing the most important key points of the SSc. In addition, these cells are very sensitive to their environment and are able to modulate their activity according to the pathophysiological context in which they are located. Autologous or allogeneic MSCs from various sources have been tested in many trials in different auto-immune diseases such as multiple sclerosis, Crohn's disease or systemic lupus erythematosus. They are characterized by a broad availability and no or low acute toxicity. However, few randomized prospective clinical trials were published and their production under ATMP regulatory procedures is complex and time-consuming. Many aspects have still to be addressed to ascertain their potential as well as the potential of their derived products in the management of SSc, probably in association with other therapies.

Uterine intravascular lymphoma as a cause of fever of unknown origin.

Primary intravascular large B cell lymphoma (IVL) remains a diagnostic challenge because of non-specific clinical, laboratory and imaging findings. The aim of the study was to analyse the major characteristics of IVL with uterine involvement. We retrospectively collected features of IVL with uterine involvement that was proven histologically or demonstrated by significant 18FDG uptake on 18FDG-PET/CT. Findings were compared to a comprehensive literature review. Five patients were identified. All of them were admitted for fever of unknown origin (FUO), with haemophagocytic lymphohistiocytosis in three cases. None had gynaecological symptom, contrasting with the literature data. Structural imaging (including whole-body CT scan and pelvic RMI) failed to yield any diagnosis. 18FDG-PET/CT showed intense uterine uptake in all cases. Endometrial biopsy was performed in three cases and was positive in one. Diagnosis was obtained from coelioscopic iliac adenopathy biopsy in one case and from total hysterectomy in another. Punch biopsy of skin lesions led to diagnosis in the two remaining cases. Bone marrow biopsy was normal in all cases. Clinicians should be aware of potential isolated uterine involvement in IVL, especially in elderly women with FUO. Normal structural imaging does not rule out the diagnosis and 18FDG-TEP/CT should be performed to guide high-yielding biopsy.

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.

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.

[Respiratory manifestations of giant cell arteritis: 8 cases and review of the literature]. / Atteinte respiratoire de la maladie de Horton: 8 observations et revue de la littérature.

BACKGROUND: Pleural and pulmonary manifestations of giant cell arteritis are rare and not well known. They can be associated to more typical signs of the disease and to an inflammatory biological syndrome which are comprised in the multisystemic manifestations of the disease. They can be inaugural, leading to a late management if unrecognized. METHODS: Retrospective and descriptive study of 8 cases over a 10 year period was conducted. Five females and three males with a 67-year-old average age were included according to the American College of Rheumatology criteria. They illustrated the clinical and/or radiological respiratory manifestations of the disease. RESULTS: Pulmonary manifestation was inaugural in six cases over eight. The time to diagnosis range was 15-60 days. Cough was the most frequent symptom (five cases over eight). Dyspnea with orthopnea was described in one case. Pleural and parenchymal radiological manifestations had no specific characteristics: pleurisy, pleural thickening, nodules of variable size, reticular lesions. Temporal artery biopsy was positive in five cases, atypical in one case and negative in two cases. Bronchial and transbronchial biopsies (in two and one cases respectively) did not find any specific lesion. Clinical and radiological signs disappeared quickly after the introduction of glucocorticoid therapy. CONCLUSION: The knowledge of these different respiratory manifestations during giant cell arteritis (persistent cough, nodules, pleural effusion) is useful for the clinician. It helps him in prescribing non invasive investigations or even a presumptive glucocorticoid therapy, in an often old and weakened patient.

[Post-treatment surveillance for potentially curable malignancies]. / Surveillance des cancers en rémission complète.

Through an enormous research effort over the past five decades and especially due to early screening, an increasing number of cancers are potentially curable. Patients expand immeasurable energy in adhering to treatment plans and supportive care. Unfortunately, nothing prepares them for the anxiety that often comes with completion of therapy. More importantly, physicians are not properly equipped with data from controlled trials to define appropriate post-treatment surveillance, data with which they could educate patients and allay their fears. The goal of post-treatment surveillance is to enable the early detection of relapses and thus enhance the possibility of subsequent cure. Accordingly special follow-up is appropriate only for patients who can receive a second-line therapy. Clinical trials support conservative, rather than aggressive, surveillance to detect curable local relapse of breast tumors and potentially surgically curable metastases (mainly in the liver) of colon cancer. For germ-cell tumors, second-line treatments are potentially curative in nearly all instances. Follow-up for other cancers depends on patients' anxiety levels and on the costs of surveillance.