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

Intérêts de la TEP dans la prise en charge des Lymphomes Malins Non Hodgkinien et des Maladies de Hodgkin au Centre Léon Bérard (A propos d'une série de 33 patients)

LYON1-BU Santé (693882101) / SudocPARIS-BIUM (751062103) / SudocSudocFranceF

Efficacy and morbidity of arc-therapy radiosurgery for cerebral arteriovenous malformations: a comparison with the natural history

International audiencePurpose: To report the results of arc-therapy radiosurgery for cerebral arteriovenous malformation (AVM) and to compare the adverse event rate with the rate expected from the natural history.Methods and materials: We performed a retrospective study of our 118 first patients with a mean follow-up of 46 months (range, 5–105 months). The AVMs had features indicating a poor prognosis at initial presentation and had already been treated by previous embolizations in 88% of patients. The mean volume of the targets was 7.4 cm3 (range, 0.3–28.3 cm3). The mean minimal and maximal dose was 17.7 Gy (range, 10–25 Gy) and 24.5 Gy (range, 17–36 Gy), respectively.Results: The crude and 5-year actuarial rate of cure (total obstruction of the AVM shunt at angiography) was 54% (60 of 112) and 77%, respectively. The only independent prognostic factor of cure was the AVM volume (crude cure rate 67% for <7 cm3 vs. 35% for ≥7 cm3; p = 0.001). No patient died. Transient and permanent complications and hemorrhage occurred in 5%, 1.7%, and 6% of patients, respectively. The annual risk of an adverse event (hemorrhage or complication) was 3.9%.Conclusion: The results of our series showed that radiosurgery, performed alone or after prior shrinkage of the AVM by embolization, is both effective and well tolerated, with a rate of adverse events comparable to that expected from the natural history

Severe Ebola Virus Infection With Encephalopathy: Evidence for Direct Virus Involvement

International audienceno abstrac

SARS-CoV-2/COVID-19: Evolving Reality, Global Response, Knowledge Gaps and Opportunities

Approximately 3 billion people around the world have gone into some form of social separation to mitigate the current SARS-CoV-2 pandemic. The uncontrolled influx of patients in need of emergency care has rapidly brought several national health systems to near-collapse with deadly consequences to those afflicted by COVID-19 and other critical diseases associated with COVID-19. Solid scientific evidence regarding SARS-CoV-2/COVID-19 remains scarce; there is an urgent need to expand our understanding of the SARS-CoV-2 pathophysiology to facilitate precise and targeted treatments. The capacity for rapid information dissemination has emerged as a double-edged sword; the existing gap of high-quality data is frequently filled by anecdotal reports, contradictory statements and misinformation. This review addresses several important aspects unique to the SARS-CoV-2/COVID-19 pandemic highlighting the most relevant knowledge gaps and existing windows-of-opportunity. Specifically, focus is given to SARS-CoV-2 immunopathogenesis in the context of experimental therapies and pre-clinical evidence and their applicability in supporting efficacious clinical trial planning. The review discusses the existing challenges of SARS-CoV-2 diagnostics and the potential application of translational technology for epidemiological predictions, patient monitoring and treatment decision-making in COVID-19. Furthermore, solutions for enhancing international strategies in translational research, cooperative networks and regulatory partnerships are contemplated. Address reprint requests to Marc Maegele, Department of Trauma and Orthopaedic Surgery, Cologne-Merheim Medical Center (CMMC), Institute for Research in Operative Medicine (IFOM), University of Witten/Herdecke, Cologne-Merheim Campus, Cologne, Germany. E-mail: [email protected]; Marcin F. Osuchowski, Ludwig Boltzmann Institute for Experimental and Clinical Traumatology in the AUVA Trauma Research Center, Donaueschingenstrasse 13, 1200 Vienna, Austria. E-mail: [email protected]. Received 22 April, 2020 Revised 29 April, 2020 Accepted 5 May, 2020 Osuchowski M: no conflict of interest Aletti F: no conflict of interest Cavaillon J-M: no conflict of interest Flohe SB: no conflict of interest Giamarellos-Bourboulis EJ: honoraria from AbbVie USA, Abbott CH, InflaRx GmbH, MSD Greece, XBiotech Inc. and Angelini Italy; independent educational grants from AbbVie, Abbott, Astellas Pharma Europe, AxisShield, bioMérieux Inc, InflaRx GmbH, and XBiotech Inc.; and funding from the FrameWork 7 program HemoSpec (granted to the National and Kapodistrian University of Athens), the Horizon2020 Marie-Curie Project European Sepsis Academy (granted to the National and Kapodistrian University of Athens), and the Horizon 2020 European Grant ImmunoSep (granted to the Hellenic Institute for the Study of Sepsis). Huber-Lang M: no conflict of interest Relja B: no conflict of interest Skirecki T: no conflict of interest Szabó A: no conflict of interest Maegele M: no conflict of interest © 2020 by the Shock Societ

Clinical features of Mycobacterium canettii infection: a retrospective study of 20 cases among French soldiers and relatives

International audienceBackground: Mycobacterium canettii forms part of the Mycobacterium tuberculosis complex. M. 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. Our study aims to describe M. canettii infections among French military or their families between 1998 and 2015. Methods: This retrospective study relied on 3 sources of data: the reference centre 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: 20 cases of M. canettii infections are reported, including 5 unpublished cases. Adenitis predominates (n = 15), especially in the cervico facial area and among children; one case was observed one 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 were comparable to tuberculosis. The presumed origin of the infection seemed to be environmental, possibly a water reservoir, and not due to human-to-human contagion

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

International audienceBackground: 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 CO­VID-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