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Saint-André-lez-Lille, France

During future space exploration missions, management of severe medical and surgical conditions will represent a challenge. Due to severe limitations in acute care capabilities, the medical system will need to focus only on the most likely and severe conditions. Using a probabilistic approach, the primary objective of this analysis is to offer recommendations for the preparation of crews and onboard medical systems, with the aim of optimizing the medical kit while maintaining the estimated mortality risk within acceptable limits. Based on the analysis of medical literature in space medicine and analogue environments, a list of expected conditions has been established. Their incidence and average mortality in similar populations have been estimated. By balancing medical kits complexity and estimated vital risk, it becomes possible to determine which therapeutic techniques are mandatory. According to the analysis, the conditions associated with the most significant risk are severe sepsis and traumatic injuries. Besides the basicmedical procedures (intravenous access, antibiotics, oxygen...), it seems essential to be able to administer blood products or substitutes and perform surgery. The results also provide a list of conditions that could probably be excluded from the medical system due to their poor outcome, complexmanagement and extremely low estimated likelihood. The results globally correspond to the conclusions of previous publications. Like numerous spin-offs of space technologies in the past, this research is useful to increase the level of care on Earth, in particular in harsh and isolated environments. © 2014 Société de réanimation de langue française (SRLF) and Springer-Verlag.

Meppiel E.,AP HP | Crassard I.,AP HP | De Latour R.P.,AP HP | De Guibert S.,AP HP | And 5 more authors.
Medicine (United States) | Year: 2015

Paroxysmal nocturnal hemoglobinuria (PNH) is a rare acquired disorder of hematopoietic stem cells characterized by hemolytic anemia, marrow failure, and a high incidence of life-threatening venous thrombosis. Cerebral venous system is the second most frequent location of thrombosis after hepatic veins. However, data about PNH-related cerebral venous thrombosis (CVT) are very scarce because of the rarity of both the disorders.We report a French study about PNH patients with CVT. Patients were recruited retrospectively, from the Société Française d'Hématologie (SFH) registry of 465 patients with PNH; the Lariboisière registry of 399 patients with CVT; and a direct contact with 26 French Hematology Units. We review cases reported since 1938 in the English and French language literature. We then compared patients of our series with cases from the literature, with non-PNH-related CVT cases from Lariboisière registry, and with PNH patients without CVT from SFH registry.Fifteen patients were included between 1990 and 2012. Most patients were women (12/15) and half of them presented associated hormonal venous thrombosis risk factors. Three patients had concomitant hepatic vein thrombosis. CVT was the first manifestation of PNH in 4 patients. No major difference in CVT characteristics was found compared with non-PNH-related CVT cases, except for a younger age at diagnosis in PNH patients (P<0.001). All patients were treated with anticoagulation therapy. One death occurred in acute stage. All surviving patients were independent 1 year after. Median survival time was 9 years. Recurrent thrombosis rate was 50% at 6 years, occurring in patients that did not have bone marrow transplantation or eculizumab therapy. Cases of death were mainly related to hepatic vein thrombosis.Prognosis of CVT was good in our series. However, these patients have a poor long-term prognosis due to PNH disease by itself. PNH treatment should be proposed as soon as possible to avoid recurrent thrombosis. Besides, inaugural CVT events encourage investigating PNH in case of cytopenia, hemolysis, abdominal veins thrombosis, or aplastic anemia history associated with the neurological complication. © 2015 Wolters Kluwer Health, Inc.

Exposure to weightlessness affects most physiological systems in the human body. Usually, the clinical manifestations of the so-called space adaptation syndrome are relatively benign. The intensivist will be mostly concerned about the cardiovascular deconditioning experienced by astronauts, which is marked by vascular remodeling and changes in blood volume, cardiac performance, autonomic nervous system and hormonal regulation. The new physiological status reached after the adaptation phase, rather than a pathological state, is likely to correspond to a new equilibrium which matches reduced cardiac loading conditions. After a space mission, the return to gravity leads to another transitioning phase, which is sometimes complicated by potentially serious manifestations. Among those, orthostatic intolerance and reduced exercise capacity represent the most serious operational risks. During and immediately after a space flight, any additional acute condition involving a risk of hemodynamic compromise (absolute or relative hypovolemia, cardiac function alteration, general anesthesia, mechanical ventilation) would most likely lead to a challenging situation. Research focusing on the question of anesthesia and critical care remains scarce, because no terrestrial model on Earth is able to accurately reproduce the changes induced by microgravity. During the history of manned space flight, severe medical events (excluding spacecraft failures) have remained uncommon, mostly thanks to an in-depth medical selection process. In the close future, the onset of a space tourism era with both more people enter zero gravity and a potentially less medically focused customer selection, could see a shift in this pattern and an increase in severe medical events. © 2014 Société de réanimation de langue française (SRLF) and Springer-Verlag.

Bourgine J.,University of Lille Nord de France | Garat A.,University of Lille Nord de France | Allorge D.,University of Lille Nord de France | Crunelle-Thibaut A.,University of Lille Nord de France | And 4 more authors.
Pharmacogenetics and Genomics | Year: 2011

BACKGROUND: Adverse effects of thiopurine drugs occur in 15-28% of patients and the majority is not explained by thiopurine-S-methyltransferase deficiency. Furthermore, approximately 9% of patients with inflammatory bowel disease are resistant to azathioprine therapy. Recently, the small guanosine triphosphatase, Rac1, was identified as an important molecular target of 6-thioguanine triphosphate, one of the active metabolite of thiopurines such as azathioprine. To date, no functional genetic polymorphism of the human Rac1 gene had been reported. OBJECTIVES: Evidence for functional genetic polymorphisms of the human Rac1 gene and to investigate their relative contribution to the development of toxicity induced by azathioprine treatment in patients with inflammatory bowel disease. METHODS: We first screened for polymorphisms in the Rac1 gene in genomic DNA samples from 92 unrelated Caucasian individuals. The functional consequences of identified polymorphisms were assessed in vitro using transient transfection assays in Jurkat and A549 cell lines. The relationship between polymorphisms of Rac1 and thiopurine response or hematotoxicity was studied in 128 patients under thiopurine treatment. RESULTS: Three single nucleotide polymorphism and one variable number tandem repeat were identified in the promoter region of Rac1 gene. Interestingly, in Jurkat T cells, the c.-289G>C substitution and c.-283-297[3] variable number tandem repeat displayed a significantly increased promoter activity (P<0.01) of 150 and 300%, respectively, compared with that of the wild-type sequence. Patients with thiopurine-S-methyltransferase mutations presented a significantly increased probability of developing hematotoxicity (odds ratio=5.68, 95% confidence interval=1.45-22.23, P=0.00625). Moreover, among the 75 patients who did not develop hematotoxicity, there was a marginally overrepresentation of functional genetic polymorphisms of Rac1 (odds ratio=0.18, 95% confidence interval=0.02-1.49, P=0.079). CONCLUSION: This study constitutes the first report of a functional genetic polymorphism that could affect Rac1 expression and thus modulate the risk of adverse drug reaction in patients under thiopurine treatment. A larger scale (case-control) study should enable us to confirm or cancel these preliminary results. © 2011 Wolters Kluwer Health | Lippincott Williams & Wilkins.

Coiffier B.,Hospices Civils de Lyon | Pro B.,Thomas Jefferson University | Prince H.M.,University of Melbourne | Foss F.,Yale Cancer Center | And 13 more authors.
Journal of Hematology and Oncology | Year: 2014

Background: Romidepsin is a structurally unique, potent, bicyclic class 1 selective histone deacetylase inhibitor approved by the US Food and Drug Administration for the treatment of patients with cutaneous T-cell lymphoma who have received ≥ 1 prior systemic therapy and patients with peripheral T-cell lymphoma (PTCL) who have received ≥ 1 prior therapy. Approval for PTCL was based on results (n = 130; median follow-up, 13.4 months) from the pivotal study of romidepsin for the treatment of relapsed/refractory PTCL. The objective is to present updated data (median follow-up, 22.3 months) and to characterize patients who achieved long-term responses (≥ 12 months) to romidepsin. Methods. Patients with PTCL who relapsed from or were refractory to ≥ 1 prior systemic therapy received romidepsin 14 mg/m§ssup§2§esup§ as a 4-hour intravenous infusion on days 1, 8, and 15 every 28 days for up to 6 cycles; patients with response or stable disease could continue romidepsin beyond 6 cycles. The primary endpoint was rate of confirmed/unconfirmed complete response (CR/CRu) determined by an Independent Review Committee. Secondary endpoints included objective response rate (ORR) and duration of response (DOR). For patients who achieved CR/CRu, baseline characteristics by DOR (≥ 12 vs < 12 months) were examined. Results: The ORR to romidepsin was 25%, including 15% with CR/CRu. The median DOR for all responders was 28 months (range, < 1-48+) and was not reached for those who achieved CR/CRu. Patients with lack of response or transient response to prior therapy achieved durable responses with romidepsin. Of the 19 patients who achieved CR/CRu, 10 had long-term (≥ 12 months) responses; none of the baseline characteristics examined - including heavy pretreatment, response to prior therapy, or advanced disease - precluded long-term responses to romidepsin. With a median progression-free survival of 29 months, patients who achieved CR/CRu for ≥ 12 months had significantly longer survival vs those with CR/CRu for < 12 months or < CR/CRu. Extended treatment and longer follow-up did not affect the reported safety profile of romidepsin. Conclusions: Treatment with romidepsin leads to highly durable responses in a subset of patients with relapsed/refractory PTCL, with responses ongoing as long as 48 months. Trial registration. NCT00426764. © 2014 Coiffier et al.; licensee BioMed Central Ltd.

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