Summary
Background
Hereditary hemorrhagic telangiectasia (HHT) is a genetic disorder associated with abnormal angiogenesis and disabling epistaxis. Tranexamic acid (TA) has been widely used in the ...treatment of these severe bleeds but with no properly designed trial.
Objectives
To demonstrate the efficacy of TA in epistaxis in HHT patients and to explore its safety of use.
Patients/Methods
A randomized, placebo‐controlled, double‐blind, cross‐over trial was conducted. Participants were randomized to receive TA (3 g a day) then placebo or the opposite sequence. The main analysis compared intra‐individual mean duration of epistaxis under TA vs. placebo on a log scale. The primary outcome was the mean duration of epistaxis per month, assessed with specific grids to be completed by participants. The number of epistaxis episodes was recorded as a secondary outcome.
Results
A total of 118 randomized patients contributed to the statistical analysis. The mean duration of epistaxis per month was significantly shorter with TA than placebo (0.19 on the log scale; SD = 0.07; P = 0.005), corresponding to a decrease of 17.3% (15.7 min) in the duration of epistaxis per month (CI 95%, 5.5–27.6). The median number of epistaxis episodes per month was 22.1 episodes in the placebo arm vs. 23.3 episodes in the TA arm. No thrombophlebitis was observed.
Conclusions
In the ATERO study, we demonstrated a significant decrease in the duration of epistaxis in HHT patients taking TA. No safety issues were recorded in our cohort of patients.
To meet the international biodiversity targets of the 2011–2020 Global Strategy for Plant Conservation, it is important to assess the success of coordinated ex situ plant conservation initiatives ...such as the European Native Seed Conservation Network (ENSCONET), which operated during 2005–2009, and the ENSCONET Consortium, which was established in 2010. In particular, analysis of the ENSCONET database (ENSCOBASE) indicates that ex situ seed banks have been making significant progress towards meeting targets 8 (at least 75% of threatened plant species in ex situ collections, preferably in the country of origin, and at least 20% available for recovery and restoration programmes) and 9 (70% of the genetic diversity of crops, including their wild relatives and other socio-economically valuable plant species, conserved, while respecting, preserving and maintaining associated indigenous and local knowledge) for native European species. However, the infraspecific diversity of threatened species stored in ENSCONET seed banks needs to be increased to meet research and conservation objectives.
Systemic sclerosis (SSc) is an autoimmune disease, characterized by fibrosis of the skin and other organs, vascular impairment and deficient immune responses. Mucosal‐associated invariant T cells ...(MAIT) have been involved in various inflammatory and autoimmune diseases. The aims of this study were to determine the frequencies of MAIT cells in the blood of patients with systemic sclerosis (SSc) and to compare their distribution in different types of SSc. Blood samples from patients with SSc and healthy controls were examined by flow cytometer to analyse the frequencies of MAIT and γδ T cells. We demonstrate that in SSc the frequencies and absolute numbers of MAIT and γδ T cells are significantly reduced in comparison with healthy controls. MAIT and γδ T cells did not correlate with C‐reactive protein, BNP, pulmonary involvement or median skin fibrosis scale, steroid amount or disease duration. In addition, MAIT and γδ T cells decrease did not stratify with gender, interstitial lung disease or active digital ulcers. Functional studies are necessary to determine the signification of MAIT cells decrease in systemic sclerosis.
Heterozygous activin receptor-like kinase 1 (
ALK1
) mutations are associated with two vascular diseases: hereditary hemorrhagic telangiectasia (HHT) and more rarely pulmonary arterial hypertension ...(PAH). Here, we aimed to understand the impact of
ALK1
mutations on BMP9 and BMP10 transcriptomic responses in endothelial cells. Endothelial colony-forming cells (ECFCs) and microvascular endothelial cells (HMVECs) carrying loss of function
ALK1
mutations were isolated from newborn HHT and adult PAH donors, respectively. RNA-sequencing was performed on each type of cells compared to controls following an 18 h stimulation with BMP9 or BMP10. In control ECFCs, BMP9 and BMP10 stimulations induced similar transcriptomic responses with around 800 differentially expressed genes (DEGs).
ALK1
-mutated ECFCs unexpectedly revealed highly similar transcriptomic profiles to controls, both at the baseline and upon stimulation, and normal activation of Smad1/5 that could not be explained by a compensation in cell-surface ALK1 level. Conversely, PAH HMVECs revealed strong transcriptional dysregulations compared to controls with > 1200 DEGs at the baseline. Consequently, because our study involved two variables, ALK1 genotype and BMP stimulation, we performed two-factor differential expression analysis and identified 44 BMP9-dysregulated genes in mutated HMVECs, but none in ECFCs. Yet, the impaired regulation of at least one hit, namely lunatic fringe (
LFNG
), was validated by RT-qPCR in three different
ALK1
-mutated endothelial models. In conclusion,
ALK1
heterozygosity only modified the BMP9/BMP10 regulation of few genes, including
LFNG
involved in NOTCH signaling. Future studies will uncover whether dysregulations in such hits are enough to promote HHT/PAH pathogenesis, making them potential therapeutic targets, or if second hits are necessary.
The contribution of the European Native Seed Conservation Network (ENSCONET, 2004-2009) and the ENSCONET Consortium (since 2010) towards meeting the 2020 Global Strategy for Plant Conservation (GSPC) ...target 8 was assessed in 2017. While the outcome was positive (62.7% of European threatened species already conserved ex situ in seed banks), the analysis showed that it was essential to provide guidance on which European native threatened species should be collected as a priority if the target was to be reached by 2020. In this paper we present a priority-setting method and its result, designed to guide collecting strategies across Europe to meet the 2020 GSPC target 8. The result of our study is a country-based checklist of European threatened taxa to be collected and stored ex situ across the seed banks of the ENSCONET Consortium by 2020. After discussing the results of the applied method, the ENSCONET Consortium Steering Committee has identified some key action points to support the implementation of such a collecting strategy across Europe in order to meet the 2020 GSPC target 8 for Europe.
Reactive haemophagocytic syndrome (HS) is a rare condition that occurs in patients with infections, haematological malignancies or autoimmune diseases. Although various microorganisms are thought to ...trigger HS, most of the literature data on this topic have been gathered in single-centre case series. Here, we sought to characterize infectious triggers in a large, multicentre cohort of patients with HS. Patients were included in the present study if HS was solely due to one or more infections. Detailed microbiological data were recorded. Of the 162 patients with HS in the cohort, 40 (25%) had at least one infection and 38 of the latter (including 14 women, 36.8%) were included. The median age was 46 years. Seven patients were presumed to be immunocompetent (18.4%), whereas 19 patients (50%) were infected with human immunodeficiency virus and 12 patients (31.6%) were immunocompromised for other reasons. Twenty-seven patients (71.1%) had a single infection, whereas six (15.8%) and five (13.1%) patients had, respectively, two and three concomitant infections. We observed pyogenic bacterial infections (n = 7), tuberculosis (n = 10), non-tuberculous mycobacteriosis (n = 3), viral infections (n = 17: 11 cytomegalovirus, three Epstein–Barr virus, two human herpesvirus 8, one herpes simplex virus 2), parasitic infections (n = 8: four disseminated toxoplasmosis, one leishmaniasis, three malaria), fungal infections (n = 5: four pulmonary pneumocystosis and one candidaemia). Eighteen patients (47.4%) received corticosteroids and/or etoposide. Twelve patients died (31.6%). All multiple infections and all deaths occurred in immunocompromised patients. When compared with patients suffering from malignancy-associated HS, patients with infection-triggered HS were younger and more likely to be immunocompromised, and had a better outcome.
This pandemic has profoundly changed our lives for many months and its long-term consequences remain largely hypothetical. The containment measures, the threats to the health of relatives, the ...constraints limiting social openings have left no one indifferent, but may have particularly impeded "adolescent separation work". Most of adolescents have been able to deploy their adaptation capacities, while for others this exceptional situation has triggered stressful reactions for those around them. Some were immediately overwhelmed by the direct or indirect manifestations of their anxiety or by their intolerance of governmental instructions, others revealed their difficulties only when the schools reopened, or even in the distant "aftermath", as shown by some studies carried out at a distance revealing a clear increase in suicidal ideation. We will not be surprised by the problems of adaptation of the most fragile, of those suffering from psychopathological disorders, but it is necessary to note an increase in the needs for psychological care. Teams dealing with the suffering of adolescents are puzzled by the increase in self-vulnerable acts, anxious school refusals, eating disorders or various forms of addiction to screens. However, everyone agrees on the key role of parents and the impact of their own suffering on that of their children, even if they are young adults. Of course, it is important that caregivers do not forget the parents in the support they aim to provide to their young patients.
Gastrointestinal involvement in systemic sclerosis can be severe, reaching the critical point of chronic intestinal pseudo-obstruction, secondary to major disorders of small bowel motility. It is ...associated with some clinical and biological characteristics, in particular the positivity of anti-fibrillarin/U3RNP antibodies. Chronic intestinal pseudo-obstruction (CIPO) is complicated by a small intestinal bacterial overgrowth that requires cyclic antibiotic therapy. CIPO leads to a reduction of the food intake, due to painful symptoms, nausea and vomiting caused by meals, and ultimately to severe malnutrition. Meal splitting is often transiently effective and patients require exogenous nutritional support, mostly parenteral. Systemic sclerosis is not an obstacle to initiation and long-term continuation of parenteral nutrition and central venous catheter implantation is not associated with an increased risk of cutaneous or infectious complications. However, continuation of long-term parenteral nutrition requires monitoring in an expert nutrition center in order to adapt nutritional volumes and intakes and to limit potentially fatal cardiac and hepatobiliary complications. In addition to nutrition, prokinetic treatments, whose side effects must be known, can be associated. Invasive procedures, whose risk-benefit ratio must be carefully assessed, can also be used to treat symptoms exclusively.
Fibrogenesis is a universal and ubiquitous process associated with tissue healing. The impairment of tissue homeostasis resulting from the deregulation of numerous cellular actors, under the effect ...of specific cytokine and pro-oxidative environments can lead to extensive tissue fibrosis, organ dysfunction and significant morbidity and mortality. This situation is frequent in internal medicine, since fibrosis is associated with most organ insufficiencies (i.e. cardiac, renal, or hepatic chronic failures), but also with cancer, a condition with common pathophysiological mechanisms. Finally, fibrosis is a hallmark of numerous systemic autoimmune diseases such as connective tissue disorders (in particular systemic sclerosis), vasculitides, granulomatoses, histiocytoses, and IgG4-associated disease. Although the process leading to tissue fibrosis may be in part irreversible, new pharmacological approaches or cell therapies bring hope in the field of fibrotic conditions.
Tuberculosis (TB) is a potential trigger of haemophagocytic syndrome (HS) but little is known about the features of TB-associated HS.
To assess the risk factors associated with HS in patients with ...TB.
We performed a multicentre case-control study assessing the medical records of adult patients diagnosed with proven TB with (TB/HS+) or without (TB/HS-) associated HS.
Twenty-one patients with TB/HS+ (24% women, median age, 37 years IQR 30-48) were included in the study. Eleven patients (52%) were infected with human immunodeficiency virus and seven patients (33%) were immunocompromised due to other reasons. TB was disseminated in 17 patients (81%). Compared with 50 control TB patients (TB/HS-), patients with TB/HS+ were more likely to be immunocompromised (86% vs. 18%;
< 0.001) and to present with disseminated TB (80% vs. 12%;
< 0.001). The outcome was poorer in patients with TB/HS+, with a higher admission rate to intensive care (71% vs. 0%;
< 0.001) and a higher risk of death (38% vs. 7%;
= 0.005).
TB/HS+ occurred more likely in immunocompromised patients and severely impaired the prognosis of TB. Further studies are needed to devise therapeutic strategies for patients with TB/HS+.
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