The impact of microgravity and gravitational countermeasures on the gut microbiome of humans enrolled in the AGBRESA study

The Artificial Gravity Bed Rest Study – AGBRESA – was the first joint study conducted by DLR, ESA and NASA to simulate the effects of microgravity on healthy subjects. Moreover, the study included the use of artificial gravity protocols in a short-arm human centrifuge as a measure to counteract the negative effects of weightlessness. The health of the gut translates into the overall wellbeing since the disruption of the gut symbiotic networks – dysbiosis – could be due to either diet, antibiotic ingestion, sleep disturbance, physical activity or psychological stresses. In recent times, the gut microbiome has changed from being a complementary addition to our digestive tract to a potentially life-changing role by directly being the source of stimuli which revealed to impact neurochemistry, behavior and overall physiological status. Combined, microbial fluctuations could alter the intestinal microbiota composition and bacterial metabolite production, or more severely, in the disruption of host intestinal barrier integrity and the immune system activity, triggering intestinal inflammation syndromes and making the gut a very relevant organ to be studied in the context of spaceflight. Thus, 12 subjects, 8 males, were subjected to bed rest at negative 6-degree inclination for a period of 60 days with a preceding baseline of 15 days and posterior recovery period of 14 days. In other to characterize the gut microenvironment of healthy humans in simulated microgravity, fecal samples were collected during the baseline stage (once), during the head-down tilt treatment (at days 10, 30, and 50) and during the recovery period (once), and the samples were then processed for 16S rRNA sequencing and taxonomic analysis of the gut microenvironment. The characterization of the prokaryote flora was conducted 1) throughout time in contrast to the baseline reference and 2) in the context of the gravitational countermeasure vs the bed-rest-only control. The analysis revealed the detection of commensal microorganisms described to positively impact the gut such as Bifidobacterium spp., Lactobacillus spp., Akkermansia spp. and Enterococus spp.. Interestingly, we were able to detect pathogens like Campylobacter hominis which has been linked to severe bowel diseases ulcerative colitis and Crohn's disease. Also, opportunistic microorganisms such as Fusobacterium spp., Prevotella spp., Pseudomonas spp., Staphylococcus and Streptococcus spp., could potentially indicate an imbalance of the microbial networks and be a good an indicator of dysbiosis. Additionally, we set aside samples to undergo proteomic and metabolite analysis to improve the characterization of the gut microenvironment under microgravity simulation and the extent of the gravitational countermeasure recovery on bowel condition. Overall, the microgravity simulation performed on the AGBRESA study did not impact dramatically the fitness of the participants. Nonetheless, the analysis of the gut provides important insights on the triggers that occur during the adaptation of human physiology to long term exposure to spaceflight conditions and whether these relate to the described complications associated with gut disease

The management of acute venous thromboembolism in clinical practice. Results from the European PREFER in VTE Registry

Venous thromboembolism (VTE) is a significant cause of morbidity and mortality in Europe. Data from real-world registries are necessary, as clinical trials do not represent the full spectrum of VTE patients seen in clinical practice. We aimed to document the epidemiology, management and outcomes of VTE using data from a large, observational database. PREFER in VTE was an international, non-interventional disease registry conducted between January 2013 and July 2015 in primary and secondary care across seven European countries. Consecutive patients with acute VTE were documented and followed up over 12 months. PREFER in VTE included 3,455 patients with a mean age of 60.8 ± 17.0 years. Overall, 53.0 % were male. The majority of patients were assessed in the hospital setting as inpatients or outpatients (78.5 %). The diagnosis was deep-vein thrombosis (DVT) in 59.5 % and pulmonary embolism (PE) in 40.5 %. The most common comorbidities were the various types of cardiovascular disease (excluding hypertension; 45.5 %), hypertension (42.3 %) and dyslipidaemia (21.1 %). Following the index VTE, a large proportion of patients received initial therapy with heparin (73.2 %), almost half received a vitamin K antagonist (48.7 %) and nearly a quarter received a DOAC (24.5 %). Almost a quarter of all presentations were for recurrent VTE, with >80 % of previous episodes having occurred more than 12 months prior to baseline. In conclusion, PREFER in VTE has provided contemporary insights into VTE patients and their real-world management, including their baseline characteristics, risk factors, disease history, symptoms and signs, initial therapy and outcomes

Human gut microbiome and metabolite dynamics under simulated microgravity

ABSTRACTThe Artificial Gravity Bed Rest – European Space Agency (AGBRESA) study was the first joint bed rest study by ESA, DLR, and NASA that examined the effect of simulated weightlessness on the human body and assessed the potential benefits of artificial gravity as a countermeasure in an analog of long-duration spaceflight. In this study, we investigated the impact of simulated microgravity on the gut microbiome of 12 participants during a 60-day head-down tilt bed rest at the :envihab facilities. Over 60 days of simulated microgravity resulted in a mild change in the gut microbiome, with distinct microbial patterns and pathway expression in the feces of the countermeasure group compared to the microgravity simulation-only group. Additionally, we found that the countermeasure protocols selectively increased the abundance of beneficial short-chain fatty acids in the gut, such as acetate, butyrate, and propionate. Some physiological signatures also included the modulation of taxa reported to be either beneficial or opportunistic, indicating a mild adaptation in the microbiome network balance. Our results suggest that monitoring the gut microbial catalog along with pathway clustering and metabolite profiling is an informative synergistic strategy to determine health disturbances and the outcome of countermeasure protocols for future space missions

NFDI4Objects

Platform for the participatory preparation of a proposal "NFDI4Objects" within the context of the NFDI and repository for files during the project's duration

The management of acute venous thromboembolism in clinical practice - study rationale and protocol of the European PREFER in VTE Registry

Background: Venous thromboembolism (VTE) is a major health problem, with over one million events every year in Europe. However, there is a paucity of data on the current management in real life, including factors influencing treatment pathways, patient satisfaction, quality of life (QoL), and utilization of health care resources and the corresponding costs. The PREFER in VTE registry has been designed to address this and to understand medical care and needs as well as potential gaps for improvement. Methods/design: The PREFER in VTE registry was a prospective, observational, multicenter study conducted in seven European countries including Austria, France Germany, Italy, Spain, Switzerland, and the UK to assess the characteristics and the management of patients with VTE, the use of health care resources, and to provide data to estimate the costs for 12 months treatment following a first-time and/or recurrent VTE diagnosed in hospitals or specialized or primary care centers. In addition, existing anticoagulant treatment patterns, patient pathways, clinical outcomes, treatment satisfaction, and health related QoL were documented. The centers were chosen to reflect the care environment in which patients with VTE are managed in each of the participating countries. Patients were eligible to be enrolled into the registry if they were at least 18 years old, had a symptomatic, objectively confirmed first time or recurrent acute VTE defined as either distal or proximal deep vein thrombosis, pulmonary embolism or both. After the baseline visit at the time of the acute VTE event, further follow-up documentations occurred at 1, 3, 6 and 12 months. Follow-up data was collected by either routinely scheduled visits or by telephone calls. Results: Overall, 381 centers participated, which enrolled 3,545 patients during an observational period of 1 year. Conclusion: The PREFER in VTE registry will provide valuable insights into the characteristics of patients with VTE and their acute and mid-term management, as well as into drug utilization and the use of health care resources in acute first-time and/or recurrent VTE across Europe in clinical practice. Trial registration: Registered in DRKS register, ID number: DRKS0000479

The management of patients with venous thromboembolism in Italy: insights from the PREFER in VTE registry

Venous thromboembolism (VTE) is the third most common cardiovascular disease. Real-life data on the clinical presentation, risk factors, diagnosis, and treatment of VTE in Italy and Europe are required to optimize the management of this disease. The PREFER in VTE registry, a prospective non-interventional real-life study, was designed to assess clinical characteristics and management of patients with VTE, use of health care resources, and on-treatment patient quality of life. Eligible consecutive patients with objectively diagnosed VTE were enrolled in the registry and followed up for 12 months. Between January and December 2013, 816 Italian and 1027 patients from 6 European countries other than Italy (European patients) were enrolled in the registry, and followed up until December 2014. Italian patients were the oldest (mean age 65.7 years) among the European patients. The Italian patients with a history of cancer were 24.6 % of whom 63.2 % had an active cancer (18.2 and 57.0 %, respectively, in Europe). Parenteral heparin was given, as initial treatment, in 73.8 % of Italian patients (66.4 % in Europe); VKA in combination with other treatments in 45.8 % (34.7 % in Europe); and VKA as the only anticoagulant treatment in 24.4 % (17.2 % in Europe). Of the Italian patients, 43.2 and 90.6 % of patients were hospitalized for deep vein thrombosis and pulmonary embolism, respectively; 65.4 % were admitted to the hospital through the emergency department. Following a real world approach, PREFER in VTE shows that the Italian patients, among and compared to the European patients, are the oldest, have a history of cancer more commonly, receive an initial treatment with heparin more commonly, and are more commonly hospitalized, particularly if affected by PE