EUSEDcollab: a network of data from European catchments to monitor net soil erosion by water

As a network of researchers we release an open-access database (EUSEDcollab) of water discharge and suspended sediment yield time series records collected in small to medium sized catchments in Europe. EUSEDcollab is compiled to overcome the scarcity of open-access data at relevant spatial scales for studies on runoff, soil loss by water erosion and sediment delivery. Multi-source measurement data from numerous researchers and institutions were harmonised into a common time series and metadata structure. Data reuse is facilitated through accompanying metadata descriptors providing background technical information for each monitoring station setup. Across ten European countries, EUSEDcollab covers over 1600 catchment years of data from 245 catchments at event (11 catchments), daily (22 catchments) and monthly (212 catchments) temporal resolution, and is unique in its focus on small to medium catchment drainage areas (median=43km2, min=0.04km2, max=817km2) with applicability for soil erosion research. We release this database with the aim of uniting people, knowledge and data through the European Union Soil Observatory (EUSO)

Impact of peroxisome proliferator-activated receptor agonists on myosteatosis in the context of metabolic dysfunction-associated steatotic liver disease

Introduction : A growing body of evidence suggests that metabolic dysfunction-associated steatotic liver disease (MASLD) could be associated with fatty infiltration of skeletal muscles, known as myosteatosis. Myosteatosis is implicated in the development of insulin resistance by altering the insulin signalling pathway, could affect muscle function and possibly contributes to the severity of liver damage. A combination of peroxisome proliferator-activated receptor (PPAR) agonists is currently being evaluated as a promising treatment for metabolic dysfunction-associated steatohepatitis (MASH), the inflammatory stage of MASLD. However, the effect of pan-PPAR agonists on myosteatosis remains to be determined. Objective: The aim of this systematic review is to evaluate the effect of PPAR agonists and their combination on myosteatosis in the context of MASLD. Methods: We searched for combination of terms including NAFLD, MAFLD, NASH, PPAR agonist, muscle fat and intramyocellular lipids published until March 2023 using PubMed and EMBASE. Only original articles have been retained. Articles were carefully selected and examined in order to identify relevant results that align with our research topic. Results: Our search yielded 34 results. After reading the titles and removing duplicates, 24 articles were evaluated according to our inclusion criteria. Eleven original manuscript articles were retained to answer our research question. The impact of the PPARα agonist on myosteatosis was assessed by triglyceride extraction in two preclinical studies in rats on a high-fat diet (HFD) and in insulin-resistant mice, and by proton magnetic resonance spectroscopy (MRS) in a clinical study in healthy and insulin-resistant elderly subjects. In rats fed a HFD, a two-week treatment significantly reduced quadriceps muscle triglyceride levels (-34%), as well as liver triglyceride levels (-54%), compared with controls. In insulin-resistant rats, it reduced quadriceps muscle (-44%) and liver (-40%) triglyceride levels compared to untreated rats. In a clinical study, a 60-day course of the PPARα agonist fenofibrate had no significant impact on soleus intramyocellular lipids (IMCL) or liver fat content in either insulin-resistant subjects or the healthy elderly group. In two studies on myocytes, treatment with PPARδ agonist increased the expression of the fatty acid oxidation genes CD36 and CPT1b. PPARγ agonists have been the subject of two preclinical studies and one clinical study. In the first preclinical study in Zucker diabetic fatty (ZDF) rats, treatment for one week with the PPARγ agonist rosiglitazone reduced IMCL (-40%) and hepatic steatosis (-89%) assessed by MRS and compared with the control group of ZDF rats, but had no impact on extramyocellular lipids. In a second preclinical study on ZDF rats, the PPARγ agonist pioglitazone reduced anterior tibial IMCL (-43%) assessed by proton MRS. In contrast, one year's treatment with rosiglitazone significantly increased the surface area of low density muscles (suggesting muscle fat infiltration) assessed by CT scan in patients with type 2 diabetes, while no change was observed in the placebo group. Combinations of PPAR agonists were evaluated in two preclinical studies and one clinical study. In the first preclinical study in ZDF rats on a HFD, cevoglitazar (a dual PPARα/γ agonist) significantly reduced the IMCL of the tibialis anterior, comparable to treatment with the PPARα agonist fenofibrate and the PPARγ agonist pioglitazone alone. Only fenofibrate and cevoglitazar significantly reduced hepatocellular lipids (MRS). In another preclinical study in ZDF rats, the combination of fenofibrate (PPARα) and rosiglitazone (PPARγ) did not significantly reduce gastrocnemius muscle triglyceride content (assessed by triglyceride extraction), but did with fenofibrate alone. In addition, gastrocnemius intramuscular triglyceride content was increased in ZDF rats treated with rosiglitazone alone. In contrast, in the latest clinical trial in type 2 diabetic patients, a 4-month treatment with the PPARα/γ agonist muraglitazar significantly decreased IMCL of the tibialis anterior as well as liver fat content assessed by MRS. Conclusion: PPAR agonists, and more specifically their combination, are a promising treatment for MASH and could also have a positive impact on reducing myosteatosis. The few discrepancies noted between the studies could be explained by the different techniques used to assess myosteatosis and the possible adipogenic effect of PPARγ agonists. Further clinical research is required to fully evaluate the efficacy of these treatments on both MASH components and myosteatosis. We believe that myosteatosis should be adequately evaluated in future studies on MASLD/MASH

EUSEDcollab: a network of data from European catchments to monitor net soil erosion by water

Abstract As a network of researchers we release an open-access database (EUSEDcollab) of water discharge and suspended sediment yield time series records collected in small to medium sized catchments in Europe. EUSEDcollab is compiled to overcome the scarcity of open-access data at relevant spatial scales for studies on runoff, soil loss by water erosion and sediment delivery. Multi-source measurement data from numerous researchers and institutions were harmonised into a common time series and metadata structure. Data reuse is facilitated through accompanying metadata descriptors providing background technical information for each monitoring station setup. Across ten European countries, EUSEDcollab covers over 1600 catchment years of data from 245 catchments at event (11 catchments), daily (22 catchments) and monthly (212 catchments) temporal resolution, and is unique in its focus on small to medium catchment drainage areas (median = 43 km2, min = 0.04 km2, max = 817 km2) with applicability for soil erosion research. We release this database with the aim of uniting people, knowledge and data through the European Union Soil Observatory (EUSO)

Efficacy and safety of baricitinib in hospitalized adults with severe or critical COVID-19 (Bari-SolidAct): a randomised, double-blind, placebo-controlled phase 3 trial

International audienceAbstract Background Baricitinib has shown efficacy in hospitalized patients with COVID-19, but no placebo-controlled trials have focused specifically on severe/critical COVID, including vaccinated participants. Methods Bari-SolidAct is a phase-3, multicentre, randomised, double-blind, placebo-controlled trial, enrolling participants from June 3, 2021 to March 7, 2022, stopped prematurely for external evidence. Patients with severe/critical COVID-19 were randomised to Baricitinib 4 mg once daily or placebo, added to standard of care. The primary endpoint was all-cause mortality within 60 days. Participants were remotely followed to day 90 for safety and patient related outcome measures. Results Two hundred ninety-nine patients were screened, 284 randomised, and 275 received study drug or placebo and were included in the modified intent-to-treat analyses (139 receiving baricitinib and 136 placebo). Median age was 60 (IQR 49–69) years, 77% were male and 35% had received at least one dose of SARS-CoV2 vaccine. There were 21 deaths at day 60 in each group, 15.1% in the baricitinib group and 15.4% in the placebo group (adjusted absolute difference and 95% CI − 0.1% [− 8·3 to 8·0]). In sensitivity analysis censoring observations after drug discontinuation or rescue therapy (tocilizumab/increased steroid dose), proportions of death were 5.8% versus 8.8% (− 3.2% [− 9.0 to 2.7]), respectively. There were 148 serious adverse events in 46 participants (33.1%) receiving baricitinib and 155 in 51 participants (37.5%) receiving placebo. In subgroup analyses, there was a potential interaction between vaccination status and treatment allocation on 60-day mortality. In a subsequent post hoc analysis there was a significant interaction between vaccination status and treatment allocation on the occurrence of serious adverse events, with more respiratory complications and severe infections in vaccinated participants treated with baricitinib. Vaccinated participants were on average 11 years older, with more comorbidities. Conclusion This clinical trial was prematurely stopped for external evidence and therefore underpowered to conclude on a potential survival benefit of baricitinib in severe/critical COVID-19. We observed a possible safety signal in vaccinated participants, who were older with more comorbidities. Although based on a post-hoc analysis, these findings warrant further investigation in other trials and real-world studies. Trial registration Bari-SolidAct is registered at NCT04891133 (registered May 18, 2021) and EUClinicalTrials.eu ( 2022-500385-99-00 )