Congestive heart failure : more common as well as an important cardiovascular outcome: reply

Non peer reviewe

Hydroxychloroquine reduces interleukin-6 levels after myocardial infarction : The randomized, double-blind, placebo-controlled OXI pilot trial

Objectives: To determine the anti-inflammatory effect and safety of hydroxychloroquine after acute myocardial infarction. Method: In this multicenter, double-blind, placebo-controlled OXI trial, 125 myocardial infarction patients were randomized at a median of 43 h after hospitalization to receive hydroxychloroquine 300 mg (n = 64) or placebo (n = 61) once daily for 6 months and, followed for an average of 32 months. Laboratory values were measured at baseline, 1, 6, and 12 months. Results: The levels of interleukin-6 (IL-6) were comparable at baseline between study groups (p = 0.18). At six months, the IL-6 levels were lower in the hydroxychloroquine group (p = 0.042, between groups), and in the on-treatment analysis, the difference at this time point was even more pronounced (p = 0.019, respectively). The high-sensitivity C-reactive protein levels did not differ significantly between study groups at any time points. Eleven patients in the hydroxychloroquine group and four in the placebo group had adverse events leading to in-terruption or withdrawal of study medication, none of which was serious (p = 0.10, between groups). Conclusions: In patients with myocardial infarction, hydroxychloroquine reduced IL-6 levels significantly more than did placebo without causing any clinically significant adverse events. A larger randomized clinical trial is warranted to prove the potential ability of hydroxychloroquine to reduce cardiovascular endpoints after myocar-dial infarction. (c) 2021 The Authors. Published by Elsevier B.V. This is an open access article under the CC BY license (http:// creativecommons.org/licenses/by/4.0/).Peer reviewe

The European land and inland water CO2, CO, CH4 and N2O balance between 2001 and 2005

Globally, terrestrial ecosystems have absorbed about 30% of anthropogenic greenhouse gas emissions over the period 2000–2007 and inter-hemispheric gradients indicate that a significant fraction of terrestrial carbon sequestration must be north of the Equator. We present a compilation of the CO2, CO, CH4 and N2O balances of Europe following a dual constraint approach in which (1) a landbased balance derived mainly from ecosystem carbon inventories and (2) a land-based balance derived from flux measurements are compared to (3) the atmospheric data-based balance derived from inversions constrained by measurements of atmospheric GHG (greenhouse gas) concentrations. Good agreement between the GHG balances based on fluxes (1294±545 Tg C in CO2-eq yr−1), inventories (1299±200 Tg C in CO2-eq yr−1) and inversions (1210±405 Tg C in CO2-eq yr−1) increases our confidence that the processes underlying the European GHG budget are well understood and reasonably sampled. However, the uncertainty remains large and largely lacks formal estimates. Given that European net land to atmosphere exchanges are determined by a few dominant fluxes, the uncertainty of these key components needs to be formally estimated before efforts could be made to reduce the overall uncertainty. The net land-to-atmosphere flux is a net source for CO2, CO, CH4 and N2O, because the anthropogenic emissions by far exceed the biogenic sink strength. The dual-constraint approach confirmed that the European biogenic sink removes as much as 205±72 Tg C yr−1 from fossil fuel burning from the atmosphere. However, This C is being sequestered in both terrestrial and inland aquatic ecosystems. If the C-cost for ecosystem management is taken into account, the net uptake of ecosystems is estimated to decrease by 45% but still indicates substantial C-sequestration. However, when the balance is extended from CO2 towards the main GHGs, C-uptake by terrestrial and aquatic ecosystems is offset by emissions of non-CO2 GHGs. As such, the European ecosystems are unlikely to contribute to mitigating the effects of climate change.JRC.H.2-Air and Climat

Common genetic variants in the CLDN2 and PRSS1-PRSS2 loci alter risk for alcohol-related and sporadic pancreatitis

Pancreatitis is a complex, progressively destructive inflammatory disorder. Alcohol was long thought to be the primary causative agent, but genetic contributions have been of interest since the discovery that rare PRSS1, CFTR, and SPINK1 variants were associated with pancreatitis risk. We now report two significant genome-wide associations identified and replicated at PRSS1-PRSS2 (1×10-12) and x-linked CLDN2 (p < 1×10-21) through a two-stage genome-wide study (Stage 1, 676 cases and 4507 controls; Stage 2, 910 cases and 4170 controls). The PRSS1 variant affects susceptibility by altering expression of the primary trypsinogen gene. The CLDN2 risk allele is associated with atypical localization of claudin-2 in pancreatic acinar cells. The homozygous (or hemizygous male) CLDN2 genotype confers the greatest risk, and its alleles interact with alcohol consumption to amplify risk. These results could partially explain the high frequency of alcohol-related pancreatitis in men – male hemizygous frequency is 0.26, female homozygote is 0.07

Extracorporeal Membrane Oxygenation for Severe Acute Respiratory Distress Syndrome associated with COVID-19: An Emulated Target Trial Analysis.

RATIONALE: Whether COVID patients may benefit from extracorporeal membrane oxygenation (ECMO) compared with conventional invasive mechanical ventilation (IMV) remains unknown. OBJECTIVES: To estimate the effect of ECMO on 90-Day mortality vs IMV only Methods: Among 4,244 critically ill adult patients with COVID-19 included in a multicenter cohort study, we emulated a target trial comparing the treatment strategies of initiating ECMO vs. no ECMO within 7 days of IMV in patients with severe acute respiratory distress syndrome (PaO2/FiO2 <80 or PaCO2 ≥60 mmHg). We controlled for confounding using a multivariable Cox model based on predefined variables. MAIN RESULTS: 1,235 patients met the full eligibility criteria for the emulated trial, among whom 164 patients initiated ECMO. The ECMO strategy had a higher survival probability at Day-7 from the onset of eligibility criteria (87% vs 83%, risk difference: 4%, 95% CI 0;9%) which decreased during follow-up (survival at Day-90: 63% vs 65%, risk difference: -2%, 95% CI -10;5%). However, ECMO was associated with higher survival when performed in high-volume ECMO centers or in regions where a specific ECMO network organization was set up to handle high demand, and when initiated within the first 4 days of MV and in profoundly hypoxemic patients. CONCLUSIONS: In an emulated trial based on a nationwide COVID-19 cohort, we found differential survival over time of an ECMO compared with a no-ECMO strategy. However, ECMO was consistently associated with better outcomes when performed in high-volume centers and in regions with ECMO capacities specifically organized to handle high demand. This article is open access and distributed under the terms of the Creative Commons Attribution Non-Commercial No Derivatives License 4.0 (http://creativecommons.org/licenses/by-nc-nd/4.0/)