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Abstract Aims Published data on cardiogenic shock (CS) are scarce and are mostly focused on small registries of selected populations. The aim of this study was to examine the current CS picture and define the independent correlates of 30 day mortality in a large non‐selected cohort. Methods and results FRENSHOCK is a prospective multicentre observational survey conducted in metropolitan French intensive care units and intensive cardiac care units between April and October 2016. There were 772 patients enrolled (mean age 65.7 ± 14.9 years; 71.5% male). Of these patients, 280 (36.3%) had ischaemic CS. Organ replacement therapies (respiratory support, circulatory support or renal replacement therapy) were used in 58.3% of patients. Mortality at 30 days was 26.0% in the overall population (16.7% to 48.0% depending on the main cause and first place of admission). Multivariate analysis showed that six independent factors were associated with a higher 30 day mortality: age [per year, odds ratio (OR) 1.06, 95% confidence interval (CI): 1.04–1.08], diuretics (OR 1.74, 95% CI: 1.05–2.88), circulatory support (OR 1.92, 95% CI: 1.12–3.29), left ventricular ejection fraction

Abstract Background Cardiogenic shock (CS) is a life-threatening condition characterized by circulatory insufficiency caused by an acute dysfunction of the heart pump. The pathophysiological approach to CS has recently been enriched by the tissue consequences of low flow, including inflammation, endothelial dysfunction, and alteration of the hypothalamic-pituitary-adrenal axis. The aim of the present trial is to evaluate the impact of early low-dose corticosteroid therapy on shock reversal in adults with CS. Method/design This is a multicentered randomized, double-blind, placebo-controlled trial with two parallel arms in adult patients with CS recruited from medical, cardiac, and polyvalent intensive care units (ICU) in France. Patients will be randomly allocated into the treatment or control group (1:1 ratio), and we will recruit 380 patients (190 per group). For the treatment group, hydrocortisone (50 mg intravenous bolus every 6 h) and fludrocortisone (50 μg once a day enterally) will be administered for 7 days or until discharge from the ICU. The primary endpoint is catecholamine-free days at day 7. Secondary endpoints include morbidity and all-cause mortality at 28 and 90 days post-randomization. Pre-defined subgroups analyses are planned, including: postcardiotomy, myocardial infarction, etomidate use, vasopressor use, and adrenal profiles according the short corticotropin stimulation test. Each patient will be followed for 90 days. All analyses will be conducted on an intention-to-treat basis. Discussion This trial will provide valuable evidence about the effectiveness of low dose of corticosteroid therapy for CS. If effective, this therapy might improve outcome and become a therapeutic adjunct for patients with CS. Trial registration ClinicalTrials.gov , NCT03773822 . Registered on 12 December 2018

Introduction: Patients with cancer have an increased risk of developing venous thromboembolism (VTE), and subsequently a higher risk of bleeding secondary to anticoagulants. Low-molecular weight heparin (LMWH) has been the standard of care for these patients, with emerging data on the use of direct oral anticoagulants (DOACs). The primary objective of the study was to determine the prevalence of major bleeding events in cancer patients taking DOACs or LMWH for VTE. Secondary objectives included the rate of first VTE recurrence and the effect of concomitant antiplatelet agents and/or significant drug interactions on major bleeding or recurrent VTE. Materials and methods: Using the electronic medical record at the University of Rochester Medical Center, we retrospectively identified adult patients with active malignancy who had a diagnosis of VTE requiring therapeutic anticoagulation within the study period of July 1st, 2015 to June 1st, 2019. Patients were excluded if they were receiving prophylactic doses of LMWH per the institution VTE guidelines. Data on anticoagulant medications were collected as well as information on major bleeding and recurrent VTE events. Results and conclusions: There is insufficient evidence of difference in risk of major bleeding among patients who received a DOAC vs LMWH (cause-specific hazard ratio (HR) = 0.77, 95% CI 0.29–2.04, P = 0.60). There was also no evidence of a difference in risk of recurrent VTE between patients who received DOAC vs. LMWH (cause-specific HR = 0.98, 95% CI 0.15–6.26, P = 0.98). These results suggest that DOACs are not significantly less safe than LMWH for patients with cancer.

BackgroundCardiogenic shock (CS) is a life-threatening condition carrying poor prognosis, potentially triggered by ventricular arrhythmia (VA). Whether the occurrence of VA as trigger of CS worsens the prognosis compared to non-VA triggers remains unclear. The aim of this study was to evaluate 1-year outcomes [mortality, heart transplantation, ventricular assist devices (VAD)] between VA-triggered and non-VA-triggered CS.MethodsFRENSHOCK is a prospective multicenter registry including 772 CS patients from 49 centers. One to three triggers can be identified in the registry (ischemic, mechanical complications, ventricular/supraventricular arrhythmia, bradycardia, iatrogenesis, infection, non-compliance). Baseline characteristics, management and 1-year outcomes were analyzed according to the VA-trigger in the CS population.ResultsWithin 769 CS patients included, 94 were VA-triggered (12.2%) and were compared to others. At 1 year, although there was no mortality difference [42.6 vs. 45.3%, HR 0.94 (0.67–1.30), p = 0.7], VA-triggered CS resulted in more heart transplantations and VAD (17 vs. 9%, p = 0.02). Into VA-triggered CS group, though there was no 1-year mortality difference between ischemic and non-ischemic cardiomyopathies [42.5 vs. 42.6%, HR 0.97 (0.52–1.81), p = 0.92], non-ischemic cardiomyopathy led to more heart transplantations and VAD (25.9 vs. 5%, p = 0.02).ConclusionVA-triggered CS did not show higher mortality compared to other triggers but resulted in more heart transplantation and VAD at 1 year, especially in non-ischemic cardiomyopathy, suggesting the need for earlier evaluation by advanced heart failure specialized team for a possible indication of mechanical circulatory support or heart transplantation.Clinical trial registrationhttps://clinicaltrials.gov, identifier NCT02703038.

Major maritime carriers are globally demanding improvements in the efficiency of port operations. Cargo carried by ships must be loaded and unloaded quickly with minimal stopover time in the port. This requirement mandates seaports to deploy cutting-edge technology to the port area so that logistic processes are increasingly efficient and reliable. In this scenario, the attack surface of such critical infrastructure is growing very rapidly and advanced security techniques must be deployed to enforce a high attack resilience. A Distributed Ledger-based Credential Management System exploiting a Distributed Ledger Technology (DLT) to enable transparent and real-time tracking of logistic vehicles and cargos within a terminal is presented in this paper. Based on a customization of Vehicular Ad-Hoc Network (VANET) security standards, the proposed scheme provides authentication, authorization, and revocation capabilities to promptly exclude misbehaving logistic vehicles from the system, while maintaining an immutable record of all the logistic vehicles’ activity. The laboratory validation demonstrates that the delay of the devised scheme is not dependent on the quay area capacity, thus being applicable in seaports of any size. Furthermore, the effectiveness of the solution is demonstrated with the field trial results obtained with the EU Horizon 2020 COREALIS project testbed deployed in the Port of Livorno.

Background: Vascular and bleeding events remain the main complications after balloon aortic valvuloplasty (BAV). While BAV is usually performed with per procedural heparin injection, BAV performed without heparin may reduce hemorrhagic events. We aimed to determine whether vascular and bleeding complications may be reduced with BAV performed without heparin. Methods: This randomized, double-blind, placebo-controlled study was conducted from January 2013 to September 2016. Patients were randomly assigned to placebo or intravenous unfractionated heparin (UH) 50 IU/kg bolus during the procedure. The primary endpoint included major vascular, bleeding and ischemic complications (stroke, transient ischemic attack, myocardial infarction) according to VARC-2 criteria. Results: Among 89 randomized patients, 82 completed the study (n = 39 in the UH group and n = 43 in the placebo group). At baseline, diabetes, sex male and renal failure were more frequent in the UH group and peripheral artery disease was more frequent in the placebo group. The primary endpoint was achieved in 7 patients (8.5%), 1 in the placebo group (2.3%) versus 6 in the UH group (15.4%). After adjustment on diabetes, sex, renal failure, peripheral artery disease, percutaneous closure device and chronic obstructive pulmonary disease, UH utilization was associated with a significant risk of major vascular, bleeding and ischemic complications (primary endpoint) (adjOR: 11.9; 95%CI: 1.2–117.2; p = 0.03). Hospitalization length was lower in the placebo group compared to the UH group (p = 0.03). Conclusions: BAV without per procedural UH was associated with a reduction of major VC and bleeding events without increasing the ischemic risk and with a shorter hospitalization length.

Ribosomes are essential nanomachines responsible for protein production. Although ribosomes are present in every living cell, ribosome biogenesis dysfunction diseases, called ribosomopathies, impact particular tissues specifically. Here, we evaluate the importance of the box C/D snoRNA-associated ribosomal RNA methyltransferase fibrillarin (Fbl) in the early embryonic development of Xenopus laevis. We report that in developing embryos, the neural plate, neural crest cells (NCCs), and NCC derivatives are rich in fbl transcripts. Fbl knockdown leads to striking morphological defects affecting the eyes and craniofacial skeleton, due to lack of NCC survival caused by massive p53-dependent apoptosis. Fbl is required for efficient pre-rRNA processing and 18S rRNA production, which explains the early developmental defects. Using RiboMethSeq, we systematically reinvestigated ribosomal RNA 2'-O methylation in X. laevis, confirming all 89 previously mapped sites and identifying 15 novel putative positions in 18S and 28S rRNA. Twenty-three positions, including 10 of the new ones, were validated orthogonally by low dNTP primer extension. Bioinformatic screening of the X. laevis transcriptome revealed candidate box C/D snoRNAs for all methylated positions. Mapping of 2'-O methylation at six developmental stages in individual embryos indicated a trend towards reduced methylation at specific positions during development. We conclude that fibrillarin knockdown in early Xenopus embryos causes reduced production of functional ribosomal subunits, thus impairing NCC formation and migration.

Background: Increased risk of new-onset atrial fibrillation (AF) after patent foramen ovale (PFO) closure was observed in randomized trials without however systematic AF screening. We aimed to evaluate the incidence of AF within 6-month following PFO closure with serial 24-hour ambulatory electrocardiogram (AECG) monitoring. Methods: All patients undergoing PFO closure were prospectively included in 2 centers. AF was defined as irregular rhythm without discernible P waves > 30 s on AECG at day 0, 1-month and 6-month follow-up. Primary endpoint was the incidence of AF within the study period. Secondary endpoints evaluated clinical outcomes within 6-month follow-up. Results: Between February 2018 and March 2019, 62 patients underwent PFO closure including 40 male (64.5%) with a mean age of 48 ± 9.5. Atrial septal aneurysm was observed in 37 patients (64.9%), 57 patients (91.9%) received an Amplatzer Occluder device (Abbott Vascular) and 5 (8.1%) an Occlutech device (Occlutech). After a mean follow-up of 7.7 ± 2.8 months, new-onset AF occurred in 3 patients (4.8%), all within the first month following PFO closure, including one per-procedural, all were asymptomatic and paroxysmal. Two patients with AF (3.2%) required chronic oral anticoagulant therapy. No adverse outcomes occurred at follow-up. No predictive factors of AF were highlighted. A total of 16 patients (25.8%) reported palpitations without AF on the AECGs. Conclusion: In highly selected patients, incidence of AF, evaluated with 3 systematic 24-hour AECG within 6-month following PFO closure, was low (

There is a large heterogeneity among patients presenting with cardiogenic shock (CS). It is crucial to better apprehend this heterogeneity in order to adapt treatments and improve prognoses in these severe patients. Notably, the presence (or absence) of a pre-existing history of chronic heart failure (CHF) at time of CS onset may be a significant part of this heterogeneity, and data focusing on this aspect are lacking. We aimed to compare CS patients with new-onset HF to those with worsening CHF in the multicenter FRENSHOCK registry. Altogether, 772 CS patients were prospectively included: 433 with a previous history of CHF and 339 without. Worsening CHF patients were older (68 +/− 13.4 vs. 62.7 +/− 16.2, p < 0.001) and had a greater burden of extra-cardiac comorbidities. At admission, acute myocardial infarction was predominantly observed in the new-onset HF group (49.9% vs. 25.6%, p < 0.001). When focusing on hemodynamic parameters, worsening CHF patients showed more congestion and higher ventricular filling pressures. Worsening CHF patients experienced higher in-hospital all-cause mortality (31.3% vs. 24.2%, p = 0.029). Our results emphasize the great heterogeneity of the patients presenting with CS. Worsening CHF patients had higher risk profiles, and this translated to a 30% increase in in-hospital all-cause mortality. The heterogeneity of this population prompts us to better determine the phenotype of CS patients to adapt their management.