Heart failure patients demonstrate impaired changes in brachial artery blood flow and shear rate pattern during moderate-intensity cycle exercise

New Findings What is the central question of this study? We explored whether heart failure (HF) patients demonstrate different exercise-induced brachial artery shear rate patterns compared with control subjects. What is the main finding and its importance? Moderate-intensity cycle exercise in HF patients is associated with an attenuated increase in brachial artery anterograde and mean shear rate and skin temperature. Differences between HF patients and control subjects cannot be explained fully by differences in workload. HF patients demonstrate a less favourable shear rate pattern during cycle exercise compared with control subjects. Repeated elevations in shear rate (SR) in conduit arteries, which occur during exercise, represent a key stimulus to improve vascular function. We explored whether heart failure (HF) patients demonstrate distinct changes in SR in response to moderate-intensity cycle exercise compared with healthy control subjects. We examined brachial artery SR during 40 min of cycle exercise at a work rate equivalent to 65% peak oxygen uptake in 14 HF patients (65 ± 7 years old, 13 men and one woman) and 14 control subjects (61 ± 5 years old, 12 men and two women). Brachial artery diameter, SR and oscillatory shear index (OSI) were assessed using ultrasound at baseline and during exercise. The HF patients demonstrated an attenuated increase in mean and anterograde brachial artery SR during exercise compared with control subjects (time × group interaction, P = 0.003 and P 0.05). In conclusion, HF patients demonstrate a less favourable SR pattern during cycle exercise than control subjects, characterized by an attenuated mean and anterograde SR and by increased OSI

Monitoring circulating dipeptidyl peptidase 3 (DPP3) predicts improvement of organ failure and survival in sepsis: a prospective observational multinational study.

BACKGROUND: Dipeptidyl peptidase 3 (DPP3) is a cytosolic enzyme involved in the degradation of various cardiovascular and endorphin mediators. High levels of circulating DPP3 (cDPP3) indicate a high risk of organ dysfunction and mortality in cardiogenic shock patients. METHODS: The aim was to assess relationships between cDPP3 during the initial intensive care unit (ICU) stay and short-term outcome in the AdrenOSS-1, a prospective observational multinational study in twenty-four ICU centers in five countries. AdrenOSS-1 included 585 patients admitted to the ICU with severe sepsis or septic shock. The primary outcome was 28-day mortality. Secondary outcomes included organ failure as defined by the Sequential Organ Failure Assessment (SOFA) score, organ support with focus on vasopressor/inotropic use and need for renal replacement therapy. cDPP3 levels were measured upon admission and 24 h later. RESULTS: Median [IQR] cDPP3 concentration upon admission was 26.5 [16.2-40.4] ng/mL. Initial SOFA score was 7 [5-10], and 28-day mortality was 22%. We found marked associations between cDPP3 upon ICU admission and 28-day mortality (unadjusted standardized HR 1.8 [CI 1.6-2.1]; adjusted HR 1.5 [CI 1.3-1.8]) and between cDPP3 levels and change in renal and liver SOFA score (p = 0.0077 and 0.0009, respectively). The higher the initial cDPP3 was, the greater the need for organ support and vasopressors upon admission; the longer the need for vasopressor(s), mechanical ventilation or RRT and the higher the need for fluid load (all p 40.4 ng/mL upon admission, a decrease in cDPP3 below 40.4 ng/mL after 24 h was associated with an improvement of organ function at 48 h and better 28-day outcome. By contrast, persistently elevated cDPP3 at 24 h was associated with worsening organ function and high 28-day mortality. CONCLUSIONS: Admission levels and rapid changes in cDPP3 predict outcome during sepsis. Trial Registration ClinicalTrials.gov, NCT02393781. Registered on March 19, 2015

Treatment patterns in anticoagulant therapy in patients with newly diagnosed atrial fibrillation in Belgium: results from the GARFIELD-AF registry

Background: AF, anticoagulation, NOACs, changing patterns of prescription. Methods: We describe baseline data and treatment patterns of patients recruited in Belgium in the Global Anticoagulant Registry in the FIELD-Atrial Fibrillation (GARFIELD-AF). Recruitment began when novel oral anticoagulants (NOACs) were introduced and provides a unique picture of changing treatment patterns over time. 1713 patients with a new (= 2), anticoagulants were used in 84.3%, leaving 15.7% unprotected. In low risk patients (CHA(2)DS(2)-VASc 0-1) anticoagulants were overused (58.7%). Factor Xa inhibitors were used more frequently than direct thrombin inhibitors. Conclusion: Guideline adherence on stroke prevention was higher in Belgium than in the rest of Europe, and increased over time. NOAC use in Belgium was the highest of Europe at the study start, with many countries catching up later. Possible reasons are discussed

Guidelines for the use of flow cytometry and cell sorting in immunological studies

International audienceThe classical model of hematopoiesis established in the mouse postulates that lymphoid cells originate from a founder population of common lymphoid progenitors. Here, using a modeling approach in humanized mice, we showed that human lymphoid development stemmed from distinct populations of CD127(-) and CD127(+) early lymphoid progenitors (ELPs). Combining molecular analyses with in vitro and in vivo functional assays, we demonstrated that CD127(-) and CD127(+) ELPs emerged independently from lympho-mono-dendritic progenitors, responded differently to Notch1 signals, underwent divergent modes of lineage restriction, and displayed both common and specific differentiation potentials. Whereas CD127(-) ELPs comprised precursors of T cells, marginal zone B cells, and natural killer (NK) and innate lymphoid cells (ILCs), CD127(+) ELPs supported production of all NK cell, ILC, and B cell populations but lacked T potential. On the basis of these results, we propose a "two-family" model of human lymphoid development that differs from the prevailing model of hematopoiesis