Value of speckle-tracking echocardiography changes in monitoring myocardial dysfunction during treatment of sepsis: potential prognostic implications

Speckle-tracking echocardiography (STE) has been increasingly used for detection of sepsis-related myocardial dysfunction. However, the impact of strain changes during sepsis treatment has not been defined. This study assessed STE at admission and during the treatment of patients with sepsis to evaluate its changes as a potential factor for predicting in-hospital outcome. This study included 26 patients with sepsis who underwent STE echocardiography on day 1 and 7 during treatment. Myocardial deformation of both ventricles was assessed using global longitudinal strain. The endpoint was in-hospital mortality. The mean age was 51.4±18.3 years, and 54% were female. The average SOFA score at T0 was 8.6±3.8 points and at day 7 was 4.9±4.7 points. The left ventricular (LV) ejection fraction at baseline was 65.6±9.1%, without changes in echocardiographic parameters during treatment. LV and RV longitudinal strain increased significantly in the patients who survived (− 18.8±3.6 at D1 vs − 20.8±2.5 at D7; p=0.003; and −21.3±4.9 at D1 vs − 24.3±5.8 at D7; p=0.035, respectively), whereas strain values remained unchanged in those who died. After adjustment for the SOFA score, RV longitudinal strain at admission was associated with in-hospital mortality [adjusted odds ratio (OR) 0.760; 95% confidence interval (CI) 0.591–0.977; p −0.033]. STE improved significantly after the first week of treatment in patients with sepsis who survived compared with those patients who died during hospitalization. RV strain at admission predicted in-hospital mortality. An improvement in STE during sepsis treatment appears to be a useful tool for predicting in-hospital outcome

Autologous serum skin test reactions in chronic spontaneous urticaria differ from heterologous cell reactions

Background: Autoimmune chronic spontaneous urticaria (CSU) is due to mast cell (MC)-activating autoantibodies, which are screened for by the autologous serum skin test (ASST) and basophil tests (BTs). Many CSU patients are positive in only one of these tests. How often this occurs and why is currently unknown. Objectives: To characterize the prevalence of mismatched ASST and BTs in CSU patients, and to investigate possible reasons for these mismatches. Methods: We determined the rates of ASST+/BT- and ASST-/BT+ mismatches in published CSU studies. We assessed sera from 48 CSU patients by ASST, two BTs (basophil histamine release assay, BHRA; basophil activation test, BAT), a MC histamine release assay (MCHRA) and by ex vivo skin microdialysis (SMD). Results: The ASST/BT mismatch rate in published CSU studies was 31% (ASST+/BT-: 22%, ASST-/BT+: 9%). In our patients, the ASST/BHRA and ASST/BAT mismatch rate was 35.4% (ASST+/BHRA-: 18.8% and ASST-/BHRA+: 16.7%) and 31.3% (ASST+/BAT-: 6.3% and ASST-/BAT+: 25.0%), respectively, and the two BTs were significantly correlated (P = 0.0002). The use of heterologous MCs, in vitro and in situ, instead of basophils produced similar results (MCHRA mismatch: 47.9%, ASST+/MCHRA-: 18.8%, ASST-/MCHRA+: 29.2%; SMD mismatch: 40.0%, ASST+/SMD-: 10.0% and ASST-/SMD+: 30.0%), and the MCHRA was highly correlated with SMD results (P = 0.0002). Conclusions: The ASST and BTs show divergent results in a third of CSU patients. Mismatches cannot be explained by the choice of basophil assay, the type of heterologous cells exposed to CSU serum in vitro (basophils vs. mast cells), nor the experimental setting of heterologous skin mast cells (in vitro vs. in situ). Thus, serum-induced whealing, in CSU patients, seems to involve autologous skin signals modulating MC degranulation

Identification of drug candidates targeting monocyte reprogramming in people living with HIV

INTRODUCTION: People living with HIV (PLHIV) are characterized by functional reprogramming of innate immune cells even after long-term antiretroviral therapy (ART). In order to assess technical feasibility of omics technologies for application to larger cohorts, we compared multiple omics data layers. METHODS: Bulk and single-cell transcriptomics, flow cytometry, proteomics, chromatin landscape analysis by ATAC-seq as well as ex vivo drug stimulation were performed in a small number of blood samples derived from PLHIV and healthy controls from the 200-HIV cohort study. RESULTS: Single-cell RNA-seq analysis revealed that most immune cells in peripheral blood of PLHIV are altered in their transcriptomes and that a specific functional monocyte state previously described in acute HIV infection is still existing in PLHIV while other monocyte cell states are only occurring acute infection. Further, a reverse transcriptome approach on a rather small number of PLHIV was sufficient to identify drug candidates for reversing the transcriptional phenotype of monocytes in PLHIV. DISCUSSION: These scientific findings and technological advancements for clinical application of single-cell transcriptomics form the basis for the larger 2000-HIV multicenter cohort study on PLHIV, for which a combination of bulk and single-cell transcriptomics will be included as the leading technology to determine disease endotypes in PLHIV and to predict disease trajectories and outcomes

Astronomical Distance Determination in the Space Age: Secondary Distance Indicators

The formal division of the distance indicators into primary and secondary leads to difficulties in description of methods which can actually be used in two ways: with, and without the support of the other methods for scaling. Thus instead of concentrating on the scaling requirement we concentrate on all methods of distance determination to extragalactic sources which are designated, at least formally, to use for individual sources. Among those, the Supernovae Ia is clearly the leader due to its enormous success in determination of the expansion rate of the Universe. However, new methods are rapidly developing, and there is also a progress in more traditional methods. We give a general overview of the methods but we mostly concentrate on the most recent developments in each field, and future expectations. © 2018, The Author(s)