Ordering CT pulmonary angiography to exclude pulmonary embolism: defense versus evidence in the emergency room

Purpose: To identify reasons for ordering computed tomography pulmonary angiography (CTPA), to identify the frequency of reasons for CTPA reflecting defensive behavior and evidence-based behavior, and to identify the impact of defensive medicine and of training about diagnosing pulmonary embolism (PE) on positive results of CTPA. Methods: Physicians in the emergency department of a tertiary care hospital completed a questionnaire before CTPA after being trained about diagnosing PE and completing questionnaires. Results: Nine hundred patients received a CTPA during 3years. For 328 CTPAs performed during the 1-year study period, 140 (43%) questionnaires were completed. The most frequent reasons for ordering a CTPA were to confirm/rule out PE (93%), elevated D-dimers (66%), fear of missing PE (55%), and Wells/simplified revised Geneva score (53%). A positive answer for "fear of missing PE” was inversely associated with positive CTPA (OR 0.36, 95% CI 0.14-0.92, p=0.033), and "Wells/simplified revised Geneva score” was associated with positive CTPA (OR 3.28, 95% CI 1.24-8.68, p=0.017). The proportion of positive CTPA was higher if a questionnaire was completed, compared to the 2-year comparison period (26.4 vs. 14.5%, OR 2.12, 95% CI 1.36-3.29, p<0.001). The proportion of positive CTPA was non-significantly higher during the study period than during the comparison period (19.2 vs. 14.5%, OR 1.40, 95% CI 0.98-2.0, p=0.067). Conclusion: Reasons for CTPA reflecting defensive behavior—such as "fear of missing PE”—were frequent, and were associated with a decreased odds of positive CTPA. Defensive behavior might be modifiable by training in using guideline

The herpesviral Fc receptor fcr-1 down-regulates the NKG2D ligands MULT-1 and H60

Members of the α- and β-subfamily of herpesviridae encode glycoproteins that specifically bind to the Fc part of immunoglobulin (Ig)G. Plasma membrane resident herpesviral Fc receptors seem to prevent virus-specific IgG from activating antibody-dependent effector functions. We show that the mouse cytomegalovirus (MCMV) molecule fcr-1 promotes a rapid down-regulation of NKG2D ligands murine UL16-binding protein like transcript (MULT)-1 and H60 from the cell surface. Deletion of the m138/fcr-1 gene from the MCMV genome attenuates viral replication to natural killer (NK) cell response in an NKG2D-dependent manner in vivo. A distinct N-terminal module within the fcr-1 ectodomain in conjunction with the fcr-1 transmembrane domain was required to dispose MULT-1 to degradation in lysosomes. In contrast, down-modulation of H60 required the complete fcr-1 ectodomain, implying independent modes of fcr-1 interaction with the NKG2D ligands. The results establish a novel viral strategy for down-modulating NK cell responses and highlight the impressive diversity of Fc receptor functions

Temporal variability of CO2 and N2O flux spatial patterns at a mowed and a grazed grassland

Spatial patterns of ecosystem processes constitute significant sources of uncertainty in greenhouse gas flux estimations partly because the patterns are temporally dynamic. The aim of this study was to describe temporal variability in the spatial patterns of grassland CO2 and N2O flux under varying environmental conditions and to assess effects of the grassland management (grazing and mowing) on flux patterns. We made spatially explicit measurements of variables including soil respiration, aboveground biomass, N2O flux, soil water content, and soil temperature during a four-year study in the vegetation periods at grazed and mowed grasslands. Sampling was conducted in 80×60 m grids of 10 m resolution with 78 sampling points in both study plots. Soil respiration was monitored nine times, and N2O flux was monitored twice during the study period. Altitude, soil organic carbon, and total soil nitrogen were used as background factors at each sampling position, while aboveground biomass, soil water content, and soil temperature were considered as covariates in the spatial analysis. Data were analyzed using variography and kriging. Altitude was autocorrelated over distances of 40–50 m in both plots and influenced spatial patterns of soil organic carbon, total soil nitrogen, and the covariates. Altitude was inversely related to soil water content and aboveground biomass and positively related to soil temperature. Autocorrelation lengths for soil respiration were similar on both plots (about 30 m), whereas autocorrelation lengths of N2O flux differed between plots (39 m in the grazed plot vs. 18 m in the mowed plot). Grazing appeared to increase heterogeneity and linkage of the spatial patterns, whereas mowing had a homogenizing effect. Spatial patterns of soil water content, soil respiration, and aboveground biomass were temporally variable especially in the first 2 years of the experiment, whereas spatial patterns were more persistent (mostly significant correlation at p<0.05 between location ranks) in the second 2 years, following a wet year. Increased persistence of spatial patterns after a wet year indicated the recovery potential of grasslands following drought and suggested that adequate water supply could have a homogenizing effect on CO2 and N2O fluxes

Association of Ficolin-3 with Severity and Outcome of Chronic Heart Failure

BACKGROUND: Inflammatory mechanisms involving complement activation has been shown to take part in the pathophysiology of congestive heart failure, but the initiating mechanisms are unknown. We hypothesized that the main initiator molecules of the lectin complement pathway mannose-binding lectin (MBL), ficolin-2 and ficolin-3 were related to disease severity and outcome in chronic heart failure. METHODS AND RESULTS: MBL, ficolin-2 and ficolin-3 plasma concentrations were determined in two consecutive cohorts comprising 190 patients from Hungary and 183 patients from Norway as well as controls. Disease severity and clinical parameters were determined at baseline, and all-cause mortality was registered after 5-years follow-up. In univariate analysis a low level of ficolin-3, but not that of MBL or ficolin-2, was significantly associated with advanced heart failure (New York Heart Association Class IV, p<0.001 for both cohorts) and showed inverse correlation with B- type natriuretic peptide (BNP) levels (r = -0.609, p<0.001 and r = -0.467, p<0.001, respectively). In multivariable Cox regression analysis, adjusted for age, gender and BNP, decreased plasma ficolin-3 was a significant predictor of mortality (HR 1.368, 95% CI 1.052-6.210; and HR 1.426, 95% CI 1.013-2.008, respectively). Low ficolin-3 levels were associated with increased complement activation product C3a and correspondingly decreased concentrations of complement factor C3. CONCLUSIONS: This study provides evidence for an association of low ficolin-3 levels with advanced heart failure. Concordant results from two cohorts show that low levels of ficolin-3 are associated with advanced heart failure and outcome. The decrease of ficolin-3 was associated with increased complement activation

Peanut‐induced anaphylaxis in children and adolescents: Data from the European Anaphylaxis Registry

Background Peanut allergy has a rising prevalence in high-income countries, affecting 0.5%-1.4% of children. This study aimed to better understand peanut anaphylaxis in comparison to anaphylaxis to other food triggers in European children and adolescents. Methods Data was sourced from the European Anaphylaxis Registry via an online questionnaire, after in-depth review of food-induced anaphylaxis cases in a tertiary paediatric allergy centre. Results 3514 cases of food anaphylaxis were reported between July 2007 - March 2018, 56% in patients younger than 18 years. Peanut anaphylaxis was recorded in 459 children and adolescents (85% of all peanut anaphylaxis cases). Previous reactions (42% vs. 38%; p = .001), asthma comorbidity (47% vs. 35%; p < .001), relevant cofactors (29% vs. 22%; p = .004) and biphasic reactions (10% vs. 4%; p = .001) were more commonly reported in peanut anaphylaxis. Most cases were labelled as severe anaphylaxis (Ring&Messmer grade III 65% vs. 56% and grade IV 1.1% vs. 0.9%; p = .001). Self-administration of intramuscular adrenaline was low (17% vs. 15%), professional adrenaline administration was higher in non-peanut food anaphylaxis (34% vs. 26%; p = .003). Hospitalization was higher for peanut anaphylaxis (67% vs. 54%; p = .004). Conclusions The European Anaphylaxis Registry data confirmed peanut as one of the major causes of severe, potentially life-threatening allergic reactions in European children, with some characteristic features e.g., presence of asthma comorbidity and increased rate of biphasic reactions. Usage of intramuscular adrenaline as first-line treatment is low and needs to be improved. The Registry, designed as the largest database on anaphylaxis, allows continuous assessment of this condition