Summary
We assessed the diagnostic potential of erythroferrone as a biomarker for iron homeostasis comparing iron deficiency cases with anaemia of inflammation and controls. The dysregulation of the ...hepcidin axis was observed by Latour et al. in a mouse model of malarial anaemia induced by prolonged Plasmodium infection leading to increased erythroferrone concentrations. In line with that, we found significantly higher erythroferrone levels in cases with malaria and anaemia in an African population, compared to asymptomatic controls. Therefore, our findings extend the previous ones of the mouse model, suggesting also a dysregulation of the hepcidin axis in humans, which should be further corroborated in prospective studies and may lay the basis for the development of improved treatment strategies according to ERFE concentrations in such patients.
To describe admission characteristics, risk factors and outcomes of patients with coronavirus disease 2019 (COVID-19) hospitalised in a tertiary care hospital in Switzerland during the early phase of ...the pandemic.
This retrospective cohort study included adult patients with a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection confirmed by polymerase chain reaction (PCR) testing and hospitalised at the cantonal hospital Aarau (Switzerland) between 26 February 2020 and 30 April 2020. Our primary endpoint was severe COVID-19 progression defined as a composite of transfer to the intensive care unit (ICU) and in-hospital mortality.
A total of 99 patients (median age 67 years interquartile range 56-76, 37% females) were included and 35% developed severe COVID-19 progression (24% needed ICU treatment, 19% died). Patients had a high burden of comorbidities with a median Charlson comorbidity index of 3 points and a high prevalence of hypertension (57%), chronic kidney disease (28%) and obesity (27%). Baseline characteristics with the highest prognostic value for the primary endpoint by means of area under the receiver operating characteristic curve were male gender (0.63) and initial laboratory values including shock markers (lactate on ambient air 0.67; lactate with O2 supply 0.70), markers of inflammation (C-reactive protein 0.72, procalcitonin 0.80) and markers of compromised oxygenation (pO2 0.75 on ambient air), whereas age and comorbidities provided little prognostic information.
This analysis provides insights into the first consecutively hospitalised patients with confirmed COVID-19 at a Swiss tertiary care hospital during the initial period of the pandemic. Markers of disease progression such as inflammatory markers, markers for shock and impaired respiratory function provided the most prognostic information regarding severe COVID-19 progression in our sample.
Midregional pro-adrenomedullin (MR-proADM) is a vasoactive peptide with key roles in reducing vascular hyperpermeability and thereby improving endothelial stability during infection. While MR-proADM ...is useful for risk stratification in patients with sepsis, clinical data about prediction accuracy in patients with severe acute respiratory syndrome coronavirus 2 disease (COVID-19) is currently missing.
We included consecutively adult patients hospitalized for confirmed COVID-19 at a tertiary care center in Switzerland between February and April 2020. We investigated the association of MR-proADM levels with in-hospital mortality in logistic regression and discrimination analyses.
Of 89 included COVID-19 patients, 19% (n=17) died while in the hospital. Median admission MR-proADM levels (nmol/L) were increased almost 1.5-fold increased in non-survivors compared to survivors (1.3 interquartile range IQR 1.1-2.3) vs. 0.8 IQR 0.7-1.1) and showed good discrimination (area under the curve 0.78). An increase of 1 nmol/L of admission MR-proADM was independently associated with a more than fivefold increase in in-hospital mortality (adjusted odds ratio of 5.5, 95% confidence interval 1.4-21.4, p=0.015). An admission MR-proADM threshold of 0.93 nmol/L showed the best prognostic accuracy for in-hospital mortality with a sensitivity of 93%, a specificity of 60% and a negative predictive value of 97%. Kinetics of follow-up MR-proADM provided further prognostic information for in-hospital treatment.
Increased levels of MR-proADM on admission and during hospital stay were independently associated with in-hospital mortality and may allow a better risk stratification, and particularly rule-out of fatal outcome, in COVID-19 patients.
Background The quantification of serum IgG4 is commonly performed during the diagnostic workup of IgG4-related diseases (IgG4-RD). According to recent literature, IgG4 values above 1.35 g/L are ...characteristic of IgG4-RD and support its diagnosis at initial presentation. The purpose of this study was to evaluate comparability and accuracy of the two main commercially available IgG4 assays (Siemens Healthineers and The Binding Site). Methods Method comparison was performed for IgG and IgG subclasses using a collective of selected samples with elevated serum IgG4. In addition, we assessed the accuracy of both assays using purified polyclonal and monoclonal IgG4 preparations. Results Our data show significant discrepancies between the two IgG subclass assays for the measurement of IgG4 and, to a lesser extent, IgG3. Conclusions The lack of standardization between the two main providers of commercially available IgG4 assays leads to significant inter-assay result discrepancies, which might potentially cause unnecessary clinical workup. We conclude that serum IgG4 assay-specific decision limits, and not an assay-independent single cut-off level for IgG4 (e.g. 1.35 g/L), should be used when assessing patients for IgG4-RD. An internationally recognized, certified reference material for IgG subclasses is urgently needed, and assay manufactures are encouraged to undertake steps toward standardization of measurements of IgG4 and other IgG subclasses.
Background
We compared high‐sensitivity cardiac troponin T (hs‐cTnT) and standard cTnT for acute myocardial infarction (AMI) diagnosis in everyday clinical practice of an emergency department (ED).
...Methods and Results
cTnT was measured in 2384 consecutive patients (60±21 years, 52% female) on ED admission. Readmissions to the ED (n=720) and mortality (n=101) were followed for an average period of 239±49 days. There were 53 AMIs (delay, 1 to 96 hours; median, 3 hours), 440 chest pain patients, 286 dyspnea patients, 785 acute or chronic cardiac diseases, and 540 neurological diseases, with the remaining having various internal diseases. The diagnostic performances of hs‐ and standard cTnT were comparable for AMI diagnosis (area under receiver operating characteristics curves ROC AUC, 0.91±0.02 versus 0.90±0.03; P=0.31). Using the 99th‐percentile cutoff, the sensitivities and specificities for AMI in the whole population were 91% and 74% for hs‐cTnT and 89% and 80% for standard cTnT. hs‐cTnT detected significantly more patients with cardiac diseases (ROC AUC, 0.77±0.01 versus 0.67±0.01; P<0.001). hs‐cTnT and standard cTnT were significant predictors of ED readmissions but not of mortality, but both were not independent predictors of ED readmissions or the combined end point of readmission or mortality in binary logistic regression analysis.
Conclusions
In unselected ED patients the diagnostic performances of hs‐cTnT and standard cTnT for AMI diagnosis did not differ significantly. hs‐cTnT detected significantly more cardiac diseases. hs‐cTnT and standard cTnT were not independent predictors of ED readmissions and mortality from all causes.
Abstract
Background
Asymptomatic
Plasmodium falciparum
parasitaemia forms a reservoir for the transmission of malaria disease in West Africa. Certain haemoglobin variants are known to protect against ...severe malaria infection. However, data on the potential roles of haemoglobin variants and nongenetic factors in asymptomatic malaria infection is scarce and controversial. Therefore, this study investigated the associations of iron homeostasis, inflammation, nutrition, and haemoglobin mutations with parasitaemia in an asymptomatic cohort from a
P. falciparum
-endemic region during the high transmission season.
Methods
A sub-study population of 688 asymptomatic individuals (predominantly children and adolescents under 15 years, n = 516) from rural Burkina Faso previously recruited by the NOVAC trial (NCT03176719) between June and October 2017 was analysed. Parasitaemia was quantified with conventional haemocytometry. The haemoglobin genotype was determined by reverse hybridization assays targeting a selection of 21
HBA
and 22
HBB
mutations. Demographics, inflammatory markers (interleukins 6 and 10, hepcidin), nutritional status (mid upper-arm circumference and body mass index), and anaemia (total haemoglobin, ferritin, soluble transferrin receptor) were assessed as potential predictors through logistic regression.
Results
Malaria parasites were detected in 56% of subjects. Parasitaemia was associated most strongly with malnutrition. The effect size increased with malnutrition severity (OR = 6.26, CI
95
: 2.45–19.4, p < 0.001). Furthermore, statistically significant associations (p < 0.05) with age, cytokines, hepcidin and heterozygous haemoglobin S were observed.
Conclusions
According to these findings, asymptomatic parasitaemia is attenuated by haemoglobin S, but not by any of the other detected genotypes. Aside from evidence for slight iron imbalance, overall undernutrition was found to predict parasitaemia; thus, further investigations are required to elucidate causality and inform strategies for interventions.
Unstable hemoglobinopathies are rare inherited disorders of hemoglobin causing a reduction of hemoglobin molecule solubility. This results in an unstable hemoglobin tetramer/globin polypeptide, which ...precipitates within the red blood cell. Affected red blood cells have a reduced lifespan due to oxidative stress and cellular rigidity, and tend to be phagocytized by spleen macrophages more rapidly. Unstable hemoglobin is frequently under- or misdiagnosed, because its clinical presentation varies broadly. Therefore, testing for unstable hemoglobinopathies is indicated in cases of unexplained hemolytic anemia. However, this approach is not systematically followed in clinical practice.
A 25-year-old Caucasian man with a recent history of a presumed viral upper respiratory infection was referred to the hematology outpatient clinic because of hemolytic anemia. The patient had scleral icterus, moderate splenomegaly, and mild macrocytic anemia with high reticulocyte count. Unconjugated bilirubin and lactate dehydrogenase were elevated. Haptoglobin was undetectable. Direct antiglobulin test was negative. Blood smear examination revealed anisopoikilocytosis, polychromasia, bite cells, and basophilic stippling, but no Heinz bodies. High-performance liquid chromatography and capillary electrophoresis showed slightly increased hemoglobin A2, normal fetal hemoglobin, and a variant hemoglobin. Deoxyribonucleic Acid sequencing revealed the heterozygous mutation c430delC in the beta-globin gene hallmark of hemoglobin Montreal II and the heterozygous mutation c287C>T in the alpha-globin gene corresponding to hemoglobin G-Georgia, indicative of the not yet described combination of double-heterozygous hemoglobin Montreal II and hemoglobin G-Georgia variants. Hemoglobinopathy Montreal II was here not associated with β-thalassemia syndrome, and carriers did not show ineffective erythropoiesis. In addition to the case report, we provide information about the largest pedigree with hemoglobinopathy Montreal II identified to date.
We emphasize that a transitory acute condition may uncover an underlying inherited red blood cell disorder. In this regard, awareness should be raised among hematologists caring for adult patients that unstable hemoglobinopathies should be considered in the differential diagnosis of unexplained hemolytic anemias.
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) disease (COVID-19) has been linked to thrombotic complications and endothelial dysfunction. We assessed the prognostic implications of ...endothelial activation through measurement of endothelin-I precursor peptide (proET-1), the stable precursor protein of Endothelin-1, in a well-defined cohort of patients hospitalized with COVID-19.
We measured proET-1 in 74 consecutively admitted adult patients with confirmed COVID-19 and compared its prognostic accuracy to that of patients with community-acquired pneumonia (n = 876) and viral bronchitis (n = 371) from a previous study by means of logistic regression analysis. The primary endpoint was all-cause 30-day mortality.
Overall, median admission proET-1 levels were lower in COVID-19 patients compared to those with pneumonia and exacerbated bronchitis, respectively (57.0 pmol/l vs. 113.0 pmol/l vs. 96.0 pmol/l, p < 0.01). Although COVID-19 non-survivors had 1.5-fold higher admission proET-1 levels compared to survivors (81.8 pmol/l IQR: 76 to 118 vs. 53.6 IQR: 37 to 69), no significant association of proET-1 levels and mortality was found in a regression model adjusted for age, gender, creatinine level, diastolic blood pressure as well as cancer and coronary artery disease (adjusted OR 0.1, 95% CI 0.0009 to 14.7). In patients with pneumonia (adjusted OR 25.4, 95% CI 5.1 to 127.4) and exacerbated bronchitis (adjusted OR 120.1, 95% CI 1.9 to 7499) we found significant associations of proET-1 and mortality.
Compared to other types of pulmonary infection, COVID-19 shows only a mild activation of the endothelium as assessed through measurement of proET-1. Therefore, the high mortality associated with COVID-19 may not be attributed to endothelial dysfunction by the surrogate marker proET-1.
Laboratories continue to offer myoglobin, creatine kinase, and the creatine MB isoenzyme for the diagnosis of MI, despite the documented inferiority of these tests to cardiac troponin measurement and ...despite the guideline recommendations. Author Contributions: All authors confirmed they have contributed to the intellectual content of this paper and have met the following 3 requirements: (a) significant contributions to the conception and design, acquisition of data, or analysis and interpretation of data; (b) drafting or revising the article for intellectual content; and (c) final approval of the published article.
Emerging biomarkers for cardiac arrhythmias Hammerer-Lercher, Angelika; Namdar, Mehdi; Vuilleumier, Nicolas
Clinical biochemistry,
January 2020, 2020-Jan, 2020-01-00, 20200101, Letnik:
75
Journal Article
Recenzirano
•Biomarkers predicting prognosis and relapse in cardiac arrhythmias are still needed.•Inflammation and autoimmunity impair fibroblast and cardiac ion channels functions.•Biomarkers of inflammation, ...fibrosis, and autoimmunity are appealing candidates.•Such biomarkers may improve recognition and risk stratification of arrhythmias. If causal mediators, such biomarkers could represent emergent therapeutic targets.
Cardiac arrhythmias are associated with substantial morbidity and mortality. Recent advances in the pathophysiological understanding of cardiac arrhythmia indicate that inflammation, fibrosis, and even autoimmune mechanisms could facilitate the development of arrhythmias by interfering either with fibroblast activation-related electrical remodeling or with the function of different cardiac ion channels, leading to the emerging concepts of autoimmune and inflammatory channelopathies. In this descriptive review, we considered recent data of the literature focusing on biomarkers reflecting the degree of inflammation, myocardial stretch, fibrosis and sustained B-cell activation as potential additional diagnostic, risk stratification tools and potential therapeutic targets in cardiac arrhythmia.
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