Plasma lipid profiles discriminate bacterial from viral infection in febrile children

Fever is the most common reason that children present to Emergency Departments. Clinical signs and symptoms suggestive of bacterial infection are often non-specific, and there is no definitive test for the accurate diagnosis of infection. The 'omics' approaches to identifying biomarkers from the host-response to bacterial infection are promising. In this study, lipidomic analysis was carried out with plasma samples obtained from febrile children with confirmed bacterial infection (n = 20) and confirmed viral infection (n = 20). We show for the first time that bacterial and viral infection produces distinct profile in the host lipidome. Some species of glycerophosphoinositol, sphingomyelin, lysophosphatidylcholine and cholesterol sulfate were higher in the confirmed virus infected group, while some species of fatty acids, glycerophosphocholine, glycerophosphoserine, lactosylceramide and bilirubin were lower in the confirmed virus infected group when compared with confirmed bacterial infected group. A combination of three lipids achieved an area under the receiver operating characteristic (ROC) curve of 0.911 (95% CI 0.81 to 0.98). This pilot study demonstrates the potential of metabolic biomarkers to assist clinicians in distinguishing bacterial from viral infection in febrile children, to facilitate effective clinical management and to the limit inappropriate use of antibiotics

Identification of regulatory variants associated with genetic susceptibility to meningococcal disease.

Non-coding genetic variants play an important role in driving susceptibility to complex diseases but their characterization remains challenging. Here, we employed a novel approach to interrogate the genetic risk of such polymorphisms in a more systematic way by targeting specific regulatory regions relevant for the phenotype studied. We applied this method to meningococcal disease susceptibility, using the DNA binding pattern of RELA - a NF-kB subunit, master regulator of the response to infection - under bacterial stimuli in nasopharyngeal epithelial cells. We designed a custom panel to cover these RELA binding sites and used it for targeted sequencing in cases and controls. Variant calling and association analysis were performed followed by validation of candidate polymorphisms by genotyping in three independent cohorts. We identified two new polymorphisms, rs4823231 and rs11913168, showing signs of association with meningococcal disease susceptibility. In addition, using our genomic data as well as publicly available resources, we found evidences for these SNPs to have potential regulatory effects on ATXN10 and LIF genes respectively. The variants and related candidate genes are relevant for infectious diseases and may have important contribution for meningococcal disease pathology. Finally, we described a novel genetic association approach that could be applied to other phenotypes

Plasma lipid profiles discriminate bacterial from viral infection in febrile children

Fever is the most common reason that children present to Emergency Departments. Clinical signs and symptoms suggestive of bacterial infection ar

Plasma lipid profiles discriminate bacterial from viral infection in febrile children

Fever is the most common reason that children present to Emergency Departments. Clinical signs and symptoms suggestive of bacterial infection are often non-specific, and there is no definitive test for the accurate diagnosis of infection. The 'omics' approaches to identifying biomarkers from the host-response to bacterial infection are promising. In this study, lipidomic analysis was carried out with plasma samples obtained from febrile children with confirmed bacterial infection (n = 20) and confirmed viral infection (n = 20). We show for the first time that bacterial and viral infection produces distinct profile in the host lipidome. Some species of glycerophosphoinositol, sphingomyelin, lysophosphatidylcholine and cholesterol sulfate were higher in the confirmed virus infected group, while some species of fatty acids, glycerophosphocholine, glycerophosphoserine, lactosylceramide and bilirubin were lower in the confirmed virus infected group when compared with confirmed bacterial infected group. A combination of three lipids achieved an area under the receiver operating characteristic (ROC) curve of 0.911 (95% CI 0.81 to 0.98). This pilot study demonstrates the potential of metabolic biomarkers to assist clinicians in distinguishing bacterial from viral infection in febrile children, to facilitate effective clinical management and to the limit inappropriate use of antibiotics

The Relation of Emergency Duties to Cardiac Death Among US Firefighters

Sudden cardiac death accounted for 42% of all firefighter duty-related fatalities over the last decade. This retrospective study analyzed available medical examiner records for duty-related firefighter fatalities among male firefighters 18 to 65 years of age that occurred between 1999 and 2014 and reported the pathoanatomic substrate for cardiac-related fatalities. Odds of duty-related cardiac death during specific duties compared with fire station duties were calculated by pathoanatomic substrate. There were 285 cardiac fatalities. Of fatalities, 80% had evidence at autopsy of coronary heart disease (CHD) and increased heart size (cardiomegaly and/or left ventricular hypertrophy). CHD alone, cardiomegaly or left ventricular hypertrophy, and causes other than CHD or increased heart size were identified in 7.7%, 6.0%, and 6.7% of fatalities, respectively. The largest proportion of deaths occurred during fire suppression (33%), although only 1% of annual occupational time was estimated to be spent performing this duty. For deaths attributed to CHD and increased heart size, fire suppression, alarm response, and physical training were associated with approximately a 112-fold, eightfold, and sevenfold increased risk of cardiac death, respectively, compared with station duties. In conclusion, the majority of firefighters who suffered a duty-related cardiac death had CHD and increased heart size, which was associated with a markedly increased risk of death during fire suppression compared with station duties. Targeted occupational medical screening for CHD and increased heart size may reduce duty-related cardiac deaths among firefighters

Pathoanatomic Findings Associated With Duty-Related Cardiac Death in US Firefighters: A Case-Control Study

Background Sudden cardiac death accounts for the greatest proportion of duty-related deaths among US firefighters. Increased understanding of the pathoanatomic causes of sudden cardiac death and the risk associated with underlying cardiac pathologies is needed to develop evidence-based screening recommendations. Methods and Results Using autopsy data for duty-related firefighter fatalities occurring between 1999 and 2014, this retrospective case-control study compared cardiac findings of male firefighters aged 18 to 65 years who died on duty of cardiac-related causes with those who died of noncardiac trauma-related causes. Data from 276 cardiac cases and 351 noncardiac trauma controls were analyzed. Among cardiac cases, the most prevalent (82%) underlying pathoanatomic substrate was comorbid coronary heart disease and cardiomegaly/left ventricular hypertrophy. Cardiac cases had a higher prevalence of cardiomegaly (heart weight >450 g), left ventricular hypertrophy (left ventricular wall thickness ≥1.2 cm), and severe coronary artery stenosis (≥75%) than trauma controls (all P450 g, coronary artery stenosis ≥75%, and evidence of a prior myocardial infarction were strong independent predictors of cardiac death, with odds ratios of 6.1 (95% confidence interval, 3.6-10.4), 9.3 (95% confidence interval, 5.3-16.1), and 6.2 (95% confidence interval, 3.4-11.3), respectively. Conclusions The majority of cardiac fatalities had evidence of both coronary heart disease and increased heart mass, and each condition was independently associated with a markedly elevated risk of cardiac death. Targeted screening for coronary heart disease, increased heart mass, and evidence of prior myocardial infarction should be considered to reduce duty-related cardiac deaths among firefighters

The Relation of Emergency Duties to Cardiac Death Among US Firefighters

Sudden cardiac death accounted for 42% of all firefighter duty-related fatalities over the last decade. This retrospective study analyzed available medical examiner records for duty-related firefighter fatalities among male firefighters 18 to 65 years of age that occurred between 1999 and 2014 and reported the pathoanatomic substrate for cardiac-related fatalities. Odds of duty-related cardiac death during specific duties compared with fire station duties were calculated by pathoanatomic substrate. There were 285 cardiac fatalities. Of fatalities, 80% had evidence at autopsy of coronary heart disease (CHD) and increased heart size (cardiomegaly and/or left ventricular hypertrophy). CHD alone, cardiomegaly or left ventricular hypertrophy, and causes other than CHD or increased heart size were identified in 7.7%, 6.0%, and 6.7% of fatalities, respectively. The largest proportion of deaths occurred during fire suppression (33%), although only 1% of annual occupational time was estimated to be spent performing this duty. For deaths attributed to CHD and increased heart size, fire suppression, alarm response, and physical training were associated with approximately a 112-fold, eightfold, and sevenfold increased risk of cardiac death, respectively, compared with station duties. In conclusion, the majority of firefighters who suffered a duty-related cardiac death had CHD and increased heart size, which was associated with a markedly increased risk of death during fire suppression compared with station duties. Targeted occupational medical screening for CHD and increased heart size may reduce duty-related cardiac deaths among firefighters

GBA1 variants in Brazilian Gaucher disease patients

Gaucher disease (GD) is an autosomal recessive lysosomal disorder caused by pathogenic variants in GBA1 which result in the deficient activity of glucocerebrosidase (GCase). There are few data on the genetic characterization of Brazilian GD patients. This study aimed at characterizing the genotype of 72 unrelated Brazilian GD patients (type I = 63, type II = 4, type III = 5; male = 31). Forty patients were from South Brazil (SB), and 32 were from other regions of Brazil (Others). The exons and exon/intron junctions of GBA1 were analyzed by Sanger sequencing in 8 patients, or by massive parallel sequencing followed by Sanger of exons 9 and 10 in 64 patients. In total, 31 pathogenic variants were identified. The most frequent allele found was N370S (p.(Asn409Ser)) (41.0%), and the most frequent genotype was N370S/RecNciI p.[Asn409Ser];[Leu483Pro;Ala495Pro;Val499=](23.6%). Three variants (N370S – in exon 9, and RecNciI and L444P (p.(Leu483Pro), in exon 10) correspond to 76.3% of total alleles in SB and 59.4% in Others. Two novel variants were described: c.326del(p.(Gln109Argfs*9)) and c.690G>A (p.(?)). Although sequencing all the exons of GBA1 is the gold-standard method for the genetic analysis of GD patients, a step analysis can be proposed for Brazilian patients, starting with analysis of exons 9 and 10. The N370S allele is the most frequently associated with GD in Brazil