Clues to Disease Activity in Juvenile Dermatomyositis: Neopterin and Other Biomarkers

Easily accessible biomarkers are urgently needed to evaluate immune activation in Juvenile Dermatomyositis (JDM). The goal of this retrospective study is to define immunological and clinical differences between untreated JDM patients with either normal or elevated (>10 mmol/L) levels of neopterin, a biomarker of macrophage activation. We included all JDM with neopterin data obtained before initiating medical therapy. We assessed T, B, NK cell populations, muscle enzymes, and disease activity scores for skin (sDAS), muscle (mDAS), total (tDAS), the duration of untreated disease, disease course, and myositis-specific antibody (MSA). Seventy-nine percent of 139 untreated JDM patients had elevated serum neopterin. The group with elevated neopterin had significantly more active disease: tDAS 11.9 vs. 8.1 (p < 0.0001), mDAS 5.8 vs. 3.1 (p < 0.0001), sDAS 6.1 vs. 4.9 (p = 0.0002), aldolase 24.0 vs. 7.6 U/L (p < 0.0001), von Willebrand factor antigen (p < 0.0001), and ESR 19.8 vs. 11.5 mm/hr (p = 0.01). The flow cytometry documented both reduced T cells (1494 vs. 2278/mm3, p = 0.008) and NK cells (145 vs. 240/mm3, p = 0.003). TNFα-308AA/AG polymorphism was more common in children with elevated neopterin than TNFα-308GG (p 0.05). We conclude that the availability of neopterin data will contribute to the rapid assessment of untreated JDM disease activity.

Role of plasma von Willebrand factor antigen in prediction of esophageal varices in pediatric and adolescent patients with portal hypertension

Background Ruptured esophageal varices (EVs) are a leading cause of death in Portal hypertension (PHT), it has been a big concern of research to screen EVs through non-invasive approaches. This study aimed to evaluate the role of plasma von Willebrand factor antigen (VWF-Ag) assay for early detection of EVs in patients with portal hypertension. This was a cross-sectional study, done on 47 portal hypertensive children and adolescents who were collected from the Pediatrics Hepatology Clinic, Children Hospital, Ain Shams University. All patients were subjected to comprehensive history taking, thorough clinical examination, routine investigations, abdominal ultrasound, upper GI endoscopy, and measurement of plasma VWF-Ag level. The patients were divided based on their endoscopic findings into two groups; a varices group which included 37 patients, and a non-varices group which included 10 patients. Results VWF-Ag rise significantly in patients with EVs, revealing a direct positive association with the degree of EVs. Conclusion The plasma VWF-Ag can be applied as a non-invasive evidence of the presence and grading of EVs.

Reliability of Plasma Von Willebrand Factor Antigen in Prediction of Oesophageal Varices in Pediatric and Adolescent Patients with Portal Hypertension

Background Ruptured oesophageal varices (OVs) is a major cause of mortality in Portal hypertension (PHT) patients, It has been a great issue of interest and research to screen and early detect OVs via oesophageal varices non-invasive methods. Objective The aim of this study was to assess the reliability of measuring plasma von willibrand factor antigen (VWF-Ag) for prediction of the occurrence of oesophageal varices in patients with portal hypertension. Subjects & Methods This was a prospective cross-sectional study, done on 47 children with portal hypertension. The children were recruited from Pediatrics Hepatology clinic, Ain Shams University. Patient’s data was collected including age, sex, etiology and duration of PHT, along with medical treatment. Also an upper GIT endoscope, abdominal doppler ultrasound, and laboratory tests including measuring of plasma VWF-Ag were done to each patient. Then the children were divided based on their endoscopic findings into two groups; variceal group which included 37 patients, and a nonvariceal group which included 10 patients Results: The results of our study revealed an elevated plasma VWF-Ag in patients with oesophageal varices, whilst normal levels of plasma VWF-Ag in the non-variceal patients. In addition, there was a direct positive correlation between increased plasma VWF-Ag and the degree of oesophageal varices. Conclusion Since the plasma VWF-Ag level correlates with the presence and degree of OVs, it can be used as a noninvasive indicator of the presence and degree of OVs, However, further studies using larger sample might be needed to support this.

Elevated von Willebrand Factor Antigen is an Early Predictor of Mortality and Prolonged Length of Stay for Coronavirus Disease 2019 (COVID-19) Inpatients

ABSTRACT Context: Coagulation factor and endothelial injury marker, von Willebrand factor antigen (vWF:Ag), is elevated in coronavirus disease 2019 (COVID-19). Objective: To assess prognostic value of vWF:Ag for COVID-19 inpatients. Design: Citrated plasma samples collected from COVID-19 inpatients for D-dimer measurement were tested for vWF:Ag. Measurements of vWF:Ag and common acute phase reactants (APRs) were correlated with clinical outcomes and length of stay (LOS). Results: We included 333 samples from a diverse group of 120 COVID-19 inpatients. There was a clear association of higher peak measurements of vWF:Ag and other APRs with adverse clinical outcomes. Peak vWF:Ag &gt;300% was associated with a 5-fold increased risk of death (Odds Ratio 5.08, P&lt;.001) and a 30-fold increased risk of prolonged (&gt;4 days) LOS (OR 29.65, P =.001). Peak D-dimer &gt;3.8 FEU mg/L was associated with a 15-fold increase in risk of death (OR 14.73, P &lt;.001) and a 5-fold increased risk of prolonged LOS (OR 4.55, P=.02). Using the earliest paired measurements of vWF:Ag and D-dimer from each patient and the same cut-offs, vWF:Ag was associated with a 3.5-fold increase in risk of death (OR 3.54, P=.004) and a 20-fold risk of prolonged LOS (OR 20.19, P=.004). Yet D-dimer was not significantly associated with either death (OR 1.9, P=.29) or prolonged LOS (OR 1.02, P=.98). Conclusions: Both peak and early post-admission vWF:Ag &gt;300% were highly predictive of death and prolonged length of stay among COVID-19 inpatients. Measurement of vWF:Ag may prove a valuable tool to guide escalation of COVID-19 treatment, particularly anticoagulation.

Functional analysis of colonization factor antigen I positive enterotoxigenic Escherichia coli identifies genes implicated in survival in water and host colonization

Enterotoxigenic Escherichia coli (ETEC) expressing the colonization pili CFA/I are common causes of diarrhoeal infections in humans. Here, we use a combination of transposon mutagenesis and transcriptomic analysis to identify genes and pathways that contribute to ETEC persistence in water environments and colonization of a mammalian host. ETEC persisting in water exhibit a distinct RNA expression profile from those growing in richer media. Multiple pathways were identified that contribute to water survival, including lipopolysaccharide biosynthesis and stress response regulons. The analysis also indicated that ETEC growing in vivo in mice encounter a bottleneck driving down the diversity of colonizing ETEC populations.