Living with diabetes: rationale, study design and baseline characteristics for an Australian prospective cohort study

Background: Diabetes mellitus is a major global public health threat. In Australia, as elsewhere, it is responsible for a sizeable portion of the overall burden of disease, and significant costs. The psychological and social impact of diabetes on individuals with the disease can be severe, and if not adequately addressed, can lead to the worsening of the overall disease picture. The Living With Diabetes Study aims to contribute to a holistic understanding of the psychological and social aspects of diabetes mellitus

Molecular Distance to Health Transcriptional Score and Disease Severity in Children Hospitalized With Community-Acquired Pneumonia

Background: Community-acquired pneumonia (CAP) is a leading cause of hospitalization and mortality in children. Diagnosis remains challenging and there are no reliable tools to objectively risk stratify patients or predict clinical outcomes. Molecular distance to health (MDTH) is a genomic score that measures the global perturbation of the transcriptional profile and may help classify patients by disease severity. We evaluated the value of MDTH to assess disease severity in children hospitalized with CAP.Methods: Children hospitalized with CAP and matched healthy controls were enrolled in a prospective observational study. Blood samples were obtained for transcriptome analyses within 24 h of hospitalization. MDTH scores were calculated to assess disease severity and correlated with laboratory markers, such as white blood cell count, c-reactive protein (CRP), and procalcitonin (PCT), and clinical outcomes, including duration of fever and duration of hospitalization (LOS). Univariate and multivariable logistic regression were applied to assess factors associated with LOS and duration of fever after hospitalization.Results: Among children hospitalized with CAP (n = 152), pyogenic bacteria (PB) were detected in 16 (11%), Mycoplasma pneumoniae was detected in 41 (28%), respiratory viruses (RV) alone were detected in 78 (51%), and no pathogen was detected in 17 (11%) children. Statistical group comparisons identified 6,726 genes differentially expressed in patients with CAP vs. healthy controls (n = 39). Children with confirmed PB had higher MDTH scores than those with RV (p < 0.05) or M. pneumoniae (p < 0.01) detected alone. CRP (r = 0.39, p < 0.0001), PCT (r = 0.39, p < 0.0001), and MDTHs (r = 0.24, p < 0.01) correlated with duration of fever, while only MDTHs correlated with LOS (r = 0.33, p < 0.0001). Unadjusted analyses showed that both higher CRP and MDTHs were associated with longer LOS (OR 1.04 [1–1.07] and 1.12 [1.04–1.20], respectively), however, only MDTH remained significant when adjusting for other covariates (aOR 1.11 [1.01–1.22]).Conclusions: In children hospitalized with CAP MDTH score measured within 24 h of admission was independently associated with longer duration of hospitalization, regardless of the pathogen detected. This suggests that transcriptional biomarkers may represent a promising approach to assess disease severity in children with CAP

Increased Prevalence of Luminal Narrowing and Stricturing Identified by Enterography in Pediatric Crohn’s Disease Patients With Elevated Granulocyte–Macrophage Colony Stimulating Factor Autoantibodies

BACKGROUND: Crohns disease (CD) patients with elevated granulocyte-macrophage colony-stimulating factor autoantibodies (GM-CSF Ab) are more likely to develop stricturing behavior requiring surgery. Computed tomography or magnetic resonance enterography (CTE or MRE) may detect luminal narrowing (LN) before stricture development. The objective of this study was to determine whether CD patients with elevated GM-CSF Ab (≥1.6 μg/mL) have a higher prevalence of LN and stricturing on CTE or MRE. METHODS: A single-center, cross-sectional study of 153 pediatric patients with CD and control subjects undergoing diagnostic CTE or MRE. Examinations were evaluated for disease activity using a novel scoring system and for the presence of LN, stricture, intra-abdominal abscess, or fistulae. Dichotomous outcomes were compared with respect to antibody status (high or low) using Fishers exact test and logistic regression, whereas continuous outcomes were evaluated using unpaired t test. RESULTS: GM-CSF Ab were elevated in CD patients (n = 114) with a median (interquartile range) GM-CSF Ab level of 2.3 μg/mL (0.5-6.6 μg/mL) compared with 0.6 μg/mL (0.3-1.3 μg/mL) in healthy and disease control subjects (n = 39) (P = 0.001). Ileal disease location was more common in CD patients with high GM-CSF Ab (P < 0.001). LN increased from 39% in CD patients with low GM-CSF Ab to 71% in those with high levels (P = 0.004) and remained significantly associated with high GM-CSF Ab in a multivariate logistic model, which included age, gender, small bowel location, and duration of disease. Stricturing prevalence on CTE or MRE examination increased from 4% in CD patients with low GM-CSF Ab to 19% in those with high GM-CSF Ab (P = 0.03). CONCLUSIONS: Pediatric CD patients with high GM-CSF Ab levels have a higher prevalence of LN on CTE or MRE. Further study will be needed to determine whether medical therapy will reduce progression to stricturing behavior in these patients