Publications

Much attention has been focused on the role of the bacterial microbiome in human health, but the virome is understudied. Although previously investigated in individuals with inflammatory bowel diseases or solid-organ transplants, virome dynamics in allogeneic hematopoietic stem cell transplantation (HSCT) and enteric graft-versus-host disease (GVHD) remain unexplored. Here we characterize the longitudinal gut virome in 44 recipients of HSCT using metagenomics. A viral 'bloom' was identified, and significant increases were demonstrated in the overall proportion of vertebrate viral sequences following transplantation (P = 0.02). Increases in both the rates of detection (P < 0.0001) and number of sequences (P = 0.047) of persistent DNA viruses (anelloviruses, herpesviruses, papillomaviruses and polyomaviruses) over time were observed in individuals with enteric GVHD relative to those without, a finding accompanied by a reduced phage richness (P = 0.01). Picobirnaviruses were detected in 18 individuals (40.9%), more frequently before or within a week after transplant than at later time points (P = 0.008). In a time-dependent Cox proportional-hazards model, picobirnaviruses were predictive of the occurrence of severe enteric GVHD (hazard ratio, 2.66; 95% confidence interval (CI) = 1.46-4.86; P = 0.001), and correlated with higher fecal levels of two GVHD severity markers, calprotectin and α1-antitrypsin. These results reveal a progressive expansion of vertebrate viral infections over time following HSCT, and they suggest an unexpected association of picobirnaviruses with early post-transplant GVHD.

Persistent pain following breast cancer surgery is a significant problem. Both inherited and acquired mechanisms of inflammation appear to play a role in the development and maintenance of persistent pain. In this longitudinal study, growth mixture modeling was used to identify persistent breast pain phenotypes based on pain assessments obtained prior to and monthly for 6months following breast cancer surgery. Associations between the "no pain" and "mild pain" phenotypes and single nucleotide polymorphisms (SNPs) spanning 15 cytokine genes were evaluated. The methylation status of the CpG sites found in the promoters of genes associated with pain group membership was determined using bisulfite sequencing. In the multivariate analysis, three SNPs (i.e., interleukin 6 (IL6) rs2069840, C-X-C motif chemokine ligand 8 (CXCL8) rs4073, tumor necrosis factor (TNF) rs1800610) and two TNF CpG sites (i.e., c.-350C, c.-344C) were associated with pain group membership. These findings suggest that variations in IL6, CXCL8, and TNF are associated with the development and maintenance of mild persistent breast pain. CpG methylation within the TNF promoter may provide an additional mechanism through which TNF alters the risk for mild persistent breast pain after breast cancer surgery. These genetic and epigenetic variations may help to identify individuals who are predisposed to the development of mild levels of persistent breast pain following breast cancer surgery.

BACKGROUND/OBJECTIVE

Previous studies showed variability in the use of diagnostic and therapeutic resources for children with febrile acute respiratory tract infections (ARTI), including antibiotics. Unnecessary antibiotic use has important public and individual health outcomes, but missed antibiotic prescribing also has important consequences. We sought to determine factors associated with antibiotic prescribing in pediatric ARTI, specifically those with pneumonia.

METHODS

We assessed national trends in the evaluation and treatment of ARTI for pediatric emergency department (ED) patients by analyzing the National Hospital Ambulatory Medical Care Survey from 2002 to 2013. We identified ED patients aged ≤18 with a reason for visit of ARTI, and created 4 diagnostic categories: pneumonia, ARTI where antibiotics are typically indicated, ARTI where antibiotics are typically not indicated, and "other" diagnoses. Our primary outcome was factors associated with the administration or prescription of antibiotics. A multivariate logistic regression model was fit to identify risk factors for underuse of antibiotics when they were indicated.

RESULTS

We analyzed 6461 visits, of which 10.2% of the population had a final diagnosis of pneumonia and 86% received antibiotics. 41.5% of patients were diagnosed with an ARTI requiring antibiotics, of which 53.8% received antibiotics. 26.6% were diagnosed with ARTI not requiring antibiotics, of which 36.0% received antibiotics. Black race was a predictor for the underuse of antibiotics in ARTIs that require antibiotics (OR: 0.72; 95% CI: 0.58-0.90).

CONCLUSIONS

For pediatric patients presenting to the ED with pneumonia and ARTI requiring antibiotics, we found that black race was an independent predictor of antibiotic underuse.