Adding Insult to Injury: Discontinuous Insurance Following Spine Trauma
JOURNAL OF BONE AND JOINT SURGERY-AMERICAN VOLUME
2015; 97A (2): 141-146
The use of bone morphogenetic protein in thoracolumbar spine procedures: analysis of the MarketScan longitudinal database
2014; 14 (12): 2929-2937
Intraoperative Neuromonitoring in Single-Level Spinal Procedures A Retrospective Propensity Score-Matched Analysis in a National Longitudinal Database
2014; 39 (23): 1950-1959
Usage of recombinant human bone morphogenetic protein in cervical spine procedures: analysis of the MarketScan longitudinal database.
journal of bone and joint surgery. American volume
2014; 96 (17): 1409-1416
Spine trauma patients may represent a group for whom insurance fails to provide protection from catastrophic medical expenses, resulting in the transfer of financial burden onto individual families and public payers. This study compares the rate of insurance discontinuation for patients who underwent surgery for traumatic spine injury with and without spinal cord injury with the rate for matched control subjects.We used the MarketScan database to perform a retrospective cohort study of privately insured spine trauma patients who underwent surgery from 2006 to 2010. Kaplan-Meier survival analysis was used to assess the time to insurance discontinuation. Cox proportional-hazards regression was used to determine hazard ratios for insurance discontinuation among spine trauma patients compared with the matched control population.The median duration of existing insurance coverage was 20.2 months for those with traumatic spinal cord injury, 25.6 months for those with traumatic spine injury without spinal cord injury, and 48.0 months for the matched control cohort (log-rank p < 0.0001). After controlling for multiple covariates, the hazard ratios for discontinuation of insurance were 2.02 (95% CI [confidence interval], 1.83 to 2.23) and 2.78 (95% CI, 2.31 to 3.35) for the trauma patients without and with spinal cord injury, respectively, compared with matched controls.Rates of insurance discontinuation are significantly higher for trauma patients with severe spine injury compared with the uninjured population, indicating that patients with disabling injuries are at increased risk for loss of insurance coverage.
View details for DOI 10.2106/JBJS.N.00148
View details for Web of Science ID 000348217200012
Profiling risk factors for chronic uveitis in juvenile idiopathic arthritis: a new model for EHR-based research
Revision rates and complication incidence in single- and multilevel anterior cervical discectomy and fusion procedures: an administrative database study
THE SPINE JOURNAL
Chapter 9: Analyses Using Disease Ontologies
PLOS COMPUTATIONAL BIOLOGY
2012; 8 (12)
Usage of recombinant human bone morphogenetic protein (rhBMP) in anterior cervical discectomy and fusion (ACDF) procedures is controversial. Studies suggest increased rates of dysphagia, hematoma or seroma, and severe airway compromise in anterior cervical spine procedures using rhBMP. The purpose of the present study was to determine and describe national utilization trends and complication rates associated with rhBMP usage in anterior cervical spine procedures.The MarketScan database from 2006 to 2010 was retrospectively queried to identify 91,543 patients who underwent ACDF with or without cervical corpectomy. Patient selection and outcomes were ascertained with use of ICD-9-CM (International Classification of Diseases, Ninth Revision, Clinical Modification) and CPT (Current Procedural Terminology) coding. A total of 3197 patients were treated with rhBMP intraoperatively. Mean follow-up was 588 days (interquartile range [IQR], 205 to 886 days) in the non-treated cohort and 591 days (IQR, 203 to 925 days) in the rhBMP-treated cohort. Multivariate logistic regression as well as propensity score analysis were used to evaluate the association of rhBMP usage with postoperative complications.In propensity score-adjusted models, rhBMP usage was associated with an increased risk of any complication (odds ratio [OR] = 1.34, 95% confidence interval [CI] = 1.2 to 1.5) and specific complications such as hematoma or seroma (OR = 1.8, 95% CI = 1.4 to 2.3), dysphagia (OR = 1.3, 95% CI = 1.1 to 1.5), and any pulmonary complication (OR = 1.5, 95% CI = 1.2 to 1.8) within thirty days postoperatively. There were no significant differences in the rates of readmission, in-hospital mortality, referral to pain management, new malignancy, or reoperation between the two cohorts. Usage of rhBMP was associated with a mean increase of $5545 (19%) in total payments to the hospital and primary physician (p < 0.001).We found an increased overall rate of postoperative complications in patients receiving rhBMP for cervical spinal fusion procedures compared with patients not receiving rhBMP. Hematoma or seroma, pulmonary complications, and dysphagia were also more common in the rhBMP cohort. Usage of rhBMP in a case was associated with $311 greater payments to the surgeon and $4213 greater payments to the hospital.Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence.
View details for DOI 10.2106/JBJS.M.01016
View details for PubMedID 25187578
Butyrate increases IL-23 production by stimulated dendritic cells
AMERICAN JOURNAL OF PHYSIOLOGY-GASTROINTESTINAL AND LIVER PHYSIOLOGY
2012; 303 (12): G1384-G1392
Advanced statistical methods used to analyze high-throughput data such as gene-expression assays result in long lists of "significant genes." One way to gain insight into the significance of altered expression levels is to determine whether Gene Ontology (GO) terms associated with a particular biological process, molecular function, or cellular component are over- or under-represented in the set of genes deemed significant. This process, referred to as enrichment analysis, profiles a gene-set, and is widely used to makes sense of the results of high-throughput experiments. The canonical example of enrichment analysis is when the output dataset is a list of genes differentially expressed in some condition. To determine the biological relevance of a lengthy gene list, the usual solution is to perform enrichment analysis with the GO. We can aggregate the annotating GO concepts for each gene in this list, and arrive at a profile of the biological processes or mechanisms affected by the condition under study. While GO has been the principal target for enrichment analysis, the methods of enrichment analysis are generalizable. We can conduct the same sort of profiling along other ontologies of interest. Just as scientists can ask "Which biological process is over-represented in my set of interesting genes or proteins?" we can also ask "Which disease (or class of diseases) is over-represented in my set of interesting genes or proteins?". For example, by annotating known protein mutations with disease terms from the ontologies in BioPortal, Mort et al. recently identified a class of diseases--blood coagulation disorders--that were associated with a 14-fold depletion in substitutions at O-linked glycosylation sites. With the availability of tools for automatic annotation of datasets with terms from disease ontologies, there is no reason to restrict enrichment analyses to the GO. In this chapter, we will discuss methods to perform enrichment analysis using any ontology available in the biomedical domain. We will review the general methodology of enrichment analysis, the associated challenges, and discuss the novel translational analyses enabled by the existence of public, national computational infrastructure and by the use of disease ontologies in such analyses.
View details for DOI 10.1371/journal.pcbi.1002827
View details for Web of Science ID 000312901500032
View details for PubMedID 23300417
IRAK-M modulates expression of IL-10 and cell surface markers CD80 and MHC II after bacterial re-stimulation of tolerized dendritic cells
2012; 144 (1-2): 49-59
The gut microbiota is essential for the maintenance of intestinal immune homeostasis and is responsible for breaking down dietary fiber into short-chain fatty acids (SCFAs). Butyrate, the most abundant bioactive SCFA in the gut, is a histone deacetylase inhibitor (HDACi), a class of drug that has potent immunomodulatory properties. This characteristic of butyrate, along with our previous discovery that conventional dendritic cells (DCs) are required for the development of experimental colitis, led us to speculate that butyrate may modulate DC function to regulate gut mucosal homeostasis. We found that butyrate, in addition to suppressing LPS-induced bone marrow-derived DC maturation and inhibiting DC IL-12 production, significantly induced IL-23 expression. The upregulation of mRNA subunit IL-23p19 at the pretranslational level was consistent with the role of HDACi on the epigenetic modification of gene expression. Furthermore, the mechanism of IL-23p19 upregulation was independent of Stat3 and ZBP89. Coculture of splenocytes with LPS-stimulated DCs pretreated with or without butyrate was performed and showed a significant induction of IL-17 and IL-10. We demonstrated further the effect of butyrate in vivo using dextran sulfate sodium (DSS)-induced colitis and found that the addition of butyrate in the drinking water of mice worsened DSS-colitis. This is in contrast to the daily intraperitoneal butyrate injection of DSS-treated mice, which mildly improved disease severity. Our study highlights a novel effect of butyrate in upregulating IL-23 production of activated DCs and demonstrates a difference in the host response to the oral vs. systemic route of butyrate administration.
View details for DOI 10.1152/ajpgi.00540.2011
View details for Web of Science ID 000312502600010
View details for PubMedID 23086919
Helicobacter pylori DNA decreases pro-inflammatory cytokine production by dendritic cells and attenuates dextran sodium sulphate-induced colitis
2011; 60 (11): 1479-1486
As essential components of the innate immune system, dendritic cells (DCs) can interact directly with pathogens as well as participate in the adaptive immune response. In cells closely related to DCs such as macrophages and monocytes, prior exposure to minute amounts of endotoxin can lead to a refractory period where subsequent exposure to higher doses fails to induce an inflammatory response; little research has investigated this effect on DCs. This study tested if murine bone marrow-derived dendritic cells (BM-DCs) respond to endotoxin- and bacterial sonicate-induced tolerance by decreased inflammatory and increased anti-inflammatory response, and the role of IRAK-M, an intracellular negative regulator of TLR signaling, in this tolerance.Tolerized BM-DCs exhibited a significant drop in TNF-? and IL-12p70 production and increased IL-10 expression compared to untolerized cells. BM-DCs also showed the ability to develop heterotolerance, in which the LPS exposure alone was able to induce tolerance to Helicobacter pylori sonicate and TLR2 agonist Pam3Cys. Furthermore, the expression of IRAK-M was increased after restimulation of tolerized BM-DCs as determined qPCR and Western blot. IRAK-M exhibited a suppressive effect on surface expression of major histocompatibilty complex class II (MHC II) and CD80 in LPS-tolerized BM-DCs. IL-10 expression in bacterial sonicate-tolerized IRAK-M-/- BM-DCs was altered as compared to wild type BM-DCs, with tolerance-induced expression of IL-10 mitigated in tolerized IRAK-M-/- BM-DCs.Along with endotoxin, bacterial sonicate is able to induce refractory tolerance in BM-DCs, and IRAK-M plays a role in modulating cell surface expression of MHC class II and CD80 and release of IL-10 during this tolerance.
View details for DOI 10.1016/j.imlet.2012.03.006
View details for Web of Science ID 000304495300007
View details for PubMedID 22472665
Helicobacter pylori Immune Escape Is Mediated by Dendritic Cell-Induced Treg Skewing and Th17 Suppression in Mice
2010; 138 (3): 1046-1054
Epidemiological data have recently emerged to suggest Helicobacter pylori may protect against certain chronic inflammatory diseases such as inflammatory bowel disease (IBD). However, the mechanism for the observed inverse association between H pylori and IBD has not been described.The frequency of immunoregulatory (IRS) to immunostimulatory (ISS) sequences within the genome of various bacteria was calculated using MacVector software. The induction of type I IFN and IL-12 responses by DNA-pulsed murine bone marrow-derived dendritic cells (BMDC) and human plasmacytoid dendritic cells (DC) was analysed by cytokine production. The effect of H pylori DNA on Escherichia coli DNA production of type I IFN and IL-12 was assessed. The in-vivo significance of H pylori DNA suppression was assessed in a dextran sodium sulphate (DSS) model of colitis. The systemic levels of type I IFN were assessed in H pylori-colonised and non-colonised patients.H pylori DNA has a significantly elevated IRS:ISS ratio. In-vitro experiments revealed the inability of H pylori DNA to stimulate type I IFN or IL-12 production from mouse BMDC or human plasmacytoid DC. H pylori DNA was also able to suppress E coli DNA production of type I IFN and IL-12. The administration of H pylori DNA before the induction of DSS colitis significantly ameliorated the severity of colitis compared with E coli DNA or vehicle control in both an acute and chronic model. Finally, the systemic levels of type I IFN were found to be lower in H pylori-colonised patients than non-colonised controls.This study indicates that H pylori DNA has the ability to downregulate pro-inflammatory responses from DC and this may partly explain the inverse association between H pylori and IBD.
View details for DOI 10.1136/gut.2010.220087
View details for Web of Science ID 000295399600005
View details for PubMedID 21471567
HPLC-electrospray mass spectrometric assay for the determination of (R,R)-fenoterol in rat plasma
JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL ANALYSIS
2008; 48 (3): 960-964
Helicobacter pylori infection increases gastric regulatory T cell (Treg) response, which may contribute to H pylori immune escape. We hypothesize that H pylori directs Treg skewing by way of dendritic cells (DCs) and thus inhibits interleukin-17(+) helper T cells (Th17) immunity.Two-photon microscopy was used to locate DCs in gastric lamina propria of mice. The induction of Th17 and Treg responses by bacteria-pulsed murine bone marrow-derived DCs was analyzed by cytokine production and stimulation of T-cell proliferation. The effect of VacA, CagA, transforming growth factor-beta (TGF-beta), and IL-10 on Th17/Treg balance was assessed. The in vivo significance of Tregs on the H pylori-specific Th17 response and H pylori density was determined by using anti-CD25 neutralizing antibodies to deplete Tregs in mice.We showed that mucosal CD11c(+) DCs are located near the surface of normal gastric epithelium, and their number increased after H pylori infection. Study of the direct interaction of DCs with H pylori showed a Treg-skewed response. The Treg skewing was independent of H pylori VacA and CagA and dependent on TGF-beta and IL-10. In vivo Treg skewing by adoptive transfer of H pylori-pulsed DCs reduces the ratio of gastric IL-17/Foxp3 mRNA expressions. The depletion of CD25(+) Tregs results in early reduction of H pylori density, which is correlated with enhanced peripheral H pylori-specific Th17, but not Th1, response.Overall, our study indicates that H pylori alters the DC-polarized Th17/Treg balance toward a Treg-biased response, which suppresses the effective induction of H pylori-specific Th17 immunity.
View details for DOI 10.1053/j.gastro.2009.11.043
View details for Web of Science ID 000275109900035
View details for PubMedID 19931266
A fast and specific liquid chromatography-mass spectrometry method for the determination of (R,R)-fenoterol ((R,R)-Fen) in rat plasma has been developed and validated. (R,R)-Fen was extracted from 125 microl of plasma using solid phase extraction and analyzed on Atlantis HILIC Silica 3 microm column. The mobile phase was composed of acetonitrile:ammonium acetate (pH 4.1; 20mM) (85:15, v/v), at a flow rate of 0.2 ml/min. The lower limit of detection (LLOD) was 2 ng/ml . The procedure was validated and applied to the analysis of plasma samples from rats previously administered (R,R)-Fen in an intravenous bolus.
View details for DOI 10.1016/j.jpba.2008.05.034
View details for Web of Science ID 000260196500064
View details for PubMedID 18617349