To compare a large panel of plasma protein inflammatory biomarkers and mid-infrared (MIR) spectral patterns between patients with confirmed fracture related infections (FRIs) and controls without ...infection.
Prospective case-control.
Academic, level 1 trauma center.
Thirteen patients meeting confirmatory FRI criteria were matched to 13 controls based on age, time after surgery, and fracture region.
Plasma levels of 49 proteins were measured using enzyme-linked immunosorbent assay (ELISA) techniques. Fourier transform infrared (FTIR) spectroscopy of dried films was used to obtain MIR spectra of plasma samples.
Plasma protein levels and MIR spectra of samples.
Multivariate analysis-based predictive model developed utilizing ELISA-based biomarkers had sensitivity, specificity, and accuracy of 69.2±0.0%, 99.9±1.0%, and 84.5±0.6%, respectively, with PDGF-AB/BB, CRP, and MIG selected as the minimum number of variables explaining group differences (P<0.05). Sensitivity, specificity, and accuracy of the predictive model based on MIR spectra were 69.9±6.2%, 71.9±5.9%, and 70.9±4.8%, respectively, with six wavenumbers as explanatory variables (P<0.05).
This pilot study demonstrates the feasibility of using a select panel of plasma proteins and FTIR spectroscopy to diagnose FRI. The preliminary data suggest that measurement of these select proteins and MIR spectra may be potential clinical tools to detect FRI. Further investigation of these biomarkers in a larger cohort of patients is warranted.
Diagnostic Level III. See Instructions for Authors for a complete description of levels of evidence.
Idiopathic pulmonary fibrosis (IPF) is a fatal interstitial lung disease characterized by progressive scarring and matrix deposition. Recent reports highlight an autoimmune component in IPF ...pathogenesis. We have reported anti-col(V) immunity in IPF patients. The objective of our study was to determine the specificity of col(V) expression profile and anti-col(V) immunity relative to col(I) in clinical IPF and the efficacy of nebulized col(V) in pre-clinical IPF models.
Col(V) and col(I) expression profile was analyzed in normal human and IPF tissues. C57-BL6 mice were intratracheally instilled with bleomycin (0.025 U) followed by col(V) nebulization at pre-/post-fibrotic stage and analyzed for systemic and local responses.
Compared to normal lungs, IPF lungs had higher protein and transcript expression of the alpha 1 chain of col(V) and col(I). Systemic anti-col(V) antibody concentrations, but not of anti-col(I), were higher in IPF patients. Nebulized col(V), but not col(I), prevented bleomycin-induced fibrosis, collagen deposition, and myofibroblast differentiation. Col(V) treatment suppressed systemic levels of anti-col(V) antibodies, IL-6 and TNF-α; and local Il-17a transcripts. Compared to controls, nebulized col(V)-induced tolerance abrogated antigen-specific proliferation in mediastinal lymphocytes and production of IL-17A, IL-6, TNF-α and IFN-γ. In a clinically relevant established fibrosis model, nebulized col(V) decreased collagen deposition. mRNA array revealed downregulation of genes specific to fibrosis (Tgf-β, Il-1β, Pdgfb), matrix (Acta2, Col1a2, Col3a1, Lox, Itgb1/6, Itga2/3) and members of the TGF-β superfamily (Tgfbr1/2, Smad2/3, Ltbp1, Serpine1, Nfkb/Sp1/Cebpb).
Anti-col(V) immunity is pathogenic in IPF, and col(V)-induced tolerance abrogates bleomycin-induced fibrogenesis and down regulates TGF- β-related signaling pathways.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Nonunion describes bone fractures that fail to heal, resulting in the fracture callus failing to fully ossify or, in atrophic cases, not forming altogether. Fracture healing is regulated, in part, by ...the balance of proinflammatory and anti‐inflammatory processes occurring within the bone marrow and surface cell populations. We sought to further understand the role of osteoimmunology (i.e., study of the close relationship between the immune system and bone) by examining immune cell gene expression via single‐cell RNA sequencing of intramedullary canal tissue obtained from human patients with femoral nonunions. Intramedullary canal tissue samples obtained by reaming were collected at the time of surgical repair for femur fracture nonunion (n = 5) or from native bone controls when harvesting autologous bone graft (n = 4). Cells within the samples were isolated and analyzed using the Chromium Single‐Cell System (10x Genomics Inc.) and Illumina sequencers. Twenty‐three distinct cell clusters were identified, with higher cell proportions in the nonunion samples for monocytes and CD14 + dendritic cells (DCs), and lower proportions of T cells, myelocytes, and promyelocytes in nonunion samples. Gene expression differences were identified in each of the cell clusters from cell types associated with osteoimmunology, including CD14 + DC, monocytes, T cells, promyelocytes, and myelocytes. These results provide human‐derived gene profiles that can further our understanding of pathways that may be a cause or a consequence of nonunion, providing the clinical rationale to focus on specific components of osteoimmunology. Clinical significance: The novel single‐cell approach may lead to clinically relevant diagnostic biomarkers during earlier stages of nonunion development and/or investigation into therapeutic options.
The ability to study the bone microenvironment of failed fracture healing may lead to biomarkers for fracture nonunion. Herein the authors describe a technique for isolating individual cells suitable ...for single-cell RNA sequencing analyses from intramedullary canal tissue collected by reaming during surgery. The purpose was to detail challenges and solutions inherent to the collection and processing of intramedullary canal tissue samples. The authors then examined single-cell RNA sequencing data from fresh and reanimated samples to demonstrate the feasibility of this approach for prospective studies.
Intramedullary canal tissue is challenging to study directly because of its inaccessibility and heterogeneous composition. In addition, single-cell RNA sequencing requires high sample purity and cell viability. The authors determined that the critical step required for producing usable samples for single-cell RNA sequencing from intramedullary canal tissue was collagenase digestion, followed by centrifugation with density gradient medium (Ficoll).
Obliterative bronchiolitis (OB) post-lung transplantation involves IL-17-regulated autoimmunity to type V collagen and alloimmunity, which could be enhanced by complement activation. However, the ...specific role of complement activation in lung allograft pathology, IL-17 production, and OB is unknown. The current study examines the role of complement activation in OB. Complement-regulatory protein (CRP) (CD55, CD46, complement receptor 1-related protein y/CD46) expression was downregulated in human and murine OB; and C3a, a marker of complement activation, was upregulated locally. IL-17 differentially suppressed complement receptor 1-related protein y expression in airway epithelial cells in vitro. Neutralizing IL-17 recovered CRP expression in murine lung allografts and decreased local C3a production. Exogenous C3a enhanced IL-17 production from alloantigen- or autoantigen (type V collagen)-reactive lymphocytes. Systemically neutralizing C5 abrogated the development of OB, reduced acute rejection severity, lowered systemic and local levels of C3a and C5a, recovered CRP expression, and diminished systemic IL-17 and IL-6 levels. These data indicated that OB induction is in part complement dependent due to IL-17-mediated downregulation of CRPs on airway epithelium. C3a and IL-17 are part of a feed-forward loop that may enhance CRP downregulation, suggesting that complement blockade could be a therapeutic strategy for OB.
OBJECTIVE:To assess whether the fixation method and vitamin D supplementation affect the risk of patient-important outcomes within 12 months of injury in nongeriatric femoral neck fracture patients.
...DESIGN:A pilot factorial randomized controlled trial.
SETTING:Fifteen North American clinical sites.
PARTICIPANTS:Ninety-one adults 18–60 years of age with a femoral neck fracture requiring surgical fixation.
INTERVENTION:Participants were randomized to a surgical intervention (sliding hip screw or cancellous screws) and a vitamin D intervention (vitamin D3 4000 IU daily vs. placebo for 6 months).
MAIN OUTCOME MEASUREMENTS:The primary clinical outcome was a composite of patient-important complications (reoperation, femoral head osteonecrosis, severe femoral neck malunion, and nonunion). Secondary outcomes included fracture-healing complications and radiographic fracture healing.
RESULTS:Eighty-six participants with a mean age of 41 years were included. We found no statistically significant difference in the risk of patient-important outcomes between the surgical treatment arms (hazard ratio 0.90, 95% confidence interval 0.40–2.02, P = 0.80) and vitamin D supplementation treatment arms (hazard ratio 0.96, 95% confidence interval 0.42–2.18, P = 0.92).
CONCLUSIONS:These pilot trial results continue to describe the results of current fixation implants, inform the challenges of improving outcomes in this fracture population, and may guide future vitamin D trials to improve healing outcomes in young fracture populations. Although the pilot trial was not adequately powered to detect treatment effects, publishing these results may facilitate future meta-analyses on this topic.
LEVEL OF EVIDENCE:Therapeutic Level II. See Instructions for Authors for a complete description of levels of evidence.
Readiness for change, as assessed by the Readiness and Motivation Interview (RMI), predicts a number of clinical outcome variables in eating disorders including enrollment in intensive treatment, ...symptom change, dropout, and relapse. Although clinically useful, the training and administration of the RMI is time consuming. The purpose of this research was to (a) develop a self-report, symptom-specific version of the RMI, the Readiness and Motivation Questionnaire (RMQ), that can be used to assess readiness for change across all eating disorder diagnoses and (b) establish its psychometric properties. The RMQ provides stage of change, internality, and confidence scores for each of 4 eating disorder symptom domains (restriction, bingeing, and cognitive and compensatory behaviors). Individuals (N = 244) with current eating disorder diagnoses completed the RMQ and measures of convergent, discriminant, and criterion validity. Similar to the RMI scores, readiness scores on the RMQ differed according to symptom domain. Regarding criterion validity, RMQ scores were significantly associated with ratings of anticipated difficulty of recovery activities and completion of recovery activities. The RMQ contributed significant unique variance to anticipated difficulty of recovery activities, beyond those accounted for by the RMI and a questionnaire measure of global readiness. The RMQ is thus an acceptable alternative to the RMI, providing global and domain-specific readiness information when time or cost prohibits use of an interview.
PDF
