Regional and experiential differences in surgeon preference for the treatment of cervical facet injuries: a case study survey with the AO Spine Cervical Classification Validation Group

Purpose: The management of cervical facet dislocation injuries remains controversial. The main purpose of this investigation was to identify whether a surgeon’s geographic location or years in practice influences their preferred management of traumatic cervical facet dislocation injuries. Methods: A survey was sent to 272 AO Spine members across all geographic regions and with a variety of practice experience. The survey included clinical case scenarios of cervical facet dislocation injuries and asked responders to select preferences among various diagnostic and management options. Results: A total of 189 complete responses were received. Over 50% of responding surgeons in each region elected to initiate management of cervical facet dislocation injuries with an MRI, with 6 case exceptions. Overall, there was considerable agreement between American and European responders regarding management of these injuries, with only 3 cases exhibiting a significant difference. Additionally, results also exhibited considerable management agreement between those with ≤ 10 and > 10 years of practice experience, with only 2 case exceptions noted. Conclusion: More than half of responders, regardless of geographical location or practice experience, identified MRI as a screening imaging modality when managing cervical facet dislocation injuries, regardless of the status of the spinal cord and prior to any additional intervention. Additionally, a majority of surgeons would elect an anterior approach for the surgical management of these injuries. The study found overall agreement in management preferences of cervical facet dislocation injuries around the globe

Effect of surgical experience and spine subspecialty on the reliability of the {AO} Spine Upper Cervical Injury Classification System

OBJECTIVE The objective of this paper was to determine the interobserver reliability and intraobserver reproducibility of the AO Spine Upper Cervical Injury Classification System based on surgeon experience (< 5 years, 5–10 years, 10–20 years, and > 20 years) and surgical subspecialty (orthopedic spine surgery, neurosurgery, and "other" surgery). METHODS A total of 11,601 assessments of upper cervical spine injuries were evaluated based on the AO Spine Upper Cervical Injury Classification System. Reliability and reproducibility scores were obtained twice, with a 3-week time interval. Descriptive statistics were utilized to examine the percentage of accurately classified injuries, and Pearson’s chi-square or Fisher’s exact test was used to screen for potentially relevant differences between study participants. Kappa coefficients (κ) determined the interobserver reliability and intraobserver reproducibility. RESULTS The intraobserver reproducibility was substantial for surgeon experience level (< 5 years: 0.74 vs 5–10 years: 0.69 vs 10–20 years: 0.69 vs > 20 years: 0.70) and surgical subspecialty (orthopedic spine: 0.71 vs neurosurgery: 0.69 vs other: 0.68). Furthermore, the interobserver reliability was substantial for all surgical experience groups on assessment 1 (< 5 years: 0.67 vs 5–10 years: 0.62 vs 10–20 years: 0.61 vs > 20 years: 0.62), and only surgeons with > 20 years of experience did not have substantial reliability on assessment 2 (< 5 years: 0.62 vs 5–10 years: 0.61 vs 10–20 years: 0.61 vs > 20 years: 0.59). Orthopedic spine surgeons and neurosurgeons had substantial intraobserver reproducibility on both assessment 1 (0.64 vs 0.63) and assessment 2 (0.62 vs 0.63), while other surgeons had moderate reliability on assessment 1 (0.43) and fair reliability on assessment 2 (0.36). CONCLUSIONS The international reliability and reproducibility scores for the AO Spine Upper Cervical Injury Classification System demonstrated substantial intraobserver reproducibility and interobserver reliability regardless of surgical experience and spine subspecialty. These results support the global application of this classification system

Fra-1/AP-1 transcription factor negatively regulates pulmonary fibrosis in vivo.

The Fra-1/AP-1 transcription factor plays a key role in tumor epithelial cell progression; however, its role in pathogenic lung fibrosis remains unclear. In the present study, using a genetic approach (Fra-1 deficient mice), we have demonstrated a novel regulatory (protective) role for Fra-1 in lung fibrosis. We found greater levels of progressive interstitial fibrosis, characterized by increased levels of inflammation, collagen accumulation, and profibrotic and fibrotic gene expression in the lungs of Fra-1(Δ/Δ) mice than in those of Fra-1(+/+) mice following bleomycin treatment. Fra-1 knockdown in human lung epithelial cells caused the upregulation of mesenchymal marker N-cadherin, concomitant with a downregulation of the epithelial phenotype marker E-cadherin, under basal conditions and in response to bleomycin and TGF-β1. Furthermore, Fra-1 knockdown caused an enhanced expression of type 1 collagen and the downregulation of collagenase (MMP-1 and MMP-13) gene expression in human lung epithelial cells. Collectively, our findings demonstrate that Fra-1 mediates anti-fibrotic effects in the lung through the modulation of proinflammatory, profibrotic and fibrotic gene expression, and suggests that the Fra-1 transcription factor may be a potential target for pulmonary fibrosis, a progressive disorder with poor prognosis and treatment

Loss of Fra-1 leads to an altered MMP and TIMP gene expression in the lung.

<p><i>MMP</i> (<b>A</b>) and <i>TIMP</i> (<b>B</b>) gene expression in the lung tissue at 31 days post-bleomycin administration (n = 4−6). <b>C:</b> Detection of MMPs activity by collagen zymography in lung tissue 31 days post-bleomycin administration. Open bars  =  vehicle; filled bars  =  bleomycin. ^∗p<0.05, PBS vs bleomycin; ^†p<0,05, <i>Fra-1</i>^Δ<i>/</i>Δ vs <i>Fra-1^+/+</i> at corresponding time point.</p

<i>Fra-1</i>^Δ<i>/</i>Δ mice develop exaggerated pulmonary fibrosis after injury. A:

<p>Representative results of Masson’s trichrome staining of the lung from the saline-treated mice (n = 3) or bleomycin treated mice for 14 (n = 3) and 31 (n = 4) days. <b>B:</b> Right lung was collected for biochemical analysis of bleomycin-induced pulmonary fibrosis as measured by hydroxyproline content at 31-day post-PBS and -bleomycin treatment (n = 5). ^∗p<0.05, PBS vs bleomycin; ^†p<0,05, <i>Fra-1</i>^Δ<i>/</i>Δ vs <i>Fra-1^+/+</i> mice. Images in <b>a</b> are shown at x4, whereas <b>a1</b> represent boxed areas of <b>a</b>, shown at x20.</p

<i>Fra-1</i>^Δ<i>/</i>Δ mice demonstrate extensive pulmonary inflammation and fibrosis at 31-day post-bleomycin administration.

<p>Mice were intratracheally administered with bleomycin (n = 14−15) or PBS (n = 12) were assessed. Representative results of three different experiments are shown. <b>A:</b> Representative images of H&E stained lung tissue sections of bleomycin-treated <i>Fra-1^+/+</i> and <i>Fra-1</i>^Δ<i>/</i>Δ mice (n = 4). <b>B:</b> Lung inflammatory cell profiles in BAL fluids at 31-day post-PBS and -bleomycin instillation (n = 5). Open bars  =  vehicle; filled bars  =  bleomycin. ^∗p<0.05, PBS vs bleomycin; ^†p<0.05, <i>Fra-1</i>^Δ<i>/</i>Δ vs <i>Fra-1^+/+</i> mice. Images in <b>a</b> and <b>b</b> are shown at x10, whereas <b>a1</b> and <b>b1</b> represent boxed areas of <b>a</b> and <b>b</b>, respectively, shown at x40.</p

<i>Fra-1</i>^Δ<i>/</i>Δ mice display greater pulmonary inflammatory responses at 7-day post-bleomycin administration.

<p>Mice (n = 8 in each genotype) were intratracheally administered with bleomycin. Left lungs were fixed for histology (n = 4) or used for mRNA analysis (n = 4). Right lobes (n = 8) were used for BAL and protein analysis. Representative results of two different experiments are shown. Samples obatined from mice treated with PBS were from <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0041611#pone-0041611-g003" target="_blank">Figure 3</a> (see below). <b>A:</b> Representative images of H&E stained lung tissue sections of bleomycin-treated <i>Fra-1^+/+</i> and <i>Fra-1</i>^Δ<i>/</i>Δ mice (n = 4). <b>B:</b> Assessment of lung inflammatory cell profiles in the BAL fluid of both genotypes (n = 5). <b>C:</b> Pro-inflammatory cytokines and chemokines gene expression after treatment with bleomycin (n = 4).^∗p<0.05, PBS vs bleomycin; ^†p<i><</i>0.05, <i>Fra-1</i>^Δ<i>/</i>Δ vs <i>Fra-1^+/+</i> mice. <b>a</b> and <b>b</b> images shown at 4× magnification, while <b>a1</b> and <b>b1</b> are boxed areas of <b>a</b> and <b>b</b>, respectively, but shown at x20.</p

Bleomycin-induced Fra-1 expression in the lung. A:

<p>At indicated period of post-bleomycin instillation, lung tissues were harvested from wildtype mice and used for <i>Fra-1</i> gene expression by real-time RT-PCR (n = 4−6). <b>B:</b> Fra-1 expression was analyzed by western blot. analysis using β-actin as reference. Only 4 samples were used in each group. ^∗p<0.05, PBS vs bleomycin treated groups.</p