Dataset Information

Elevation of Inflammatory Cytokines and Proteins after Intra-Articular Ankle Fracture: A Cross-Sectional Study of 47 Ankle Fracture Patients.

ABSTRACT:

Introduction

Intra-articular fractures are the leading etiology for posttraumatic osteoarthritis (PTOA) in the ankle. Elevation of proinflammatory cytokines following intra-articular fracture may lead to synovial catabolism and cartilage degradation. We aimed to compare cytokine levels in injured and healthy ankle joints, examine the longer-term cytokine levels in fractured ankles, and investigate the association between cytokine levels in fractured ankles and plasma.

Materials and methods

In this cross-sectional study, synovial fluid (SF) and plasma of forty-seven patients with acute intra-articular ankle fractures and eight patients undergoing implant removal were collected prior to surgery. We determined concentrations of sixteen inflammatory cytokines, two cartilage degradation proteins, and four metabolic proteins and compared the levels in acutely injured ankles with those of the healthy contralateral side or during metal removal. Cytokine levels in injured ankles were also compared to serum cytokine levels. Nonparametric Wilcoxon rank-sum and Spearman tests were used for statistical analysis, and a p value below 0.05 was considered significant.

Results

Compared to the healthy ankles, the synovial fluid in ankles with acute intra-articular fracture had elevated levels of several proinflammatory cytokines and proteases (IL-1?, IL-2, IL-6, IL-8, IL-12p70, TNF, IFN?, MMP-1, MMP-3, and MMP-9) and anti-inflammatory cytokines (IL-1RA, IL-4, IL-10, and IL-13). The levels of cartilage degradation products (ACG, CTX-2) and metabolic mediators (TGF-?1 and TGF-?2) were also significantly higher. Synovial concentrations of ACG, IL-12-p70, IFN?, IL-4, and bFGF correlated with serum levels. While most of the examined synovial cytokines were unchanged after implant removal, IL-4 and IL-6 levels were upregulated.

Conclusions

We show that an acute ankle fracture is followed by an inflammatory reaction and cartilage degeneration. These data contribute to the current understanding of the protein regulation behind the development of PTOA and is a further step towards supplementing the current surgical treatment. This cross-sectional study was "retrospectively registered" on the 31th October 2017 at ClinicalTrials.gov (NCT03769909). The registration was carried out after inclusion of the first patient and prior to finalization of patient recruitment and statistical analyses: https://clinicaltrials.gov/ct2/show/NCT03769909?term=NCT03769909&draw=2&rank=1.

SUBMITTER: Pham TM

PROVIDER: S-EPMC7811423 | biostudies-literature | 2021

REPOSITORIES: biostudies-literature

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Publications

Elevation of Inflammatory Cytokines and Proteins after Intra-Articular Ankle Fracture: A Cross-Sectional Study of 47 Ankle Fracture Patients.

Pham That Minh TM Frich Lars Henrik LH Lambertsen Kate Lykke KL Overgaard Søren S Schmal Hagen H

Mediators of inflammation 20210108

<h4>Introduction</h4>Intra-articular fractures are the leading etiology for posttraumatic osteoarthritis (PTOA) in the ankle. Elevation of proinflammatory cytokines following intra-articular fracture may lead to synovial catabolism and cartilage degradation. We aimed to compare cytokine levels in injured and healthy ankle joints, examine the longer-term cytokine levels in fractured ankles, and investigate the association between cytokine levels in fractured ankles and plasma.<h4>Materials and me ...[more]

PMID: 33505222

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Project description:BackgroundSeveral malreduction criteria have been proposed for ankle surgery, but the criteria of most importance for functional outcome remain undetermined. Furthermore, the acute inflammatory response in the ankle joint after fracture is hypothesized to result in osteoarthritis development, but no study has investigated the correlation between the levels of these inflammatory cytokines and post-surgical functional outcomes. We aimed to identify malreduction criteria and inflammatory cytokines associated with functional outcome after ankle surgery.MethodsDuring surgery, synovial fluid from the fractured and healthy contralateral ankles of 46 patients was collected for chemiluminescence analysis of 22 inflammatory cytokines and metabolic proteins. The quality of fracture reduction was based on 9 criteria on plain X-rays and 5 criteria on weight-bearing computed tomography (WBCT) scans. After 3 and 12 months, we recorded scores on American Orthopedic Foot and Ankle Society (AOFAS) scale, the Danish version of Foot Function Index (FFI-DK), EQ-5D-5L index score, the Kellgren-Lawrence score, and joint space narrowing.ResultsTibiofibular (TF) overlap (p = 0.02) and dime sign (p = 0.008) correlated with FFI-DK. Tibiotalar tilt correlated positively with joint space narrowing at 3 months (p = 0.01) and 12 months (p = 0.03). TF widening correlated with FFI-DK (p = 0.04), AOFAS (p = 0.02), and EQ-5D-5L (p = 0.02). No consistent correlations between synovial cytokine levels and functional outcomes were found at 12 months.ConclusionsMalreduction of TF overlap, TF widening, and tibiotalar tilt were the most important criteria for functional outcome after ankle surgery. Increased inflammatory cytokine levels after fracture did not affect functional outcome at 12 months.Trial registrationThis cohort study is registered the 10th of December 2018 at ClinicalTrials.gov ( NCT03769909 ), was approved by the local committee on health ethics (The Regional Committees on Health Research Ethics for Southern Denmark: J.No. S-20170139), and was reported to the National Danish Data Protection Agency (17/28505).

Project description:PurposeIn the surgical treatment for lower-leg intra-articular fractures, the fragments have to be positioned and aligned to reconstruct the fractured bone as precisely as possible, to allow the joint to function correctly again. Standard procedures use 2D radiographs to estimate the desired reduction position of bone fragments. However, optimal correction in a 3D space requires 3D imaging. This paper introduces a new navigation system that uses pre-operative planning based on 3D CT data and intra-operative 3D guidance to virtually reduce lower-limb intra-articular fractures. Physical reduction in the fractures is then performed by our robotic system based on the virtual reduction.Methods3D models of bone fragments are segmented from CT scan. Fragments are pre-operatively visualized on the screen and virtually manipulated by the surgeon through a dedicated GUI to achieve the virtual reduction in the fracture. Intra-operatively, the actual position of the bone fragments is provided by an optical tracker enabling real-time 3D guidance. The motion commands for the robot connected to the bone fragment are generated, and the fracture physically reduced based on the surgeon's virtual reduction. To test the system, four femur models were fractured to obtain four different distal femur fracture types. Each one of them was subsequently reduced 20 times by a surgeon using our system.ResultsThe navigation system allowed an orthopaedic surgeon to virtually reduce the fracture with a maximum residual positioning error of [Formula: see text] (translational) and [Formula: see text] (rotational). Correspondent physical reductions resulted in an accuracy of 1.03 ± 0.2 mm and [Formula: see text], when the robot reduced the fracture.ConclusionsExperimental outcome demonstrates the accuracy and effectiveness of the proposed navigation system, presenting a fracture reduction accuracy of about 1 mm and [Formula: see text], and meeting the clinical requirements for distal femur fracture reduction procedures.

Project description:IntroductionThe presence of leukocytes in platelet concentrates is deemed to cause deleterious effects when injected intra articularly. The aim of this study is to analyse both local and systemic effects induced by leukocyte-rich Platelet-rich Plasma (PRP) injections through a proteomic characterization of serial synovial fluid and blood samples obtained from subjects treated for knee OA. Secondary aim was to compare the effects on knee homeostasis and systemic response with those obtained with visco-supplementation.MethodsThirty-six OA patients treated either by autologous L-PRP or HA intra-articular knee injections, administered in series of three at one-week intervals, were analyzed. Just before the injection, 1 ml of synovial fluid was collected through the same needle way. In the same time, a peripheral blood sample was obtained and plasma separated. A further peripheral blood sample was collected at 2, 6, and 12 months. L-PRP, plasma and synovial fluid were tested by multiplex bead-based sandwich immunoassay by means of the Bio-Plex suspension array system (Bio-Rad Laboratories) for the presence of pro- and anti-inflammatory cytokines (IL-1beta, IL-6, IL-8, IL-17 and IL-4, IL-10, IL-13) and growth factors (FGF-b, HGF, PDGF-AB/BB).ResultsIn general, pro-inflammatory cytokine levels were similar at basal condition and after treatment whereas anti-inflammatory ones were nearly undetectable. L-PRP administration did not modulate significant changes of cytokine concentrations either in synovial fluid or plasma, whatever the time points analyzed. No different trend was observed between L-PRP and HA administration in terms of pro- and anti-inflammatory cytokines, as well as growth factors.ConclusionsIn contrast with the evidence reported by "in vitro" studies, where a cellular pro-inflammatory response appears to be induced by the presence of leukocytes, these results suggest that the presence leukocyte-rich PRP doesn't induce a relevant in vivo up regulation of pro-inflammatory mediators.

Dataset Information

Elevation of Inflammatory Cytokines and Proteins after Intra-Articular Ankle Fracture: A Cross-Sectional Study of 47 Ankle Fracture Patients.

Introduction

Materials and methods

Results

Conclusions

Publications

Elevation of Inflammatory Cytokines and Proteins after Intra-Articular Ankle Fracture: A Cross-Sectional Study of 47 Ankle Fracture Patients.

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