Aims

This Delphi study assessed the challenges of diagnosing soft-tissue knee injuries (STKIs) in acute settings among orthopaedic healthcare stakeholders.

Introduction

Positive reports from implant designer centres on the use of fibular nails in the complex ankle fractures has resulted in a marked increase in their use nationally. Our aim in this study was to report on the outcomes of the use of all fibular nails in two major trauma centres.

Aims

To identify unanswered questions about the prevention, diagnosis, treatment, and rehabilitation and delivery of care of first-time soft-tissue knee injuries (ligament injuries, patella dislocations, meniscal injuries, and articular cartilage) in children (aged 12 years and older) and adults.

In relation to regenerative therapies in osteoarthritis and cartilage repair, mesenchymal stromal cells (MSCs) have immunomodulatory functions and influence macrophage behaviour. Macrophages exist as a spectrum of pro-(M1) and anti-(M2) inflammatory phenotypic subsets. In the context of cartilage repair, we investigated MSC-macrophage crosstalk, including specifically the priming of cartilage cells by macrophages to achieve a regenerative rather than fibrotic outcome. Human monocytes were isolated from blood cones and differentiated towards M1 and M2 macrophages. Monocytes (Mo), M1 and M2 macrophages were cultured directly and indirectly (trans-well system) with human bone marrow derived MSCs. MSCs were added during M1 polarisation and separately to already induced M1 cells. Outcomes (M1/M2 markers and ligands/receptors) were evaluated using RT-qPCR and flow cytometry. Influence on chondrogenesis was assessed by applying M1 and M2 macrophage conditioned media (CM) sequentially to cartilage derived cells (recapitulating an acute injury environment). RT-qPCR was used to evaluate chondrogenic/fibrogenic gene transcription. The ratio of M2 markers (CD206 or CD163) to M1 markers (CD38) increased when MSCs were added to Mo/M1 macrophages, regardless of culture system used (direct or indirect). Pro-inflammatory markers (including TNFβ) decreased. CXCR2 expression by both M1 macrophages and MSCs decreased when MSCs were added to differentiated M1 macrophages in transwell. When adding initially M1 CM (for 12 hours) followed by M2 CM (for 12 hours) sequentially to chondrocytes, there was a significant increase of Aggrecan and Collagen type 2 gene expression and decrease in fibroblastic cell surface markers (PDPN/CD90). Mo/M1 macrophages cultured with MSCs, directly or indirectly, are shifted towards a more M2 phenotype. Indirect culture suggests this effect can occur via soluble signaling mediators. Sequential exposure of M1CM followed by M2CM to chondrocytes resulted in increased chondrogenic and reduced fibrotic gene expression, suggesting that an acute pro-inflammatory stimulus may prime chondrocytes before repair.

Introduction

The knee is the most commonly injured joint in sporting accidents, leading to substantial disability, time off work and morbidity (1). Treatment and assessment vary around the UK (2), whilst there remains a limited number of high-quality randomised controlled trials assessing first time, acute soft tissue knee injuries (3,4). As the clinical and financial burden rises (5), vital answers are required to improve prevention, diagnosis, treatment, rehabilitation, and delivery of care. In association with the James Lind Alliance, this BASK, BOSTAA and BOA supported prioritising exercise was undertaken over a year.

Abstract

Abstract

Aim

This study assesses the ability of the JS-BACH classification of bone infection to predict clinical and patient-reported outcomes in prosthetic joint infection (PJI).

Introduction

Topical diclofenac has proven efficacy and safety in the management of osteoarthritic pain. Its therapeutic efficacy is dependent on its ability to deliver pharmacodynamically active concentrations to the underlying tissues in the affected joint. However, the disposition of topical diclofenac is not fully characterized, and no studies have been performed using diclofenac diethylamine 2.32% gel.

This was a retrospective study of registry data from a National Orthopaedic Hospital for all THRs with 10-year follow-up data. Inclusion criteria were all THRs with a minimum of 10-year follow-up data. All metal-on-metal (MoM) THRs and MoM resurfacings were excluded from the analysis due to the high rate of revision associated with these bearings. Univariate and multivariate analyses controlling for confounding variables were performed to compare outcomes. A total of 1,697 THRs were performed in 1,553 patients. The four significant predictors for revision were fixation type (p<0.01), surface bearing type (p<0.01), age (P<0.05) and head size (p<0.05). Gender, BMI and approach had no effect on revision rates. The lowest 10-year all-cause revision rates were seen in cemented THRs at 1.7%. Ceramic-on-poly bearings had the lowest revision rate at only 1.2%. Metal-on-poly bearings had a 1.7% revision rate. Ceramic on ceramic bearings had a 7.1% revision rate with 1 revision for squeak and 1 revision for ceramic head fracture. The causes for revision in order of decreasing frequency were as follows: Infection (n=13, 0.7%), dislocation (n=7, 0.4%), periprosthetic fracture (n=3, 0.2%) and aseptic loosening (n=2, 0.1%). There were 2 re-revisions at 10 years in total. The smaller 22.225mm head sizes had a significantly lower revision rate than other head sizes (p<0.05). Ceramic-on-poly bearings, cemented fixation and smaller head sizes perform better in the experience of this registry. However, with multivariate analysis, these differences were shown to be insignificant.

Our aim was to investigate the molecular features of progressive severities of cartilage damage, within the phenotype of Anteromedial Gonarthrosis (AMG).

Ten medial tibial plateau specimens were collected from patients undergoing unicompartmental knee replacements. The cartilage within the area of macroscopic damage was divided into equal thirds: T1(most damaged), to T3 (least damaged). The area of macroscopically undamaged cartilage was taken as a 4th sample, N. The specimens were prepared for histological (Safranin-O and H& E staining) and immunohistochemical analysis (Type I and II Collagen, proliferation and apoptosis). Immunoassays were undertaken for Collagens I and II and GAG content. Real time PCR compared gene expression between areas T and N.

There was a decrease in OARSI grade across the four areas, with progressively less fibrillation between areas T1, T2 and T3. Area N had an OARSI grade of 0 (normal). The GAG immunoassay showed decreased levels with increasing severity of cartilage damage (p< 0.0001). There was no significant difference in the Collagen II content or gene expression between areas. The Collagen I immunohistochemistry showed increased staining within chondrocyte pericellular areas in the undamaged region (N) and immunoassays showed that the Collagen I content of this macroscopically and histologically normal cartilage, was significantly higher than the damaged areas (p< 0.0001). Furthermore, real time PCR showed a significant increase in Collagen I expression in the macroscopically normal areas compared to the damaged areas (p=0.04).

In AMG there are distinct areas, demonstrating progressive cartilage loss. We conclude that in this phenotype the Collagen I increase, in areas of macroscopically and histologically normal cartilage, may represent very early changes of the cartilage matrix within the osteoarthritic disease process. This may be able to be used as an assay of early disease and as a therapeutic target for disease modification or treatment.

Introduction: Anteromedial gonarthrosis (AMG) is a distinct phenotype of osteoarthritis (OA), with a specific pattern of disease. There is full thickness cartilage loss anteromedially, progressing to an area of damaged cartilage, and then to an area of macroscopically and histologically normal cartilage posteriorly. It can be considered to be a spatial model of OA progression. Apoptosis, or chondrocyte cell death, has been shown to be a feature of OA cartilage, however the triggers are poorly understood; similarly, reactive oxygen species (ROS) have been implicated in OA. They have never been studied in a replicable topographical model of OA. This study characterises the regional levels of cell death and implicated ROS in AMG using a number of immunohistochemical studies.

Method: Ten tibial resection specimens were obtained from patients undergoing unicompartmental knee arthroplasty. Eight above knee amputations (from patients with peripheral vascular disease) were used as age matched controls. Cross sections taken through all regions were paraffin embedded. Routine histology was performed and immunohistochemical studies were conducted for Terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL), Active Caspase 3, Cytochrome C, Active Bax, Bim, 3-Nitrotyrosine and Forkhead Box O3A (FOXO 3A).

Results: Cell death, as detected by TUNEL appeared predominantly in the surface layer of chondrocytes of damaged cartilage (p< 0.001). Median values were 23% in superficial cartilage (range 0 – 51) compared to 0% in deeper cartilage (range 0 – 15). There was a significant difference in TUNEL staining between regions (p=0.001). This ranged from 26% (most damaged) to 4% (undamaged). There was a good correlation with degree of cartilage damage (ρ=0.66, p< 0.001) asdefined by histological grade and TUNEL was significantly higher (p< 0.001) in AMG compared to the control samples which showed an average of 2% TUNEL overall. Upstream markers of apoptosis (Active Caspase 3, Cytochrome C, Active Bax), assessed qualitatively, were present in a similar distribution to that of TUNEL staining. 3-Nitrotyrosine was also shown to be a predominantly surface phenomenon. There was a significant difference (p< 0.001) between regions, ranging from 58% (most damaged) to 10% (undamaged). Again, this was significantly higher that the control samples (p< 0.001). In line with indicators of ROS mediated damage, Bim and FOXO3A were also detected.

Discussion: The mechanism of apoptosis in OA cartilage has not been studied in depth, and understanding the biochemical and molecular responses of ‘stressed’ chondrocytes may provide invaluable information about the specific causes of cell death. Such cellular responses may provide targets for disease modification, thus delaying or preventing the need for joint arthroplasty. We conclude that AMG is a phenotype demonstrating cartilage at progressive stages of disease. Apoptosis involves the intrinsic mitochondrial pathway and ROS appear to be implicated. Further work is needed to provide evidence of what lies further upstream of markers demonstrated in this study.

The aim of this study was to find evidence of tissue hypoxia and apoptosis (programmed cell death) have on a human model of rotator cuff failure.

We studied twenty seven patients with no tear mild impingment (3), no tear moderate impingment (3), no tear severe impingment (3), partial tear (3), small tear (3), moderate tear (3), large tear (3), massive tear (3) and control (3) who were undergoing shoulder arthroscopy, subacromial decompression and potential rotator cuff repair. A supraspinatus tendon biopsy was taken during debridement/repair on all cases (ethics number C01.071). Control tendon was obtained from the subscapularis tendon of patients undergoing stabilization surgery.

Biopsies were analysed using two immunocytological techniques. A monoclonal antibody against BNIP-3 (a pro-apoptotic marker of hypoxia) and TUNEL (an apoptotic marker). An immunofluorescent nuclear counterstain DAPI (4 6-Diamidino-2-phenylindole dihy-drochloride) was used to stain all cells. Positive cells and total cell number were then counted in 10 high powered fields per section.

The results showed a significant increase in BNIP-3 expression in the cuff tears compared with intact tendons. This increase was least in the massive tears. Apoptosis increases from mild impingement to massive cuff tears (mean 7.3% to 21%)

Aim: The aim of this study was to asses the accuracy of skyline radiographs in the assessment of the patellofemoral joint, when compared to open intraoperative assessment.

Methods: Eighty nine patients undergoing knee replacement surgery were included in the study. Skyline radiographs were obtained preoperatively. These radiographs were assessed and graded by an experienced musculoskeletal radiologist using the Altman and Ahlbäck classifications. The grades were calculated for both the medial and lateral facets of the PFJ. Intraoperative assessment of the Patellofemoral joint was undertaken at the time of surgery. The damage was graded using the modified Collins classification (0: Normal, 1: Superficial damage, 2: Partial thickness cartilage loss, 3: Focal Full thickness cartilage loss < 2cm2, 4: Extensive full thickness cartilage loss < 2cm2). Data was obtained for the Medial Facet, Lateral Facet and Trochlea.

Results: Spearman’s rank correlation coefficient between the radiographic and macroscopic changes within the lateral PFJ were poor with both the Altman 0.22 (p=0.0350) and Ahlbäck 0.24 (p=0.018). The correlation of the medial PFJ was slightly better with a coefficient for Altman 0.42 (P< 0.0001) and Ahlbäck 0.34 (P> 0.001).

Conclusion: In conclusion skyline radiographs provide a poor to moderate preoperative assessment of the degree of osteoarthritis within the patella-femoral joint. This has significant implications for establishing radiographic criteria for planning patella-femoral joint replacement.

The aim of this study was to investigate the molecular features of progressive severities of cartilage damage, within the phenotype of Anteromedial Osteoarthritis of the Knee (AMOA).

Ten medial tibial plateau specimens were collected from patients undergoing unicompartmental knee replacements. The cartilage within the area of macroscopic damage was divided into equal thirds: T1(most damaged), to T3 (least damaged). The area of macroscopically undamaged cartilage was taken as a 4th sample, N. The specimens were prepared for histological (Safranin-O and H& E staining) and immunohistochemical analysis (Type I and II Collagen). Immunoassays were undertaken for Collagens I and II and GAG content. Real time PCR compared gene expression between areas T and N.

There was a decrease in OARSI grade across the four areas, with progressively less fibrillation between areas T1, T2 and T3. Area N had an OARSI grade of 0 (normal).

The GAG immunoassay showed decreased levels with increasing severity of cartilage damage (ANOVA P< 0.0001). There was no significant difference in the Collagen II content or gene expression between areas. The Collagen I immunohistochemistry showed increased staining within chondrocyte territorial areas in the undamaged region (N) and immunoassays showed that the Collagen I content of this macroscopically and histologically normal cartilage, was significantly higher than the damaged areas (ANOVA P< 0.0001). Furthermore, real time PCR showed that there was a significant increase in Collagen I expression in the macroscopically normal areas (p=0.04).

In AMOA there are distinct areas, demonstrating progressive cartilage loss. We conclude that in this phenotype the Collagen I increase, in areas of macroscopically and histologically normal cartilage, may represent very early changes of the cartilage matrix within the osteoarthritic disease process. This may be able to be used as an assay of early disease and as a therapeutic target for disease modification or treatment.

Anteromedial osteoarthritis is a distinct phenotype of osteoarthritis. The arthritic lesion on the tibia is localised to the anteromedial quadrant with an intact ACL. Deficiency of the ACL leads to a progression to tricompartmental disease. Within the spectrum of intact ACL a varying degree of ligament damage is seen. Our aim was to correlate the progression of ACL damage to the geographical extent of disease and the degree of cartilage loss on the tibial plateau.

We systematically digitally mapped 50 tibial plateau resection specimens from clinical photographs of patients undergoing unicompartmental arthroplasty, additionally the damage to their ACL was graded (0: normal, 1:synovium loss, 2:longitudinal splits)

These images were imported into image analysis software. Accurate measurements were made of the dimensions of the specimen. Measurements included the AP distance to the anterior and posterior aspect of the lesion, and the distance to the start of the macroscopically non damaged cartilage. The areas of cartilage damage and full thickness loss were also recorded. The results were represented as a % of total area to account for variation in size of the resection specimens. We compared % of full thickness loss in patients with normal to those with damaged, but functionally intact ligaments.

All specimens had a similar macroscopic appearance. A significant difference was seen with the progression of ACL damage and area of eburnation of bone. Using an unpaired t test, a significant difference in area of % full thickness cartilage loss (P=0.047) was seen between patients with a normal and longitudinal splits within their ACL. No correlation between the clinical status of the ACL and start or finish point of cartilage loss on the tibial plateau

We surmise that the progression from anteromedial to tricompartmental osteoarthritis of the knee may be related to the graduated damage of the ACL.

A sibling risk study that shows a statistically significant increase in risk for anteromedial osteoarthritis of the knee.

Anteromedial osteoarthritis is a distinct phenotype of osteoarthritis. Previous studies have shown a genetic aetiology to both hip and knee osteoarthritis. The aim of this study was to determine the sibling risk of antero-medial osteoarthritis of the knee.

We conducted a retrospective cohort study of 132 probands with primary anteromedial osteoarthritis, who had undergone unicompartmental arthroplasty. Sibling were identified as having symptomatic knee problems by postal Oxford Knee Score (OKS). A positive OKS was defined as an OKS+/− 2SD of the mean of the proband group. Sibling spouses were used as controls. Those siblings & spouses that were symptomatic from the OKS were invited to undergo Knee X-rays, to look for radiological signs of osteoarthritis. Osteoarthritis was diagnosed as greater than Grade II on the Kell-gren Lawrence classification. The pattern of disease was noted and it was considered if the sibling were suitable for a unicompartmental knee arthroplasty. The prevalence and sibling risk of anteromedial osteoarthritis was determined using a randomly selected single sibling per proband family. The prevalence was determined in the 103 single proband sibling pairs.

There was a statistically significant risk within the sibling group P= 0.024 using the Chi square test. The relative risk of anteromedial osteoarthritis was. 3.21(95% CI 1.08 to 9.17)

Genetic factors play a major role in the development of anteromedial osteoarthritis.

The aim of this study was to observe the macroscopic and microscopic appearance of the Coracoacromial ligament and Subacromial bursa during Subacromial decompression and correlate it with the outcome at 3 months. Twenty patients with Subacromial Impingement without Rotator Cuff tear and five patients with large/massive irreparable Rotator Cuff tears who underwent a Subacromial Decompression. Patients with other shoulder pathology were excluded. Patients completed an Oxford Shoulder Score pre-operatively and their injection history was noted. At operation the shape of the acromion was noted. The macroscopic appearance of the CA ligament and the Subacromial bursa was classified as normal, mild/moderate and severe. Biopsies of the Subacromial bursa and CA ligament were taken and were analysed using histological and contempory immunocytochemical techniques. A histological analysis was performed using Mayer’s Haemotoxylin and Eosin, Toluidine Blue and Congo Red. Sections were stained with primary antibodies against PCNA (Proliferating cell nuclear antigen), Mast Cell Tryptase, CD3 (T-cell), CD20 (B cell), CD 34 (QBEnd 10), CD45 (Leucocyte Common Antigen), CD68 and D2–40 (Lymphatic Endothelial Marker). Post operatively the patients completed an Oxford Shoulder Score at 3 months. All the patients demonstrated an improvement in their Oxford Shoulder Score. The histological analysis demonstrated thickening of the synovial membrane and increased vascularity within the bursa and ligament. Increased numbers of inflammatory cells were present within the ligament and bursa of patients with impingement compared with massive rotator cuff tears. There was a relationship between outcome and the appearance of the bursa and ligament.

Antero-medial osteoarthritis of the knee displays a well recognised pattern of cartilage damage on the medial tibial plateau. Anteriorly there is a full thickness cartilage defect, with transition to a partial thickness defect, becoming full thickness in the posterior third of the plateau. The retained posterior cartilage is macroscopically normal, but no previous study has assessed its histo-logical features. This study characterises the histological changes, to examine if antero-medial OA of the knee represents a model of progressive osteoarthritic cartilage damage.

Five unicompartmental resection specimens of patients with idiopathic single compartment antero-medial osteoarthritis were assessed. The samples were stained with H& E and Saffinin-O stains and reviewed using the Mankin system, an established method for scoring osteoarthritic changes in cartilage (range 0 [normal] to 14 [grossly osteoarthritic]) Digital images of the histology were reviewed by two observers to exclude inter and intra observer error. Each specimen was assessed at 4 interval points (A,B,C,D) along the A-P axis starting from the most posterior aspect of the exposed bone to the area of macroscopically normal cartilage. Three repeat measurements were taken from the macroscopically normal region (D1,D2,D3). The scores were compared to historical age matched controls of non-osteoarthritic cartilage, where a Mankin grade of < 3 suggests normal cartilage.

From anterior to posterior the H& E staining showed a consistent decrease in structural integrity and cellularity of the cartilage, matched by a qualitative decrease in GAG content (Saffinin-O staining). Mean Mankin scores showed a progressive decrease in score; A = 14.0 (95% CI 0), B = 5.8 (95%CI 2.4), C = 4.4 (95%CI 2.5), D = 1.0 (95%CI 0.9) {p=0.04 ANOVA}. Repeated measurements at the macroscopically normal area showed the Mankin grade was maintained; D1= 1.0 (95%CI 0.9), D2 = 0.6 (95%CI 0.5), D3 = 0.6 (95%CI 0.6).

The results show that the retained posterior cartilage in antero-medial arthritis has a consistently normal Mankin grade. We suggest the defect represents a model of progressive cartilage damage from near normal (posterior) to the grossly osteoarthritic state (anterior).