To determine radiographic variables that predict the need for distal extension of the fusion beyond Cobb-to-Cobb levels in treating thoracolumbar/lumbar (TL/L) scoliosis (Lenke 5) in adolescent patients. We reviewed the medical notes and radiographs of the senior author's consecutive series of 53 adolescent patients with TL/L scoliosis treated by posterior instrumented spinal arthrodesis using an all-pedicle screw construct. Our patients were categorised into 2 groups: patients with instrumented fusion between Cobb-to-Cobb levels of the TL/L curve (Group 1), and patients that required distal extension beyond the caudal Cobb level (Group 2). Pearson correlation and binary logistic regression analyses (significance p<0.05) were performed to identify variables that predict the need for distal extension.Aim:
Method:
Lowest instrumented vertebra (LIV) selection is critical to preventing complications following posterior spinal arthrodesis (PSA) for thoracolumbar/lumbar adolescent idiopathic scoliosis (TL/L AIS), but evidence guiding LIV selection is limited. This study aimed to investigate the efficacy of PSA using novel unilateral convex segmental pedicle screw instrumentation (UCS) in correcting TL/L AIS, to identify radiographic parameters correlating with distal extension of PSA, and to develop a predictive equation for distal fusion extension using these parameters. We reviewed data (demographic, clinical, radiographic, and SRS-22 questionnaires) preoperatively to 2-years' follow-up for TL/L AIS patients treated by PSA using UCS between 2006 to 2011. 53 patients were included and divided into 2 groups: Group-1 (n=36) patients had PSA between Cobb-to-Cobb levels; Group-2 (n=17) patients required distal fusion extension. A mean curve correction of 80% was achieved. Mean postoperative LIV angle, TL/L apical vertebra translation (AVT), and trunk shift were lower than previous studies. Six preoperative radiographic parameters significantly differed between groups and correlated with distal fusion extension: thoracic curve size, thoracolumbar curve size, LIVA, AVT, lumbar flexibility index, and Cobb angle on lumbar convex bending. Regression analysis optimised an equation (incorporating the first five parameters) which is 81% accurate in predicting Cobb-to-Cobb fusion or distal extension. SRS-22 scores were similar between groups. We conclude that TL/L AIS is effectively treated by PSA using UCS, six radiographic parameters correlate with distal fusion extension, and a predictive equation incorporating these parameters reliably informs LIV selection and the need for fusion extension beyond the caudal Cobb level.
The aim of this study was to characterise injury patterns and examine whether survival had improved over the last decade of conflict in Iraq and Afghanistan. A logistical regression model was applied to all UK casualty data from the Joint Theatre Trauma Registry. There were 2785 casualties over the 10-years. 72% of casualties from hostile action were injured by blast weapons. The extremities were the post commonly injured body region, being involved in 43% of all injuries sustained. The New Injury Severity Score that was observed to be associated with a 50% chance of survival rose every year from 38 in 2003 to 62 in 2012. The odds ratio of surviving with a Trauma and Injury Severity Score (TRISS) of 50% rose by 1.349 (95% CI = 1.265–1.442) per year. The actual TRISS value associated with a 50% chance of survival dropped every year from 35.3% in 2003 to 0.9 in 2010 and was un-calculable in 2011–12. This study confirms that the last decade of conflict has been characterised by blast wounds and injuries involving the extremities. A consistent improvement in survival over the 10 years has been demonstrated, to the point that traditional metrics for measuring improvement in trauma care have been exhausted.
To evaluate the efficacy of bone marrow derived stromal cells (BMSC) for the treatment of non-unions in fractures. An ethically approved single centre randomised control trial recruited 35 patients for treatment of non-unions with BMSC during 2006–2010. Autologous BMSC were culture expanded at the Good Manufacturing Practice (GMP) standard Oscell® laboratory in the hospital. Following Aim
Methods
Intervertebral disc cells exist in a challenging physiological environment. Disc degeneration occurs early in life implying that disc cells may no longer be able to maintain a functional tissue. We hypothesise that disc cells have a stress response different from most other cells because of the disc environment. We have compared the stress response of freshly isolated and cultured bovine nucleus pulposus (NP) cells with bovine dermal fibroblasts, representative of cells from a vascularised tissue. Freshly isolated and passaged bovine NP cells and dermal fibroblasts were cultured for 3 days then subjected to either thermal stress at 45°C for 1h followed by recovery times of 6, 24 and 48h or nutrient stress involving culture without serum for 6, 24 and 48 h. At each time point, cell number and viability were assessed and heat shock protein 70 (Hsp70) measured in cell lysates by an enzyme-linked immunosorbent assay.Background
Methods
The potential of cells derived from human umbilical cord(UC) for orthopaedic cell engineering is evaluated by dissecting the UC into four distinct anatomical structures – cord lining (CL), Wharton's Jelly (WJ), umbilical cord artery (UCA) and umbilical cord vein (UCV). Cells from individual anatomical layers were grown by explant culture technique for 21 days. Tri-lineage differentiation and growth kinetics of cells from each layer were compared. Flowcytometry was done according to ISCT criteria to ascertain their surface antigen expressions. Cells from all four layers differentiated into bone, cartilage and fat. Osteogenic and chondrogenic differentiation was variable for each type of cells. All cells expressed surface antigens characteristic of mesenchymal stem cells (MSC). These cells can form a potential cell source in cell engineering to produce bone and cartilage although individual cell type needs to be characterised from each anatomical layer of UC and identify the best cell type for cell engineering.
Stem cells are a key component of regenerative medicine strategies. Particular areas of musculoskeletal application include cartilage and bone regeneration in arthritis and trauma. There are several types of stem cell and this article will focus on the adult derived cells. The review includes current issues and future developments.
Plantar fasciitis is thought to be a self limiting condition best treated by conservative measures, but despite this many patients have a prolonged duration of symptoms and for some surgery may be indicated. Partial plantar fascial release is reported to have a short term success rate of up 80%, but anecdotally this was not thought to represent local experience. An audit of long term patient reported outcomes following surgery was performed. A total of 26 patients (29 feet) were identified retrospectively and case notes were reviewed for each patient. Patients were contacted by letter and invited to complete two validated patient reported outcome score questionnaires (foot and ankle visual analogue scale (VAS) and MOXFQ). The average age of the patients was 42.4(range 28–61) for males and 46.2 (range 33–60) for female patients, with a female:male ratio of 2.7:1. Preoperative treatments included orthotics (29), steroid injections (23), physiotherapy (21) and cast immobilisation (11). The average duration of treatment prior to surgical intervention was 3.1 years (range 1–5). All patients were reviewed post operatively and discharged from follow up at an average of 31 weeks, at which time 38% remained symptomatic. We conclude that the results from open partial plantar fascial release are poor and it is a technique of dubious clinical value.
Proteoglycans (PGs) have long been known to be important to the functioning of the intervertebral disc. The most common PG is aggrecan, but there are also small leucine-rich proteoglycans (SLRPs) which constitute only a small percentage of the total PGs. However, they have many important functions, including organising the collagen, protecting it from degradation and attracting growth factors to the disc. We have examined how the core proteins of these molecules vary in intervertebral discs from patients with different pathologies. Discs were obtained from patients with scoliosis (n=7, 19–53y), degenerative disc disease (DDD) (n=6, 35–51y) and herniations (n=5, 33–58y). Proteoglycans were extracted and the SLRPs (biglycan, decorin, fibromodulin, keratocan and lumican) were characterised via Western blotting following enzymatic digestion with chondroitinase ABC and keratanase.Background
Methods
This article reviews the current knowledge of
the intervertebral disc (IVD) and its association with low back
pain (LBP). The normal IVD is a largely avascular and aneural structure
with a high water content, its nutrients mainly diffusing through
the end plates. IVD degeneration occurs when its cells die or become
dysfunctional, notably in an acidic environment. In the process
of degeneration, the IVD becomes dehydrated and vascularised, and
there is an ingrowth of nerves. Although not universally the case,
the altered physiology of the IVD is believed to precede or be associated
with many clinical symptoms or conditions including low back and/or
lower limb pain, paraesthesia, spinal stenosis and disc herniation. New treatment options have been developed in recent years. These
include biological therapies and novel surgical techniques (such
as total disc replacement), although many of these are still in
their experimental phase. Central to developing further methods
of treatment is the need for effective ways in which to assess patients
and measure their outcomes. However, significant difficulties remain
and it is therefore an appropriate time to be further investigating
the scientific basis of and treatment of LBP.
Autologous chondrocyte implantation (ACI) has been used for many years for the treatment of symptomatic defects in articular joints, predominantly the knee. Traditionally, cells were implanted behind a periosteal membrane, but in more recent times Chondrogide, a membrane consisting of porcine collagens I and III, has been used. There have been trials comparing the clinical outcome of these two groups of patients; in this study we compare the histological outcome using the two different patch types. In a study of 100 patients having received ACI treatment of cartilage defects in the knee, 41 received Chondrogide (ACI-C) and 59 received periosteum (ACI-P). All of these patients had a post-operative biopsy taken at a mean of 16.9±9.2 months and 20.8±23.2 months for ACI-C and ACI-P respectively for histology using the ICRS II scoring system. Lysholm scores, a measure of knee function, were obtained pre- and post-operatively at the time of biopsy and statistical differences tested for via a Mann-Whitney U-test. The mean age of the two groups at treatment was 37±8 and 35±10 years, the size of defect treated was 6.1±5.4 and 4.4±2.7 cm2 and the biopsy follow-up time was 50.6±22.2 and 81.2±34.8 months for ACI-C and ACI-P patients respectively. Both groups exhibited a significant improvement in Lysholm score from pre-operative to the time of biopsy (14.3±25.7; n=100), although there was no significant difference in improvement in Lysholm score between the two patch types. There was no significant difference between the histology score of the two groups, nor was the score found to correlate with the Lysholm score at that time. The individual components of the ICRS II score did not differ significantly with patch type (even for the surface architecture) apart from cellular morphology which was 6.5±3 and 8.2±1.6 for ACI-C and ACI-P respectively. The histological quality of repair tissue formed with ACI-C differed little from that seen with ACI-P, despite the former group being biopsied ∼4 months sooner after treatment and being used to treat defects which were 39% larger. Hence Chondrogide appears just as suitable as periosteum for use as a patch in the procedure of ACI.
Autologous Chondrocyte Implantation (ACI) is a procedure which is gaining acceptance for the treatment of cartilage defects in the knee with good results and a long term durable outcome. Its use in other joints has been limited, mainly to the ankle. We aimed to assess the outcome of ACI in the treatment of chondral and osteochondral defects in the hip. Fifteen patients underwent ACI for chondral or osteochondral defects in the femoral head with a follow up of upto 8 years (mean of 2 years) in our institution with a mean age of 37 years at the time of operation. Pre-operatively hip function was assessed by using the Harris Hip Score and MRI. Post-operatively these were repeated at 1 year and hip scores repeated annually. Failure was defined as a second ACI to the operated lesion or a conversion to a hip resurfacing or replacement.Background
Methods
Hyaline cartilage defects are a significant clinical problem for which a plethora of cartilage repair techniques are used. One such technique is cartilage replacement therapy using autologous chondrocyte or mesenchymal stem cell (MSC) implantation (ACI). Mesenchymal stem cells are increasingly being used for these types of repair technique because they are relatively easy to obtain and can be expanded to generate millions of cells. However, implanted MSCs can terminally differentiate and produce osteogenic tissue which is highly undesirable, also, MSCs generally only produce fibrocartilage which does not make biomechanically resilient repair tissue, an attribute that is crucial in high weight-bearing areas. Tissue-specific adult stem cells would be ideal candidates to fill the void, and as we have shown previously in animal model systems [Dowthwaite et al, 2004, J Cell Sci 117;889], they can be expanded to generate hundreds of millions of cells, produce hyaline cartilage and they have a restricted differential potential. Articular chondroprogenitors do not readily terminally differentiate down the osteogenic lineage. At present, research focused on isolating tissue-specific stem cells from articular cartilage has met with modest success. Our results demonstrate that using differential adhesion it is possible to easily isolate articular cartilage progenitor populations from human hyaline cartilage and that these cells can be subsequently expanded in vitro to a high population doubling whilst maintaining a normal karyotype. Articular cartilage progenitors maintain telomerase activity and telomere length that are a characteristic of progenitor/stem cells and differentiate to produce hyaline cartilage. In conclusion, we propose the identification and characterisation of a novel articular cartilage progenitor population, resident in human cartilage, which will greatly benefit future cell-based cartilage repair therapies.
Hyaline cartilage defects are a significant clinical problem for which a plethora of cartilage repair techniques are used. One such technique is cartilage replacement therapy using autologous chondrocyte or mesenchymal stem cell (MSC) implantation (ACI). Mesenchymal stem cells are increasingly being used for these types of repair technique because they are relatively easy to obtain and can be expanded to generate millions of cells. However, implanted MSCs can terminally differentiate and produce osteogenic tissue which is highly undesirable, also, MSCs generally only produce fibrocartilage which does not make biomechanically resilient repair tissue, an attribute that is crucial in high weight-bearing areas. Tissue-specific adult stem cells would be ideal candidates to fill the void, and as we have shown previously in animal model systems [ At present, research focused on isolating tissue-specific stem cells from articular cartilage has met with modest success. Our results demonstrate that using differential adhesion it is possible to easily isolate articular cartilage progenitor populations from human hyaline cartilage and that these cells can be subsequently expanded In conclusion, we propose the identification and characterisation of a novel articular cartilage progenitor population, resident in human cartilage, which will greatly benefit future cell-based cartilage repair therapies.
Fragmentation of SLRPs, including decorin, biglycan, lumican, keratocan and fibromodulin, has been shown to occur in osteoarthritic articular cartilage. We have previously shown an increased expression of lumican and keratocan, in osteoarthritic articular cartilage. The long-term aim of this project is to develop ELISAs for the detection of SLRP metabolites, and validate these potential biomarkers with synovial fluid and serum samples from a large cohort of normal and osteoarthritic patients. Initially, we aimed to determine whether SLRPs could be detected in synovial fluid and whether they were post-translationally modified with glycosaminoglycan (GAG) attachments; and whether bovine nasal cartilage (BNC) would be a plentiful source of native SLRP for ELISA development. Proteoglycans were extracted from BNC in guanidine hydrochloride. BNC extract and bovine synovial fluid was separated on an associative CsCl gradient. BNC CsCl cuts containing sulphated GAG were further purified using anion exchange chromatography. SLRPs in each fraction were detected using Western Blotting. Human recombinant lumican was expressed in Chinese hamster ovary (CHO) cells. Monoclonal antibodies that recognise epitopes on the core protein of human and bovine lumican and decorin were purified from hybridoma media using Protein G and Protein A affinity chromatography respectively. Monoclonal antibody activity against native and recombinant SLRPs was then determined using a direct ELISA. Preliminary tests showed that bovine synovial fluid contains keratocan and lumican with GAG attachments. BNC is a good source of post-translationally modified decorin, keratocan and biglycan but lumican was present predominantly without GAG attachments. Human recombinant lumican was successfully expressed with GAG attachments by CHO cells. Initial tests showed that the mAb against decorin was able to detect native decorin, with GAG attachments, in direct ELISA conditions. We have identified a plentiful source of native SLRP and begun ELISA development to ascertain whether these proteoglycans are potential biomarkers of OA.
The mechanical disadvantage and detrimental effect to articular cartilage following meniscectomy has been well documented in the literature. Meniscal repair in the avascular (white on white zone) is controversial and would be deemed inappropriate by many. Prospective data collection on all meniscal repairs between 1999 and 2008. 423 patients underwent meniscal repair at our unit during this time. We identified 88 patients who underwent a meniscal repair of a non peripheral tear (white on white zone) where there was no co-existent ACL injury or instability. There were 74 males and 14 females with a mean age of 26 years (13-54). There were 50 medial meniscal tears and 38 lateral tears, all in the non peripheral area of the meniscus. The criterion for failure was any reoperation on the same meniscus requiring excision or re fixation.Background
Methods
Avascular meniscal tears can be repaired with good clinical outcomes. The mechanical disadvantage and detrimental effect to articular cartilage following meniscectomy has been well documented in the literature. Meniscal repair in the avascular (white on white zone) is controversial and would be deemed inappropriate by many.Hypothesis
Background
A new surgical hybrid technique involving the combination of autologous bone plug(s) and autologous chondrocyte implantation (AOsP-ACI) was used and evaluated as a treatment option in 15 patients for repair of large osteochondral defects in knee (N=12) and hip joints (N=3). Autologous Osplugs were used to contour the articular surface and the autologous chondrocytes were injected underneath a biological membrane covering the plug. The average size of the osteochondral defects treated was 4.5cm2. The average depth of the bone defect was 26mm. The patients had a significant improvement in their clinical symptoms at 12 months with significant increase in the Lysholm Score and Harris Hip Score (p = 0.031). The repaired tissue was evaluated using Magnetic Resonance Imaging, Computerised Tomography, arthroscopy, histology and immunohistochemistry (for expression of type I and II collagen). Magnetic Resonance Imaging, Computerised Tomography and histology at 12 months revealed that the bone plug became well integrated with the host bone and repair cartilage. Arthroscopic examination at 12 months revealed good lateral integration of the AOsP-ACI with the surrounding cartilage. Immunohistochemistry revealed mixed fibro-hyaline cartilage. We conclude that the hybrid AOsP-ACI technique provides a promising surgical approach for the treatment of patients with large osteochondral defects. This study highlights the use of this procedure in two different weightbearing joints and demonstrates good early results which are encouraging. The long term results need to be evaluated.
