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Orthopaedic Proceedings
Vol. 95-B, Issue SUPP_16 | Pages 22 - 22
1 Apr 2013
Tan H Cuthbert RJ Jones E Churchman S McGonagle D Giannoudis PV
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We hypothesise that the Masquelet induced membrane used for the reconstruction of large bone defects were likely to involve mesenchymal stem cells (MSCs), given the excellent resultant skeletal repair. This study represents the first characterisation in humans of the induced membrane formed as a result of the Masquelet technique.

Methods

Induced membranes and matching periosteum were harvested from 7 patients. Cytokines (BMP2, VEGF, SDF1) and cell lineage markers (CD31, CD271, CD146) were studied by immunohistochemisty. Flow cytometry was used to measure the cellularity and cellular composition. MSCs were enumerated using a colony forming unit fibroblast assay. In expanded cultures, a 96-gene array card was used to assess their transcriptional profile. Alkaline phophatase, alizarin red and calcium assays were employed to measure their in vitro osteogenic potential

Results

Membrane was more cellular(p=0.028), had more MSC phenotype(p=0.043) compared to matched periosteum. The molecular profiles were similar, except for 2-fold abundance of SDF-1 in membrane (p=0.043)compared to periosteum. Membrane and periosteum had a similar proportion of endothelial cells and CFU-F colonies; expanded MSCs from both sources were highly osteogenic.


Orthopaedic Proceedings
Vol. 95-B, Issue SUPP_16 | Pages 25 - 25
1 Apr 2013
KOUROUPIS D JONES E BABOOLAL T GIANNOUDIS PV
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Introduction

The concept of “bone graft expanders” has been popularised to increase the volume and biological activity of the implanted Material.

HYPOTHESIS

Orthoss® granules support exogenously seeded MSCs and attract neighbouring host MSCs.


The Bone & Joint Journal
Vol. 95-B, Issue 2 | Pages 230 - 238
1 Feb 2013
Giannoudis PV Kanakaris NK Delli Sante E Morell DJ Stengel D Prevezas N

Over a five-year period, adult patients with marginal impaction of acetabular fractures were identified from a registry of patients who underwent acetabular reconstruction in two tertiary referral centres. Fractures were classified according to the system of Judet and Letournel. A topographic classification to describe the extent of articular impaction was used, dividing the joint surface into superior, middle and inferior thirds. Demographic information, hospitalisation and surgery-related complications, functional (EuroQol 5-D) and radiological outcome according to Matta’s criteria were recorded and analysed. In all, 60 patients (57 men, three women) with a mean age of 41 years (18 to 72) were available at a mean follow-up of 48 months (24 to 206). The quality of the reduction was ‘anatomical’ in 44 hips (73.3%) and ‘imperfect’ in 16 (26.7%). The originally achieved anatomical reduction was lost in12 patients (25.8%). Radiologically, 33 hips (55%) were graded as ‘excellent’, 11 (18.3%) as ‘good’, one (1.7%) as ‘fair’ and 15 (25%) as ‘poor’. A total of 11 further operations were required in 11 cases, of which six were total hip replacements.

Univariate linear regression analysis of the functional outcome showed that factors associated with worse pain were increasing age and an inferior location of the impaction. Elevation of the articular impaction leads to joint preservation with satisfactory overall medium-term functional results, but secondary collapse is likely to occur in some patients.

Cite this article: Bone Joint J 2013;95-B:230–8.


The Journal of Bone & Joint Surgery British Volume
Vol. 94-B, Issue 5 | Pages 698 - 703
1 May 2012
Soni A Tzafetta K Knight S Giannoudis PV

Controversy continues to surround the management of patients with an open fracture of the lower limb and an associated vascular injury (Gustilo type IIIC). This study reports our 15-year experience with these fractures and their outcome in 18 patients (15 male and three female). Their mean age was 30.7 years (8 to 54) and mean Mangled Extremity Severity Score (MESS) at presentation was 6.9 (3 to 10). A total of 15 lower limbs were salvaged and three underwent amputation (two immediate and one delayed). Four patients underwent stabilisation of the fracture by external fixation and 12 with an internal device. A total of 11 patients had damage to multiple arteries and eight had a vein graft. Wound cover was achieved with a pedicled flap in three and a free flap in six. Seven patients developed a wound infection and four developed nonunion requiring further surgery. At a mean follow-up of five years (4.1 to 6.6) the mean visual analogue scale for pain was 64 (10 to 90). Depression and anxiety were common. Activities were limited mainly because of pain, and the MESS was a valid predictor of the functional outcome. Distal tibial fractures had an increased rate of nonunion when associated with posterior tibial artery damage, and seven patients (39%) were not able to return to their previous occupation.


The Journal of Bone & Joint Surgery British Volume
Vol. 93-B, Issue 7 | Pages 970 - 974
1 Jul 2011
Giannoudis PV Kanakaris NK Dimitriou R Mallina R Smith RM

Isolated fractures of the anterior column and anterior wall are a relatively rare subgroup of acetabular fractures. We report our experience of 30 consecutive cases treated over ten years. Open reduction and internal fixation through an ilioinguinal approach was performed for most of these cases (76.7%) and percutaneous techniques were used for the remainder. At a mean follow-up of four years (2 to 6), 26 were available for review. The radiological and functional outcomes were good or excellent in 23 of 30 patients (76.7%) and 22 of 26 patients (84.6%) according to Matta’s radiological criteria and the modified Merlé d’Aubigné score, respectively.

Complications of minor to moderate severity were seen in six of the 30 cases (20%) and none of the patients underwent secondary surgery or replacement of the hip.


The Journal of Bone & Joint Surgery British Volume
Vol. 93-B, Issue 4 | Pages 517 - 524
1 Apr 2011
Cox G McGonagle D Boxall SA Buckley CT Jones E Giannoudis PV

The scarcity of mesenchymal stem cells (MSCs) in iliac crest bone marrow aspirate (ICBMA), and the expense and time in culturing cells, has led to the search for alternative harvest sites. The reamer-irrigation-aspirator (RIA) provides continuous irrigation and suction during reaming of long bones. The aspirated contents pass via a filter, trapping bony fragments, before moving into a ‘waste’ bag from which MSCs have been previously isolated. We examined the liquid and solid phases, performed a novel digestion of the solid phase, and made a comparative assessment in terms of number, phenotype and differentiation capacity with matched ICBMA.

The solid fraction from the filtrate was digested for 60 minutes at 37°C with collagenase. Enumeration was performed via the colony-forming unit fibroblast (CFU-F) assay. Passage (P2) cells were differentiated towards osteogenic, adipogenic and chondrogenic lineages, and their phenotypes assessed using flow cytometry (CD33, CD34, CD45, CD73, CD90, and CD105).

MSCs from the RIA phases were able to differentiate at least as well as those from ICBMA, and all fractions had phenotypes consistent with other established sources. The median number of colonies for the three groups was: ICBMA = 8.5 (2 to 86), RIA-liquid = 19.5 (4 to 90), RIA-solid = 109 (67 to 200) per 200 μl. The mean total yield of cells for the three groups was: ICBMA = 920 (0 to 4275), RIA-liquid = 114 983 (16 500 to 477 750), RIA-solid = 12 785 (7210 to 28 475).

The RIA filtrate contains large numbers of MSCs that could potentially be extracted without enzymatic digestion and used for bone repair without prior cell expansion.


The Journal of Bone & Joint Surgery British Volume
Vol. 91-B, Issue 10 | Pages 1354 - 1359
1 Oct 2009
Giannoudis PV Nikolaou VS Kheir E Mehta S Stengel D Roberts CS

We investigated whether patients who underwent internal fixation for an isolated acetabular fracture were able to return to their previous sporting activities.

We studied 52 consecutive patients with an isolated acetabular fracture who were operated on between January 2001 and December 2002. Their demographic details, fracture type, rehabilitation regime, outcome and complications were documented prospectively as was their level and frequency of participation in sport both before and after surgery. Quality of life was measured using the EuroQol-5D health outcome tool (EQ-5D).

There was a significant reduction in level of activity, frequency of participation in sport (both p < 0.001) and EQ-5D scores in patients of all age groups compared to a normal English population (p = 0.001). A total of 22 (42%) were able to return to their previous level of activities: 35 (67%) were able to take part in sport at some level. Of all the parameters analysed, the Matta radiological follow-up criteria were the single best predictor for resumption of sporting activity and frequency of participation.


The Journal of Bone & Joint Surgery British Volume
Vol. 89-B, Issue 4 | Pages 503 - 509
1 Apr 2007
Giannoudis PV Tzioupis C Moed BR

Our aim was to evaluate the efficacy of a two-level reconstruction technique using subchondral miniscrews for the stabilisation of comminuted posterior-wall marginal acetabular fragments before applying lag screws and a buttress plate to the main overlying posterior fragment. Between 1995 and 2003, 29 consecutive patients with acute comminuted displaced posterior-wall fractures of the acetabulum were treated operatively using this technique.

The quality of reduction measured from three standard plain radiographs was graded as anatomical in all 29 hips. The clinical outcome at a mean follow-up of 35 months (24 to 90) was considered to be excellent in five patients (17%), very good in 16 (55%), good in six (21%) and poor in two (7%). The use of the two-level reconstruction technique appears to provide stable fixation and is associated with favourable results in terms of the incidence of post-traumatic osteoarthritis and the clinical outcome. However, poor results may occur in patients over the age of 55 years.


The Journal of Bone & Joint Surgery British Volume
Vol. 86-B, Issue 6 | Pages 861 - 867
1 Aug 2004
Gopal S Giannoudis PV Murray A Matthews SJ Smith RM

We studied the outcome and functional status of 33 patients with 34 severe open tibial fractures (Gustilo grade IIIb and IIIc). The treatment regime consisted of radical debridement, immediate bony stabilisation and early soft-tissue cover using a muscle flap (free or rotational). The review included standardised assessments of health-related quality of life (SF-36 and Euroqol) and measurement of the following parameters: gait, the use of walking aids, limb-length discrepancy, knee and ankle joint function, muscle wasting and the cosmetic appearance of the limb. Personal comments and overall patient satisfaction were also recorded. The mean follow-up was 46 months (15 to 80).

There were 30 Gustilo grade IIIb fractures and and four grade IIIc fractures. Of the 33 patients, 29 had primary internal fixation and four, external fixation; 11 (34%) later required further surgery to achieve union and two needed bone transport procedures to reconstruct large segmental defects. The mean time to union was 41 weeks (12 to 104). Two patients (6.1%) developed deep infection; both resolved with treatment.

The mean SF-36 physical and mental scores were 49 and 62 respectively. The mean state of health score for the Euroqol was 68. Patients with isolated tibial fractures had a better outcome than those with other associated injuries on both scoring systems. Knee stiffness was noted in seven patients (21%) and ankle stiffness in 19 (56%); 12 patients (41%) returned to work. Our results compare favourably with previous outcome measurements published for both limb salvage and amputation. All patients were pleased to have retained their limbs.


The Journal of Bone & Joint Surgery British Volume
Vol. 84-B, Issue 4 | Pages 492 - 496
1 May 2002
Giannoudis PV Snowden S Matthews SJ Smye SW Smith RM

We have carried out a prospective, randomised trial to measure the rise of temperature during reaming of the tibia before intramedullary nailing. We studied 34 patients with a mean age of 35.1 years (18 to 63) and mean injury severity score of 10 (9 to 13). The patients were randomised into two groups: group 1 included 18 patients whose procedure was undertaken without a tourniquet and group 2, 16 patients in whom a tourniquet was used. The temperature in the bone was measured directly by two thermocouples inserted into the cortical bone near the isthmus of the tibial diaphysis. Reaming was carried out to at least 1.5 mm above the required diameter of the nail. Blood loss was assessed by recording the preoperative and postoperative haemoglobin (Hb) level.

The minimum clinical follow-up was six months. In group 1 (no tourniquet), the mean Hb dropped 2.8 g/dl from 14.3 ± 1.02 g/dl to 11.5 ± 1.04 g/dl (p = 0.0001), whereas with the tourniquet, the mean decrease was 1.3 g/dl from 14 ± 1 g/dl to 12.7 ± 1.3 g/dl (p = 0.007). This difference was not statistically significant. The mean initial tibial temperature was 35.6°C (sd 0.6) and rose with reaming to levels between 36.3°C and 51.6°C. The highest temperatures were obtained with the largest reamers (11 and 12 mm, p = 0.0001) and the most rapid rise with the smallest diameters of medullary canal (8 or 9 mm). The rise of temperature was transient (20s).

We were unable to identify any effect of the use of a tourniquet on the temperature achieved. Reamed intramedullary tibial nailing induces a transient elevation of temperature which is directly related to the amount of reaming.


The Journal of Bone & Joint Surgery British Volume
Vol. 82-B, Issue 5 | Pages 655 - 658
1 Jul 2000
Giannoudis PV MacDonald DA Matthews SJ Smith RM Furlong AJ De Boer P

We assessed factors which may affect union in 32 patients with nonunion of a fracture of the diaphysis of the femur and 67 comparable patients whose fracture had united. These included gender, age, smoking habit, the use of non-steroidal anti-inflammatory drugs (NSAIDs) the type of fracture (AO classification), soft-tissue injury (open or closed), the type of nail, the mode of locking, reaming v non-reaming, infection, failure of the implant, distraction at the fracture site, and the time to full weight-bearing. Patients with severe head injuries were excluded. Both groups were comparable with regard to gender, Injury Severity Score and soft-tissue injury.

There was no relationship between the rate of union and the type of implant, mode of locking, reaming, distraction or smoking. There were fewer cases of nonunion in more comminuted fractures (type C) and in patients who were able to bear weight early. There was a marked association between nonunion and the use of NSAIDs after injury (p = 0.000001) and delayed healing was noted in patients who took NSAIDs and whose fractures had united.