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Orthopaedic Proceedings
Vol. 98-B, Issue SUPP_23 | Pages 43 - 43
1 Dec 2016
Romanò C Malizos K Blauth M Capuano N Mezzoprete R Logoluso N Drago L
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Aim

Aim of this study is to present the first clinical trial on an antibiotic-loaded fast-resorbable hydrogel coating*, in patients undergoing internal osteosynthesis for closed fractures.

Method

In this prospective, multi-centre, randomized, controlled, prospective study, a total of 260 patients were randomly assigned, in five European orthopaedic centres, to receive the antibiotic-loaded DAC coating or to a control group, without coating. Pre- and post-operative assessment of laboratory tests, wound healing, clinical scores and x-rays were performed at fixed time intervals.


Orthopaedic Proceedings
Vol. 98-B, Issue SUPP_23 | Pages 80 - 80
1 Dec 2016
Malizos K Capuano N Mezzoprete R D'Arienzo M Van Der Straeten C Drago L Romanò C
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Aim

Infection remains among the first reasons of failure of joint prosthesis. According to various preclinical reports, antibacterial coatings of implants may prevent bacterial adhesion and biofilm formation. Aim of this study is to present the first clinical trial on an antibiotic-loaded fast-resorbable hydrogel coating*, in patients undergoing hip or knee prosthesis.

Method

In this multi-center, randomized, prospective, study, a total of 380 patients, scheduled to undergo primary or revision total hip or knee joint replacement, using a cementless or a hybrid implant, were randomly assigned, in six European orthopedic centers, to receive the antibiotic-loaded DAC coating or to a control group, without coating. Pre- and post-operative assessment of clinical scores, wound healing, laboratory tests and x-ray were performed at fixed time intervals.


Orthopaedic Proceedings
Vol. 97-B, Issue SUPP_16 | Pages 6 - 6
1 Dec 2015
Kostopoulou F Papathanasiou I Anastasopoulou L Aidarinis C Mourmoura E Malizos K Tsezou A
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Toll-like receptors (TLRs) are crucial components of the immune system that recognize microbial infection and trigger anti-microbial host defense responses. Gram positive bacteria are causative factors of bone infections, as they alter the balance of coordinated activities during bone remodeling, stimulating osteoclastogenesis. The aim of the study was to investigate whether genetic variation in TLR2 and TLR4 genes predisposes to bone infections’ susceptibility.

One hundred and twenty patients with bone infections (osteomyelitis) and 200 healthy controls were genotyped for two single nucleotide polymorphisms (SNPs), R753Q [A/G] in TLR2 gene and T399I [C/T] in TLR4 gene. DNA was extracted from whole blood and the above SNPs were typed with PCR-RFLP (Polymerase Chain Reaction- Restriction Fragment Length Polymorphism) method for genotype identification. All patients were infected by Gram-positive bacteria, predominantly Staphylococcus aureus. Statistical analysis was carried out using the chi-square test.

We observed a significantly increased frequency in patients carrying the GA genotype of TLR2 R753Q polymorphism compared to controls (p<0.05). We also found that the A allele was more common in patients than in controls. All individuals carrying the A allele were heterozygous for this variant, while homozygous mutant individuals were not detected in the patients and the control group. In contrast, we found that the TLR4 T399I [C/T] SNP was similarly distributed among the two groups (patients and controls). The mechanism through which TLR2 mediates its effect in bone infections is under investigation.

A significant difference was observed in the genotype frequency of TLR2 R753Q [A/G] polymorphism in patients, suggesting that genetic variability in TLR2 gene may be associated with susceptibility to osteomyelitis in response to bacterial invasion in the bone.


Orthopaedic Proceedings
Vol. 97-B, Issue SUPP_16 | Pages 83 - 83
1 Dec 2015
Papadopoulos A Karatzios K Malizos K Varitimidis S
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Report of a case of migrating periprosthetic infection from a hip replacement to a contralateral knee joint undergoing a total knee replacement.

We present a 74-year old female patient who underwent a total hip arthroplasty of the left hip after a subcapital fracture of the femur. Four months after the index procedure the patient presented with signs and symptoms of infection of the operated joint. Staph aureus and Enterococcus faecalis were recognized as the infecting bacteria. The implants were removed, cement spacers were placed and a total hip arthroplasty was performed again after three months. Unfortunately, infection ensued again and the patient underwent three more procedures until the joint was considered clean and t he hip remained flail without implants. The patient elected to undergo a total knee arthroplasty due to severe osteoarthritis of right knee. Intraoperatively tissue samples were taken and sent for cultures which identified Enterococcus faecalis present in the knee joint. Enterococcus migrated from the infected hip to nonoperated knee joint. Intravenous antibiotics were administered for three weeks but the knee presented with infection of the arthroplasty ten months after its insertion. The implants were removed the joint was debrided and cement spacers were inserted.

The patient decided not to proceed with another procedure and she remains with the cement spacers in her knee.

Rare report of migrating periprosthetic infection. Nosocomial enterococci acquired resistance cannot be ruled out. Unique characteristics in enterococci antibiotic resistance and biofilm formation.


Orthopaedic Proceedings
Vol. 97-B, Issue SUPP_16 | Pages 138 - 138
1 Dec 2015
Malizos K Scarponi S Simon K Blauth M Romanò C
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Infection is among the first reasons for failure of orthopedic implants. Various antibacterial coatings for implanted biomaterials are under study, but only few technologies are currently available in the clinical setting. Previous studies showed the in vitro and in vivo efficacy and safety of a fast resorbable (<96 h) hyaluronic and polylactic acid based hydrogel, loaded with antibiotic or antibiofilm agents (DAC®, Novagenit Srl, Mezzolombardo, TN). Aim of this study is to report the results of the largest clinical trial in trauma and orthopedic patients.

In this prospective, controlled, study, a total of 184 patients (86 treated with internal osteosinthesis for closed fractures and 98 undergoing cementless total hip or knee joint prosthesis) were randomly assigned in three European orthopaedic centers to receive antibiotic-loaded DAC coating or to a control group, without coating. Pre- and post-operative assessment of laboratory tests, wound healing (ASEPSIS score), clinical score (SF-12 score) and x-rays were performed at fixed time intervals. Statistical analysis was performed with Fisher exact test or Student's t test. Significance level was set at p<0.05.

The study was approved by the local Ethical Committee and all patients provided a written informed consent.

On average, wound healing, clinical scores, laboratory tests and radiographic findings did not show any significant difference between the two-groups at a mean 12 months follow-up (min: 6, max: 18 months).

Four surgical site infections and two delayed union were observed in the control group compared to none in the treated group.

No local or systemic side effects, that could be related to DAC hydrogel coating, were noted and no detectable interference with bone healing or osteointegration could be found

This is the largest study, with the longest follow-up, reporting on clinical results after the use of a fast-resosrbable anti-bacterial hydrogel coating for orthopaedic and trauma implants. Our results show the safety of the tested coating in different indications; although not statistically significant, the data also show a trend towards surgical site infection reduction, as previously demonstrated in the animal models.


Orthopaedic Proceedings
Vol. 97-B, Issue SUPP_15 | Pages 29 - 29
1 Dec 2015
Seaton R Sarma J Malizos K Militz M Menichetti F Riccio G Jeannot G Trostmann U Pathan R Hamed K
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Of the 6075 patients enrolled in EU-CORE registry, 206 patients had orthopaedic device-related infections. Significant underlying diseases were reported in 71% patients, most frequently cardiovascular disease (38%). The common sites of infection were knee (40%) and hip (33%). Among the 170 patients with available culture results, 135 (79%) were positive. Coagulase-negative staphylococci (CoNS, 44%) and Staphylococcus aureus (43%, of those 47% were methicillin resistant) were the most commonly isolated pathogens. Daptomycin was used empirically in 48% patients and as second-line therapy in 67% patients. During daptomycin therapy, 67% patients had undergone surgery (debridement, 61%; removal of foreign device, 39%; incision and drainage, 9%). Over half of the inpatients (54%) received concomitant antibiotics. Daptomycin was most frequently prescribed at a dose of 6 mg/kg/day (48%), with a median duration of therapy of 16 (range, 1–176) days. The overall clinical success rate was 85%, and was similar whether daptomycin was administered as first- or second-line therapy. The success rates achieved for infections caused by S. aureus and CoNS were 86% and 83%, respectively. Among the 79 patients who entered the long-term follow-up, 85% had a sustained response. Adverse events (AEs) and serious AEs possibly related to daptomycin were reported in 4.4% and 1.9% patients, respectively.

Results from this real-world clinical experience showed that daptomycin is an effective and well-tolerated treatment option for orthopaedic device-related infections with a high success rate up to 2 years of follow-up.


Orthopaedic Proceedings
Vol. 94-B, Issue SUPP_XIV | Pages 37 - 37
1 Apr 2012
Dramis A Grimer R Malizos K Tillman R Abudu A Jeys L Carter S
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Aim

To determine the overall survival of patients with Pelvic Ewing's Sarcoma treated in our unit and to identify prognostic factors in pelvic primaries that could be used to select patients who would most likely benefit from high intensity treatment.

Method

Between 1977 and 2009, 80 male and 66 female patients aged 2 to 60 (mean, 18) years with Pelvic Ewing's Sarcomas were retrospectively reviewed from the Royal Orthopaedic Hospital Oncology Service Registry. Treatments included surgery, radiotherapy, chemotherapy, or any of them in combination. Event-free (from presentation to recurrence) and overall (from presentation to death/latest follow-up) survival rates were calculated using the Kaplan- Meier method.

Influence of various factors (age at diagnosis, gender, tumour site, metastasis at presentation, surgery (and surgical margins), radiotherapy, and type of treatment on survival was assessed using SPSS 14.0 statistical software.


Orthopaedic Proceedings
Vol. 93-B, Issue SUPP_III | Pages 362 - 362
1 Jul 2011
Samara S Dailiana Z Malizos K Varitimidis S Chassanidis C Koromila T Kollia P
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Avascular necrosis (AVN) is a disorder leading to femoral head (FH) destruction, while BMPs are known for their osteogenic ability. In this study we analyzed BMP-2, BMP-4, BMP-6 and BMP-7 expression at the RNA and protein level in the normal and necrotic sites of the FHs.

Quantitative RT-PCR for BMP-2,-4,-6,-7 genes was performed in samples from the normal and necrotic sites of 52 FHs with AVN. Protein levels of BMP-2,-4,-6 were estimated by Western Blot analysis. Statistical analysis was performed using the t-test (p< 0.05).

BMP-2 and BMP-6 mRNA levels were higher in the normal than the necrotic site (BMP-2 and BMP-6, normal vs necrotic: 16.8 vs 7.5 and 2 vs 1.66, respectively). On the contrary, BMP-4 mRNA levels were higher in the necrotic (1.2) than the normal site (0.97), while BMP-7 mRNA levels were low in both sites. At the protein level, BMP-2 expressed higher in the normal (0.63) than the necrotic region (0.58), while BMP-4 and BMP-6 detected at higher levels in the necrotic site (BMP-4 and BMP-6, normal vs necrotic: 0.51 vs 0.61 and 0.52 vs 0.57, respectively).

Different mRNA levels between the normal and necrotic site, as well as discrepancies between the gene and protein BMPs expression levels suggest a different regulation mechanism between the two regions. Better understanding of the expression pattern of BMPs could lead to a more successful use of these molecules in the prevention and treatment of AVN


Orthopaedic Proceedings
Vol. 93-B, Issue SUPP_III | Pages 373 - 373
1 Jul 2011
Giannakos R Bargiotas K Tsougias G Hantes M Varitimidis S Malizos K
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The evaluation of the outcome of CCK prostheses in primary TKA

Between 2002 and 2008 we implanted 34 CCK knees in 31 patients. Mean age was 69 (58–79) 10 patients were operated because of valgus knee and lateral compartment arthritis, 8 because of post-traumatic ligamentous laxity and/or bone loss and the remaining patients presented with advanced OA and varus deformity exceeding 30 degrees. All patients were followed regularly with radiographs annually and there were assessed clinically with KSS and Womac score. The findings were compared with a group of patients with similar characteristics and a CR prosthesis.

Mean follow-up was 3 years (6–1) There was no revision in this group neither was any radiological abnormality. Clinical outcome in terms of KSS and WOMAC score was excellent and comparable to the CR group.

The main indication for a CCK prosthesis is the ligamentous insufficiency. There is enough evidence to support its superiority as a treatment option in valgus knees but long term performance is yet unclear.

CCK prostheses are a reliable solution for unstable or imbalanced knees their long term behaviour though, is yet unclear


Orthopaedic Proceedings
Vol. 93-B, Issue SUPP_III | Pages 355 - 355
1 Jul 2011
Chassanidis C Kollia P Samara S Koromila T Varitimidis S Malizos K Dailiana Z
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Periosteum is a specialized connective tissue that surrounds bone, containing progenitor cells that develop into osteoblasts. The osteo-progenitor cells along with growth factors, such as BMPs, play critical role in development, reconstruction and bone formation. Aim: to evaluate the expression of BMPs in human periosteum and in different subrgroups, including different donor sites, gender, and smoking habits.

Gene expression of BMPs 2,4,6,7 was performed in 60 periosteal samples using quantitative RT-PCR. Samples were obtained from 32 men/28 women, 22 smokers/38 non-smokers, 29 lower/31 upper extremities.

BMP2 gene expression was significantly higher (median: 12.02, p< 0.05) than the mRNA levels of BMPs 4,6,7 (median: 1.36, 2.55, 0.04) in all samples. BMP2 mRNA levels were higher in large compared to small bones (median: 13.4 vs 9.48), while BMPs 4,6,7 gene expression was similar (1.3 vs 1.4, 2.7 vs 2.1, 0.04 vs 0.03, respectively). In lower extremities, BMPs mRNA levels were higher than in the upper; the same was detected in non-smokers versus smokers group (BMPs2,4,6,7: 13.9 vs 1.5, 3.1 vs 0.048, 8.7 vs 1.06, 1.6 vs 0.026, respectively). mRNA transcripts of BMP2 were higher in men than women (median: 13.1 vs 10.8).

In our study, BMP2 expression is characteristically higher than that of BMP4, BMP6 and BMP7, highlighting the critical role that BMP2 plays in bone homeostasis. Furthermore, the elevated expression of BMP2 in men towards women, and of all BMPs of the lower extremity samples indicate the effect of hormones and mechanical factors in periosteal BMPs gene regulation; while the effect of smoking is reflected in the reduction of BMPs expression in smokers.


Orthopaedic Proceedings
Vol. 93-B, Issue SUPP_III | Pages 348 - 348
1 Jul 2011
Giannakos R Bargiotas K Papatheodorou L Varitimidis S Karachalios T Malizos K
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The evaluation of the middle term behaviour of the Wagner-type stems in dysplastic femurs and the presentation of the technical and surgical differences with the implantation of a Wagner stem.

Between 1997 and 2008 we implanted 64 Wagner stems in 58 patients. Average age at the time of implantation was 64 years. 52 patients was operated because of DDH, and 12 had had previous osteotomy. All patients were prospectively evaluated radiographically and clinically at annual intervals. Functional outcome was assessed with Harris Hip Score and Oxford Score.

Mean follow-up of these series was 4 years (11-1)One stem was revised because of fracture of the lesser trochander and two more patients were re-operated for open reduction. With the re-operation as end-point and 95% Confidence Interval survivorship rate was 98, 5%. There were no progressive radiolucent lines. Stem migration was at an average 2mm (1–6) during the first two years and remained stable thereafter. There was no deep infection in these series. After the second year a dense zone is evident in all Gruen zones at the implant –bone interface with a width of 2–3 mm.

Dysplasia of the proximal femur may pose significant technical problems during THA due to the distortion of the geometry and the narrowing of the femoral canal. The sort, conical Wagner type stems can offer a very good alternative is such patients. They allow control of the anteversion and they are able get a good press-fit despite the metaphyseal/diaphyseal mismatch and the femoral bowing.

Wagner type stems are a reliable alternative when performing THA in patients with dysplastic femurs.


Orthopaedic Proceedings
Vol. 93-B, Issue SUPP_III | Pages 355 - 355
1 Jul 2011
Tsezou A Simopoulou T Kostopoulou F Malizos K
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The aim of the study was to investigate the expression of genes regulating cholesterol efflux in human chondrocytes and to study the effect of an LXR agonist on cholesterol efflux and lipid accumulation in osteoarthritic chondrocytes.

Human cartilage was obtained from 24 patients with primary osteoarthritis (OA) undergoing total knee replacement surgery. Normal cartilage was obtained from 8 individuals undergoing fracture repair surgery, with no history of joint disease. ATP-binding-cassette transporter A1(ABCA1), apolipoprotein A1 (ApoA1), and liver X receptors(LXRα and LXRβ) mRNA expression levels were evaluated using real-time PCR. The effect of the synthetic LXR agonist TO-901317 was studied after treatment of osteoarthritic chondrocytes and subsequent investigation of ABCA1 and ApoA1 mRNA expression levels. Cholesterol efflux was evaluated in osteoarthritic chondrocytes radiolabeled with [1,2(n)-3H] cholesterol after LXR treatment, while intracellular lipid accumulation was studied after Oil-red-O staining. Apoptosis was evaluated using flow cytometry.

ApoA1, ABCA1, LXRα and LXRβ mRNA expressions were significantly lower in osteoarthritic chondrocytes compared to normal. Treatment of osteoarthritic chondrocytes with the LXR agonist TO-901317 significantly increased ApoA1 and ABCA1 mRNA expression levels as well as cholesterol efflux, while it significantly reduced apoptosis. Additionally, osteoarthritic chondrocytes presented intracellular lipids deposits, while no deposits were found after treatment with TO-901317.

Our findings suggest that impaired expression of genes regulating cholesterol efflux may be a critical player in osteoarthritis, while the ability of the LXR agonist to facilitate cholesterol efflux and decrease apoptosis suggests that it may be a target for therapeutic intervention in osteoarthritis.


Orthopaedic Proceedings
Vol. 93-B, Issue SUPP_III | Pages 365 - 365
1 Jul 2011
Karachalios T Zibis A Zintzaras E Bargiotas K Karantanas A Malizos K
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Percutaneous fixation with iliosacral screws has been shown to be a safe and reproducible method for the management of certain posterior pelvic injuries. However, the method is contraindicated in patients with sacral anatomical variations and dysmorphism. The incidence and the pattern of S1 anatomical variations were evaluated in 61 volunteers (35 women and 26 men) using MRI scans of the sacrum. S1 dimensions (12 parameters) in both the transverse and coronal planes were recorded and evaluated. Individuals were divided in four groups based on the S1 body size and the asymmetry of dimensions on the transverse and coronal planes. In 48 (78.6%) patients, dimensions in both planes were symmetrical despite the varying size of the S1 body. In 9 (14.8%) patients, coronal plane dimensions were disproportionally smaller compared to those of the transverse plane with a varying size of S1 body making effective iliosacral screw insertion a difficult task. In 2 (3.3%) patients there was a combination of large transverse plane and small coronal plane dimensions, with large S1 body size. A preoperative imaging study of S1 body size and coronal plane dimensions and an intraoperative fluoroscopic control of S1 dimensions on the coronal plane are suggested for safe iliosacral screw fixation


Orthopaedic Proceedings
Vol. 93-B, Issue SUPP_III | Pages 372 - 372
1 Jul 2011
Giotikas D Karydakis G Karachalios T Roidis N Bargiotas K Malizos K
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Advance medial pivot total knee replacement has been designed to reflect contemporary data regarding knee kinematics. We report the clinical outcome of 284 replacements in 225 consecutive patients. All patients were prospectively followed for a mean of 7.6 years (5 to 9) using validated rating systems, both objective and subjective.

All patients showed a statistically significant improvement (p~0.01) on the Knee Society clinical rating system, WOMAC questionnaire, SF-12 questionnaire, and Oxford knee score. The majority of patients (92%) were able to perform age appropriate activities with a mean knee flexion of 117° (85 to 135). Survival analysis showed a cumulative success rate of 99.1% (95% CI, 86.6 to 100) at five years and 97.5% (95% CI, 65.6 to 100) at seven years. Two (0.7%) replacements were revised due to aseptic loosening, one (0.35%) due to infection and one (0.35%) due to a traumatic dislocation. In only two (0.7%) replacements, progressive radiological lucent lines (combined with beta angle of 85°) were observed


Orthopaedic Proceedings
Vol. 93-B, Issue SUPP_III | Pages 360 - 360
1 Jul 2011
Tsezou A Papathanasiou I Orfanidou T Malizos K
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The Wnt/b-catenin signaling pathway participates in normal adult bone and cartilage biology and seems to be involved in cartilage degeneration and subsequent OA progression. The aim of this study was to investigate the activation of Wnt/b-catenin pathway in osteoarthritis and the role of LRP5, a coreceptor of Wnt/b-catenin pathway, in human osteoarhritic chondrocytes.

Human cartilage was obtained from 11 patients with primary osteoarthritis (OA) undergoing total knee and hip replacement surgery. Normal cartilage was obtained from 5 healthy individuals. b-catenin and LRP5 mRNA and protein levels were investigated using real time PCR and western blot analysis, respectively. Blocking LRP5 expression was performed using small interfering (siRNA) against LRP5 and subsequent MMP-13 mRNA and protein levels were evaluated by real time RCR and western blot analysis, respectively.

We confirmed the activation of Wnt/b-catenin pathway in osteoarthritis, as we observed significant upregulation of b-catenin mRNA and protein expression in osteoarthritic chondrocytes. We also observed that LRP5 mRNA and protein expression was significantly up-regulated in osteoarthritic cartilage compared to normal. Also, blocking LRP5 expression using siRNA against LRP5 resulted in a significant decrease in MMP-13 mRNA and protein expressions.

Our findings suggest that the upregulation of LRP5 mRNA and protein expression in osteoarthritic chondrocytes results in an increased activation of Wnt/b-catenin pathway in osteoarthritis. The observed reduction of MMP-13 expression after blocking LRP5 expression in osteoarthritic chondrocytes, suggests the involvement of LRP5 in the progression and pathogenesis of osteoarthritis.


Orthopaedic Proceedings
Vol. 93-B, Issue SUPP_III | Pages 354 - 355
1 Jul 2011
Tsezou A Orfanidou T Varytimidis S Malizos K
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Cartilage calcification induces the synthesis of degrading enzymes, such as matrix metalloproteinases (MMPs) and prostaglandin E2 leading to tissue degeneration. The aim of the study was to investigate the effect of vitamin D on the calcification process in osteoarthritic cartilage.

We evaluated the effect of vitamin D on klotho (KL), Fibroblast Growth Factor 23 (FGF23) and Fibroblast Growth Factor Receptor 1c (FGFR1c) mRNA and protein expression levels by real-time PCR and western blot analysis, respectively. Possible interactions between klotho and FGF23 on the receptor FGFR1c in normal chondrocytes were investigated using immunoprecipitation assay. The direct effect of 1,25 dihydroxyvitamin D3 (1,25D) on KL, FGF23 and FGFR1c promoter was also evaluated.

We found that FGF23 and FGFR1c mRNA expression levels were significantly increased in osteoarthritic chondrocytes compared to normal, while KL mRNA levels were decreased (p=0.001 for all genes). We showed that klotho-FGF23-FGFR1c form complexes in normal chondrocytes and confirmed the participation of klotho in the initiation of FGF23-FGFR1c signalling. Treatment of normal chondrocytes with 1,25D resulted in a significant dose and time dependent increase of FGF23 and FGFR1c mRNA levels and in an increase of KL mRNA levels in osteoarthritic chondrocytes compared to untreated (p=0.001). We revealed, for the fist time, the presence of conserved, canonical VDREs in the proximal promoters of KL, FGF23 and FGFR1c.

We propose a common regulatory scheme of mineral homeostasis and aging in osteoarthritic chondrocytes evidenced by the positive/negative feedback actions by KL, FGF23, FGFR1c and 1,25D, through binding of vitamin D receptor (VDR) on the promoters of the above mentioned genes.


Orthopaedic Proceedings
Vol. 93-B, Issue SUPP_III | Pages 355 - 355
1 Jul 2011
Tsezou A Kostopoulou F Poultsides L Simopoulou T Malizos K
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Our study aimed to investigate the role of an HMG-CoA reductase inhibitor (atorvastatin) in human osteoarthritic chondrocytes and to test the in vivo effects of intra-articular injections of atorvastatin in a rabbit experimental osteoarthritis model.

Human articular osteoarthritic chondrocytes were cultured in the presence and absence of atorvastatin. mRNA and protein expression of MMP-13, COL2A1 and aggrecan were measured using real-time PCR and Western Blot analysis.

New Zealand rabbits (n=15) underwent bilateral anterior cruciate ligament transection (ACLT) to induce osteoarthritic degeneration and received intra-articular injections of atorvastatin and normal saline in the left and right knees respectively. The first injection was at the time of ACLT and injections were repeated every 3 days for 3 weeks. Data were obtained from macroscopic and histological evaluation as well as from gene expression analysis for COL2A1, aggrecan and MMP-13.

Incubation of the cultures with atorvastatin produced a decreasing effect in MMP-13 expression. Regarding aggrecan and COL2A1 expression a significant increase was observed.

Gross morphologic evaluation showed that the joints which received atorvastatin injections, showed minimal cartilage erosion, compared to the non-treated knees where the cartilage was markedly eroded, especially on the medial knee compartment. These results were supported by histological and gene expression analysis. The mRNA expression of MMP-13 was significantly reduced in the cartilage of the statin-treated knee joints, while the expression of COL2A1 and aggrecan was increased.

The clinical relevance of our results indicates a potential protective effect of atorvastatin on articular cartilage undergoing osteoarthritic degeneration.


Orthopaedic Proceedings
Vol. 93-B, Issue SUPP_III | Pages 362 - 362
1 Jul 2011
Samara S Kollia P Dailiana Z Chassanidis C Papatheodorou L Koromila T Malizos K
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We evaluated the contribution of specific gene polymorphisms of IL-1a/IL-1R/IL-1RA/IL-4Ra/IL-1b/IL-12/γIFN/TGF-b/TNF-a/IL-2/IL-4/IL-6/IL-10 cytokines in patients with AVN.

DNA was extracted from 112 patients and 238 healthy Greek individuals. DNA analysis was performed by the PCR-SSP method and the use of the Protrans kit. Statistical analysis was performed by χ2 test.

In the patients, the TC frequency of the IL-1a (nt-889) was 52% while in normal was 40%. The C/G allele frequency of TGF-b codon 25 in patients was 9% C and 91% G vs 13% C and 87% G in normal. At position −238 of TNFa, 11% of the patients had the GA genotype in contrast to 1% of the controls. The GG/GG haplotype of TNFa gene promoter (nt. −308 and −238) was more frequent in both groups, while the GG/GA haplotype detected in 9% and 1% of the patients and controls, respectively. At the −1082 position of the IL-10 gene, the GG genotype was detected in 15% of the controls and 7% of the patients. Also, the GCC/GCC haplotype in IL-10 (positions -1082/-819/-592) was higher in the controls (15%) than the patients (7%).

The genotypes TC (nt-889) of IL-1a, GC (codon 25) of TGF-b, GC (nt-1082) of IL-10 and GA (nt −238) of TNFa, are more prevalent in the patients than the healthy individuals (p< 0.05). Based on our results, the presence of one of the above mentioned polymorphisms or the simultaneous carriage of more than one may contribute to the risk for osteonecrosis


Orthopaedic Proceedings
Vol. 93-B, Issue SUPP_II | Pages 141 - 141
1 May 2011
Koromila T Dailiana Z Chassanidis C Samara S Michalitsis S Tzavara C Georgoulias P Malizos K Aleporou-Marinou V Kollia P
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Introduction: Osteoporosis is a common skeletal disease characterized by a combination of low bone mass and altered bone microarchitecture with a consequent increase of fragility. The human CER1 is a novel candidate gene for osteoporosis that can bind directly to bone morphogenetic proteins and inhibit their activity. In this study we evaluated the contribution of five novel gene single-nucleotide polymorphisms (SNPs) of CER1 in blood samples from osteoporotic and control groups.

Materials and Methods: Peripheral blood samples from 100 postmenopausal women with osteoporosis and 50 healthy Greek women, between 45 and 85 years of age, were collected and DNA was extracted. CER1 polymorphisms genotyping was carried out by PCR and sequencing of the whole gene. Bone mineral density (BMD) was examined by DXA. Statistical analysis was performed using Pearson χ2 or Fisher’s exact test in order to compare allelic frequency distribution.

Results: Genetic analysis of the CER1 gene revealed five SNPs at the positions 239C> G (rs3747532), 1058G> T (rs1494360), 2160A> G, 2355A> G (rs17289263), and 2749T> C of the CER1 gene. The above genotypes were distributed differently among osteoporotic and controls. In osteoporotic patients, the SNPs frequencies were: 78.6% heterozygotes and 3.6% homozygotes for 239C> G SNP, 66.7% and 4.3% heterozygotes and homozygotes, respectively, with T allele at the position 1058, 52.4% heterozygotes and 9.5% homozygotes for the polymorphic site A> G nt.2160, 51.2% heterozygotes and 2.4% homozygotes for the G allele at 2355 position of the CER1 gene, whereas only heterozygotes (38.9%) for the 2749T> C polymorphic site were determined (P< 0.001). However, in the control group the polymorphisms were detected only in heterozygosity and the overall distributions of the polymorphisms 239C> G, 1058G> T, 2160A> G, 2355A-> G, and 2749T> C, were 38.9%, 31.3%, 15.6%, 9.4%, 6.9% (P< 0.001), respectively.

Discussion: All the above polymorphisms, except the SNP rs3747532, are correlated with osteoporotic patients for the first time. Allele frequencies of the control group are significantly lower than those of osteoporotic for any of the five polymorphisms. These data provide the first evidence of an association (and most possible significant cumulative contribution) between the aforementioned genotypes in CER1 gene and the risk for osteoporosis in postmenopausal women.


Orthopaedic Proceedings
Vol. 93-B, Issue SUPP_II | Pages 97 - 98
1 May 2011
Tsezou A Iliopoulos D Malizos K Simopoulou T
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Osteoarthritis is a complex joint disease in which all involved tissues play an important role in its onset and progression. It has been suggested that osteoarthritis is likely to be a systemic disease involving stromal cell differentiation and lipid metabolism while altered lipid metabolism has been implicated as a critical player in its pathogenesis.

As excessive accumulation of free cholesterol is toxic for the cells, the accumulation of lipids in chondrocytes may signify a causal relationship to development and/or progression of osteoarthritis; therefore we investigated the expression of genes regulating reverse cholesterol transport, as ABCA1, ApoA1, LXRa, LXR_, in human osteoarthritic chondrocytes. We also investigated the effect of an LXR agonist on ABCA1 and ApoA1 expression and, for the first time, on cholesterol effiux and lipid accumulation in osteoarthritic chondrocytes.

Articular cartilage samples were obtained from femoral condyles and tibial plateaus of patients with primary OA undergoing knee replacement surgery while normal cartilage was obtained from eight individuals undergoing fracture repair surgery, with no history of joint disease. Total cellular RNA was extracted from all samples and ABCA1, ApoA1, and LXRα and LXRβ mRNA and protein expression levels were evaluated using real-time PCR and Western blot analysis respectively.

The effect of the synthetic LXR agonist TO-901317 was studied after treatment of osteoarthritic chondrocytes and subsequent investigation of ABCA1 and ApoA1 mRNA expression levels. Cholesterol effiux was evaluated in osteoarthritic chondrocytes radiolabeled with [1,2(n)-3H] cholesterol after LXR treatment, while intracellular lipid accumulation was studied after Oil-red-O staining.

ApoA1 and ABCA1 mRNA levels were significantly lower in osteoarthritic cartilage compared to normal (p< 0.01 and p< 0.001 respectively). In addition, the two subtypes of the LXR, namely LXRα and LXRβ, mRNA levels were also found to be significantly lower in osteoarthritic cartilage (p< 0.05 and p< 0.01 respectively). The differential expression pattern of the cholesterol effiux genes between normal and osteoarthritic cartilage remained the same at the protein level as well. Treatment of osteoarthritic chondrocytes with the LXR agonist TO-901317 significantly increased ApoA1 and ABCA1 expression levels, as well as cholesterol effiux. Additionally, osteoarthritic chondrocytes presented intracellular lipids deposits, while no deposits were found after treatment with TO-901317.

Our findings suggest that impaired expression of genes regulating cholesterol effiux may be a critical player in osteoarthritis, while the ability of the LXR agonist to facilitate cholesterol effiux suggests that it may be a target for therapeutic intervention in osteoarthritis.


Orthopaedic Proceedings
Vol. 93-B, Issue SUPP_II | Pages 219 - 219
1 May 2011
Karamanis N Papanagiotou M Varitimidis S Basdekis G Stamatiou G Dailiana Z Malizos K
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Introduction: The aim of this study is to present the effect of various local anaesthetics, in particular solution concentrations, in peri- and post-operative analgesia in patients with carpal tunnel syndrome (CTS).

Material and Method: 105 patients with CTS (81 female, 24 male, ages 27–79) underwent carpal tunnel release under local anaesthesia. The patients were divided into 5 groups (xylocaine 2%, ropivacaine 0.75%, ropivacaine 0.375%, chirocaine 0.5%, chirocaine 0.25%). A tablet of Gabapentin (Neurontin) 400mg was administered to some patients of each group (41 pts of the 105pts) 12 hours prior to surgery. All patients were evaluated immediately after surgery, in 2 weeks and 2 months postoperatively according to VAS pain score, grip strength, finger active motion and two point discrimination. Postoperative complications were also reported.

Results: Anesthesia was immediate after the local injection. All patients improved postoperativelly regarding relief from pain and paresthesias. There was no statistically significant difference in grip strength before and after surgery. Only 10 patients used paracetamol immediately after surgery, without any statistically significant correlation to any group of patients. 1 patient developed complex regional pain syndrome 2 months after surgery.

Conclusion: The use of local anaesthesia in carpal tunnel release surgery is beneficial in providing immediate intraoperative effect and recovery and mobilization after surgery. Rehabilitation seems to be irrelevant of the type of local anaesthetic that was used during the procedure. Small solution concentrations of local anaesthetics (ropivacaine 0.375%, chirocaine 0.25%) provide adequate analgesia during surgery and provide a normal postoperative course.


Orthopaedic Proceedings
Vol. 93-B, Issue SUPP_II | Pages 88 - 88
1 May 2011
Giannakos R Bargiotas K Papatheodorou L Karamanis N Varitimidis S Karachalios T Malizos K
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Aim: The evaluation of the middle term behaviour of the Wagner-type stems in dysplastic femurs and the presentation of the technical and surgical differences with the implantation of a Wagner stem.

Materials and Methods: Between 1997 and 2008 we implanted 64 Wagner stems in 58 patients. Average age at the time of implantation was 64 years. 52 patients was operated because of DDH, and 12 had had previous osteotomy. All patients were prospectively evaluated radiographically and clinically at annual intervals. Functional outcome was assessed with Harris Hip Score and Oxford Score.

Results: Mean follow-up of these series was 4 years (11-1)One stem was revised because of fracture of the lesser trochander and two more patients were re-operated for open reduction. With the re-operation as end-point and 95% Confidence Interval survivorship rate was 98, 5%. There were no progressive radiolucent lines. Stem migration was at an average 2mm (1–6) during the first two years and remained stable thereafter. There was no deep infection in these series. After the second year a dense zone is evident in all Gruen zones at the implant –bone interface with a width of 2–3 mm.

Discussion: Dysplasia of the proximal femur may pose significant technical problems during THA due to the distortion of the geometry and the narrowing of the femoral canal. The sort, conical Wagner type stems can offer a very good alternative is such patients. They allow control of the anteversion and they are able get a good press-fit despite the metaphyseal/diaphyseal mismatch and the femoral bowing.

Conclusions: Wagner type stems are a reliable alternative when performing THA in patients with dysplastic femurs


Orthopaedic Proceedings
Vol. 93-B, Issue SUPP_II | Pages 217 - 217
1 May 2011
Dailiana Z Basdekis G Varitimidis S Karamanis N Kazantzi V Rizos P Fotiadis D Iohom G Tokmakova K Molchovski P Malizos K
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Introduction: The value of arthroscopy, fluoroscopy, and e-learning courses (focusing on minimally invasive surgical techniques) for the treatment of intra-articular distal radius fractures (I-ADRF), remains controversial. This study compares the outcomes after fluoroscopically assisted (FA) reduction and external fixation of distal radius fractures, with or without concomitant arthroscopic evaluation.

Materials and Methods: Forty-seven patients with I-ADRF underwent FA external fixation and percutaneous pinning. Among them 23 had additional arthroscopic evaluation of their wrist. For teaching purposes procedures with the use of fluoroscopy and arthroscopy were recorded and adapted as a course for the On-line Performance Support Environment for Minimally Invasive Orthopaedic Surgery (“OnLineOrtho” EU- sponsored project). The context of these courses was incorporated in an intelligent medical performance support environment. The duration of the procedure, the surgical findings and the outcomes were recorded.

Results: The follow-up period ranged from 24 to 62 months and the patients were evaluated at 3, 6, 12 and 24 months. The addition of arthroscopy prolonged the procedure by 25 minutes but diminished the number of images obtained by the image intensifier by 5. After arthroscopic evaluation the placement of subchon-dral pins was changed, because of step-off, in 11 of 23 patients. Also tears of the TFCC (14 of 23 patients), perilunate ligaments (16) were depicted. Patients who underwent additional arthroscopic evaluation had significantly better supination, extension and flexion at all time points than those who had only fluoroscopically assisted surgery. The value added by e-courses and the online performance support system is highlighted through the recognition of the systems effectiveness in e-training.

Discussion: During reduction and fixation of I-ADRF, arthroscopy is a very useful tool for the inspection of the articular surface, the ligaments and the TFCC. Long-term evaluation revealed that patients with additional arthroscopy returned to their previous activities in shorter periods and had better supination, flexion, and extension than patients with FA procedures. Fluoroscopy is essential for the minimally invasive surgical treatment of intra-articular distal radius fractures, whereas arthroscopy is an additional valuable tool that improves the outcome, and e-courses are useful adjuncts for teaching purposes.


Orthopaedic Proceedings
Vol. 92-B, Issue SUPP_IV | Pages 620 - 620
1 Oct 2010
Samara S Chassanidis C Dailiana Z Kollia P Koromila T Malizos K Papatheodorou L
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Introduction: Avascular necrosis (AVN) of the femoral head (FH) is a painful disorder of the hip that leads to hip collapse. The pathology of AVN involves ischemic events leading to the death of bone. Several biological substances participate in the balance between osteoclasts and osteoblasts, like osteoprotegerin, RANK and RANKL. The expression of these genes affects the maturation and function of osteoblasts and osteoclasts and determines the rate of bone remodeling. In this study, we investigate the expression of OPG, RANK and RANKL in osteonecrotic FHs derived from 44 patients with AVN.

Methods and Materials: RNA and proteins were isolated from both necrotic and normal site of FHs of 44 patients diagnosed with AVN.

Quantitative RT-PCR was performed for OPG, RANKL and RANK molecules by using the Light Cycler FastStart DNA Master Hybridization Probes kit (Roche).

Western Blotting: 22 bone tissues were run on 4–12% NuPAGE gel (Invitrogen). Anti-OPG, anti-RANKL and anti-actin antibodies were used and membranes were immersed in ECL.

Results: Quantitative RT-PCR: The mRNA levels of OPG were higher in the necrotic (median: 5.25) than the normal site (median: 4.19) of the FHs and their difference was statistically significant (p< 0.05). The expression of RANK and RANKL was significantly lower than that of OPG following a similar pattern between the necrotic and normal site. The mRNA values of RANK and RANKL were higher in the necrotic sites [necrotic median: 1.0/normal median: 0.85, necrotic median: 0.8, normal median: 0.3, respectively] than the normal, although they were not statistically significant.

Western Blotting analysis: Normal sites from all FHs showed comparable OPG protein levels (median: 0.57) which were similar to those of normal (median: 0.63). Similar pattern to that of OPG was observed also for RANKL protein expression, where the median value for RANKL/F-actin ratio was 0.49 and 0.5 in normal and necrotic sites of FHs, respectively.

Discussion: OPG, RANK and RANKL are key genes for maintaining the balance between osteoblasts and osteoclasts. Our results show marked differences in the expression of OPG between the necrotic and the normal sites of the FHs; however, mRNA levels of RANKL varied insignificantly between normal and necrotic part of FH while mRNA levels of RANK gene remain similar in both sides of FHs. In contrast, the production of OPG and RANKL at the protein level showed no remarkable divergence. This indicates that the expression and production pattern of RANK may play the key role in the maintenance of the balance between osteoblasts and osteoclasts in AVN.


Orthopaedic Proceedings
Vol. 92-B, Issue SUPP_IV | Pages 615 - 615
1 Oct 2010
Chassanidis C Dailiana Z Kollia P Koromila T Malizos K Samara S Varitimidis S
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Introduction: Periosteum is a tissue with pluripotential mesenchymal cells (MSCs). During fracture repair several growth factors are released from periosteum, including bone morphogenetic proteins (BMPs), which induce the differentiation of bone marrow stromal cells towards the osteoblastic lineage, therefore increasing the pool of mature bone forming cells and enhance the differentiated function of osteoblasts.

The purpose of our study is to evaluate the expression of periosteal BMPs mRNA from fracture samples, collected within 24 hours of fracture and to compare it with BMPs expression from periosteal samples of normal (non-fractured) bones.

Materials and Methods: Periosteum samples were collected from 25 patients with recent fracture (during the past 24 hours) (age: 12–80) and 25 individuals without fracture (age: 10–73). BMPs (BMP2, BMP4, BMP6) mRNA levels were analysed by Real Time RT-PCR by using the Light Cycler machine and PBGD as a housekeeping gene.

Results: BMP2 mRNA levels were significantly higher (p< 0.05) in normal samples (median:12.15) than in fracture (median:4.39). BMP6 and BMP4 mRNA expression followed similar pattern to that of BMP2 but in significant lower levels. In normal samples, BMP4 mRNA median levels were 1.99, while in fracture samples the levels were significantly lower (median:0.35), (p< 0.05). BMP6 mRNA levels were also higher in normal samples (median:2.21) than in fractures (median:1.87) (p> 0.05). Furthermore, the decrease of BMPs mRNA levels in fracture samples was higher for BMP4 followed by BMP2 and BMP6.

Discussion: Our results indicate high BMP2 mRNA levels expressed from periosteal cells. In recent fractures there is a significant reduction of BMP2 compared to normal samples; however, the expression of BMP2 remains more elevated in comparison to the other BMPs highlighting the potential role of BMP2 at the initiation of healing process of fractures. BMP6 and BMP4 expression was similar among normal periosteal cells while levels of BMP6 were higher than BMP4 in fracture periosteal cells. The suppression of BMP6 expression was minimum and less significant than BMP2 and BMP4 suppression indicating the potential role of BMP6 at the early stages of MSCs differentiation in periosteum. On the other hand, BMP4 remains in low levels in any confrontation and seems that plays a minor role in early healing process of fracture. BMPs are considered to play central role in fracture response and bone remodelling but further investigation has to be done as much in their correlation and toward other growth factors as in their expression levels during bone fracture repair process.


Orthopaedic Proceedings
Vol. 92-B, Issue SUPP_IV | Pages 554 - 554
1 Oct 2010
Michalitsis S Dailiana Z Karamanis N Malizos K Papakostidou I Varitimidis S
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Aim: According to the literature, mortality rate after hip fracture (HF) approaches 20% per year. Morbidity, mortality and rehabilitation after HF are the objectives of this study.

Material: We followed 192 patients (72 men −120 women, age: 78.6 years), who suffered from HF: intertrochanteric (64%), subcapital (30%) or subtrochanteric (6%). Before the injury 70% of the elderly lived with relatives, yet self-assisted, 17% with relatives but were unabled, 10% completely independent and 3% unabled and alone or instituted. Gait before injury was independent in 50%, while 48% used a walking aid and 2% were in bed.

Results: In a minimum postoperative 12-month follow-up, 75% of the patients were questioned. Mortality rate was 21,8% (men 37,5% - women 12,5%): 7% deceased while in hospital, 57% during the 1st trimester and 36% in the next 9 months. Mean average hospital stay: 8,3 days and the mean interval from injury to operation: 2,7 days (0–13). Direct postoperative complications were recorded in 26,5%. Rehabilitation was continued for 32% of patients in specialized centers and for 7% at home and 35% of patients regained their pre-injury functional level, whereas 37% needed a walking frame. Family members modified their activities in 40% of cases.

Conclusions: Mortality and morbidity in elderly patients with HF overcome 21% and 26% respectively, whereas only 35% of patients regained their pre-injury functional level. Despite the beneficial effect of family support, the lack of organized rehabilitation program and the delay of operation are potential negative factors for the patients outcome.


Orthopaedic Proceedings
Vol. 92-B, Issue SUPP_IV | Pages 504 - 504
1 Oct 2010
Hantes M Basdekis G Karidakis G Liantsis A Malizos K Venouziou A
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Aim: To determine the quantity and the quality of the bone bridge between the bone tunnels, in both the femoral and tibial side, after double-bundle anterior cruciate ligament (ACL) reconstruction.

Material and methods: Twenty-seven patients undergoing primary double-bundle ACL reconstruction with hamstring tendon autograft were included in this prospective study. Computed tomography (CT) was performed in all patients at a mean of 13 months postoperatively. The amount of the bone bridge between the bone tunnels was measured, in both the femoral and tibial side, on an axial plane at three locations:

at the level of the joint line

at the mid-portion of the bone bridge and

at the base of the bone bridge.

In addition, the bone density of the bone bridge was measured in Hounsfield units (HU) in the same locations. Bone density of the anterior tibial cortex lateral femoral condyle, and adjacent cancellous area, and were measured for comparisons.

Results: CT confirmed that the bone bridge was triangular in shape in all cases in both the femoral and tibial side. On the femoral side, at the level of joint line (apex of the bone bridge) the mean thickness of the bone bridge was 1.7 mm, at the mid-portion the mean thickness of the bone bridge was 3.7 mm and at the base of the bone bridge the mean thickness was 7.1 mm. On the tibal side, at the level of joint line (apex of the bone bridge) the mean thickness of the bone bridge was 1.5 mm, at the mid-portion the mean thickness of the bone bridge was 3.2 mm and at the base of the bone bridge the mean thickness was 6.5 mm. Bone density at the mid-portion and at the base of the bone bridge was similar to the cancellous bone for both the femoral and tibial side. However, the bone density of the bone bridge, at the level of the joint line, for the femoral side was 860 HU and this was not statistically significant in comparison to the density of the lateral femoral cortex (960 HU). Similarly, the bone density of the bone bridge, at the level of the joint line, for the tibial side was 885 HU and this was not statistically significant in comparison to the density of the anterior tibial cortex (970 HU).

Conclusions: Our study demonstrated one year after double-bundle ACL reconstruction the thickness of the triangular bone bridge between the bone tunnels is sufficient at the mid-portion and at the base of the triangle but is thin at the level of the joint line. However, the bone bridge at the apex of the triangle is very strong since its density is similar to that of cortical bone. We believe that the “corticalization” of the bone bridge at the level of the joint line on both the femoral and tibial side is important and contributes significantly to avoid communication of the bone tunnels.


Orthopaedic Proceedings
Vol. 92-B, Issue SUPP_IV | Pages 614 - 614
1 Oct 2010
Chassanidis C Dailiana Z Kollia P Koromila T Malizos K Samara S Varitimidis S
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Aims: Previous work at this institution has demonstrated that perfusion beneath circumferential negative pressure wound therapy (NPWT) is decreased, which conflicts with most studies on NPWT and perfusion. This study investigates perfusion beneath non-circumferential NPWT in humans and also discusses the potential methodology flaw common to all previous research in this field.

Methods: Tests were conducted on both lower limbs of six volunteers (N=12). Volunteers were sequentially randomised into two groups, which would receive different suction pressures (−400 mmHg and −125 mmHg). A doughnut shaped NPWT dressing was placed over the shin of each leg. The central hole allowed for measurement of the transcutaneous partial pressure of oxygen (tcpO2), an indirect measure of perfusion. Readings were taken every five minutes throughout the experiment. After acquiring readings for 15 minutes to establish a baseline, suction was switched on and readings were taken for another 15 minutes. Suction was then disconnected and readings were taken for 15 minutes. Suction was then reapplied and the sequence was repeated. Data were analysed using the Wilcoxon and Mann-Whitney tests.

Results: On applying suction pressures of −400 mmHg, there was a significant reduction of the tcpO2 (mean reduction 7.35 mmHg, SD 7.4, p< 0.0005). At −125 mmHg, there was also a significant reduction of the tcpO2 (mean reduction 5.10 mmHg, SD 7.4, p< 0.0005). Although there was a tendency for greater reductions in the −400 mmHg group this was not significantly different to the −125 mmHg group (p=0.07).

Conclusion: NPWT reduces tissue perfusion, with higher suction pressure resulting in greater reductions in perfusion. Studies on perfusion using laser Doppler, which report findings contrary to these, may be flawed due to the measuring technique of this device. The compressive forces of NPWT are likely to result in false increased readings on application of suction when using the laser Doppler.

This represents a paradigm shift in our understanding of NWPT and that these dressings should be used with caution on tissues with compromised perfusion.


Orthopaedic Proceedings
Vol. 91-B, Issue SUPP_II | Pages 315 - 315
1 May 2009
Tsezou A Poultsides L Satra M Malizos K
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It is known that wide variability exists among patients in the susceptibility to and outcome from infection. Polymorphisms in genes coding for proteins involved in the response to bacterial pathogens as tumor necrosis factor-alpha(TNF-a), interleukin (IL)-1alpha, IL-1beta, IL-1 receptor agonist, IL-6, IL-10 can influence the amount or function of the protein produced in response to bacterial stimuli. These genetic polymorphisms may influence the susceptibility to and outcome from infection.

The aim of the study was to investigate whether genetic variation in genes coding for components of the innate immune response might be a critical determinant of the inflammatory response and the risk for and outcome from severe bacterial infection in individuals with musculoskeletal infections. The relationship between single nucleotide polymorphisms (SNPs) in the above mentioned genes and susceptibility to infection was evaluated.

Forty patients with musculoskeletal infections hospitalised at the Orthopaedic Clinic of University Hospital of Larissa, as well as 80 healthy controls were included in the study. Genomic DNA was isolated from peripheral blood from all cases and controls and was extracted according to standard procedures. The following genes with their polymorphic positions were studied: IL 1α (IL 1α promoter −889), IL 1β (IL 1β promoter −511, pos. +3962), IL 1R (IL 1R pos. pst1 1970), IL 1RA (IL 1RA pos. mspa1 11100), IL 4Rα (IL 4Rα pos. +1902), IL 12 (IL 12 promoter −1188), TGF-β (TGF-β exon 1 codon 10, codon 25), TNF-α (TNF-α promoter −308, −238), IL 2 (IL 2 promoter −330, pos. +166), IL 4 (IL 4 promoter −1098, −590, −33), IL 6 (IL 6 promoter −174, pos. +nt 565) and IL 10 (IL 10 promoter −1082, −819, −592). Genotype distribution and allele frequencies in patients and controls were evaluated.

There was a significant difference in genotype and allele frequency of IL-1a (T/C −889) p=0.000 (CC, TC) between patients and the control group. Moreover, 2 SNPs of interleukin 4 [IL-4 (T/G −1098) p=0.000 (GG, GT) p=0.009 (TT) and IL-4 (T/C-590) p=0.000 (CC, CT) p=0.006 (TT)] showed significant genotypic and allelic differences between the two groups. Finally, 2 SNPs of interleukin 6 [IL-6 (G/C-174) p=0.000 (CC) p=0.014 (GG), IL-6 G/A nt565) p=0.000 (AA,GA,GG)] and TNF-a [(G/A-308) p=0.034 (AG)] showed significant differences in genotype and allele frequencies between patients and the control group.

We observed, for the first time, significant differences in genotype and allele frequencies of TNF-a (G/A-308), IL-1a (T/C -889), IL-4 (T/G -1098), IL-4 (T/C-590), IL-6 (G/C-174) and IL-6 G/A (nt565) in patients with musculoskeletal infections, a fact which points towards the involvement of cytokine gene polymorphisms in the pathogenesis of infection.


Orthopaedic Proceedings
Vol. 91-B, Issue SUPP_II | Pages 306 - 306
1 May 2009
Gougoulias N Paridis D Bargiotas K Moraitis T Dailiana Z Malizos K
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Foot osteomyelitis is a common problem for which management is variable and few guidelines exist.

To present our treatment protocol and the results in 36 patients (20 men, 16 women, mean age: 49.5 years) with osteomyelitis distal to the ankle, followed up for 17.6 months (range: 3–64).

Bone infection involved toes (n=4), lesser metatarsals (n=11), hallux (n=3), midfoot (n=4), calcaneus (n=9), whereas 4 cases presented as generalised osteomyelitis. Postoperative infection was the cause in 10 cases. Eleven patients were classified as host-type A, 14 as B and 11 as C. A draining sinus was present in 28 cases. The treatment protocol included surgical debridement, the bead-pouch technique for local antibiotic administration and closure primarily (n=27), or by secondary healing (n=5), skin graft (n=2), local fasciocutaneous (n=1), or free vascularised muscle flap (n=1). Systemic antibiotics according to cultures were administered for 5–7 days. Generalized Charcot osteomyelitis was an indication for amputation.

Mean hospital stay was 13.8 days (range 1–34) and 2.7 (range 1–7) surgical procedures per patient were recorded. Infection control was achieved in 26 cases (72.2%), whereas amputations were performed in 10 cases (27.8%). Below-knee amputation was undertaken in 4 host-type C patients with Charcot osteomyelitis of the foot. Ray amputations were performed in 4 diabetic feet. Six amputees were classified as host-C and 3 as host-B. One host-type A patient with recurrent post-traumatic toe osteomyelitis, underwent a distal phalanx amputation as definitive solution. Amputation rates were 55% among host-C, 22% among host-B and 9% among host-A patients (p< 0.001).

Diffuse foot osteomyelitis in systemically compromised patients resulted in high amputation rates. Better results were obtained in non-compromised hosts and focal osteomyelitis.


Orthopaedic Proceedings
Vol. 91-B, Issue SUPP_II | Pages 306 - 307
1 May 2009
Gougoulias N Paridis D Karachalios T Varitimidis S Bargiotas K Malizos K
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Distal tibia and ankle sepsis can threaten the viability of the limb. We present the management protocol and results in 37 patients with chronic infection of the distal tibia and ankle, followed up for a mean of 4 years.

The mean age was 45.6 years. Host type A were 21 patients, type B were 9, and type C were 7 patients. Treatment included radical debridement, multiple cultures sampling and local antibiotic application. Twenty seven patients required bone stabilisation, whereas 3 host C patients were amputated. Soft tissue coverage included 5 free muscle flaps, 3 soleus flaps and 5 pedicle fasciocutaneous local flaps. Bone defects of a mean of 6.3 cm (3–13cm) in 20 cases were treated with distraction histogenesis (13 cases) or the free fibula vascularised graft (7 cases).

Mean hospitalisation time was 26.2 days (host-A: 19.6 vs. host B/C: 32.2, p=0.036). Host-A patients required 2.3 operative procedures whereas host-B/C 3.9 (p=0.01). Union occurred in 26/27 (96%) of cases requiring fixation (one ankle arthrodesis revision/host-B patient). External fixation frames were kept in situ for a mean of 31.7 weeks (12–85). Mean leg length discrepancy was 0.6 cm. Ankle arthrodesis was performed in 7 patients (5% among host-A patients vs. 38% among B/C). Independent ambulation was achieved in (35/37) 95%. All patients were satisfied with the result. Bacteriology revealed Staph. aureus in 71%, whereas 38% were polymicrobial (7% in host-A vs. 88% in B/C patients, p< 0.001). Infection recurrence occurred in 5.4% (none in host-A vs. 13% in B/C patients, p=0.03), whereas the overall complication rate was 43% (24% in host-A vs. 75% in B/C patients, p=0.02).

Functional limb salvage without leg length discrepancy was possible in 92% of cases. Systemically compromised patients required longer hospitalisation, more operative procedures, had frequently polymicrobial infections and more complications.


Orthopaedic Proceedings
Vol. 91-B, Issue SUPP_II | Pages 311 - 311
1 May 2009
Poultsides L Karachalios T Karydakis G Roidis N Bargiotas K Varitimidis S Malizos K
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Two-staged revision TKA is a common strategy for the management of infected TKA (i-TKA) in properly selected patients. However, there is considerable variation in the parameters (e.g. the duration of intravenous administration of antibiotics and of the time interval between the stages, the intraoperative use of frozen sections, the use of knee aspiration etc.) of the treatment protocol among Orthopaedic Centres making the comparative evaluation of results difficult. The aim of this study is to present a standardised two-staged revision protocol with satisfactory mid-term clinical outcome.

Thirty-four consecutive cases of infected primary TKAs were treated in our department between 2000 and 2006. For 24 of them the postoperative follow-up is greater than 2 years. All patients underwent the same treatment protocol: knee aspiration prior to implant removal and surgical debridement, more than 5 specimens for frozen sections and cultures (aerobic, anaerobic and fungi) during the first stage, custom antibiodic impregnated cement spacers, intravenous administration of antibiotics for 3 weeks followed by 3 weeks of per os administration based on culture and antibiogram, a 6-week interval free from antibiotics, second aspiration and second stage with repetition of frozen sections and cultures. In the case of positive frozen section specimens during the second stage the implantation of a new prosthesis was cancelled and a different management strategy was introduced. Preoperative and postoperative data were collected in the form of Total Knee Society Score (knee score and functional score), Oxford-12 Score, laboratory parameters and radiographs at regular intervals.

At the final follow-up 22 out of 24 patients were free of infection. In four patients (2 Host C and 1 Host B) the 2nd stage was repeated (2–6 times) due to polymicrobial infection and positive intraoperative frozen sections. In one of them a knee arthrodesis was finally performed. The diagnostic accuracy of knee aspiration before the 1st stage was low. Total Knee Society Score rose from a preoperative average of 64 (50 to 95) to a postoperative average of 145 (130 to 180). The Oxford 12 score also rose from a preoperative average of 52 (44 to 58) to a postoperative average of 30 (23 to 38). At the final follow-up no radiological signs of implant loosening were observed.

The above standardised protocol of two-staged revision in i-TKA, when indicated, can provide satisfactory mid-term clinical results.


Orthopaedic Proceedings
Vol. 91-B, Issue SUPP_II | Pages 314 - 314
1 May 2009
Poultsides L Karydakis G Karachalios T Kaitelidou D Papakonstantinou V Liaropoulosb L Malizos K
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Deep infection following total knee arthroplasty (TKA) is a devastating complication for the patient and a costly one for patients, surgeons, hospitals and payers. The aim of this study is to compare revision TKA for infection, revision TKA for aseptic loosening and primary TKA with respect to their impact on hospital and surgeon resource utilisation. The evaluation of hospital cost was carried out on a microeconomic basis in order to best evaluate the true cost.

Demographic, clinical and economic data were obtained for 25 consecutive patients with an infection after TKA who underwent a two-stage revision arthroplasty (Group 1), 25 consecutive patients who underwent revision of both components because of aseptic loosening (Group 2) and 25 consecutive patients who underwent a primary TKA (Group 3), all of which where admitted at our institution between January 2000 and December 2005. The economic evaluation included both surgical treatment and hospitalisation cost. Because fixed charges do not depict accurately real resource consumption, total cost was calculated through direct cost analysis. All direct health sector costs such as medical supplies, drugs, implants, laboratory and radiology tests, salaries and wages and overhead expenses, including equipment and plant depreciation were calculated. All patients were followed up for a twelve-month period.

Revision procedures for infection were associated with longer operative time, more blood loss and a higher total number of operations compared with both revisions for aseptic loosening and primary TKA. Furthermore, revisions for infection compared to revisions due to aseptic loosening and primary TKAs were associated with twofold and 2.6 times higher total number of hospitalisations, 2.5 and 5.6 times higher total number of inpatient days, 10.2 and 53.8 times higher cost of inpatient drugs and 1.2 and 2.37 times higher cost of implants, respectively. The costing evaluation of the three operative techniques is still on progress.

Patients’ treatment with an infection after TKA is associated with significantly greater hospital and physician resource utilisation compared with that used for patients with a revision due to aseptic loosening or a primary TKA.


Orthopaedic Proceedings
Vol. 91-B, Issue SUPP_II | Pages 307 - 307
1 May 2009
Dailiana Z Poultsides L Varitimidis S Papatheodorou L Liantsis A Malizos K
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Flaps constitute an integral part of the treatment of soft tissue and skeletal infections of the extremities, focusing on the coverage and augmentation of the local biology.

In a 6-year period, a total of 33 septic defects of the upper (6) and lower (27) extremities were treated with 4 free and 29 pedicled flaps, after extensive surgical debridement of the septic site. In the lower extremity, treatment included 3 free (2 latissimus dorsi and 1 serratus anterior), and 24 pedicled flaps (5 heads of gastrocnemius, 7 soleus, 1 abductor hallucis, 9 reverse fasciocutaneous, 1 combined medial head of gastrocnemius and soleus and 1 extensor longus hallucis) for 3 cases of soft tissue sepsis and 24 septic defects of the skeleton. In the upper extremity, 1 free vascularised fibular graft (combined with muscle-skin) and 5 pedicled flaps (2 homodigital, 1 heterodigital, 1 cross-finger, 1 periosteal) were used for 3 soft tissue and 3 skeletal septic defects. All but one flaps of the lower extremities were covered with split thickness skin (simultaneously or within 7 days), whereas flaps of the upper extremity included skin in all cases.

Three flaps (2 reverse fasciocutaneous and one soleus) were revised (with latissimus dorsi, serratus anterior and extensor longus hallucis flaps respectively) in a mean period of 4 months due to persistent infection and 4 skin grafts were revised due to superficial infection. In a minimum follow-up period of 9 months (9–60 months) full coverage of the defect and treatment of infection was accomplished in all patients, resulting in a good functional and aesthetic outcome. Except for 2 patients, all were able to walk and use their extremity and returned to previous activities.

The use of flaps in the treatment of septic skeletal or soft tissue defects leads to a functional upper or lower extremity and successfully prevents amputation.


Orthopaedic Proceedings
Vol. 91-B, Issue SUPP_I | Pages 149 - 149
1 Mar 2009
Karachalios T Giotikas D Moraitis T Karidakis G Roides N Malizos K
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In order to evaluate the short- and long-term clinical and radiological results of MIS in TKA, a prospective randomized trial was designed in our department. All patients admitted to the department under the care of one surgeon specializing in Joint Replacement surgery were assigned to participate in the study, signed a concern form, and randomly allocated into two groups. For patients of group A, a TKA was performed using the mini mid-vastus approach; for patients of group B the surgery was performed using a conventional medial parapatellar incision. The Genesis II prosthesis and MIS instrumentation were used for all patients.

Pre and postoperative clinical and radiological data were collected for all patients at regular time intervals (pre, 1st d, 3rd d, 6th d, 3rd w, 6th w, 3rd m, 6th m, 9th m, 1st y, and every year thereafter). Early postoperative pain was also evaluated using a VAS scale and the ability of early SLR was also recorded.

Until now 80 patients (40 MIS, 40 Controls) have entered the study with a follow-up of more than 6 months. In 5 patients (12.5%) of group A the MIS surgery was abandoned in favor of conventional surgery due to technical problems.

Patients in MIS group A had knees with greater range of motion at 3 w, 6 w and 3 months, better function at 3 and 6 months, and less blood loss. In contrast, the same patients experienced greater pain during the first 3 postoperative days. Surgery lasted 16 minutes more on average for the MIS group A. On radiological evaluation technical errors were observed in 5 patients of MIS group A.


Introduction The aim of this study was firstly to investigate the prevalence of icaABCD-operon which codes the production of the polysaccharide intracellular adhesin(PIA), responsible for biofilm production, in a collection of clinically significant staphylococci isolated from orthopaedic infections and secondly to assess the relationship between biofilm production and the presence or not of ica-operon.

First Step – Material & Methods Between 1/2003 and 12/2005 200 CoNS were isolated from orthopaedic patients associated with soft tissue and bone infections(group I) and 200 CoNS from blood cultures of hospitalized patients from different wards of the same Hospital(group II). Identification was carried out by Gram-stain, catalase and coagulase tests and the API Staph System. Detection of icaADBC genes was performed by PCR. Production of biofilm was tested by the method of Christensen.

Results In group I, 62(31.37%) carried the entire ica-operon; from these isolates biofilm formation was detected in 35(17.5%). 5 isolates, despite biofilm production, did not carry any gene of ica-operon. In group II, 70(35.5%) carried entire the ica-operon; biofilm formation was detected in 37(18.5%) of these isolates. 3 S. capitis, 1 S. epidermidis and 1 S. hominis carried only the icaADB, icaA and icaB genes respectively.

Second Step – Material & Methods Based on the observation of PIA-production only in (50%) of ica(+) CoNS, 20 S. epidermidis isolates recovered from clinical specimens (pus) of orthopaedic patients and belonging to distinct PFGE clones, were selected on the basis of the presence of the entire ica operon. Nevertheless, only 10 of them produced biofilm. Nucleotide sequence analysis of ica-operon was carried out in all isolates; expression of icaADBC genes was also tested by RT-PCR.

Results Sequencing analysis revealed that all isolates carried an intact ica-operon, without point mutations. Concerning icaADBC mRNA production, all genes of ica-operon were expressed in biofilm-producing isolates, whereas in the no-biofilm producing strains the icaA and icaC genes were not expressed, while a faint expression was observed for the icaB and icaD genes.

Discussion Biofilm-forming capacities of CoNS from orthopaedic infections was not significantly greater than those from other infections (p> 0,05). The capacity of ica-operon(+) staphylococcal isolates to form biofilm seems to be dependent on the expression of ica-genes, specifically of icaA and icaC. The inability of ica(+) isolates to produce biofilm emphasizes that some unknown mechanisms influence icaADBC expression. Finally, the recognition of biofilm-producing CoNS without carrying any gene of ica operon underlined the existence of unidentified also mechanisms controlling biofilm production, apart from icaADBC expression.


Orthopaedic Proceedings
Vol. 91-B, Issue SUPP_I | Pages 130 - 130
1 Mar 2009
GOUGOULIAS N PARIDIS D BARGIOTAS K MORAITIS T DAILIANA Z MALIZOS K
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Introduction: Management strategies and results in 30 cases of foot osteomyelitis are presented.

Patients-Methods: From 1/2003 – 1/2006, 30 patients (15 men, 15 women, mean age 47.7 years, range 1.5–82) presenting with foot osteomyelitis were treated. Mean hospital stay was 12.6 days (range 1–45) and 1.3 hospital admissions were recorded (range 1–4). The follow-up period averaged 15.7 months (range 3–56). Bone infection involved the toes in 3 cases, the metatarsals in 9, the head of the hallux in 2, the midfoot in 3, the calcaneus in 9, whereas 3 cases presented as generalized charcot’s osteomyelitis. Eleven patients were classified as host-type A, 10 as B and 9 as C. Nine patients were diabetic, one rheumatoid, four had vascular insufficiency, two had insensate feet. An open calacaneal fracture was the cause in two cases, whereas ORIF of a closed calacaneal fracture in one, ORIF of metatarsal fractures in one and hallux valgus corrective surgery in two. One paediatric patient with calcaneal osteomyelitis developed subtalar arthritis. A draining sinus/wound was present in 24 cases. Each patient underwent an average of 2.3 surgical procedures (range 1–7). The treatment protocol included surgical debridement, use of the bead-pouch technique for local antibiotic administration and closure primarily (n=23), or by secondary healing (n=3), skin graft (n=2), local fasciocutaneous (n=1), or free vascularized muscle flap (n=1). Systemic antibiotics according to cultures were administered for 5–7 days. Amputation was undertaken if salvaging or reconstructive procedures could not be undertaken.

Results: Infection control (salvageable cases) was achieved in 23 cases (76.7%), whereas amputations were performed in 7 cases (23.3%). Four amputees were classified as host C (57.1%), whereas a significantly lower rate of patients successfully treated (21.7%) were host-C (p=0.0008). A below knee amputation was undertaken in two host-type C patients with generalized osteomyelitis of the foot. One 1st ray and two 1st and 2nd ray amputations were performed for not salvageable diabetic feet infections. Finally in 3 cases of posttraumatic chronic toe osteomyelitis in host-type A patients, a distal phalanx amputation was the definite solution. One patient developed a septic TKR in the contralateral leg and one diabetic patient developed osteomyelitis at a different location in the earlier affected foot.

Conclusions: The treatment strategy of radical debridement, local antibiotic delivery by the bead-pouch technique and use of flaps if needed, successfully treated salvageable feet. Amputation was the solution in neglected cases and in immunocompromised patients.


Orthopaedic Proceedings
Vol. 91-B, Issue SUPP_I | Pages 45 - 45
1 Mar 2009
Poultsides L Varitimidis S Dailiana Z Klitsaki A Theodorou E Stamatiou G Malizos K
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Introduction: TKA is usually performed under general or spinal anaesthesia (SA). Most of the patients who undergo this procedure are old and their postoperative rehabilitation could be compromised due to the adverse effects of the relevant anaesthesia. Lumbar Plexus and Sciatic nerve Block (LPSB) have been increasingly applied for intraoperative and postoperative analgesia. The aim of this study is to compare the time required for the performance of the anaesthesia technique, the quality of intraoperative anaesthesia and postoperative analgesia, the incidence of intraoperative or postoperative complications, the blood loss at the recovery room and the required intraoperative intravenous (IV) administration of fluid volume.

Material & Methods: Fifty (50) patients, mean age 70± 5years, ASA I-III were randomly divided into two groups to receive spinal anaesthesia (group A) or LPSB (group B). Patients in group A (n=25) received hyperbaric Bupi-vacaine 0.5% plus 15mcq Fentanyl through atraumatic 25g needle. Lumbar plexus and sciatic nerve block were performed with a 15cm insulated needle (Brown) and nerves were identified by a peripheral electric nerve stimulator. 30 and 15 ml of Ropivacaine (0.5%) were used for each block respectively. All patients received 0.2mg/ Kg of Midazolam and 50μg of Fentanyl IV. The success of the technique was defined as a complete sensory and motor block. All patients received postoperatively Patient-Controlled Anaesthesia (PCA) with morphine intravenously. Time to perform blockade, sensory and complete motor block, hemodynamic parameters, blood loss, IV fluid volume, postoperative analgesic requirements and satisfaction score were recorded. Results were analyzed with Chi Square test and Student’s t-test (level of significance: p< 0.05).

Results: Demographic data, operating time and hemo-dynamic parameters were similar in both groups. Three patients (group B) had insufficient blocks and were converted to general anaesthesia. Although SA is performed and accomplishes complete motor and sensory blockade faster (p< 0,05), LPSB leaded to decreased necessity of intraoperative fluid loading and blood loss at the recovery room (p< 0,05). Overall patient’s satisfaction till leaving the recovery room, Visual Analogue Score (VAS) intraoperatively, 4 and 8hours postoperatively and analgesic counts (recorded through the PCA) in the first 24hours were statistically significant between two groups, in favor of patients with LPSB.

Conclusion: PLSB is an effective alternative to spinal anesthesia taking into account basic clinical and anaesthesiological parameters intraoperatively and immediate postoperatively. Concerning postoperative pain and required administration of analgesics during the first 24hours, LPSB is more efficient compared to SA, underlining the importance of overall patient’s satisfaction during the first postoperative day.


Orthopaedic Proceedings
Vol. 91-B, Issue SUPP_I | Pages 85 - 86
1 Mar 2009
PAPATHEODOROU L POULTSIDES L HANTES M GRAFANAKI K STATHOPOULOS C MALIZOS K
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INTRODUCTION: The process of ligamentization includes the histological and structural remodelling of the tendons graft to ligamentous tissue. There is little information documenting the mechanism of ligamentization process in molecular level. A number of essential genes are involved in this process and their expression can be regulated through complex biochemical pathways. Animal studies have shown that transcutaneous application of low intensity pulsed ultrasound (LiUS) accelerate the tendon and ligament healing process and recent reports have proven the efficacy of the transosseous application of LiUS for both enhancement and monitoring of the bone healing. The purpose of this study is to investigate the effect of transosseous low-intensity pulsed ultrasound (LiUS) during lingamentization process on the healing at tendon graft-bone interface in rabbits, by examining the expression levels of TGF-β1, biglycan and collagen I using semi-quantitive RT-PCR.

MATERIALS AND METHODS: Twenty-eight New Zealand rabbits were used in this study. The anterior cruciate ligament was excised and replaced with the long digital extensor. Custom-made ultrasound transducers were implanted onto the bone fragment and along the surface of the bone tunnel at the right knees of the rabbits (study group). The LiUS-treated animals received 200-μsec bursts of 1 MHz sine waves with pulse repetition rates of 1 KHz and average intensity of 30 mW/cm2, for 20 minutes daily, while the left knee received no LiUS (control group). Semi-quantitative RT-PCR was performed from RNA samples representing both study and control groups at 1, 2, 3, 5, 7, 8, 9, 12, 14 and 21 days, using specific primers.

RESULTS: Analysis of the RT-PCR products showed that there is significant up-regulation of biglycan and collagen-encoding genes in the study group compared to the control group. In addition, TGFb1-encoding gene exhibits a bimodal profile. In the study group, it represses its mRNA levels from day 1 until day 9 and then the initial expression levels are restored. The control group showed no essential alteration of expression levels for TGFb1.

DISCUSSION: Transosseous LiUS treatment affects the expression levels of significant genes like TGF-β1, big-lycan and collagen type I. All the above studied genes mediate important biochemical pathways in lingamentization process and possibly enhance the healing rate of the tendon graft-bone interface in a bone tunnel in rabbits. The present report is supportive of the hypothesis that transosseous application of LiUS enhances tendon graft healing to bone through effects on molecular level. These present findings suggest that indeed ultrasound treatment after joint ligament reconstruction may facilitate earlier rehabilitation.


Orthopaedic Proceedings
Vol. 91-B, Issue SUPP_I | Pages 52 - 52
1 Mar 2009
Bargiotas K Papatheodorou L Hantes M Karachalios T Malizos K
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Aim: We present the surgical technique and early functional and radiological results of cementless acetabular reconstruction with Monoblock Trabecular Metal (MTM) (Zimmer Warsaw, Indiana) cups in patients with Developmental Dysplasia of the Hip (DDH).

Materials and Methods: From 1997 to 2004, 70 hips (57 patients) with DDH were received an MTM acetabular component. There where 7 men and 49 women. Average age was 50 years (range 35 to 77). According to the classification of Hartofilakidis et al there where 14 hips with high dislocation, 15 with low type I, 16 with low type II, 8 with low type III dislocation and 17 with hip dysplasia. In all patients a MTM cup was implanted in the true acetabulum through a standard posterior approach. Morselized graft was used in 6 cases and a structural graft only in one. Diameter of the cup was ranging from 42 to 56 mm with 54 out of 70 cups being smaller than 50 mm. Screws where used in 12 out of 70 cases A femoral shortening osteotomy was utilized in only two high dislocation cases.

All patients where followed up prospectively and evaluated clinically and radiologicaly at three, six months at one year and yearly thereafter. The clinical outcome was assessed with the Harris Hip score (HHS) and Oxford Score (OS).

Results: Average follow up was 50 months (range 103 to 24). There were no revisions for aseptic loosening, radiologic loosening or cup migration during last evaluation. Two patients developed non-progressive radiolucencies in zone one.

There were four dislocations in this group. One required open reduction and head replacement while another one needed cup revision due to mal orientation. There were five femoral fractures treated intraoperatively with wires, two patients developed transient sciatic nerve palsy and two non fatal PE.

Harris Hip Score was 91 (range 69 to 97) compared with 48 (range 24 to 58) before surgery. The outcome was excellent in 59 hips, very good in 8, good in two and fair in one. Leg length discrepancy more than 2 cm was evident in five unilateral cases (range 2 to 4.5). Trendelebourgh sign was evident in four patients.

Conclusion: MTM acetabular component achieved adequate initial stability in this demanding group of patients and they have excellent radiological and clinical results. Posterior approach without femoral osteotomy provided adequate exposure in almost all cases.


The Journal of Bone & Joint Surgery British Volume
Vol. 90-B, Issue 6 | Pages 778 - 785
1 Jun 2008
Varitimidis SE Basdekis GK Dailiana ZH Hantes ME Bargiotas K Malizos K

In a randomised prospective study, 20 patients with intra-articular fractures of the distal radius underwent arthroscopically- and fluoroscopically-assisted reduction and external fixation plus percutaneous pinning. Another group of 20 patients with the same fracture characteristics underwent fluoroscopically-assisted reduction alone and external fixation plus percutaneous pinning. The patients were evaluated clinically and radiologically at follow-up of 24 months. The Disabilities of the Arm, Shoulder, and Hand (DASH) questionnaire and modified Mayo wrist score were used at 3, 9, 12 and 24 months postoperatively. In the arthroscopically- and fluoroscopically-assisted group, triangular fibrocartilage complex tears were found in 12 patients (60%), complete or incomplete scapholunate ligament tears in nine (45%), and lunotriquetral ligament tears in four (20%). They were treated either arthroscopically or by open operation. Patients who underwent arthroscopically- and fluoroscopically-assisted treatment had significantly better supination, extension and flexion at all time points than those who had fluoroscopically-assisted surgery. The mean DASH scores were similar for both groups at 24 months, whereas the difference in the mean modified Mayo wrist scores remained statistically significant.

Although the groups are small, it is clear that the addition of arthroscopy to the fluoroscopically-assisted treatment of intra-articular distal radius fractures improves the outcome. Better treatment of associated intra-articular injuries might also have been a reason for the improved outcome.


Orthopaedic Proceedings
Vol. 88-B, Issue SUPP_I | Pages 36 - 36
1 Mar 2006
Zachos V Dailiana Z Karantanas A Varitimidis S Zibis A Malizos K
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Introduction: To assess the value of MR imaging (MRI) with regard to union, graft viability and proximal pole bone marrow status, after use of vascularized bone grafts (VBG) for treating scaphoid nonunions (SN).

Methods: VBG from the distal radius were used to treat 52 SN. Clinical and imaging evaluation was used for the pre- and postoperative assessment of all patients. Apart of radiographs obtained in all cases, 19 patients were also assessed postoperatively with MRI at 3 months (15 of 19 were assessed preoperatively with MRI) and 15 had serial MRI evaluations (6–12 months). The clinical follow-up time of this subgroup of 19 patients ranged from 6 to 27 months.

Results: All patients showed clinical signs of union within 12 weeks from the procedure. 3-months MRI showed viability of the bone graft in all cases. At 3 months union was established with plain radiographs in 14 patients; plain MRI showed union in 13 patients but contrast-enhanced MRI revealed union in all cases. Eight patients were considered to have osteonecrosis of the proximal pole intraoperatively: 4 showed proximal pole necrosis with postoperative plain radiographs and 5 of them with plain postoperative MRI. Contrast-enhanced MRI at 3 months showed postoperative reversal of necrotic changes in all 8 scaphoids. Serial MRI at 6 and 12 months, revealed resolution of the bone marrow oedema of the surrounding bones and full graft incorporation in all cases.

Conclusions: Contrast-enhanced MRI is able to assess the viability of the proximal pole and to demonstrate the early union after treatment of SN with VBG allowing thus earlier mobilisation.


Orthopaedic Proceedings
Vol. 88-B, Issue SUPP_I | Pages 93 - 93
1 Mar 2006
Hantes M Zachos V Basdekis G Zibis A Dailiana Z Malizos K
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Purpose: To evaluate the differencies in graft orientation between transtibial and anteromedial portal technique using magnetic resonance imaging (MRI) in anterior cruciate ligament (ACL) reconstruction.

Materials and Methods: Fifty one patients who undergoing arthroscopically ACL reconstruction underwent MRI of their reconstructed knee. Thirty patients had ACL reconstruction using the transtibial technique (group A) while in the rest 21 the anteromedial technique (group B) was used. In the femoral part graft orientation was evaluated using the femoral graft angle (FGA). The FGA was depicted at the coronal views by two axes: the anatomical axis of the femur and the axis of the femoral tunnel. In the tibial part graft orientation was evaluated using the tibial graft angle (TGA). The TGA was specified as the angle between the axis of the graft and a line parallel to the tibial plateau at the sagittal view.

Results: The mean FGA for group A was 12.52° while for the group B was 27.06°. This difference was statistically significant (p< 0.001 paired t-test). The mean TGA for group A was 64.24° while for the group B was 63.11° but this was not statistically significant.

Conclusions: Using the anteromedial portal technique the ACL graft is placed in a more oblique direction in comparison with the transtibial technique in the femoral part. This may have an impact in rotatory knee stability. However, there are no differencies between the two techniques in graft orientation in the tibial part.


Orthopaedic Proceedings
Vol. 88-B, Issue SUPP_I | Pages 112 - 112
1 Mar 2006
Karachalios T Hantes M Zibis A Zachos V Karantanas A Malizos K
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Background: Clinical tests used for the detection of knee meniscal tears do not present acceptable diagnostic sensitivity and specificity values. Diagnostic accuracy is improved by arthroscopic evaluation or performing magnetic resonance imaging (MRI) tests. The objective of this study was to evaluate the diagnostic accuracy of a new dynamic clinical examination test for the detection of meniscal tears.

Methods: Two hundred and thirteen symptomatic patients with recent knee injuries who all were clinically examined, had MRI tests and underwent arthroscopic surgery and 197 asymptomatic volunteers who all were clinically examined and had MRI tests of their normal knees were included in this study. For clinical examination the medial and lateral joint line tenderness test, McMurray test, Apley compression and distraction test, Thessaly test at 5° and Thessaly test at 20° of flexion were used. For al clinical tests sensitivity, specificity, negative predictive value and diagnostic accuracy rates were calculated against arthroscopic and magnetic resonance imaging data.

Results: Thessaly test at 20° of flexion showed a high diagnostic accuracy rate at the level of 94% and a low number of false negative recordings in detecting tears of both the medial and lateral meniscus. Other traditional clinical examination tests, with the exception of joint line tenderness which presented a diagnostic accuracy rate of 88% in detecting lateral meniscal tears, showed inferior rates.

Conclusions: Thessaly test at 20° of flexion can be safely used as a first line screening clinical test for the detection of meniscal tears reducing the need and the cost of modern magnetic resonance imaging methods.


Orthopaedic Proceedings
Vol. 88-B, Issue SUPP_I | Pages 21 - 21
1 Mar 2006
Varitimidis S Poultsides L Dailiana Z Passias A Kitsiopoulou E Malizos K
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Introduction: Surgery in the foot and ankle is usually performed under general or spinal anaesthesia. Peripheral nerve blocking is gaining the preference of both surgeons and patients. The aim of this study is to evaluate the adequacy of anaesthesia with the method of triple nerve blocking at the region of the knee.

Materials and methods: One hundred and forty-four patients (79 men and 65 women) that were diagnosed with ankle and foot injuries or diseases underwent surgery using triple nerve blocking at the knee region as a method of anaesthesia. Surgical procedures included bone and soft tissue procedures and especially fracture fixation, osteotomies, tendon repairs, neuroma and tumor excisions, nerve decompressions and arthrodeses. The common peroneal, tibial and saphenous nerves were blocked with injection of 8 ml ropivacaine 2% for each nerve. The injection was performed by an Orthopaedic surgeon with the use of a neurostimulator. An anesthesiologist was available when necessary.

Results: Ninety-four patients tolerated the procedure without the need of additional injection of anaesthesia or analgesia. In 45 patients additional injection of local anesthetic was necessary. Five patients needed intravenous injection of analgesia in order to complete the procedure. Patients were mobilized the day of surgery, reducing in that way hospital stay. Hospitalization ranged from 0 to 1 days with 58 patients discharged the day of the operation. No complication related to the injection of the anestheric was observed.

Conclusion: Triple nerve blocking at the knee, as a method of anaesthesia, is proposed for certain procedures in the foot and ankle; it allows early mobilization of patients and reduces length of hospital stay. If the neurostimulator is used appropriately, the rate of patients that needs additional analgesia intraoperatively is diminished and no adverse effects of the local anestheric are observed. Complications observed with the practice of spinal or general anesthesia are avoided.


Orthopaedic Proceedings
Vol. 88-B, Issue SUPP_I | Pages 187 - 187
1 Mar 2006
Basdekis G Varitimidis S Dailiana Z Hantes M Bargiotas K Malizos K
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Purpose: Arthroscopy offers a view of intra-articular pathology, but its use in the treatment of intra-articular distal radius fractures remains controversial. This study compares functional and radiologic outcomes of arthroscopically assisted (AA) versus fluoroscopically assisted (FA) reduction and external fixation (EF) of distal radius fractures.

Type of study: double randomised prospective, comparison of 2 different procedures.

Methods: Between January 2000 and December 2003, 20 patients with comminuted intra-articular distal radius fractures underwent AA EF and percutaneous pinning and 20 patients underwent and FA EF reduction and pinning.

Results: Follow-up period was 9–27 months. Evaluation was clinical (grip strength, range of motion) and radiographic (palmar tilt, radial shortening, stepoff). The Disabilities of the Arm, Shoulder, and Hand (DASH) questionnaire and the MAYO wrist score were used 3-9-12 months postoperatively. In 9/20 patients of AA group the subchodral pins were changed after artrhroscopic view because of stepoff. The following tears were found: TFCC (12 of 20 patients), SL (9/20), LT (4/20). Patients who underwent AA surgery had significantly better supination; wrist extension; and flexion compared with the FA surgery group (86 vs 75; 76 vs 65; and 76 vs 63 degrees respectively). Radial shortening and DASH scores were better for the AA group compared to the FA group (AA:12, FA:25) the 3rd and 6th postoperative month but the difference decreased after the 12th month.

Conclusions: A reduction and fixation of intra-articular distal radius fractures provides improved inspection of the ulnarsided components of the injury. Long term evaluation revealed that patients with AA procedures returned in decreased periods to their previous activities (based on DASH score) and had better of supination, flexion, and extension than patients with FA surgery.


Orthopaedic Proceedings
Vol. 88-B, Issue SUPP_I | Pages 94 - 94
1 Mar 2006
Hantes M Zachos V Basdekis G Zibis A Varitimidis S Dailiana Z Malizos K
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Purpose: The aim of this study was to document donor site problems one year after anterior cruciate ligament (ACL) reconstruction and to compare the differencies between hamstring and patellar tendon autografts.

Materilas and Methods: Sixty-four patients undergoing primary arthroscopically ACL reconstruction were randomized to have a central third bone patellar tendon bone (PT) autograft (30 patients) or a doubled semiten-dinosus/doubled gracilis (HS) autograft (34 patients). The postoperative rehabilitation regimen was identical for both groups. All patients were examined one year postoperatively. Objective parameters evaluated included pre and postoperative IKDC and Lysholm score, side-to-side KT-1000 maximum-manual arthrometer differences. The Shelbourne score was used to evaluate anterior knee symptoms. Loss of sensitivity in the anterior knee region postoperatively as well as scar sensitivity were also recorded.

Results: Three patients (10%) in the PT group had anterior knee symptoms while only one (3%) in the HS group. The mean Shelbourne score was 98 for the HS group and 93 for the PT group but this was not statistically significant. However, 8 pateints (23%) had disturbed sensitivity in the anterior knee region in the HS group, but none in the PT group and this was statistically significant (p< 0.005). Scar sensitivity was present in 3 patients (10%) in the PT group and in one (3%) in the HS group. No differencies were found postoperatively between the groups regarding IKDC, Lysholm score and side-to-side KT-1000 measurements.

Conclusions: Although,notstatisticallysignificantpatients in the PT group had more anterior knee symptoms and scar sensitivity, one year postoperatively. In contrast, harvesting of hamstring tendons produces significantly more sensory nerve complications in the anterior knee region than harvesting the middle third of patellar tendon. Both grafts seem to improve equally patients’ performance.


Orthopaedic Proceedings
Vol. 87-B, Issue SUPP_III | Pages 250 - 250
1 Sep 2005
Dailiana Z Rigopoulos N Varitimidis S Damdounis A Karachalios T Malizos K
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Introduction: Osteomyelitis and septic arthritis (SA) below the elbow are severe conditions affecting the function and viability of the hand. Factors predisposing to these conditions and parameters affecting prognosis are emphasized.

Material and Methods: In a 4 years period, 16 patients with SA (4) or osteomyelitis (12) were treated in a University Orthopaedic Department providing care to a rural population of 1.000.000, Nine had history of trauma in unhygienic environment, 3 had immunodeficiency and in 4 osteomyelitis was iatrogenic [previous fixation of fractures (3) and vein catheterization (1)]. SA was located in the wrist (2) and thumb joints (2) and osteomyelitis involved the radius (3), ulna (1), metacarpals (3) and phalanges (5). Ten patients received oral antibiotics in other centers. The mean delay from onset of symptoms to referral to our center was 22 days. Apart of antibiotics administration, surgical treatment included debridement and irrigation for SA and excision of necrotic bone, stabilization (external fixators), use of antibiotic beads and secondary bridging with bone graft for osteomyelitis. Additional procedures (amputations, arthrodesis) were also required in some cases.

Results: Cultures were positive in 9 of 16 cases [Staph. aureus (5) and enterobacter cloacae (3)]. Patients underwent multiple procedures (mean: 3.8) and 4 underwent amputation of a digit (2) and hand (2) due to the rapid extension of infection threatening and finally taking the lives of 2 elderly and immunosuppressed patients. Mean follow-up period of the 12 surviving and non-amputated patients was 18 months. Union was accomplished in all cases. Functional results were excellent or very good in 10 of 12 patients and good in 2 patients. All patients were satisfied and returned to their previous occupations.

Conclusions: Osteomyelitis and SA below the elbow was frequent in population living in unhygienic environment or working with soil. All cases received medical treatment with delay. Immunosuppressing conditions favored the extension of infection and threatened patients lives. Delay in treatment in combination to immunosuppression resulted to significant morbidity. Early treatment including surgical drainage, thorough debridement and antibiotic administration is necessary for elimination of skeletal infection and salvage of the hand and patients life.


Orthopaedic Proceedings
Vol. 87-B, Issue SUPP_III | Pages 245 - 246
1 Sep 2005
Dailiana Z Varitimidis S Rigopoulos N Hantes M Karachalios T Malizos K
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Introduction: Suppurative conditions in closed cavities/tunnels require surgical drainage and irrigation for elimination of infection. The purpose of this study is to evaluate the pattern of extension of infections in hand compartments and the necessity for intraoperative and continuous postoperative catheter irrigation.

Material and Methods: Compartmental infections of the hand and wrist (CIHW) were diagnosed in 42 consecutive patients involving the flexor tendon sheaths (pyogenic flexor tenosynovitis) (28); the tip (3); the carpal tunnel (2); or extended to multiple compartments including the above mentioned and the thenar, midpalmar, web and Parona’s (9). Three patients had diabetes mellitus, 2 suffered from bites, 15 had penetrating injuries and 7 were working with animals or meat products. Fifteen were previously treated in other centers. After meticulous clinical evaluation to define all the involved compartments, all patients were treated with drainage of the respective compartments, sheath irrigation and appropriate antibiotics, whereas continuous postoperative catheter irrigation was used in 24. Hand therapy started the third postoperative day.

Results: Mean follow-up time was 20 months. The most common pathogen was S. aureus (14 patients) whereas cultures were negative in 15. Three patients received additional fungal treatment. Results were excellent or very good in 25 hands and good in 12 regaining full or near full ROM. Recurrence of infection in 4 (that were initially treated inadequately in other centers or had intraoperative sheath irrigation without postoperative continuous irrigation) necessitated a revision of the procedure with extensive debridement and continuous postoperative irrigation. Finally, 1 patient developed complex regional pain syndrome.

Conclusions: A high index of suspicion and profound knowledge of the anatomy is essential for early diagnosis and prompt surgical treatment of CIHW. Initially «benign» infections often extend in multiple compartments of the hand as a result of inadequate initial treatment. Intraoperative irrigation is not always adequate for the resolution of infection, especially in neglected cases or cases with underlying conditions. Early surgical debridement of all the involved compartments in combination to continuous postoperative irrigation, administration of appropriate antibiotics and precocious onset of hand therapy is the treatment of choice for these potentially debilitating, infectious conditions of the hand.


Orthopaedic Proceedings
Vol. 86-B, Issue SUPP_III | Pages 369 - 369
1 Mar 2004
Zibis A Karantanas A Dailiana Z Varitimidis S Malizos K
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Purpose: To assess þbular graft viability and the evolution of the subsequent bone healing into the hosting tunnel. Methods and Materials: Eight patients (10 grafts) with femoral head AVN were examined with 4 consecutive MRI examinations at 2w, 6w, 3m, and 6m postoperatively using a 1T scanner. A dynamic 3D-T1-w TFE sequence (9 sections every 8s) was applied for estimating the perfusion in the graft (SI curve). Multiplanar imaging in the axis of the graft was used for a delayed fat-suppressed T1-w Spin Echo sequence (acquisition matrix 512, slice thickness 3mm). The following parameters were evaluated: a) more or less than 50% increased SI in the graft, b) maximum SI close to the graft, c) maximum width of the medullary enhancement close to the graft, d) width of osteonecrotic area. The þnal MRI examination together with plain x-ray þlms and clinical examination were used to assess outcome. Results: The decrease of% enhancement area in the graft medulla, the gradual decrease of the enhancement in and around the graft, correlated well with the clinical þndings. The dynamic study and the parameter c, showed no correlation with the clinical status. In 2 cases, enhancement close to the upper end of the graft and in the necrotic zone, suggested expanding inversion of the process. Conclusion: High resolution enhanced MRI, may offer an additional means for assessment of the healing process of vascularized peroneal grafts in patients with femoral head necrosis.