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Orthopaedic Proceedings
Vol. 93-B, Issue SUPP_III | Pages 362 - 362
1 Jul 2011
Giannoudis P Kanakaris N Tzioupis C Nikolaou V Kontakis G
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To evaluate the effectiveness of Pulsed-Lavage and of Versajet-hydrosurgery in removing two Staphylococcus aureus strains from porcine tissue and graphite powder from simulated fractures.

Overnight broth cultures (NCTC-6571) and S.aureus strains were diluted to yield inocula containing 1x103c. f.u. ml-1. Initially 8 porcine legs were used; porcine tissues were inoculated with 10ml of either of the two S.aureus strains. Control tissues were inoculated with PBS. All inoculated samples were irrigated with 300ml of saline using the pulsed-lavage system or using the Versajet. 10ml of each of the following were plated out in triplicate:

inoculum pre-incubation

inoculum post-incubation,

each left over inoculum following removal of tissue and dilutions of 10-1 and 10-2 and

Wash from all samples.

Eight additional porcine legs were used where 2 incisions were made down to bone in a cross-hatch pattern. 1g of graphite powder was infiltrated into each fracture site to simulate a contaminated open fracture. Each fracture site was irrigated with 500ml saline through pulsed-lavage or Versajet.

The average microbiological reduction using Pulsed-Lavage or Versajet was 2% and 15% respectively. The clinical S.aureus strain was more adherent than the laboratory strain. The Versajet maintained a 12–16% reduction of S.aureus, whereas pulsed-lavage did not reduce contamination. The number of graphite particles was significantly reduced with the use of the Versajet system compared with the pulsed-lavage.

Versajet system was more effective in removal of foreign particles and more effectively reduced the micro-biological load of both examined S.aureus strains in a porcine model. Further studies are indicated to evaluate the efficacy of this system in clinical practice


Orthopaedic Proceedings
Vol. 93-B, Issue SUPP_III | Pages 345 - 345
1 Jul 2011
Giannoudis P Stavlas P Tzioupis C Singh R Kontakis C
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To estimate the prevalence of clavicular fractures, number of cases required operative treatment, and whether removal of the implant is a frequent necessity.

Between November 2005 and Nov 2007 all patients presenting in our institution with clavicular fractures were eligible for participation. Patients below 18 years of age, and pathological fractures were excluded. Retrospective review of clinical notes and radiographs. Demographic details, mode of injury, treatment protocol, operative procedures performed, time to union, complications post-surgery stabilization, and the number of cases that required implant removal were documented and analysed in a computerized database. The mean time of follow up was 24 weeks (12–48).

Out of 16,280 adult fractures that presented to our institution, 200 (1.23%), (137 males) patients met the inclusion criteria with a mean age of 43 years (19–95) and a mean ISS of 9 (4–38). There were 4 of the medial, 153 of the middle and 43 of the lateral clavicle fractures (3 were open). 178 (89%) patients were treated non-operatively and 22 (11%) operatively. Indications for surgery included open fracture, bony spike/skin threatened, grossly displaced/comminuted fracture, polytrauma and non-union. Mean time to radiological union was 14 weeks (5–38 weeks). Out of the 200 patients 12 (6%) developed non-union. Out of the 22 operated patients, 7 (32%) required plate removal and 1 had screw removal. Indications for removal of implant included, periprosthetic fracture (1), prominent metal work through skin (3), pain in shoulder (2), pressure symptoms (1). Post removal of implant, 6 (75%) patients claimed improvement in symptoms. Functional outcome was excellent/good in 90% of cases.

The incidence of clavicular fractures was 1.23%. A small number of patients (11%) required operative treatment out of which one third had metal work removal. The majority of clavicular fractures can be treated non-operative with good functional results.


Orthopaedic Proceedings
Vol. 93-B, Issue SUPP_III | Pages 305 - 305
1 Jul 2011
Giannoudis P Mallina R Perry S Tzioupis C Pape H
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Purpose: The role of the pro-inflammatory cytokine HMGB1 (alarmins) has not been investigated in the clinical setting. This study aims to assess its relationship to IL-6 release, ISS, and to quantify the second hit phenomenon after femoral nailing.

Methods: 22 (13 males, mean age 37.5y) consecutive patients were entered into this prospective randomised trial. All patients underwent stabilisation of the femoral shaft fracture with reamed (10 patients) or unreamed nailing. Patient demographics, ISS, and complications were recorded prospectively. Peripheral blood samples were collected on admission, induction of anaesthesia, entry into femoral canal, wound closure and on day 1, 3, and 6. Serum HMGB1 and IL-6 concentrations were measured using ELISAs. 6 healthy volunteers formed the control group.

Results: The median ISS was 14.5 (9–29). Admission median HMGB1 and IL-6 concentrations were 7.2 ng/ml and 169 pg/ml respectively. A direct correlation was observed between ISS and IL-6 concentrations. HMGB1 concentrations reached to peak levels on day-6. On the contrary, the median concentration of IL-6 peaked around day 1 postoperatively (reamed: 780 vs. unreamed: 376 pg/ml) and then showed a downward trend. The median increase of HMGB1 by day 6 was 4.21ng/ml in the reamed and 2.98ng/ml in the unreamed population; the median increase of IL-6 by day 1 measured 462 pg/ml and 232 pg/ml in the respective groups.

Conclusion: Femoral nailing and reaming induces a second hit response as supported by the post-operative increased levels of IL-6. There appears to be an inverse relationship in the concentrations of IL-6 and HMGB-1. Serum concentration of IL-6 unlike HMGB-1 strongly correlate with ISS. While IL-6 has been suggested as a marker of assessment of the early inflammatory response, alarmins can provide useful information at the later stage of an evolving immune-inflammatory process.


Orthopaedic Proceedings
Vol. 93-B, Issue SUPP_III | Pages 356 - 356
1 Jul 2011
Mallina R Kanakaris N Tzioupis C Pape H Giannoudis P
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The role of the pro-inflammatory cytokine HMGB1 (alarmins) has not been investigated in the clinical setting. This study aims to assess its relationship to IL-6 release, ISS, and to quantify the second hit phenomenon after femoral nailing.

22 (13 males, mean age 37.5y) consecutive patients entered in this prospective randomised trial. All patients underwent stabilisation of the femoral shaft fracture with reamed (10 patients) or unreamed nailing. Patient demographics, ISS, and complications were recorded prospectively. Peripheral blood samples were collected on admission, induction of anaesthesia, entry into femoral canal, wound closure and on day 1, 3, and 6. Serum HMGB1 and IL-6 concentrations were measured using ELISAs. 6 healthy volunteers formed the control group.

The median ISS was 14.5 (9–29). Admission median HMGB1 and IL-6 concentrations were 7.2 ng/ml and 169 pg/ml respectively. A direct correlation was observed between ISS and IL-6 and HMGB1 concentrations. HMGB1 concentrations reached to peak levels on day-6. On the contrary, the median concentration of IL-6 peaked around day 1 postoperatively (reamed: 780 vs. unreamed: 376 pg/ml) and then showed a downward trend. The median increase of HMGB1 by day 6 was 4.21ng/ml in the reamed and 2.98ng/ml in the unreamed population; the median increase of IL-6 by day 1 measured 462 pg/ml and 232 pg/ml in the respective groups. Day 6 concentration of HMGB1 in patients with an ICU stay > 5 days (n=4), compared to the rest of the patients (n=16), was 11.04ng/ml (6.13 – 35.84) vs. 7.14ng/ml (4.06 – 12.8), (p=0.03).

Femoral nailing and reaming induces a second hit as supported by the post-operative increased levels of both IL-6 and HMGB1. While IL-6 has been suggested as a marker of assessment of the early inflammatory response, alarmins can provide useful information at the later stage of an evolving immuno-inflammatory process.


Orthopaedic Proceedings
Vol. 93-B, Issue SUPP_II | Pages 214 - 214
1 May 2011
Sellei R Köhler D Tzioupis C Sop A Tarkin I Pohlemann T Pape H
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Background: Unstable pelvic ring fractures are frequently associated with severe hemodynamic instability and mortality. Hemorrhage control of these disrupted pelvic fractures requires an urgent reduction of the intrapelvic volume and immediate mechanical stabilization. The aim of this study was to investigate the control of the intrapelvic volume and pelvic stability by different modes of external stabilization in a cadaver model.

Methods: Various degrees of pelvic ring instability were induced in unembalmed human torsos. Haemorrhage induced volume displacement into the presacral and retroperitoneal space (RPP) was assessed by positioning two infusion lines right in front of the sacroiliac joint. The abdominal pressure measurement (IAP) was obtained by a percutaneous catheter in the abdominal cavity. Baseline pressure measurements of the intra pelvic volume were documented before and after dissection for uni-as bilateral instability. Reduction of pelvic instability was performed by non invasive T-POD® Pelvic Stabilizer, a supraacetabular, iliac crest fixator, application of the pelvic C-Clamp without and with pelvic packing.

Results: Baseline measurements (RPP) of the intact pelvis showed an average increase of 8,03 cmH2O per 1000 cc of infused fluid. In case of uni- and bilateral instability the pressure decreased to a rate of 2,88 and 1,48 cmH2O per 1000 cc. Following the application of each device an increase of RPP of 3,5 cmH2O (pelvic binder), 3,2 cmH2O (anterior frames), 5,4 cmH2O (C-Clamp) and 8,4 cmH2O (C-Clamp + packing) per 1000 cc was obtained in case of unilateral instability. In bilateral disruptions a significantly lower increase of pressure up to 4,0 cmH2O was seen.

Conclusions: We investigated the efficacy of various external stabilization Methods: on potential hemorrhage on experimentally induced uni- and bilateral pelvic ring fractures. In case of intact pelvis the retroperitoneal space responds to fluid application with rapidly rising pressures. The application of external devices enable the reduction of the pelvic volume and thereby the retroper-itoneal pressure increase. The C-clamp combined with pelvic packing resulted to be superior.


Orthopaedic Proceedings
Vol. 93-B, Issue SUPP_I | Pages 30 - 30
1 Jan 2011
Morley J Tzioupis C Pape H Giannoudis P
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Patients with a femoral shaft fracture requiring intra-medullary nailing were recruited to investigate if the femoral canal could be a potential source of inflammatory cytokines, previously implicated in the pathogenesis of life-threatening inflammatory complications.

Femoral and peripheral blood samples were obtained at the time of surgery from patients with a femoral shaft fracture requiring intramedullary nailing. The local femoral intramedullary and peripheral release of a group of ten Th1 and Th2 cytokines concentrations (IL-1b, IL-2, IL-4, IL-5, IL-6, IL-8, IL-10, GM-CSF, TNF-a and IFN-g) after femoral shaft fracture and intramedullary reaming, if performed, was measured using a Human Cytokine Antibody 10-plex Bead Kit. A control group of patients(n=3) undergoing hip replacement was established to allow comparison with the normal femoral intramedullary cytokine environment.

21 patients with a femoral shaft fracture were recruited. Femoral shaft fracture caused a significant increase in the local femoral concentrations of IL-6 (median 3967pg/ml; range 128–25,689pg/ml) and IL-8 (median 238pg/ml; range 8–8,288pg/ml) compared to the femoral control group(p=0.0005 and p=0.001 respectively). No significant local femoral release of the other cytokines was demonstrated. In the patients who underwent intramedullary reaming of the femoral canal (n=6), a further significant local release of IL-6 (median post-ream 15,903pg/ml; range 1,854–44,922pg/ml) and IL-8 (median post-ream 1,443pg/ml; range 493–3,734pg/ml) was demonstrated (p=0.01 and p=0.03 respectively), thus showing that intramedullary reaming can cause a significant local inflammatory response.

Femoral shaft fracture produces a local inflammatory response releasing large amounts of the cytokines IL-6 and IL-8 into the local femoral environment but not of the other Th1 and Th2 cytokines studied. Reaming, produced significant elevation in local femoral IL-6 and IL-8 concentration, suggesting a local femoral response as a result of this procedure. Possibly, local femoral environment may act as a cell-priming or stimulating zone, for circulating inflammatory cells.


Orthopaedic Proceedings
Vol. 92-B, Issue SUPP_IV | Pages 621 - 621
1 Oct 2010
Tzioupis C Giannoudis P Gilbert T Kumta P Pape C Roy A Sfeir C Usas A
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Aim: The aim of the current study is to investigate if viscosupplemetation therapy will increase the effect of microfracture technique by acting the quality and quantity of the new cartilage after microfracture.

Material and Method: Full thickness chondral defects were created to intercondylar notch as a nonweightbearing area by using a handle drill bit. Microfracture holes between bridges were performed with a 1mm K wire.

The present study was performed on 30 mature white rabbits (male range, 2800–3500 gr). The right knees were accepted as study and left knees as control group. Group 1 was received intraarticular 0.1ml sodium hyaluronate treatment, rabbits in group 2 were received 0.1 ml Serum Physiologique once a week for three weeks. Biopsy was taken from both knees at the 3rd and 6th week. Histopathological evaluation was performed by a pathologist who is blind to study according to modified Mankin score.

Results: Although the difference of the scores between study and control group was not statistically different at the third week, it was seen different at the sixth week histologically.

Conclusion: Hyaluronic acid may be benefecial in the treatment of chondral lesion addition to arthroscopic microfracture technique.


Orthopaedic Proceedings
Vol. 92-B, Issue SUPP_II | Pages 346 - 346
1 May 2010
Tzioupis C Riexen D Dumont C Pardini D Mueller M Gruner A Krettek C Pape H Giannoudis P
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Patients with bilateral femur shaft fractures are known to have a higher rate of complications when compared with those who have unilateral fractures. Many contributing factors have been considered responsible, however due to the heterogeneity of the studied populations solid conclusions cannot be substantiated. Patients included in our study were separated according to the presence of a unilateral (group USF) (n=146) versus bilateral femur shaft fracture (group BSF) (n=19)Endpoints of the study included the incidence of systemic (SIRS, Sepsis, Acute Lung Injuries) complications. The perioperative assessment included documentation of clinical and laboratory data assessing blood loss, coagulopathy, wound infection, and pneumonia. Local (wound infection, compartment syndrome etc.) and systemic complications (ALI, MOF, Sepsis) were documented. Statistical analyses were conducted to examine the relation between the occurrence of unilateral versus bilateral femoral fractures and variables indexing patient demographic characteristics and other indicators of initial injury severity. Independent sample t-tests were used to examine treatment group differences for variables that approximated a Gaussian distribution. For non-normal indicators of injury severity Mann-Whitney tests were performed. Pearson chi-square tests were performed for binary indicators of injury severity, except when expected cell counts did not exceed 5 participants. When this occurred, the Fisher exact test was used Evidence indicated that patients who suffered a bilateral femoral fracture were significantly more likely to have hemothorax and receive a blood transfusion upon admission to the hospital in comparison to patients who suffered a unilateral femoral fracture. Bivariate analyses also indicated that patients with bilateral femoral fractures exhibited a longer clinical recovery time and were more likely to experience clinical complications in comparison to those with unilateral fractures. However, there were no significant differences between the fracture groups in terms of the number of hours spent on a ventilator or the occurrence of pneumonia, acute lung injury, acute respiratory distress, sepsis, and multiple organ failure following surgery. Patients in borderline condition spent significantly more time in the ICU in comparison to those in stable condition. The high incidence of posttraumatic complications in poly-trauma patients with bilateral femur shaft fractures is caused by the accompanying injuries rather than by the additional femur fracture itself. It also documents that a thorough preoperative assessment can help differentiate those who have a high like hood of developing systemic complications from those who do not.


The Journal of Bone & Joint Surgery British Volume
Vol. 92-B, Issue 3 | Pages 329 - 334
1 Mar 2010
Cox G Einhorn TA Tzioupis C Giannoudis PV

Biochemical markers of bone-turnover have long been used to complement the radiological assessment of patients with metabolic bone disease. Their implementation in daily clinical practice has been helpful in the understanding of the pathogenesis of osteoporosis, the selection of the optimal dose and the understanding of the progression of the onset and resolution of treatment. Since they are derived from both cortical and trabecular bone, they reflect the metabolic activity of the entire skeleton rather than that of individual cells or the process of mineralisation.

Quantitative changes in skeletal-turnover can be assessed easily and non-invasively by the measurement of bone-turnover markers. They are commonly subdivided into three categories; 1) bone-resorption markers, 2) osteoclast regulatory proteins and 3) bone-formation markers. Because of the rapidly accumulating new knowledge of bone matrix biochemistry, attempts have been made to use them in the interpretation and characterisation of various stages of the healing of fractures. Early knowledge of the individual progress of a fracture could help to avoid delayed or nonunion by enabling modification of the host’s biological response.

The levels of bone-turnover markers vary throughout the course of fracture repair with their rates of change being dependent on the size of the fracture and the time that it will take to heal. However, their short-term biological variability, the relatively low bone specificity exerted, given that the production and destruction of collagen is not limited to bone, as well as the influence of the host’s metabolism on their concentration, produce considerable intra- and inter-individual variability in their interpretation. Despite this, the possible role of bone-turnover markers in the assessment of progression to union, the risks of delayed or nonunion and the impact of innovations to accelerate fracture healing must not be ignored.


The Journal of Bone & Joint Surgery British Volume
Vol. 91-B, Issue 4 | Pages 426 - 433
1 Apr 2009
Musahl V Tarkin I Kobbe P Tzioupis C Siska PA Pape H

The operative treatment of displaced fractures of the tibial plateau is challenging. Recent developments in the techniques of internal fixation, including the development of locked plating and minimal invasive techniques have changed the treatment of these fractures. We review current surgical approaches and techniques, improved devices for internal fixation and the clinical outcome after utilisation of new methods for locked plating.


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

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

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


The Journal of Bone & Joint Surgery British Volume
Vol. 88-B, Issue 4 | Pages 421 - 426
1 Apr 2006
Pountos I Jones E Tzioupis C McGonagle D Giannoudis PV


Orthopaedic Proceedings
Vol. 86-B, Issue SUPP_II | Pages 179 - 179
1 Feb 2004
Kalos S Giannakopoulos A Brantzikos T Tzioupis C Scouteris G
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Aims: The aim of this prospective study is to compare the results regarding non-union and AVN of two different methods of treatment after displaced femoral neck fractures in young and middle age population.

Methods: Between 1980–1998 we treated 91 patients with displaced femoral neck fractures. In 56 patients (Group A) we performed open reduction, dynamic screw fixation and gluteus minimus muscle pedicle bone graft from greater trochanter inserted through a tunnel prepared parallel to screw. 38 patients had fracture Type Garden III and 18 Garden IV. In 35 patients (Group B) after closed reduction the fracture was fixed with three parallel canullated screws. 24 had fracture Type Garden III and 11 Type IV. All patients were operated within 24 hours. After reduction, Garden Index of 1600±100/1800±100 was acceptable. Follow up varied between 3 to 12 years. Fischer’s Exact test was used to evaluate the results.

Results: 3 patients (5,4%) of Group A and 2 patients (5,7%) of Group B developed non-union. AVN was evident in 9 patients (17%) of Group A and in 6 patients (16,2%) of Group B.

Conclusions: Displaced intracapsular hip fractures are a challenge. Preservation of the femoral head should be the goal of treatment. The rate of non-union in the 2 groups (p:0, 942) as well that of AVN (p:0, 893) did not seem to differ statistically significally. The use of muscle pedicle bone graft did not seem to alter the incidence of complications. We believe that open reduction should be performed in fractures that cannot be reduced closed in younger patients.


Orthopaedic Proceedings
Vol. 86-B, Issue SUPP_II | Pages 186 - 186
1 Feb 2004
Scouteris G Giannakopoulos Á Tzioupis C Dagiakidis Ì Rizonaki A Kontozoglou Í Seretis F
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Purpose: The aim of this study is the evaluation of the results of the treatment of knee osteoarthritis in varus knee with high tibial osteotomy.

Method: Between 1985 – 1991, 54 patients (62 cases) were treated with high tibial osteotomy, which was fixed with A. Renieri technique. The patients were divided in three groups:

- patients who were further treated with TKR

- patients who died without any further surgical treatment

- patients who are still alive and were treated only with high tibial osteotomy

Our study showed that 15 patients (19 cases) needed TKR within mean time 7 years from the osteotomy, 14 patients(15 cases) died without any further surgical treatment in mean time 9 years from the osteotomy and 25 patients (28 cases) who are still alive were treated only with high tibial osteotomy and twelve years later the results are good in 66% and poor in 34%.

Results: As shown from our study high tibial osteotomy with correction of the knee axis and changes of the weight bearing helped in the treatment of pain and delayed the development of knee osteoarthritis in 39 patients (43 cases), who are still alive or died without any further operation after the osteotomy. 15 patients (19 cases) needed TKR after 7 years mean time.

Conclusions: Despite the satisfactory results of TKR, osteoarthritis of knee can be treated with high tibial osteotomy mainly in younger patients, so that TKR if needed, can be performed later. The operation is relatively easy with less complication rate and does not impend the possible TKR later.