A blow-out fracture of the orbit is defined as one with orbital wall and or floor fracture without orbital rim involvement. The management of this injury and its timing continue to be a matter of some debate. One of the main reasons for this debate is the lack of unifying objective, quantitative, clinical measures of diplopia severity that encompass both the clinical and patient perspectives. This thesis consists of two distinct studies: one study examines the factors associated with outcome of blow-out fractures, whilst the other examines the patient perspective and experience of this type of fracture. The aim of this thesis is to study the impacts and determine the factors that influence management outcomes with regard to diplopia. A combination of retrospective data and qualitative data was used to help achieve this aim. The retrospective study demonstrated binocular single vision assessment to be a valuable tool in assessing management outcome. In addition, the data demonstrate it has a significant prognostic value in blow-out fractures of the orbit: lower pre-operative diplopia scores, the more chance of improvement in diplopia scores after surgery. Lower pre-operative diplopia scores were associated with a longer follow up time and a greater number of follow up visits required. Demographic factors, surgical timing, type of surgical approach and surgical implant material were shown to have no significant influence on diplopia. Orbital fat herniation in the absence of orbital muscle involvement, as determined by CT scan interpretation, appears to have no significant influence on diplopia when compared to fractures where no tissue herniation was observed on diplopia scores in blow-out fractures. The impact of blow-out fractures from the patient’s perspective was reflected through distress and frustration which negatively influence patients’ daily activities, including their employment. This distress and frustration was reported to centre around the individual’s fear of losing their vision. This misconception appears to be due to potentially ineffective patientclinician communication.

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Complex regional pain syndrome (CRPS) is a common problem presenting to orthopaedic surgeons or pain therapists, most frequently encountered following trauma. The cardinal features are of pain, hypersensitivity, vasomotor instability and joint stiffness. The exact cause remains unproven, however an exaggerated inflammatory response and free radical induced cellular damage has been proposed. A small number of previous studies have highlighted a potential role for antioxidants in the prevention of the condition. Over the last three decades pain researchers have developed and agreed on a set of modified International Association of the Study of Pain (IASP) diagnostic criteria. Orthopaedic researchers have developed their own criteria that have been subject to much debate as to their validity. The diagnosis of CRPS in two hundred and sixty-two patients from a previous study have been reanalysed using the Atkins and modified IASP diagnostic criteria of Bruehl. The incidence of CRPS was similar using either criteria (Bruehl 20.61% vs. Atkins 22.52%). Using the Bruehl criteria as a gold standard, there was strong diagnostic agreement (K = 0.79, sensitivity = 0.87, specificity = 0.94). Two hundred and eleven patients who had sustained an isolated distal radial fracture were recruited for a prospective double-blinded randomised control trial to assess the efficacy of five hundred milligrams of ascorbic acid in order to prevent CRPS. Using an intention to treat analysis one hundred and ninety-six were reviewed at a minimum of nine weeks. There was no significant difference in the incidence of CRPS (chi-squared=1.196, p=0.305) or the incidence or severity of the individual features of the condition between the two treatment groups. The results of this study suggest that prophylaxis with ascorbic acid does not prevent the occurrence of CRPS when diagnosed with validated criteria following a distal radial fracture.

The aims of this thesis were to investigate certain aspects of the regulation of osteogenesis by BMPs and their physiological inhibitors; to determine whether the balance between the two could have an effect on fracture repair; and to suggest strategies for using this information to provide orthopaedic surgeons with better ways to treat recalcitrant fractures . BMP-2 and its inhibitor chordin were produced endogenously during the in vitro osteogenic differentiation of human mesenchymal stem cells (MSCs) in response to dexamethasone. The addition of exogenous BMP-2 increased the rate of osteogenic differentiation of the MSCs. Knockdown of the BMP inhibitor chordin led to an increase in the rate of osteogenic differentiation of human MSCs, secondary to an increase in the bioavailability of BMP-2. These results raise the possibility that the impaired healing of delayed- and non-unions reflects alterations in the ratios of BMPs to their inhibitors. They further suggest that it may be possible to increase the rate of osteogenesis, and thus improve fracture repair in vivo, by down-regulating the endogenous production of BMP inhibitors. To evaluate these possibilities further, the presence of BMP-2 and -14, as well as their inhibitors chordin and noggin, were investigated by semi-quantitative immunohistochemistry in human fracture biopsies. The expression of BMP-2, BMP-14, chordin and noggin during fracture repair was demonstrated in areas of cartilage and bone formation. Levels of expression of these proteins were compared between healing and non-healing human fractures. There was a decreased relative expression of BMP-2 and BMP-14, compared to the BMP inhibitors, in the non-healing fractures v/s the healing fractures. This suggests an imbalance between BMPs and their inhibitors in fractures that do not heal. These data indicate novel ways to reduce rates of non-union by the local application of BMP-2 or BMP-14, or the blocking of BMP antagonists. Fracture healing may also be impaired by drugs used clinically. The antibiotic tobramycin, commonly used to treat or prevent infections of bone, was shown to reduce the osteogenic potential of human MSCs in vitro. An in vivo study was carried out to determine whether a clinically relevant dose of tobramycin would impair fracture repair induced by BMP-2. The biomechanical and radiological properties of the repair tissue, induced by BMP-2 in a rat femoral defect model, were not affected by the presence of tobramycin. Overall, this thesis demonstrates that the balance between BMPs and their inhibitors has a major influence on the rate of fracture repair and that this balance is altered in non-healing fractures. The data suggest novel, clinically relevant, biological strategies for enhancing bone healing.

Τα κατάγματα της κοτύλης είναι σοβαρά ενδαρθρικά κατάγματα, υψηλής ενέρ-γειας κακώσεις που συμβαίνουν κυρίως σε τροχαία ατυχήματα ή από πτώσεις από μεγάλο ύψος και τα θύματα είναι συνήθως νεαροί ενήλικες. Συχνά συνο-δεύονται από κακώσεις σε άλλα μέρη του σώματος που μπορεί να είναι απει-λητικές για τη ζωή ή να απαιτήσουν νο-σηλεία σε Μονάδα Εντατικής Θεραπείας. Για πολλές δεκαετίες η αντιμετώπισή τους ήταν συντηρητική με πτωχά αποτε-λέσματα στις περισσότερες περιπτώσεις. Κατά τις τελευταίες δεκαετίες όμως η αντιμετώπισή τους άλλαξε και έγινε χει-ρουργική στα παρεκτοπισμένα κατάγμα-τα ή αυτά που αφορούν φορτιζόμενη ε-πιφάνεια της κοτύλης, καθώς αυτή προ-σφέρει ικανοποιητικότερα αποτελέσμα-τα. Οι επιπλοκές τόσο της συν-τηρητικής όσο και της χειρουργικής αντιμετώπισης περιλαμβάνουν τη μετα-τραυματική οστεοαρθρίτιδα και την άσηπτη νέκρωση της μηριαίας κεφαλής. Επιπλοκές που παρατηρούνται κυρίως μετά από χειρουργική αντιμετώπιση εί-ναι η έκτοπη οστεοποίηση, η πάρεση του ισχιακού νεύρου, η πνευμονική εμβολή και η φλεγμονή του χειρουργικού τραύματος. Μελετήθηκαν κλινικά και ακτινολο-γικά 75 ασθενείς που αντιμετωπίστηκαν χειρουργικά για παρεκτοπισμένο κάταγ-μα κοτύλης τουλάχιστο κατά 3 mm, σε ένα διάστημα 6 ετών. Η διάρκεια της μετεγχειρητικής παρακο-λούθησης ήταν από 10 – 15 έτη με μέσο όρο 12,5 έτη. Συνοδές κακώσεις παρατηρήθηκαν στο 46% των ασθενών που απαίτησαν χειρουργική αντιμετώπιση ή παρατε-ταμένη νοσηλεία στη Μονάδα Εντατικής θεραπείας. Το συνολικό ικανοποιητικό κλινικό αποτελέσματα που περιλαμβάνει τους ασθενείς με άριστο ή καλό κλινικό απο-τέλεσμα ήταν 80%. Υπήρξε στενή συ-σχέτιση μεταξύ κλινικού και ακτινολο-γικού αποτελέσματος. Η πιο συχνή επι-πλοκή ήταν η έκτοπη οστεοποίηση, που παρατηρήθηκε σε 19 ασθενείς (25,3%). Στην εκτεταμένη λαγονομηριαία προ-σπέλαση παρατηρήθηκε η μεγαλύτερη επίπτωση έκτοπης οστεοποίησης, ενώ η οστεοτομία του μείζονος τροχαντήρα στην προσπέλαση Kocher – Langenbeck μείωσε ελαφρά την επίπτωση της έκτο-πης οστεοποίησης. Επιπλέον, μετατραυ-ματική οστεοαρθρίτιδα παρατηρήθηκε σε 8 ασθενείς (10,7%) και άσηπτη νέ-κρωση της μηριαίας κεφαλής σε 6 (8%). Άλλες επιπλοκές ήταν μία εν τω βάθει φλεβοθρόμβωση, μία πνευμονική εμβο-λή, μία ψευδάρθρωση τροχαντήρα και μία πάρεση ισχιακού. Συμπερασματικά, ο στόχος της χει-ρουργικής αντιμετώπιης των καταγμά-των της κοτύλης είναι η ανατομική ανά-ταξη και η συναρμογή με τη μηριαία κεφαλή προκειμένου να επιτευχθεί καλό μακροχρόνιο αποτέλεσμα. Στις περισσό-τερες περιπτώσεις η προσπέλαση Kocher – Langenbeck είναι επαρκής και η ο-στεοτομία του μείζονος τροχαντήρα, η οποία ενδείκνυται για τα συνδυασμένα κατάγματα, προσφέρει διεύρυνση του χειρουργικού πεδίου, διευκολύνει την ανάταξη και την τοποθέτηση των υλικών και παρά τις υφιστάμενες διαφωνίες, δε φαίνεται να σχετίζεται με την ανάπτυξη έκτοπης οστεοποίησης. / Fractures of the acetabulum are severe intra-articular fracture, highenergy injuries, they are usually the result of Road Traffic Accidents or fall from a height and the victims are usually young adults. They are often accompanied by other skeletal or visceral injuries than may be lifethreatening or may require prolonged treatment in the Intensive Care Unit. For many decades their treatment was conservative with poor results in most cases. In the past few decades their treatment has changed to surgical in displaced ones or those than involve the loaded area of the acetabulum, because the surgical treatment has better results. Complications of both conservative and surgical treatment are post-traumatic osteoarthrosis and osteonecrosis of the femoral head. Complications observed mainly after surgical treatment are heterotopic ossification, sciatic nerve palsy, pulmonary embolism and surgical wound infection. Seventy-five patients were studied clinically and roentgenographically with a displaced acetabular fracture of at least 3 mm that were treated surgically over a six-year period. The duration of the follow-up was from 10 to 15 years, with a mean of 12.5 years. Forty-six percent of the patients had associated injuries that required surgical intervention or prolonged treatment in the intensive care unit. The over-all satisfactory clinical result, grouping together the excellent and good results, is 80%. There was a good correlation between clinical and radiological results. The most common complication was heterotopic ossification observed in 19 patients (25.3%). The extended iliofemoral approach had the greater incidence of heterotopic ossification (40%) and the osteotomy of the greater trochanter in the Kocher- Langenebeck approach slightly decreased the incidence of heterotopic ossification. Moreover, post-traumatic osteoarthrosis was seen in 8 patients (10.7%) and osteonecrosis of the femoral head in 6 (8%). One case of deep vein thrombosis, one pulmonary embolism, one non-union of the greater trochanter and one sciatic nerve palsy were other post-surgical complications. In conclusion, surgical treatment of the acetabular fractures in order to achieve anatomical reduction of the acetabulum and congruency with the femoral head, is the ultimate goal for excellent functional outcome in long- term. In most of them, K-L approach is adequate and trochanteric osteotomy, which is indicated for associated acetabular fractures, greatly facilitates the exposure, anatomical reduction and metal work application, and despite the exsisting controversy, it is not correlated to the incidence of heterotopic ossification.

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