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Purpose: Although bone transport is a well-recognised technique to address segmental bone defects, optimal management of docking sites is not absolutely determined. Some surgeons routinely intervene in all cases, and others prefer to observe and intervene only if spontaneous union does not occur. Primary aim of the study was to compare rates of docking site union between patients who underwent routine docking site intervention and those who did not., Methods: A systematic literature review using the keywords "bone transport", "docking", "tibia", and "femur" was performed in PubMed using PRISMA guidelines. Studies published in English from January 2000 to August 2022 were included and assessed independently by two reviewers. Pooled analysis was undertaken dividing patients into two groups: those managed by routine intervention and those initially observed., Results: Twenty-three clinical studies met the eligibility criteria for pooled analysis, including 1153 patients, 407 in the routine intervention and 746 in the observed group. The rate of union after initial treatment was 90% in the routine intervention group and 66% in the observed group (p < 0.0001). Overall union rates at the end of treatment were similar at 99% in both groups. Patients in the observed group required an average of 2.2 procedures to achieve union overall compared with 3.8 in the routine intervention group. Time in frame was similar between groups., Conclusion: Based on the current literature, routine docking site interventions cannot be recommended, since this may lead to unnecessary interventions in two thirds of patients. Timely selective intervention in those at high risk or after a defined period of observation would appear to be a logical approach., (© 2023. The Author(s).)

Purpose: The cost implications of limb reconstruction techniques have not been adequately investigated. Aim of this pilot study was to compare the direct medical cost of tibial bone defects managed with distraction osteogenesis-Ilizarov method (ILF), or with Masquelet technique (MIF)., Methods: Data of 20 random patients treated in a single centre were analysed. Inclusion criteria included acute tibial defects, or post-debridement of nonunions with complete follow-up and successful union. The endpoint of clinical efficacy was the time-to-defect union. Comparisons were made between equally sized subgroups (ILF vs. MIF)., Results: The average defect length was 5.6 cm (2.6-9.6 cm). The overall cost of 20 cases reached £452,974 (mean £22,339, range £13,459-£36,274). Statistically significant differences favoring the MIF were found regarding the average time-to-union; number of surgeries, of admissions and follow-up visits, as well as the mean intraoperative cost (£8857 vs. £14,087). These differences lead to significant differences of the mean cost of the overall treatment (MIF £18,131 vs. ILF £26,126). Power analysis based on these data indicated that 35 patients on each group would allow detection of a 25% difference, with an alpha value of 0.05 and probability (power) of 0.9., Conclusions: The results and analysis presented highlight factors affecting the high financial burden, even in a best-case scenario, this type of surgery entails. Larger pivotal studies should follow to improve the cost efficiency of clinical practice., (© 2022. Crown.)

Aims: To determine whether a psychological screening tool - the Posttraumatic Adjustment Scale (PAS), predicts later psychological distress for admissions to a Major Trauma Centre (MTC) and to identify whether there was an unmet need in relation to the psychological support offered., Methods: Patient demographics and details of their injuries were retrieved from the Trauma Audit & Research Network (TARN) database. All patients admitted to Leeds General Infirmary MTC were approached for inclusion in the study over a three-month period. The PAS was administered to all participants at baseline. Following discharge, patients were sent two validated psychological measures via post, the Impact of Events Scale - Revised (IES-R) and the Clinical Outcomes in Routine Evaluation System (CORE-10). Relationships between continuous variables were examined using a Spearman's rank test (SR). The diagnostic accuracy of the different psychological screening systems was examined and compared using Receiver Operator Characteristic (ROC) analysis., Results: Eighty-two patients completed the PAS, 26 of whom had been referred to clinical psychology and 56 who were not. Fifty-seven of these patients (70%) returned follow-up IES-R and CORE-10 data, 20 who had been referred to psychology and 37 who had not. The PAS-P score recorded shortly after admission correlated strongly with the CORE-10 (SR rs 0.54, p<0.0001) and IES-R (SR rs 0.63, p<0.0001) scores recorded at early follow up. A PAS-P of more than 10 predicted the development of PTSD symptoms (IES-R 33 or more) or moderate global psychological distress (CORE-10 15 or more) with 72% sensitivity and 71% specificity. To identify patients who went on to develop psychological symptoms according to either measure (IES-R 33 or more or CORE-10 15 or more), the PAS-P was more sensitive than clinician referral (71% vs 52%, p<0.05) with similar specificity (72% vs 75%, p=0.78)., Conclusions: In an unselected group of trauma inpatients treated in a MTC, the PAS is an effective means of identifying those who are likely to go on to suffer PTSD symptoms or psychological distress. It may useful to use the PAS as a measure to formalise psychology referrals., Competing Interests: Declarations of interest None., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Objectives: To report our experience and clinical results of using the Masquelet technique for the treatment of tibial nonunions and acute traumatic tibial bone defects., Design: Retrospective study of prospectively collected data (Level IV)., Setting: Level I trauma center in the UK., Patients/participants: Consecutive patients with tibial nonunions and open fractures associated with bone loss.Intervention: Two-stage Masquelet Procedure for the tibia., Main Outcome Measurements: Clinical and imaging assessment at 6 weeks, 3,6,9,12 months, or until pain-free mobilization and union., Results: There were 17 eligible patients, with a mean size of bone defect of 6 cm (range, 4-8 cm) and an 88.2% union rate at a mean of 8 months (range 5-18 months). Mean range of motion was 95 degrees of knee flexion (range 80°-130°). All patients but 2 returned to their previous occupation., Conclusions: The Masquelet technique is simple, effective, and has a high rate of success for the management of a variety of situations including acute bone loss or infected nonunions and is associated with a low incidence of complications., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2022 The Authors. Published by Wolters Kluwer Health, Inc. on behalf of the Orthopaedic Trauma Association.)

Aim and Objective: This study was designed to test and compare the mechanical performance of the biplanar ArthroSave KneeReviver and a circular frame construct with the intended use of providing a mechanically favourable environment for cartilage regeneration across a knee joint., Materials and Methods: Three similar constructs of the two devices were applied to biomechanical testing sawbones, with the knee distracted by 8 mm. The constructs were vertically loaded to 800 N in an Instron testing machine at 20 mm/minute. Tests were conducted in neutral hip flexion and at 12° of hip flexion and extension, to mimic leg position in gait. Displacement measurements were taken from the Instron machine, and three-dimensional joint motion was recorded using an Optotrak Certus motion capture system., Results: Overall axial rigidity was similar between the two devices (circular frame, 81.6 N/mm ± 5.9; and KneeReviver, 79.5 N/mm ± 25.1 with hip neutral) and similar in different hip positions. At the point of joint contact, the overall rigidity of the circular frame increased significantly more than the KneeReviver (491 N/mm ± 27 and 93 N/mm ± 32, respectively, p <0.001). There was more variability between models in the KneeReviver. There was more off-axis motion in the KneeReviver, mainly due to increasing knee flexion on loading. This was exacerbated with the hip in flexion and extension but remained small, with the maximal off-axis displacement being 7 mm/3°., Conclusion: The circular frame provides a similar mechanical environment to the novel KneeReviver device, for which most clinical data are available. These findings suggest that both devices appear a viable option for knee joint distraction (KJD). Further clinical data will help inform mode of application., Clinical Significance: KJD is a relatively novel technique for use in osteoarthritis (OA), and it remains unclear which distraction devices provide appropriate mechanics. Our testing gives evidence to support either option for further use., How to Cite This Article: Chowdhury JMY, Lineham B, Pallett M, et al . Comparison of Mechanical Performance between Circular Frames and Biplanar Distraction Devices for Knee Joint Distraction. Strategies Trauma Limb Reconstr 2021;16(2):71-77., Competing Interests: Source of support: Nil Conflict of interest: None, (Copyright © 2021; Jaypee Brothers Medical Publishers (P) Ltd.)

Aim and Background: A systemic method for the application of Ilizarov fixators and on-table fracture reduction is described in this instructional article. This technique has been developed from the unit's practice in adult patients. The indications, underlying principles and rationale for the method are also discussed., Technique: The basic concept involves the construction of a series of concentric, colinear rings aligned with the mechanical axis of the limb. An orthogonal ring block is initially placed on the proximal segment and extended distally. Wire to ring reduction techniques are used resulting in the contact, alignment and stability required for early full weight-bearing, free movement of knee and ankle, and subsequent healing., Conclusion and Clinical Significance: Our step-by-step guide takes the reader through a systematic approach to surgery along with tips and tricks on how to achieve reduction and avoid the common pitfalls. With this method, it is possible to achieve an on-table reduction and correction of a multiplanar deformity without the use of expensive hexapod technology. This may allow less experienced users reproduce the technique with a shorter learning curve., How to Cite This Article: Messner J, Prior CP, Pincher B et al . Ilizarov Method for Acute Paediatric Tibial Fractures. Strategies Trauma Limb Reconstr 2021;16(1):46-52., Competing Interests: Source of support: Nil Conflict of interest: None, (Copyright © 2021; Jaypee Brothers Medical Publishers (P) Ltd.)

Aim: The aim of this study was to identify variables that may predict later psychological distress in patients following admission to a Major Trauma Centre (MTC) and to determine whether a psychological screening tool, the Posttraumatic Adjustment Screen (PAS), administered on admission was able to contribute to this., Methods: Patients referred to the MTC clinical psychology service completed the PAS during their inpatient stay over an eight-month period. Following discharge from hospital, patients were telephoned (1 month, 3 months and 6 months post injury) by a member of the clinical psychology team and asked two validated questionnaires; the Impact of Events Scale revised (IES-R) (measure of posttraumatic stress symptoms) and the CORE-10 (measure of global psychological distress). In addition, patients' data from the local Trauma Audit & Research Network (TARN) database was reviewed to identify information related to injury and other demographic data. Patients were divided into groups for comparison based upon their PAS scores using previously described severity cut offs for posttraumatic stress symptoms and depression. Receiver Operator Characteristic and Multiple Linear Regression analysis was used to examine for significant baseline predictors of psychological distress during follow up according to the IES and CORE-10 scores., Results: One hundred and fourteen patients completed the PAS over the study period. Follow-up psychological data was available for 63 (56%) of patients. Except for the patient's home address, no baseline parameter examined in this study regarding patient demographics, injury or treatment was associated with reported psychological symptoms in the first six months post injury as measured by the IES-R or CORE-10 scores. Multiple linear regression analysis revealed that both PAS-P and PAS-D were significant predictor variables for patients reporting significant symptoms of posttraumatic stress and global psychological distress (according to IES-R and CORE-10 scores) in the first six months post injury., Conclusions: Psychological screening on admission may be helpful in identifying patients admitted to MTCs who are at risk at developing posttraumatic stress symptoms and psychological distress following major trauma., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Aims: Anatomical atlases document classical safe corridors for the placement of transosseous fine wires through the calcaneum during circular frame external fixation. During this process, the posterior tibial neurovascular bundle (PTNVB) is placed at risk, though this has not been previously quantified. We describe a cadaveric study to investigate a safe technique for posterolateral to anteromedial fine wire insertion through the body of the calcaneum., Materials and Methods: A total of 20 embalmed cadaveric lower limbs were divided into two groups. Wires were inserted using two possible insertion points and at varying angles. In Group A, wires were inserted one-third along a line between the point of the heel and the tip of the lateral malleolus while in Group B, wires were inserted halfway along this line. Standard dissection techniques identified the structures at risk and the distance of wires from neurovascular structures was measured. The results from 19 limbs were subject to analysis., Results: In Group A, no wires pierced the PTNVB. Wires were inserted a median 22.3 mm (range 4.7 to 39.6) from the PTNVB; two wires (4%) passed within 5 mm. In Group B, 24 (46%) wires passed within 5 mm of the PTNVB, with 11 wires piercing it. The median distance of wires from the PTNVB was 5.5 mm (range 0 to 30). A Mann-Whitney U test showed that this was significantly closer than in Group A (Hodges-Lehmann shift, 14.06 mm; 95% confidence interval (CI) 10.52 to 16.88; p < 0.0001). In Group B, with an increased angle of insertion there was greater risk to the PTNVB (r s = -0.80; p < 0.01)., Conclusion: Insertion of wires using an entry point one-third along a line from the point of the heel to the tip of the lateral malleolus (Group A) appears to be the safer technique. An insertion angle of up to 30° to the coronal plane can be used without significant risk to the PTNVB. Insertion of wires halfway along a line from the point of the heel to the tip of the lateral malleolus (Group B) carried a significantly higher risk of injury to neurovascular structures and, if necessary, an angle of insertion parallel to the coronal plane should be used. Cite this article: Bone Joint J 2018;100-B:1054-9.

Purpose: With an ageing population, the incidence of trauma in those aged over 65 years is increasing. Strategies for dealing with these patients must be developed. At present the standard management of open tibial fractures in the UK is described by the BOAST4 guidelines (from the British Orthopaedic Association and British Association of Plastic & Aesthetic Surgeons). It is not clear to what extent these are appropriate for older patients. We describe our experience of managing elderly patients presenting with open tibial fractures., Method: Patients were identified via prospectively collected national and departmental databases. These data were supplemented by review of the patient records and radiographs. Data collated included patient demographics, injury details, orthopaedic and plastic surgery operative details, and long-term outcomes., Results: Between January 2013 and June 2016, 74 patients aged over 65 years were admitted with open lower limb fractures. 54 of these were open tibial fractures and these patients formed the study group. 19 patients required soft-tissue reconstruction for Gustilo and Anderson IIIB tibial fractures (age range, 67-95 years). In these patients, there were 7 midshaft (AO 42), 1 proximal (AO 41), and 11 distal (AO 43) fractures. 13 patients were treated with internal fixation and 6 with circular frames. The median length of hospital stay was 27 days (range, 4-85). 14 patients received loco-regional flaps and 5 underwent free tissue transfer with one requiring preoperative femoral angioplasty. There were no flap losses. Four patients had fasciocutaneous flaps, 3 tibialis anterior transposition, 2 an extensor digitorum brevis flap, 1 a hemisoleus flap, and 4 were skin grafted. All patients went on to unite and return to their premorbid weight-bearing status (4 using walking frames, 3 using sticks, and 12 walking independently)., Conclusion: Although the literature suggests a significantly higher complication rate in elderly patients with open fractures, we have demonstrated comparable rates of flap survival and bony union to those observed in younger patients. Challenges are presented in terms of patient physiology and these must be carefully managed pre- and postoperatively. These challenges are reflected in prolonged hospital stays., (Crown Copyright © 2018. Published by Elsevier Ltd. All rights reserved.)

Background: The Taylor Spatial Frame™ (TSF) is a versatile variant of the traditional Ilizarov circular fixator. Although in widespread use, little comparative data exist to quantify the biomechanical effect of substituting the tried-and-tested Ilizarov construct for the TSF hexapod system., Questions/purposes: This study was designed to investigate the mechanical properties of the TSF system under physiologic loads, with and without the addition of a simulated bone model, with comparison to the standard Ilizarov frame., Methods: The mechanical behaviors of three identical four-ring TSF and Ilizarov constructs were tested under levels of axial compression, bending, and rotational torque to simulate loading during normal gait. An acrylic-pipe fracture model subsequently was mounted, using fine wires and 5 mm half pins, and the testing was repeated. Load-deformation curves, and so rigidity, for each construct were calculated, with statistical comparisons performed using paired t-tests., Results: Under axial loading, the TSF was found to be less rigid than the Ilizarov frame (645 ± 57 N/mm versus 1269 ± 256 N/mm; mean difference, 623 N/mm; 95% CI, 438.3-808.5 N/mm; p < 0.001), but more rigid under bending and torsional loads (bending: 42 ± 9 Nm/degree versus 78 ± 13 Nm/degree; mean difference, 37 Nm/degree; 95% CI, 25.0-47.9 Nm/degree; p < 0.001; torsion: 16 ± 2 Nm/degree versus 5 ± 0.35 Nm/degree; mean difference, 11 Nm/degree; 95% CI, 9.5-12.2 Nm/degree; p < 0.001). On mounting the bone models, these relationships broadly remained in the half-pin and fine-wire groups, however the half-pin constructs were universally more rigid than those using fine wires. This effect resulted in the TSF, using half pins, showing no difference in axial rigidity to the fine-wire Ilizarov (107 ± 3 N/mm versus 107 ± 4 N/mm; mean difference, 0.05 N/mm; 95% CI, -6.99 to 7.1 N/mm; p > 0.999), while retaining greater bending and torsional rigidity. Throughout testing, a small amount of laxity was observed in the TSF construct on either side of neutral loading, amounting to 0.72 mm (±0.37 mm) for a change in loading between -10 N and 10 N axial load, and which persisted with the addition of the synthetic fracture model., Conclusions: This study broadly shows the TSF construct to generate lower axial rigidity, but greater bending and torsional rigidity, when compared with the Ilizarov frame, under physiologic loads. The anecdotally described laxity in the TSF hexapod strut system was shown in vitro, but only at low levels of loading around neutral. It also was shown that the increased stiffness generated by use of half pins produced a TSF construct replicating the axial rigidity of a fine-wire Ilizarov frame, for which much evidence of good clinical and radiologic outcomes exist, while providing greater rigidity and so improved resistance to potentially detrimental bending and rotational shear loads., Clinical Relevance: If replicated in the clinical setting, these findings suggest that when using the TSF, care should be taken to minimize the observed laxity around neutral with appropriate preloading of the construct, but that its use may produce constructs better able to resist bending and torsional loading, although with lower axial rigidity. Use of half pins in a TSF construct however may replicate the axial mechanical behavior of an Ilizarov construct, which is thought to be conducive to bone healing.

This prospective study was undertaken at a regional tertiary referral centre to evaluate the results of treatment of bone defects managed with the induced membrane (IM) technique. Inclusion criteria were patients with bone defects secondary to septic non-union, chronic osteomyelitis and acute fracture with bone loss. Pathological fractures with bone loss were excluded. Data collection included patient demographics, pathology, previous surgical intervention, size of bone defect, type of graft implanted, time-to-union and complications/reinterventions. The minimum time of follow up was 12 months. Forty-three patients (32 males) met the inclusion criteria with a mean age of 47.9 years (range 18-80 years). 22 patients had an acute traumatic bone loss associated with open fracture and 21 presented with an infected non-union or underlying osteomyelitis requiring bone excision. The most common microorganisms grown were staphylcoccous aureus and coagulase negative staphylococcous. The mean length of the bone defect area was 4.2 cm (range 2-12 cm). All patients were managed with the two stage technique receiving composited grafting (Autologous bone graft (Iliac crest/RIA), graft expander as required, osteoprogenitor cells, growth factor) during the second stage. There was one failure (humeral infected non-union) in a previous background of bone radiation that necessitated reconstruction with a free fibula vascularized graft. One patient had a fall and sustained implant failure (humeral defect) 3 months after reconstruction and following re-plating progressed to union 4 months later. Two patients required re-grafting due to failure of healing in one of the defect sides. One patient presented with a discharging sinus 2 years after successful healing of a tibial defect that was treated successfully with soft tissue and bone debridement without necessitating further interventions. One patient despite union (distal 1/3 tibia) underwent a below knee amputation due to a dysfunctional ankle/foot (previous foot compartment syndrome-regional pain syndrome). Of those patients, with lower limb injuries, 4 patients had leg length discrepancies of 1 cm, 1.5 cm, 2 cm (two patients) respectively. The mean time to radiological union was 5.4 months (range 2-12 months). The average time of healing of 1 cm bone defect was 1.24 months. Patients with upper limb reconstruction recovered earlier than those with lower limb injuries. At the latest follow up all patients were able to mobilize full weight bearing without residual pain. The induced membrane technique appears to be an alternative good option for the management of large bone defects secondary to acute bone loss or infected non-unions. The incidence of re-interventions was low in this challenging cohort of patients. The technique should be considered in the surgeon's armamentarium as it is effective and is associated with a low rate of complications., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Background: Fine-wire circular frame (Ilizarov) fixators are hypothesized to generate favorable biomechanical conditions for fracture healing, allowing axial micromotion while limiting interfragmentary shear. Use of half-pins increases fixation options and may improve patient comfort by reducing muscle irritation, but they are thought to induce interfragmentary shear, converting beam-to-cantilever loading. Little evidence exists regarding the magnitude and type of strain in such constructs during weightbearing., Questions/purposes: This biomechanical study was designed to investigate the levels of interfragmentary strain occurring during physiologic loading of an Ilizarov frame and the effect on this of substituting half-pins for fine-wires., Methods: The "control" construct was comprised of a four-ring all fine-wire construct with plain wires at 90°-crossing angles in an entirely unstable acrylic pipe synthetic fracture model. Various configurations, substituting half-pins for wires, were tested under levels of axial compression, cantilever bending, and rotational torque simulating loading during gait. In total three frames were tested for each of five constructs, from all fine-wire to all half-pin., Results: Substitution of half-pins for wires was associated with increased overall construct rigidity and reduced planar interfragmentary motion, most markedly between all-wire and all-pin frames (axial: 5.9 mm ± 0.7 vs 4.2 mm ± 0.1, mean difference, 1.7 mm, 95% CI, 0.8-2.6 mm, p < 0.001; torsional: 1.4% ± 0.1 vs 1.1% ± 0.0 rotational shear, mean difference, 0.3%, 95% CI, 0.1%-0.5%, p = 0.011; bending: 7.5° ± 0.1 vs 3.4° ± 0.1, mean difference, -4.1°, 95% CI, -4.4° to -3.8°, p < 0.001). Although greater transverse shear strain was observed during axial loading (0.4% ± 0.2 vs 1.9% ± 0.1, mean difference, 1.4%, 95% CI, 1.0%-1.9%, p < 0.001), this increase is unlikely to be of clinical relevance given the current body of evidence showing bone healing under shear strains of up to 25%. The greatest transverse shear was observed under bending loads in all fine-wire frames, approaching 30% (29% ± 1.9). This was reduced to 8% (±0.2) by incorporation of sagittal plane half-pins and 7% (±0.2) in all half-pin frames (mean difference, -13.2% and -14.0%, 95% CI, -16.6% to 9.7% and -17.5% to -10.6%, both p < 0.001)., Conclusions: Appropriate use of half-pins may reduce levels of shear strain on physiologic loading of circular frames without otherwise altering the fracture site mechanical environment at levels likely to be clinically important. Given the limitations of a biomechanical study using a symmetric and uniform synthetic bone model, further clinical studies are needed to confirm these conclusions in vivo., Clinical Relevance: The findings of this study add to the overall understanding of the mechanics of circular frame fixation and, if replicated in the clinical setting, may be applied to the preoperative planning of frame treatment, particularly in unstable fractures or bone transport where control of shear strain is a priority.

Total radiation exposure accumulated during circular frame treatment of distal tibial fractures was quantified in 47 patients treated by a single surgeon from February 2007 until Oct 2010. The radiation exposures for all relevant radiology procedures for the distal tibial injury were included to estimate the radiation risk to the patient. The median time of treatment in the frame was 169 days (range 105-368 days). Patients underwent a median of 13 sets of plain radiographs; at least one intra operative exposure and 16 patients underwent CT scanning. The median total effective dose per patient from time of injury to discharge was 0.025mSv (interquartile range 0.013-0.162 and minimum to maximum 0.01-0.53). The only variable shown to be an independent predictor of cumulative radiation dose on multivariate analysis was the use of CT scanning. This was associated with a 13-fold increase in overall exposure. Radiation exposure during treatment of distal tibial fractures with a circular frame in this group was well within accepted safe limits. The fact that use of CT was the only significant predictor of overall exposure serves as a reminder to individually assess the risk and utility of radiological investigations on an individual basis. This is consistent with the UK legal requirements for justification of all X-ray imaging, as set out in the Ionising Radiation (Medical Exposure) Regulations 2000 [1]., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Patients undergoing major orthopaedic surgery of the lower extremities or spine are at increased risk of venous thromboembolism (VTE). Although consensus exists as to the need for routine thromboprophylaxis in high risk patients, some aspects of this approach, such as the timing of the first dose and overall duration of the anticoagulation regimen, are subject to debate. Reviewing the available literature, there appears to be little evidence to support initiation of thromboprophylaxis more than 12 hours before surgery. Perioperative thromboprophylaxis (2 hours pre to 6 hours post -op) has been associated with an increased risk of bleeding complications whilst initiating prophylaxis more than 12 hours after surgery appears to increase the incidence of subsequent thromboembolic complications. Overall evidence would appear to support initiation of thromboprophylaxis 6 to 9 hours postoperatively, though further confirmatory studies investigating this variable in isolation would be useful to guide clinical decision making. Although evidence exists supporting extended duration thromboprophylaxis after major orthopaedic procedures, further evidence is required, using clinically important end points, prior to adoption of such an approach in all patients. Stratification of prophylaxis duration, based on risk factors for thromboembolic or bleeding complications, would seem a more rational approach than strict adherence to guidelines.

For decades, parenteral drugs, such as the low molecular weight heparins and unfractionated heparins or vitamin K antagonists, have been used as anticoagulants for prevention of venous thromboembolism following major lower limb surgery. However, these regiments have limitations that rendered the quest for new anticoagulants mandatory. Recently, research has been focused on the development of orally active small molecules that directly target thrombin or activated factor X (FXa). These regiments exhibit a number of characteristics that an "ideal" anticoagulant should possess. Currently, two agents, dabigatran etexilate and rivaroxaban, which inhibit thrombin and FXa, respectively have been approved in the European Union and Canada for venous thromboprophylaxis in patients undergoing elective hip- or knee-replacement surgery. Other agents are at an early or late stage of clinical evaluation. In this study, we summarize the current evidence for these new developed or under development drugs regarding their applications in the filed of lower limb orthopaedic surgery.

Anatomical atlases document safe corridors for placement of wires when using fine-wire circular external fixation. The furthest posterolateral corridor described in the distal tibia is through the fibula. This limits the crossing angle and stability of the frame. In this paper we describe a new, safe Retro-Fibular Wire corridor, which provides greater crossing angles and increased stability. In a cadaver study, 20 formalin-treated legs were divided into two groups. Wires were inserted into the distal quarter of the tibia using two possible corridors and standard techniques of dissection identified the distance of the wires from neurovascular structures. In both groups the posterior tibial neurovascular bundle was avoided. In group A the peroneal artery was at risk. In group B this injury was avoided. Comparison of the groups showed a significant difference (p < 0.001). We recommend the Retro-Fibular wire technique whereby wires are inserted into the tibia mid-way between the posteromedial border of the fibula and the tendo Achillis, at 30 degrees to 45 degrees to the sagittal plane, and introduced from a posterolateral to an anteromedial position. Subsequently, when using this technique in 30 patients, we have had no neurovascular complications or problems relating to tethering of the peroneal tendons.

Objective: To examine the differences between severely injured older patients (aged over 65 years) compared with similarly injured younger adults in terms of incidence, inpatient mortality and factors predicting outcome., Methods: Data prospectively entered into the Trauma Audit and Research Network (TARN) database from our level I trauma unit over a 5-year period were retrospectively examined, with 3172 patients included in the final analysis., Results: Older patients accounted for 13.8% of those with severe injuries (Injury Severity Score 16 or more) and almost 2% of our trauma admissions overall. High energy injuries were responsible for the majority of these injuries though relatively minor trauma became increasingly important in older patients. Mortality rates in the older patients were more than twice those seen in the adult population (19% in the under 40's to almost 50% in the over 75's). Age, Injury Severity Score and Glasgow Coma Score continued to be predictive of mortality in older patients but other factors relevant in younger adults were not., Conclusions: Patients in the older group without physiological derangement on admission were still at a relatively high risk of inpatient mortality. This was in contrast to the younger patients, suggesting that it might be more difficult to predict which older patients might benefit from more aggressive monitoring or treatment. Despite increased mortality in older patients, significant survival rates were achieved even in the oldest. Active treatment should not be withdrawn on the basis of age alone.

In infections following orthopaedic surgery, isolated staphylococci are reported to be methicillin resistant (MRSA) in up to 50% of cases. Linezolid, the first in a new class of antibiotics, has excellent efficacy against gram positive organisms that are resistant to other therapies and is 100% orally bioavailable. We report early results of its use for the treatment of resistant infections in orthopaedic practice. Infections were characterised according to the UK Nosocomial Infections National Surveillance Service classification of surgical infections as superficial, deep or organ/space. Osteomyelitis, joint sepsis and deep infection involving orthopaedic implants were included into the final category. Outcome was recorded as clinical, microbiological and blood parameter cure or fail. Over the 12-month study period, 54 patients received linezolid therapy, 41% of these had significant co-morbidity that might affect their ability to fight infection. Sixty-seven percent of infections were in association with implanted metal work. The majority of patients were treated with vancomycin for a short period before linezolid was used as oral 'switch' therapy for longer-term administration, allowing early discharge in all cases. MRSA was isolated in 87% of the patients treated. The mean length of linezolid therapy was 39 days (2-151). Clinical success was achieved in 90% of patients overall. Though there were no life-threatening complications, adverse event rates were significantly higher than those recorded in the literature, with 19% of patients needing to cease therapy. Linezolid offers an alternative to traditional treatments for resistant infections and can facilitate early discharge. Patients need to be monitored closely, particularly where long-term therapy is planned.

Background: Abbreviated Injury Scale (AIS)-based systems-the Injury Severity Score (ISS), New Injury Severity Score (NISS), and AISmax-are used to assess trauma patients. The merits of each in predicting outcome are controversial., Methods: A large prospective database was used to assess their predictive capacity using receiver operator characteristic curves., Results: In all, 10,062 adult, blunt-trauma patients met the inclusion criteria. All systems were significant outcome predictors for sepsis, multiple organ failure (MOF), length of hospital stay, length of intensive care unit (ICU) admission and mortality (p < 0.0001). NISS was a significantly better predictor than the ISS for mortality (p < 0.0001). NISS was equivalent to the AISmax for mortality prediction and superior in patients with orthopaedic injuries. NISS was significantly better for sepsis, MOF, ICU stay, and total hospital stay (p < 0.0001)., Conclusions: NISS is superior or equivalent to the ISS and AISmax for prediction of all investigated outcomes in a population of blunt trauma patients. As NISS is easier to calculate, its use is recommended to stratify patients for clinical and research purposes.

Background: Recently, there has been a move away from early total care in patients with severe, multiple injuries to damage control orthopedics (DCO) in an attempt to limit the physiologic insult resulting from operative treatment after trauma. For femoral shaft fracture, this entails initial external fixation and subsequent conversion to an intramedullary nail (IMN). We sought to quantify the inflammatory response to initial surgery and conversion and link this to subsequent organ dysfunction and complications., Methods: Patients with femoral shaft fracture and a New Injury Severity Score of 20 or more were included. Data were retrospectively collected for 4 days at admission and at exchange procedure (external fixation to intramedullary nail), and the Systemic Inflammatory Response Syndrome (SIRS) score and the Marshall multiorgan dysfunction score were calculated., Results: One hundred seventy-four patients met the inclusion criteria. The DCO group had significantly more severe injuries (New Injury Severity Score of 25.4 vs. 36.2, p < 0.0001) and significantly more head and thoracic injuries (both p < 0.0001). The mean SIRS score was significantly higher in the IMN group, from 12 hours until 72 hours postoperatively (p < 0.05). The mean peak postoperative SIRS score was significantly higher in the IMN group than in the DCO group, at the primary procedure and at conversion, as was the time with an SIRS score greater than 1. At conversion in the DCO group, the preoperative SIRS score correlated with magnitude and duration of elevation in the SIRS and multiorgan dysfunction scores (p < 0.0001)., Conclusion: It would appear that despite more severe injuries in the DCO group, patients had a smaller, shorter postoperative SIRS and did not suffer significantly more pronounced organ failure than the IMN group. DCO patients undergoing conversion while their SIRS score was raised suffered the most pronounced subsequent inflammatory response and organ failure. According to these data, DCO treatment was associated with a lesser systemic inflammatory response than early total care for femur fractures. The inflammatory status of the patient may be a useful adjunct in clinical decision making regarding the timing of conversion to an intramedullary device.

Bone morphogenetic proteins (BMPs) have been extensively studied since the discovery of agents within bone that could induce bone formation at ectopic sites by Urist in the 1960s. Extensive preclinical research has been carried out showing the efficacy of these products in promoting bone healing. Clinical trials are encouraging, with meta-analysis of results revealing better rates of healing than treatment with autologous bone grafting (risk ratio [RR]: 0.845; 95% confidence interval [CI]: 0.772 - 0.924; p < 0.001 for clinical outcome and RR: 0.884; 95% CI: 0.825 - 0.948; p < 0.001 for radiological outcome). Preclinical and clinical safety assessments have revealed little evidence of toxic effects and there have been few reports of adverse events related to their use. A small rate of immunological reaction following administration, resulting in antibody formation, has been observed in some patients, without clinical consequence, although the long-term implications of this are unknown. Ongoing research is revealing that BMPs act on an extremely wide range of body tissues in a variety of manners and this is far from fully understood. It should be noted, however, that given the role of BMP as a differentiation factor, the production of undifferentiated neoplastic tissue seems unlikely. It has also been shown in an animal model that artificially administered BMP can cross the placenta and subsequently be detected in the growing embryo. As this area has been little investigated, use in pregnancy is currently contraindicated. Until the long-term safety profile is more fully documented it would seem sensible to continue to carefully control use and monitor patients closely. However, the current evidence is very promising.

gamma-Tocopherol, commonly found in seed oils, is the major tocopherol in the U.S. diet, is superior to alpha-tocopherol in preventing neoplastic transformation, and demonstrates unique reactivity toward NO2. This article describes the products of reaction between gamma-tocopherol and low concentrations of gaseous nitrogen dioxide (NO2), as well as their endogenous formation in NO-producing RINm5F cells. gamma-Tocopherol in hexane reacts with NO2 to yield two products identified as 2,7,8-trimethyl-2(4,8,12-trimethyltridecyl)-5,6-chromaquinone++ +, "tocored," and 2,7,8 trimethyl-2(4,8,12-trimethyltridecyl) 5-nitro, 6-chromanol, "tocoyellow." Physical data for these two compounds and reaction characteristics are described. The formation of tocored is consistent with a proposed mechanism of gamma-tocopherol-mediated reduction of NO2 to NO involving initial reaction by NO2 at the C-5 position to form an intermediate nitrite ester tocopheryl radical, which then reacts internally to release NO and form 5,6 epoxy gamma-tocopherol. Tautomerization and further oxidation of the latter intermediate by NO2 yields tocored as the main product observed. The reaction of gamma-tocopherol with NO2 to form NO occurs independently of light, whereas alpha-tocopherol requires light to generate NO from NO2. gamma-Tocopherol and aminoguanidine, an NO synthase inhibitor, were superior to alpha-tocopherol in preventing RINm5F cell toxicity induced by Interleukin-1 beta (IL-1 beta). Both tocored and tocoyellow were observed to form in RINm5F cells loaded with gamma-tocopherol and producing NO constitutively, although a consistent increase in these products as a result of induced NO synthesis was not observed.

Plasma samples were collected at monthly intervals for a period of 1 year from a group of healthy nonsmoking men and women (n = 21) living in Honolulu, HI. Analysis of plasma cholesterol and triglyceride levels showed marked seasonal variations, with higher mean levels in winter months and lower values in the summer. Cholesterol and triglycerides were highly and inversely correlated with plasma levels of the provitamin A carotenoids. Mean beta- and alpha-carotene levels were highest in late summer and fall. Plasma retinol levels were significantly lower in the summer and higher in the winter. Variations (either between individuals or seasonally) in plasma retinol were unrelated to plasma provitamin A carotenoid levels. Plasma levels of alpha-tocopherol, gamma-tocopherol, beta-cryptoxanthin, and lutein were also higher in the winter and lower in the summer. Significant seasonal correlations, both positive and negative, with environmental variables, such as temperature, solar UV radiation, and rainfall, are noted for many of these plasma micronutrients. The number of samples required to accurately characterize long-term plasma levels for an individual generally ranged from 1 to 4. However, plasma retinol levels exhibited the highest ratio of intra- to interindividual variability, suggesting the need for multiple sampling (> 8 samples) for this micronutrient. Some of this variability for retinol was associated with seasonal changes. Assessment by a diet history of food and supplement intake of micronutrients and phytochemicals for 1 year showed good agreement with 1-year mean plasma levels for most carotenoids, vitamin C, and alpha-tocopherol. Retinol, gamma-tocopherol, cholesterol, and triglyceride levels in plasma were unrelated to estimates of dietary intake.(ABSTRACT TRUNCATED AT 250 WORDS)

Plants are more susceptible to the toxic effects of nitrogen dioxide when exposure takes place in the dark. Beta-carotene and other common carotenoids react with nitrogen dioxide in the dark to yield intermediate nitrosating agents consistent with the formation of nitrate esters. Simultaneous exposure of carotenoids to NO2 and light significantly reduced formation of nitrosating intermediates and resulted in the release of nitric oxide (NO) into the gas phase. Light-mediated reduction of NO2 to NO by carotenoids may be an important mechanism for preventing damage in plants exposed to NO2. The formation of nitrosating agents from the reaction of carotenoids with NO2 suggests that their ability to prevent nirosative damage associated with NO2 exposure in both plants and animals may be limited in the absence of light.

Plasma levels of triglycerides, retinol, cholesterol, lipid-phase antioxidants (alpha-, gamma-tocopherols, beta-carotene, alpha-carotene, lycopene, beta-cryptoxanthin and lutein/zeaxanthin), and thiobarbituric acid-reactive substances (TBA-RS), as an indicator of lipid peroxidation, were repeatedly determined in nine individuals over a 3-month period. Levels of TBA-RS were positively correlated with plasma triglycerides and gamma-tocopherol, and negatively correlated with plasma carotenoids. These results were consistent with in vitro cell culture studies which showed increased TBA-RS for cells supplemented with linolenic acid and decreased levels when treated with beta-carotene. We conclude that TBA-RS measurements in plasma accurately reflect the level of peroxidizable substrate as modified by the presence of a variety of dietary antioxidants, particularly carotenoids. Although the inter- and intra-individual variabilities for TBA-RS are comparable with the micronutrients and antioxidants measured in this study, high interassay variability and the strong association with the more commonly measured plasma triglycerides suggest the TBA-RS assay to be of limited use in epidemiologic studies. However, this assay does appear to be useful in cell culture studies where experimental conditions can be better controlled. Low ratios of inter- to intra-individual variability in some of the plasma micronutrient and lipid-phase antioxidants measured suggest that multiple samples may be required to characterize individuals in studies evaluating the relation between these plasma constituents and disease incidence.

In the vitamin E group, alpha-tocopherol is generally considered to be the most potent antioxidant with the highest vitamin bioactivity, yet gamma-tocopherol is produced in greater amounts by many plants and is the principal tocopherol in the United States diet. This report describes a fundamental difference in the chemical reactivities of alpha-tocopherol and gamma-tocopherol with nitrogen dioxide (NO2), which leads to the formation of a nitrosating agent from alpha-tocopherol, but not from gamma-tocopherol. Nitric oxide (NO) is a major product of the reaction of gamma-tocopherol with NO2, while alpha-tocopherol reacts with NO2 to form an intermediate tocopheroxide analogue. The biological significance of gamma-tocopherol is suggested by limited epidemiological data as well as the observation that it is a more potent inhibitor than alpha-tocopherol of neoplastic transformation during the postinitiation phase in 3-methylcholanthrene-treated C3H/10T1/2 murine fibroblasts. This latter property suggests the superiority of gamma-tocopherol in a mammalian biological assay and a role for endogenous NO production in promotion of neoplastic transformation.

Triphenylmethane (TPM) was found to inhibit 3-methyl-cholanthrene-induced neoplastic transformation of 10T1/2 cells in a dose-dependent manner (ED50 = 2.8 microM). This activity was independent of any effect on intercellular communication and did not appear to be directly related to the general antioxidant properties of TPM as measured by cellular thiobarbituric acid-reactive substances. Triphenylmethanol (TPMOL) and diphenylmethane also inhibited transformation (ED50 = 6.9 and 90 microM respectively). TPM had no effect on the proliferation of exponentially growing cells. At higher concentrations TPM and its analogues enhanced plating efficiency of cells indicating no significant toxicity for these compounds at levels up to 50 microM. The inhibitory effects of TPM on transformation were reversible when TPM was removed from the medium. While TPM had no effect on the growth of fully transformed cell lines, it was able to inhibit the growth of 1/3 neoplastic foci in the presence (but not absence) of 10T1/2 cells. TPM was found to stimulate protein kinase C (PKC) activity for both crude C3H10T1/2 cytosolic PKC and purified PKC obtained from rat brain. The ability of TPM to stimulate PKC activity appeared to be dependent on [CaCl2] and the order of reagent addition in the assay. Tamoxifen, a structurally related compound to TPM, was also found to enhance PKC activity over the same concentration range but was less potent than TPM. The biological effects of TPM and related compounds indicate that they function in a manner distinct from other highly unsaturated transformation inhibitors such as carotenoids and retinoids. The inability of triphenylene to inhibit transformation suggests that a reactive methyl carbon may be essential for activity.

The dynamics of distribution of radiolabelled F(ab')2 fragments of a monoclonal anti-CEA antibody have been studied in the nude mouse bearing a CEA-producing human colon carcinoma. Our results showed that the fragment was rapidly cleared from all normal organs reaching about 1% of that injected by 24 hr. Specific tumour localization occurred as early as 2 hr after injection and was complete by 4 hr. The amount of fragment localized in tumour was 4% of the injected dose, equivalent to that obtained with the intact antibody. Greatly improved tumour:normal tissue ratios were obtained with the fragment compared to intact IgG. However, the residence time of the fragment was much shorter (24 hr) than that of intact antibody (more than 3 days). Tumour localization indices suggested that fragments were superior to intact IgG at locating tumour specifically. The specificity indices based on lung, spleen and liver were much higher than those for intact antibody, reflecting the lack of Fc-receptor binding of fragments and their reduced excretion by these organs. The 'fragment index' enabled tumour:normal tissue ratios for the fragment and intact IgG to be compared. Together with the distribution study at different time points, this simplifies the task of defining a 'time window' in which tumour imaging and therapy might be optimal.

The specific activity of argininosuccinate synthetase (micromoles of 14CO2 per milligram of protein per hour) was 0.00104 and 0.00087 in fibroblasts derived from two patients with citrullinemia, and was undetectable in both fibroblasts and cultured lymphocytes from a third patient. In five obligate heterozygotes the specific activity in fibroblasts was 0.012-0.029 and in nine control subjects was 0.058 +/- 0.014 (0.030-0.076). In both control and patient cells, the maximum activity was obtained at pH 8.5 and there was no inhibition of normal argininosuccinate synthetase by any of the mutant cells.

The relationship between tumour size and the uptake of three radiolabelled anti-CEA localising antibodies (A5B7, 1H12 and PK2G) into a human colon tumour xenograft (MaWi) has been examined. For tumour weights greater than 100 mg (109-873 mg) there was a strong positive correlation between absolute uptake and tumour weight with mean uptakes per gram of 9.8 (r = 0.92), 5.0 (r = 0.93) and 5.3 (r = 0.94) for A5B7, 1H12 and PK2G respectively. For tumour weights below 100 mg (17-99 mg) the percentage uptake per gram (specific uptake) increased markedly reaching 80% of the injected dose for A5B7. The above phenomena could be modelled by representing uptake by the surface area of a sphere and tumour weight by its volume. Transformation of this model produced a linear relationship suitable for regression analysis of the experimental data. The slopes of the regression lines for the three antibodies were very close to that predicted by the model suggesting that their uptake into MaWi xenografts is proportional to surface area. The main discrepancy of the actual data was shown by the intercepts which relate to the variation in uptake between different antibodies. This model provides a possible means of correcting for the effect of tumour size when investigating the uptake of antibodies into xenografts.

A new monoclonal anti-CEA antibody (1H12) has been raised which has localising characteristics in a human colon tumour xenograft which could make it suitable for human immuno-radiotherapy. The amount of 1H12 localising in tumour reached about 5% of the injected dose by 7 hours. This rate appeared to be related to the concentration of 1H12 in the blood pool since non-excretory normal organs such as colon and stomach accumulated similar amounts up to 4 hours. Whereas 1H12 was lost from normal organs after 4 hours, the amount in the tumour continued to increase slightly reaching a maximum concentration of 6.5% of the injected dose by day 9. Prolonged retention of 1H12 in tumour enabled increasing tumour: normal tissue ratios to be attained during the residence time of the antibody thus providing scope for maximising the dose of radiation delivered to tumour cells. Preliminary dose escalation showed that up to 500 micrograms of 1H12 could be administered with increasing concentrations of antibody localising in tumour. Saturation of the tumour site was evident in only one mouse where 1.09 micrograms of 1H12 actually localised--equivalent to 60 micrograms per gram of tumour.

A monoclonal anti-CEA antibody (1H12) has been examined for the effect of dosage on tumour localisation in immunodeprived mice xenografted with human colon carcinoma. Increased doses produced a linear rise in the absolute concentration found in the tumour but this was found to depend on tumour size, with the smaller tumours (mean weight 44 mg) accumulating significantly more antibody compared to larger tumours (mean weight 146 mg). With the smallest tumour (18 mg), in which saturation was achieved, a 500 micrograms dose produced a concentration in tumour of 60 micrograms/g. In the larger tumours a dose of 256 micrograms produced a mean concentration of 5.2 micrograms/g. Prolonged retention of 1H12 by tumour up to 8 days, observed at doses of 4, 128 and 256 micrograms, indicated that the dynamics of localisation is unaffected by dosage. Increased doses of 125I-1H12 caused an increase in the levels of radioactivity associated with all normal tissues studied. Thus at 8 days after injection an increase from 4 to 128 micrograms produced 50% and 42% declines in the tumour to blood and liver ratios, respectively. Cumulative localisation of 1H12 in tumour, from 4 h to 8 days, relative to normal tissue clearance was diminished on increasing dosage. This study shows that attempted therapy with escalated amounts of intact antibody is likely to be limited by a protracted excretory process and measures aimed at accelerating circulatory clearance are necessary.

A method of epitope analysis is described in which the binding of one monoclonal antibody (MAb) to radiolabeled carcinoembryonic antigen (CEA) competes with the subsequent binding of an immobilised second MAb. From the degree of blocking obtained, we have identified both structurally related and independent epitopes on CEA. Using this technique to study fifteen MAbs, we have been able to recognise at least 6 unrelated epitopes of the CEA glycoprotein. Further characterisation of these epitopes was accomplished by means of immunohistochemistry. Of the fifteen MAbs, 6 were specific for CEA and reacted with at least 3 unrelated regions of the glycoprotein. Of the remaining 9 MAbs, 2 cross-reacted with erythrocytes, 5 with components of liver and 7 with polymorphonuclear neutrophils. Cross-reactions with liver were varied showing differential antibody specificity for bile canaliculi, Kupffer cells and bile duct epithelium. A high degree of correlation between epitope relatedness and immunohistochemical specificity was found. Two CEA-specific and 4 cross-reactive MAbs were also shown to react with ion-sensitive sites on the CEA glycoprotein.

The significance of circulatory clearance of tumour-localising IgG and F(ab')2 for potential cancer therapy has been studied in immunodeprived mice bearing a carcinoembryonic antigen (CEA)-producing colon tumour. Intact radiolabelled anti-CEA (1H12) exhibited a prolonged localisation in tumour up to 8 days with injected doses between 4 and 256 g. Increased dosage caused a rise in the absolute concentration in tumour which, for the highest dose, reached 5.1 micrograms/g at 3 days after injection. A concomitant increase in concentration of 1H12 in blood occurred, which with the highest dose, remained above that in the tumour up to 7 days after injection. With F(ab')2 fragments (prepared from anti-CEA, 1C12) increased doses up to 380 micrograms also resulted in an increased uptake in tumour reaching almost 3 micrograms/g for a 234-micrograms dose. Circulatory clearance of F(ab')2-1C12 was essentially complete by 2 days for all doses up to 234 micrograms. Differences in clearance between 1H12 and F(ab')2-1C12 were reflected in the tumour to blood ratios. For high doses of 1H12 this ratio did not exceed unity up to 8 days. With F(ab')2, however, the tumour to blood ratio remained unaffected by dosage after 2 days. Our data suggest that F(ab')2 fragments clear sufficiently quickly to allow compensation by dosage for their premature escape from tumour. Therapeutic administration of intact antibody, however, appears to be limited by a protracted excretory process.