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Conditions and thresholds applied for evidence weighting of within-codon concordance (PM5) for pathogenicity vary widely between laboratories and expert groups. Because of the sparseness of available clinical classifications, there is little evidence for variation in practice.

Systemic antibiotics reduce infection in open fractures. Local delivery of antibiotics can provide higher doses to wounds without toxic systemic effects. This study investigated the effect on infection of combining systemic with local antibiotics via polymethylmethacrylate (PMMA) beads or gel delivery.An established Staphylococcus aureuscontaminated fracture model in rats was used. Wounds were debrided and irrigated six hours after contamination and animals assigned to one of three groups, all of which received systemic antibiotics. One group had local delivery via antibiotic gel, another PMMA beads and the control group received no local antibiotics. After two weeks, bacterial levels were quantified. Combined local and systemic antibiotics were superior to systemic antibiotics alone at reducing the quantity of bacteria recoverable from each group (p = 0.002 for gel; p = 0.032 for beads). There was no difference in the bacterial counts between bead and gel delivery (p = 0.62). These results suggest that local antibiotics augment the antimicrobial effect of systemic antibiotics. Although no significant difference was found between vehicles, gel delivery offers technical advantages with its biodegradable nature, ability to conform to wound shape and to deliver increased doses. Further study is required to see if the gel delivery system has a clinical role.Cite this article: Bone Joint J2015;97-B:1423–7.

This is a retrospective study of survivors of recent conflicts with an open fracture of the femur. We analysed the records of 48 patients (48 fractures) and assessed the outcome. The median follow up for 47 patients (98%) was 37 months (interquartile range 19 to 53); 31 (66%) achieved union; 16 (34%) had a revision procedure, two of which were transfemoral amputation (4%).The New Injury Severity Score, the method of fixation, infection and the requirement for soft-tissue cover were not associated with a poor outcome. The degree of bone loss was strongly associated with a poor outcome (p = 0.00204). A total of four patients developed an infection; two with S. aureus, one with E. coliand one with A. baumannii.This study shows that, compared with historical experience, outcomes after open fractures of the femur sustained on the battlefield are good, with no mortality and low rates of infection and late amputation. The degree of bone loss is closely associated with a poor outcome.Cite this article: Bone Joint J2015;97-B:842–6.

ObjectivesSevere extremity injuries are the most significant injury sustained in combat wounds. Despite optimal clinical management, non-union and infection remain common complications. In a concerted effort to dovetail research efforts, there has been a collaboration between the UK and USA, with British military surgeons conducting translational studies under the auspices of the US Institute of Surgical Research. This paper describes 3 years of work.MethodsA variety of studies were conducted using, and developing, a previously validated rat femur critical-sized defect model. Timing of surgical debridement and irrigation, different types of irrigants and different means of delivery of antibiotic and growth factors for infection control and to promote bone healing were investigated.ResultsEarly debridement and irrigation were independently shown to reduce infection. Normal saline was the most optimal irrigant, superior to disinfectant solutions. A biodegradable gel demonstrated superior antibiotic delivery capabilities than standard polymethylmethacrylate beads. A polyurethane scaffold was shown to have the ability to deliver both antibiotics and growth factors.DiscussionThe importance of early transit times to Role 3 capabilities for definitive surgical care has been underlined. Novel and superior methods of antibiotic and growth factor delivery, compared with current clinical standards of care, have been shown. There is the potential for translation to clinical studies to promote infection control and bone healing in these devastating injuries.

This is a case series of prospectively gathered data characterising the injuries, surgical treatment and outcomes of consecutive British service personnel who underwent a unilateral lower limb amputation following combat injury. Patients with primary, unilateral loss of the lower limb sustained between March 2004 and March 2010 were identified from the United Kingdom Military Trauma Registry. Patients were asked to complete a Short-Form (SF)-36 questionnaire. A total of 48 patients were identified: 21 had a trans-tibial amputation, nine had a knee disarticulation and 18 had an amputation at the trans-femoral level. The median New Injury Severity Score was 24 (mean 27.4 (9 to 75)) and the median number of procedures per residual limb was 4 (mean 5 (2 to 11)). Minimum two-year SF-36 scores were completed by 39 patients (81%) at a mean follow-up of 40 months (25 to 75). The physical component of the SF-36 varied significantly between different levels of amputation (p = 0.01). Mental component scores did not vary between amputation levels (p = 0.114). Pain (p = 0.332), use of prosthesis (p = 0.503), rate of re-admission (p = 0.228) and mobility (p = 0.087) did not vary between amputation levels.These findings illustrate the significant impact of these injuries and the considerable surgical burden associated with their treatment. Quality of life is improved with a longer residual limb, and these results support surgical attempts to maximise residual limb length.Cite this article: Bone Joint J2013;95-B:224–9.

The aim of this study was to report the pattern of severe open diaphyseal tibial fractures sustained by military personnel, and their orthopaedic–plastic surgical management.The United Kingdom Military Trauma Registry was searched for all such fractures sustained between 2006 and 2010. Data were gathered on demographics, injury, management and preliminary outcome, with 49 patients with 57 severe open tibial fractures identified for in-depth study. The median total number of orthopaedic and plastic surgical procedures per limb was three (2 to 8). Follow-up for 12 months was complete in 52 tibiae (91%), and half the fractures (n = 26) either had united or in the opinion of the treating surgeon were progressing towards union. The relationship between healing without further intervention was examined for multiple variables. Neither the New Injury Severity Score, the method of internal fixation, the requirement for vascularised soft-tissue cover nor the degree of bone loss was associated with poor bony healing. Infection occurred in 12 of 52 tibiae (23%) and was associated with poor bony healing (p = 0.008). This series characterises the complex orthopaedic–plastic surgical management of severe open tibial fractures sustained in combat and defines the importance of aggressive prevention of infection.Cite this article: Bone Joint J2013;95-B:101–5.

Most animal studies indicate that early irrigation and debridement reduce infection after an open fracture. Unfortunately, these studies often do not involve antibiotics. Clinical studies indicate that the timing of initial debridement does not affect the rate of infection but these studies are observational and fraught with confounding variables. The purpose of this study was to control these variables using an animal model incorporating systemic antibiotics and surgical treatment.We used a rat femur model with a defect which was contaminated with Staphylococcus aureusand treated with a three-day course of systemic cefazolin (5 mg/kg 12-hourly) and debridement and irrigation, both of which were initiated independently at two, six and 24 hour time points. After 14 days the bone and hardware were harvested for separate microbiological analysis.No animal that received antibiotics and surgery two hours after injury had detectable bacteria. When antibiotics were started at two hours, a delay in surgical treatment from two to six hours significantly increased the development of infection (p = 0.047). However, delaying surgery to 24 hours increase the rate of infection, but not significantly (p = 0.054). The timing of antibiotics had a more significant effect on the proportion of positive samples than earlier surgery. Delaying antibiotics to six or 24 hours had a profoundly detrimental effect on the infection rate regardless of the timing of surgery. These findings are consistent with the concept that bacteria progress from a vulnerable planktonic form to a treatment-resistant biofilm.

Aim: To define the components and organization of a modern leg ulcer service that is acceptable to patients cost effective and produces high quality outcomes.Method: Analysis of data from published literature as well as experience from the organisation of a leg ulcer service in Gloucestershire.Synthesis: Assessment of leg ulcers requires the services of a vascular laboratory to assess the venous and arteria systems. Effective systems of compression must be employed. Staff and patients must be educated to understand the principals behind their use. For some patients pinch-grafting may be appropriate. Where arterial disease is present in the lower limb, reconstructive surgery should be used for the lower limb vessels The organisation of such a service must ensure good liaison between General Practitioners, community nurses and hospital specialists. Many patients may be managed in community leg ulcer clinics. In some cases, the advice of specialists such as rheumatologists and dermatologists may be required.Conclusions: A national framework for leg ulceir management is needed within which resources are made available in a way that satisfy local needs. Such a framework must be based on management protocols derived from evidence-based practices that have been developed through the experiences of modern leg ulcer services.

Objective: To identify independent risk factors for delayed healing and increased recurrence of chronic venous leg ulcers.Design: Prospective study.Setting: Community-based leg ulcer service.Patients: Six hundred and thirty-three limbs in 587 consecutive patients with an ankle-brachial pressure index (ABPI) ≥0.85.Method: Potential risk factors were initially assessed in a one-stop clinic incorporating clinical evaluation, ABPI and venous duplex imaging. Limbs were treated within a defined protocol. Twenty-four-week healing and 3-year ulcer recurrence rates were determined.Results: Of 12 potential risk factors age (p< 0.001), ulcer chronicity (p< 0.001) and popliteal vein reflux (p< 0.005) were independent risks for delayed healing. Of 13 potential risk factors rheumatoid arthritis (p<0.005) and healing time (p< 0.05) were independent risks for ulcer recurrence. Isolated superficial venous reflux treated by saphenous vein surgery predicted reduced ulcer recurrence (p< 0.005).Conclusion: Targeting in primary care of ulcer patients with specific characteristics might encourage earlier referral and appropriate resource management. Leg ulcer patients with superficial venous reflux might benefit from surgical correction.

The Epstein-Barr virus nuclear antigen (EBNA) 1 binds to and activates DNA replication from the latent origin of Epstein-Barr virus. Six different fragments of EBNA1 that retain DNA binding activity were expressed in bacteria, purified, and crystallized. Two fragments, EBNA470-619 and EBNA470-607, formed well ordered crystals that diffracted beyond 2.5-A resolution. Two different EBNA470-619 crystals were grown from sodium formate, pH 6-6.5. One crystal belonged to the trigonal space group P3 with unit cell dimensions a = b = 86.5 A and c = 31.8 A and with two molecules in the asymmetric unit. The other crystal, which appeared only twice and was likely related to the P3 crystal form, belonged to the trigonal space group P312 with cell dimensions a = b = 86.7 A and c = 31.8 A. Crystals of EBNA470-607 were grown by lowering the salt concentration to 0-100 mM NaCl at pH 6.0. These crystals belonged to the orthorhombic space group P2(1)2(1)2(1) and had cell dimensions a = 59 A, b = 66.9 A, and c = 69.8 A with two molecules in the asymmetric unit.

The EBNA1 protein of Epstein-Barr virus (EBV) activates DNA replication by binding to multiple copies of its 18-bp recognition sequence present in the Epstein-Barr virus latent origin of DNA replication, oriP. Using electrophoretic mobility shift assays, we have localized the minimal DNA binding domain of EBNA1 to between amino acids 470 and 607. We have also demonstrated that EBNA1 assembles cooperatively on the dyad symmetry subelement of oriP and that this cooperative interaction is mediated by residues within the minimal DNA binding and dimerization domain of EBNA1.

We studied the effects of the timing of tourniquet release in 88 patients randomly allocated for release after wound closure and bandaging (group A), or before the quadriceps layer had been closed allowing control of bleeding before suture (group B). The groups were similar in mean age, weight, gender, preoperative knee score, radiographic grading, and prosthesis implanted.Patients in group B had less postoperative pain, achieved earlier straight-leg raising, and had fewer wound complications. Five patients in group A had to return to theatre, three for manipulation under anaesthesia, one for secondary closure of wound dehiscence, and one for drainage of a haematoma. The last patient later developed a deep infection, which was treated by a two-stage revision. There were no significant differences between the two groups in operating time, or the decrease in haemoglobin concentration at 48 hours postoperatively.Some of the adverse effects of the use of a tourniquet for knee surgery can be significantly reduced by early tourniquet release, with haemostasis before the quadriceps mechanism and the wound are closed.

Objective: To investigate the effect of ankle motility on chronic venous leg ulcer healing, and to relate this to calf pump function and muscle bulk.Methods: This was a prospective cohort study undertaken in a leg ulcer clinic. Ankle motility, calf-ankle circumference ratio and calf pump power (derived from digital photoplethysmography) were assessed as to their effect on ulcer healing rate. Thirty consecutive patients undergoing multi-layer compression bandaging for open chronic venous ulcers were included.Results: Ankle motility was an independent risk factor for ulcer healing (p= 0.001, hazard ratio 1.08, 95% CI 1.03–1.13). Ankle motility correlated with calf-ankle circumference ratio (r= 0.48, p<0.01). No relationship was found between photoplethysmography-derived calf pump power, ankle motility or ulcer healing rate.Conclusions Ulcers in legs with poor ankle motility are slower to heal and this may be related to reduced calf muscle bulk. Ankle exercises or physiotherapy could be considered in such patients.

This paper describes the use of the Neurosign 100 Nerve Monitor and vagus nerve stimulation in the identification and assessment of the integrity of the recurrent laryngeal nerve (RLN) during thyroid and parathyroid surgery.Vocal fold function was assessed pre- and post-operatively in all patients undergoing thyroid and parathyroid surgery. The nerve monitor, used in association with endotracheal electrodes, was used to confirm correct RLN identification and demonstrate its integrity at the completion of surgery.There were 21 unilateral and 19 bilateral neck explorations. In these 40 patients, 57 of 59 RLNs were identified. The nerve monitor demonstrated RLN continuity in all but one case (equipment failure: electrode misplacement) after initial identification. Vagus nerve stimulation was performed in 21 patients without adverse sequelae. Damage to the RLN was identified in one of these patients, in whom direct RLN stimulation close to the larynx had failed to indicate discontinuity. Post-operatively this patient had a transient unilateral vocal fold palsy.The use of the Neurosign 100 Nerve Monitor is no substitute for meticulous surgery. Stimulation of the vagus nerve may be a more sensitive means of assessing RLN integrity during thyroid and parathyroid surgery than stimulation of the RLN itself. Confirmation of RLN integrity allows the surgeon to proceed with confidence to the contralateral side of the neck during hazardous bilateral explorations.

We present a case of life-threatening retroperitoneal sepsis after injection sclerotherapy for first-degree hemorrhoids.

A 2‐year‐old boy presented with a suspected urethrocutaneous fistula. He had been born at 26 wk gestation and spent 14 wk in the special care baby unit with severe respiratory problems and an episode of meningitis. He had not had a urinary catheter in situ or urinary tract infections. Bilateral inguinal hernias had been repaired. At presentation he was below the 3rd centile for height and weight but had reached all other developmental milestones.