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Objective: In this feasibility study, firstly, we aimed to assess whether intramuscular pH (IMpH) could be measured with a glass-tipped electrode. Secondly, we aimed to explore whether we could monitor changes in skeletal muscle pH before and throughout static (isometric) and after dynamic (treadmill) exercise, comparing individuals with intermittent claudication (IC) to a group of healthy controls., Methods: Forty participants with IC (mean age ± SD) 68 ± 8) and 40 healthy volunteers (63 ± 10) were recruited. Participants in the IC group had an ankle brachial pressure index of <0.7 (mean: 0.62 ± 0.13). The first 20 participants in each group underwent isometric ankle dorsiflexion for 120 s at 30% of maximum voluntary contraction and the remainder underwent treadmill exercise (3.6 km/h, 5° incline) to maximal walking distance. A sterilised reusable 1.5 mm shatterproof, heat strengthened glass tipped pH probe inserted using a peripheral venous cannula and in combination with a pH meter was used to measure IMpH of the tibialis anterior muscle prior to, during and continuously for 1 h after exercise., Results: Resting IMpH was similar between the groups (median 6.8 (interquartile range (IQR) 6.7-6.9)) for IC individuals and 6.7 (6.6 to 6.8) for controls). Following isometric exercise, the magnitude of the decrease in IMpH was greatest in the IC group (median ΔpH max. in patients -0.2 (IQR: -0.2 to -0.1) versus -0.1 (IQR: -0.2 to -0.1) in the control group ( p =  0.002). After treadmill exercise, the magnitude of the decrease in IMpH (ΔpH max) was greatest in individuals with IC (median ΔpH max. in patients -0.3 (IQR: -0.3 to -0.3) versus 0 (IQR: -0.2 to 0) in the control group, p =  0.04., Conclusions: IMpH monitoring with a flexible glass probe inserted into the tibialis anterior muscle is viable and changes in IMpH during static and dynamic exercises are detected., Competing Interests: Declaration of conflicting interestsThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Aims: Complete ruptures of the ulnar collateral ligament (UCL) of the thumb are a common injury, yet little is known about their current management in the UK. The objective of this study was to assess the way complete UCL ruptures are managed in the UK., Methods: We carried out a multicentre, survey-based cross-sectional study in 37 UK centres over a 16-month period from June 2022 to September 2023. The survey results were analyzed descriptively., Results: A total of 37 centres participated, of which nine were tertiary referral hand centres and 28 were district general hospitals. There was a total of 112 respondents (69 surgeons and 43 hand therapists). The strongest influence on the decision to offer surgery was the lack of a firm 'endpoint' to stressing the metacarpophalangeal joint (MCPJ) in either full extension or with the MCPJ in 30° of flexion. There was variability in whether additional imaging was used in managing acute UCL injuries, with 46% routinely using additional imaging while 54% did not. The use of a bone anchor was by far the most common surgical option for reconstructing an acute ligament avulsion (97%, n = 67) with a transosseous suture used by 3% (n = 2). The most common duration of immobilization for those managed conservatively was six weeks (58%, n = 65) and four weeks (30%, n = 34). Most surgeons (87%, n = 60) and hand therapists (95%, n = 41) would consider randomizing patients with complete UCL ruptures in a future clinical trial., Conclusion: The management of complete UCL ruptures in the UK is highly variable in certain areas, and there is a willingness for clinical trials on this subject., Competing Interests: B. J. F. Dean and M.Mikhail report a British Society for Surgery of the Hand (BSSH) pump priming grant for this study. B. J. F. Dean also reports a British Medical Association Doris Hillier grant which was unrelated to this study. B. J. F. Dean is also a member of the BSSH research committee. D. J. Beard holds a Senior Investigator grant from the National Institute for Health and Care Research, unrelated to this study. M. Mikhail reports a BSSH grant to the ULCTEAR steering group for this study, allocated under his name. N. Riley reports consulting fees from Acumend, Arthrex, and Meshworks, unrelated to this study., (© 2024 Mikhail et al.)

This paper describes a modification of the traditional fascial tongue surgical approach to the distal humerus. In particular, we describe the reflection and utilisation of radial and ulnar triceps bundles to allow complete visualisation of the distal humerus. This extensile technique allows access to the entirety of the distal humerus and provides excellent visualisation to the operating surgeon. Indications for the surgical approach include open reduction with internal fixation of fractures (both intra- and extra-articular) and total elbow replacement. Whilst standard approaches to the distal humerus are well described, this modification describes a new surgical approach that improves access and visualisation of the traditional fascial tongue technique. Alternative approaches to improve visualisation include an olecranon osteotomy; the triceps bundle modification allows excellent exposure to the distal humerus whilst avoiding complications associated with an olecranon osteotomy. The surgical technique is illustrated with intra-operative photographs, which aim to aid in guiding the surgeon in undertaking critical steps of this approach., How to Cite This Article: Rankin IA, Dixon J, Goffin J, et al. A Modified Surgical Approach to the Distal Humerus: The Triceps Bundle Technique. Strategies Trauma Limb Reconstr 2024;19(2):99-103., Competing Interests: Source of support: Nil Conflict of interest: NoneConflict of interest: None, (Copyright © 2024; The Author(s).)

Objectives: To assess fracture union rates using novel intramedullary plate technique. Post-operative humeral neck-shaft angles, patient range of motion and complication profile were secondary outcomes of interest., Methods: Single surgeon, retrospective case series of surgical technique at major trauma centre in Scotland. A 2.0mm mini-fragment plate was secured to the humeral head to act as an intramedullary strut during fixation in complex proximal humerus fractures. Fracture union and neck-shaft angle were assessed radiologically, whilst range of motion and complication profiles were assessed clinically., Results: Twelve patients were followed up for an average of 10 months post-operatively. All achieved bony union with a mean neck-shaft angle of 128°. Mean range of motion values were 100° forward elevation, 83° abduction, 60° internal rotation and 37° external rotation. Four patients required further surgical intervention- two for hardware prominence, one for adhesive capsulitis and one for subsequent rotator cuff failure. There were no cases of avascular necrosis or infection., Conclusion: This novel technique addresses the established biomechanical propensity of proximal humerus fractures to fail in varus collapse and screw cut-out. This method provides an alternative to arthroplasty in the most severe proximal humerus fractures and is readily adopted via standard orthopaedic kit., Competing Interests: None, (2024 © BY THE ARCHIVES OF BONE AND JOINT SURGERY.)

Introduction: The recent past has seen a significant increase in the number of trauma and orthopaedic randomised clinical trials published in "the big five" general medical journals. The quality of this research has, however, not yet been established., Methods: We therefore set out to critically appraise the quality of available literature over a 10-year period (April 2010-April 2020) through a systematic search of these 5 high-impact general medical journals (JAMA, NEJM, BMJ, Lancet and Annals). A standardised data extraction proforma was utilised to gather information regarding: trial design, sample size calculation, results, study quality and pragmatism. Quality assessment was performed using the Cochrane Risk of Bias 2 tool and the modified Delphi list. Study pragmatism was assessed using the PRECIS-2 tool., Results: A total of 25 studies were eligible for inclusion. Over half of the included trials did not meet their sample size calculation for the primary outcome, with a similar proportion of these studies at risk of type II error for their non-significant results. There was a high degree of pragmatism according to PRECIS-2. Non-significant studies had greater pragmatism that those with statistically significant results (p < 0.001). Only 56% studies provided adequate justification for the minimum clinically important difference (MCID) in the population assessed. Overall, very few studies were deemed high quality/low risk of bias., Conclusions: These findings highlight that there are some important methodological concerns present within the current evidence base of RCTs published in high-impact medical journals. Potential strategies that may improve future trial design are highlighted., Level of Evidence: Level 1., (© 2021. The Author(s).)

Aims: Tourniquets have potential adverse effects including postoperative thigh pain, likely caused by their ischaemic and possible compressive effects. The aims of this preliminary study were to determine if it is possible to directly measure intramuscular pH in human subjects over time, and to measure the intramuscular pH changes resulting from tourniquet ischaemia in patients undergoing knee arthroscopy., Methods: For patients undergoing short knee arthroscopic procedures, a sterile calibrated pH probe was inserted into the anterior fascial compartment of the leg after skin preparation, but before tourniquet inflation. The limb was elevated for three minutes prior to tourniquet inflation to 250 mmHg or 300 mmHg. Intramuscular pH was recorded at one-second intervals throughout the procedure and for 20 minutes following tourniquet deflation. Probe-related adverse events were recorded., Results: A total of 27 patients were recruited to the study. Mean tourniquet time was 21 minutes (10 to 56). Tourniquet pressure was 300 mmHg for 21 patients and 250 mmHg for six patients. Mean muscle pH prior to tourniquet inflation was 6.80. Muscle pH decreased upon tourniquet inflation, with a steeper fall in the first ten minutes than for the rest of the procedure. Change in muscle pH was significant after five minutes of tourniquet ischaemia (p < 0.001). Mean muscle pH prior to tourniquet release was 6.58 and recovered to 6.75 within 20 minutes following release. No probe related adverse events were recorded., Conclusion: It is possible to directly measure skeletal muscle pH in human subjects over time. Tourniquet ischaemia results in a decrease in human skeletal muscle pH over time during short procedures. Cite this article: Bone Joint Res  2021;10(6):363-369.

Purpose: We present the Aberdeen Weight-Bearing Test (Knee), an objective test specific for anterior knee discomfort assessed via load bearing. We assess its validity by performing it on normal subjects with no knee symptoms and subjects who had undergone anterograde tibial nailing., Methods: Two scales are placed parallel on the floor with the dials concealed from the subject. The subject then kneels with one knee on each scale. The weight through each knee is recorded at 0, 15, 30, 45, and 60 s. The proportion of total body weight on each leg at each timepoint is calculated, and a ratio calculated from the values. A value of 1 equates to equal weight on each leg. The test was performed on 53 normal subjects and 38 subjects who had undergone tibial nailing., Results: In the normal group, no significant difference in mean ratio of weight distribution (left:right) was seen at any timepoint (mean ratio range = 0.98-0.99, p value range = 0.18-0.64). In the tibial nail group, a difference was observed in mean ratio of weight distribution (injured:uninjured) favouring the uninjured leg, reaching significance at 0, 15, 30, and 45 s (mean ratio range = 0.88-0.94, p value range = 0.01-0.02). At 60 s, the mean ratio was 0.93 (p = 0.09)., Conclusion: The Aberdeen Weight-Bearing Test (Knee) is an objective, easily reproducible, specific test for anterior knee discomfort. It produces different results in individuals who have undergone anterograde tibial nailing compared to individuals with no knee symptoms.

Purpose: Acute compartment syndrome is a condition whereby tissue ischaemia occurs due to increased pressure in a closed myofascial compartment. It is a surgical emergency, with rapid recognition and treatment-the keys to good outcomes., Methods: The available literature on diagnostic aids was reviewed by one of the senior authors 15 years ago. Now, we have further reviewed the literature, to aim to ascertain what progress has been made., Results: In this review, we present the evidence around a variety of available diagnostic options when investigating a potential case of acute compartment syndrome, including those looking at pressure changes, localised oxygenation, perfusion, metabolic changes and available blood serum biomarkers., Conclusions: A significant amount of work has been put into developing modalities of diagnosis for acute compartment syndrome in the last 15 years. There is a lot of promising outcomes being reported; however, there is yet to be any conclusive evidence to suggest that they should be used over intracompartmental pressure measurement, which remains the gold standard. However, clinicians should be cognizant that compartment pressure monitoring lacks diagnostic specificity, and could lead to unnecessary fasciotomy when used as the sole criterion for diagnosis. Therefore, pressure monitoring is ideally used in situations where clinical suspicion is raised.

Leadership is one of the GMC's Generic Professional Capabilities for all medical specialties, but engagement in leadership activities is not currently routinely built into general practice (GP) training. We explored whether GP trainees in their first year of speciality training (ST1) could engage with a leadership activity in their practice placement. GP trainees were invited to participate in a voluntary leadership activity, with a small menu of optional activities to choose from. Evaluation was through electronic survey of trainees and educational supervisors (ESs) before and after the GP placement, and through trainee focus groups after the placement. 89 trainees and 191 supervisors were surveyed at the start of the trial. Trainees felt supported by supervisors and practice team members. Both groups felt that leadership skills were important for a trainee's future career. Supervisors placed more emphasis on this than trainees. Identified barriers included lack of protected time, other training priorities, lack of empowerment, and personal issues. Most trainees and their supervisors felt that a leadership activity was possible during the first year of general practice training. More work needs to be done to see if these results are generalisable to trainees across demographic subgroups, and in other years of training.

The majority of femoral fractures are surgically treated with intramedullary nails. Non-union rate is low but challenging and costly if it occurs. There have been encouraging results from the use of augmentative plating as a treatment for non-union of femoral fractures. We performed a systematic review of the literature to compare union rates, time to union and complications between exchange nailing and augmentative plating as a primary procedure following a diagnosis of femoral non-union following initial nailing. We found a total of 21 papers, which found the mean union rate of augmentative plating to be 99.8% compared to 74% (P = 2.05 -12 ) found for exchange nailing. Times to union were comparable at 5.9 months for augmentative plating and 6.3 months for exchange nailing (P = 0.68916), and complication rate was 4% for augmentative plating compared to 20% for exchange nailing. From the evidence available, plate augmentation provides a more reliable union rate if used as the first operative intervention on a non-union of a femoral fracture compared to exchange nailing.Level of Evidence IV Systematic review of therapeutic studies.

Background: Surgical treatment is the optimal strategy for managing intertrochanteric fractures as it allows for early rehabilitation and functional recovery. The purpose of the study was to assess the cost-effectiveness of commonly used cephalomedullary nails for the treatment of unstable intertrochanteric hip fractures., Methods: A decision analytic model was developed from a US payer's perspective using clinical data from a pairwise meta-analysis of randomised controlled trials (RCTs) and comparative observational studies comparing the integrated twin compression screw (ITCS) nail versus two single-screw or blade cephalomedullary nails [single lag screw (SLS) nail and single helical blade (SHB) nail]. The model considered a cohort of 1000 patients with a mean age of 76, as reported in the clinical studies over a 1-year time period. Cost data was obtained from the Center for Medicare and Medicaid Services website and published literature and adjusted for inflation. One-way and probabilistic sensitivity analyses were conducted to assess the effect of uncertainty in model parameters on model conclusions., Results: The model estimated 0.546 quality-adjusted life years (QALYs) and 0.78 complications avoided by using the ITCS nail and 0.455 QALYs and 0.67 complications avoided for the standard of care, using SLS or SHB nails. The cost per patient was $34,336 for patients treated with an ITCS nail and $37,036 for patients treated with the standard of care respectively, resulting in a cost saving of $2700 in favour of the ITCS nail. More savings were observed when the ITCS nail was compared to the SHB ($3280 per patient) and SLS ($1652 per patient). The findings were robust to a range of both one-way and the probabilistic sensitivity analyses., Conclusion: In conclusion, the ITCS nail can be considered a cost saving intervention in patients undergoing intertrochanteric fracture fixation with an intramedullary device. Clinicians and policy makers should be encouraged to adopt healthcare technologies such as ITCS that will help them to provide quality healthcare despite falling budgets.

Background: Ankle fractures are amongst the most common surgically treated musculoskeletal injuries. Intramedullary (IM) fixation of the lateral malleolus had been attempted as early as the 1990s. In recent years, dedicated implants have emerged. This review evaluates the design characteristics of the technology used to perform IM fixation of distal fibular fractures., Materials and Methods: A search of electronic databases was performed. Medical subject headings (MeSH) and free-text terms were used to optimise search sensitivity and specificity., Results: We identified 10 different surgical technologies for IM fixation of lateral malleolar fractures reported across 12 articles, including both improvised and custom-designed Orthopaedic implants. Most implants were inserted through percutaneous surgical techniques., Conclusion: Advances in technology have improved the feasibility of intramedullary fixation as a treatment option for lateral malleolus fractures. The implants we reviewed had very diverse morphological and mechanical properties. Intra-medullary fixation may outperform extra-medullary fixation of the lateral malleolus, particularly in patients at high risk of soft tissue complications. Robust scientific evidence is awaited., Level of Evidence: Level IV evidence., (Copyright © 2018. Published by Elsevier Ltd.)

The surgical treatment of proximal humerus fractures remains controversial primarily due to the high complication rate associated with the available fixation methods. In an attempt to reduce the incidence of serious complications and subsequent poor clinical outcomes, proximal humerus locking plates have become popular but even these implants cannot overcome the risk of complications, especially those associated with loss of fracture reduction and screw cut-out/migration through the humeral head. In an attempt to address these issues, we have reviewed the literature, investigating the most likely causes for these predominantly mechanical complications and propose technical solutions.

Background: Intertrochanteric hip fractures are common and devastating injuries especially for the elderly. Surgical treatment is the optimal strategy for managing intertrochanteric fractures as it allows early rehabilitation and functional recovery. The relative effects of internal fixation strategies for intertrochanteric fracture after operation remain limited to relatively small studies which create uncertainty in attempts to establish evidence-based best practice., Methods: We conducted a systematic review and meta-analysis of randomised controlled trials (RCTs) and observational studies to assess the clinical effectiveness of two commonly used intramedullary devices: a twin screw integrated cephalomedullary nail (InterTAN) versus a single screw cephalomedullary nail (proximal femoral nail antirotation) in patients with intertrochanteric fractures. The following outcomes were considered: revisions, implant-related failures, non-unions, pain, Harris Hip Score and intraoperative outcomes. Odds ratios or mean differences with 95% confidence intervals in brackets are reported., Results: Six studies met the inclusion criteria, two randomised controlled trials and four observational studies enrolling 970 patients with mean age of 77 years, and 64% of patients were female. There was a statistically significant difference (p value < 0.05) for revisions OR 0.27 (0.13 to 0.56), implant-related failures OR 0.16 (0.09 to 0.27) and proportion of patients complaining of pain OR 0.50 (0.34 to 0.74). There was no difference in non-unions and Harris Hip Score (p value > 0.05). There was a significant difference in blood loss and fluoroscopy usage in favour of PFNA, whilst no difference in operating times were observed between the two devices., Conclusions: Our meta-analysis suggests that a twin screw integrated cephalomedullary nail InterTAN is clinically more effective when compared to a single screw cephalomedullary nail proximal femoral nail antirotation resulting in fewer complications, fewer revisions and fewer patients complaining of pain. No difference has been established regarding non-unions and Harris Hip Score. Intraoperative outcomes favour PFNA with less blood loss and fluoroscopy usage. Further studies are warranted to explore the cost-effectiveness of these and other implants in managing patients with intertrochanteric fractures.

For many years intramedullary nails have been a well accepted and successful method of diaphyseal fracture fixation. However, delayed and non unions with this technique do still occur and are associated with significant patient morbidity. The reason for this can be multi-factorial. We discuss a number of technical considerations to maximise fracture reduction, fracture stability and fracture vascularity in order to achieve bony union., (Crown Copyright © 2017. Published by Elsevier Ltd. All rights reserved.)

Introduction: We describe a minimally invasive technique to stabilise unstable ankle fractures by inserting a 100mm screw up the fibula medullary canal along with percutaneous screw fixation of the medial malleolus if required. This technique is utilised in patients with poor soft tissues and significant co-morbidities where the fracture cannot be adequately controlled by a cast alone., Patients and Methods: Retrospective review of 23 patients the average age being 70 years (29-89) and 74% had significant co-morbidities. Postoperative radiographs were examined for adequacy of reduction using the method described by Mclenna and Ungersma. Patient based functional and health questionnaires were performed, reviewed and scored., Results: Six patients were lost during the follow-up period due to death caused by issues unrelated to the ankle fracture. There were no reported intraoperative complications, no postoperative wound infections and no non-unions. There was two complications one loss of fixation, and another required removal of the screw due to irritation. Radiographic reduction was good in 52%, fair in 44% and poor in 4%. Patient questionnaire results were 70 (20-100) for the Abbreviated Olerud and Molander score and the SF-12 physical component score was 42 and mental component was 44., Conclusions: With appropriate patient selection percutaneous screw fixation is an excellent technique supplementing cast immobilisation of unstable ankle fractures with poor soft tissues., (Copyright © 2015 European Foot and Ankle Society. Published by Elsevier Ltd. All rights reserved.)

Nitric oxide (NO) is a free radical signalling molecule involved in various physiological and pathological processes, including cancer. Both tumouricidal and tumour promoting effects have been attributed to NO, making its role in cancer biology controversial and unclear. To investigate the specific role of tumour-derived NO in vascular development, C6 glioma cells were genetically modified to include a doxycycline regulated gene expression system that controls the expression of an antisense RNA to inducible nitric oxide synthase (iNOS) to manipulate endogenous iNOS expression. Xenografts of these cells were propagated in the presence or absence of doxycycline. Susceptibility magnetic resonance imaging (MRI), initially with a carbogen (95% O2/5% CO2) breathing challenge and subsequently an intravascular blood pool contrast agent, was used to assess haemodynamic vasculature (ΔR2*) and fractional blood volume (fBV), and correlated with histopathological assessment of tumour vascular density, maturation and function. Inhibition of NO production in C6 gliomas led to significant growth delay and inhibition of vessel maturation. Parametric fBV maps were used to identify vascularised regions from which the carbogen-induced ΔR2* was measured and found to be positively correlated with vessel maturation, quantified ex vivo using fluorescence microscopy for endothelial and perivascular cell staining. These data suggest that tumour-derived iNOS is an important mediator of tumour growth and vessel maturation, hence a promising target for anti-vascular cancer therapies. The combination of ΔR2* response to carbogen and fBV MRI can provide a marker of tumour vessel maturation that could be applied to non-invasively monitor treatment response to iNOS inhibitors., (© 2016 UICC.)

Background: The AAOS guidelines are unable to recommend for or against operative treatment of distal radius fractures in older patients., Aims: This study compares the outcomes of older patients (≥60 years) against a cohort of younger patients treated with volar locking plate (VLP) fixation., Methods: We assessed 78 patients, comparing range of movement (ROM), grip and pinch strength, subjective Visual Analogue Score (VAS) for pain and function and composite outcome scores., Results: There was no difference in clinical outcomes between the two groups at six months., Conclusion: Open reduction and VLP for distal radius fractures gives comparable outcomes in the older population.

Purpose: To compare 4 recognized upper-limb scoring systems that are regularly used to assess wrist function after injury., Methods: We reviewed 116 patients 6 months after volar locking plate fixation for distal radius fractures. Two purely subjective and 2 composite scoring systems composed of both subjective and objective components were compared along with visual numerical scores for pain and function and objective measures of function. Each score was standardized into a scale from 0 to 100., Results: The distribution of the standardized total scores was statistically significantly different and indicated marked variability between scoring systems and therefore the information provided. Overall, the subjective scoring systems correlated well with each other and with both visual numerical scores for pain and function. However, the composite scores and objective measures of function correlated poorly with the subjective scores including the visual numerical scores., Conclusions: Results from wrist scoring systems should be interpreted with caution. It is important to ensure that the component parts of each score are taken into consideration separately because total scores may be misleading., Clinical Relevance: Composite scores may be outdated and should be avoided., (Copyright © 2016 American Society for Surgery of the Hand. Published by Elsevier Inc. All rights reserved.)

Trauma is an important matter of public health and a major cause of mortality. Since the late 1980s trauma care provision in the United Kingdom is lacking when compared to the USA. This has been attributed to a lack of organisation of trauma care leading to the formation of trauma networks and Major Trauma Centres in England and Wales. The need for similar centres in Scotland is argued currently. We assessed the activity of two quite different trauma systems by obtaining access to comparative data from two hospitals, one in the USA and the other in Scotland. Aggregate data on 5604 patients at Aberdeen Royal Infirmary (ARI) from 1993 to 2002 was obtained from the Scottish Trauma Audit Group. A comparable data set of 16,178 patients from Massachusetts General Hospital (MGH). Direct comparison of patient demographics; injury type, mechanism and Injury Severity Score (ISS); mode of arrival; length of stay and mortality were made. Statistical analysis was carried out using Chi-squared and Cochran-Mantel-Haenszel. There were significant differences in the data sets. There was a higher proportion of penetrating injuries at MGH, (8.6% vs 2.6%) and more severely injured patients at MGH, patients with an ISS>16 accounted for nearly 22.1% of MGH patients compared to 14.0% at ARI. ISS 8-15 made up 54.6% of ARI trauma with 29.6% at MGH. Falls accounted for 50.1% at ARI and 37.9% at MGH. Despite the higher proportion of severe injuries at MGH and crude mortality rates showing no difference (4.9% ARI vs 5.2% MGH), pooled odds ratio of mortality was 1.4 (95% confidence interval 1.2-1.6) showing worse mortality outcomes at ARI compared to MGH. In conclusion, there were some differences in case mix between both data sets making direct comparison of the outcomes difficult, but the effect of consolidating major trauma on the proportion and number of severely injured patients treated in the American Level 1 centre was clear with a significant improvement in mortality in all injury severity groups., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

Purpose: A number of outcome measures (instruments) are used to assess shoulder pain and function in clinical practice. No clear 'gold standard' exists and it is thought that different instruments will give a different answer. Our aim is to statistically compare four commonly used outcome measures in a group of trauma patients and to identify whether instruments which combine objective and subjective components differ from those which are purely subjective., Methods: Forty-four patients undergoing internal fixation of proximal humeral fractures were recruited between 2003 and 2008. Each was asked to complete a number of outcome measures: University of Los Angeles score (UCLA); Constant and Murley score (Constant); Oxford Shoulder Score (OSS); Quick form of the Disabilities of the Arm, Shoulder and Hand questionnaire (QuickDASH). Each were measured on a different scale but were standardised to 0-100 for comparison., Results: Purely subjective instruments gave higher scores (better function and/or less pain). Statistical differences were found between each pair of instruments (p < 0.001), except for the comparison between UCLA and QuickDASH (p = 0.403). The study found inconsistencies between instruments, with outcomes varying depending on whether subjective or objective measurements were being assessed., Conclusions: Outcome measures are useful tools, but clinicians need to be aware that their choice of instrument should be made carefully, taking into account the reason behind its use with regard to outcome.

During human pregnancy, natural killer (NK) cells accumulate in the maternal decidua, but their specific roles remain to be determined. Decidual NK (dNK) cells are present during trophoblast invasion and uterine spiral artery remodelling. These events are crucial for successful placentation and the provision of an adequate blood supply to the developing fetus. Remodelling of spiral arteries is impaired in the dangerous pregnancy complication pre-eclampsia. We studied dNK cells isolated from pregnancies at 9-14 weeks' gestation, screened by uterine artery Doppler ultrasound to determine resistance indices which relate to the extent of spiral artery remodelling. dNK cells were able to promote the invasive behaviour of fetal trophoblast cells, partly through HGF. Cells isolated from pregnancies with higher resistance indices were less able to do this and secreted fewer pro-invasive factors. dNK cells from pregnancies with normal resistance indices could induce apoptotic changes in vascular smooth muscle and endothelial cells in vitro, events of importance in vessel remodelling, partly through Fas signalling. dNK cells isolated from high resistance index pregnancies failed to induce vascular apoptosis and secreted fewer pro-apoptotic factors. We have modelled the cellular interactions at the maternal-fetal interface and provide the first demonstration of a functional role for dNK cells in influencing vascular cells. A potential mechanism contributing to impaired vessel remodelling in pregnancies with a higher uterine artery resistance is presented. These findings may be informative in determining the cellular interactions contributing to the pathology of pregnancy disorders where remodelling is impaired, such as pre-eclampsia., (Copyright © 2012 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.)

Background: The purpose of the study was to evaluate whether use of a bi-polar radiofrequency (RF) ablation wand would cause excess heating, which may lead to collateral damage to the surrounding tissues during arthroscopic subacromial decompression. Cadaveric studies have shown that high temperatures can potentially be reached when using RF ablation wands in arthroscopic shoulder surgery. Only 1 other published study assesses these temperature rises in the clinical setting., Methods: Fifteen patients were recruited to participate in the study. A standard arthroscopic subacromial decompression was performed using continuous flow irrigation, with intermittent use of the RF ablation wand for soft tissue debridement. The temperature of the irrigation fluid within the subacromial bursa and the outflow fluid from the suction port of the wand were measured during the procedure using fiber-optic thermometers., Results: The mean peak temperature recorded in the subacromial bursa was 32.0°C (29.3-43.1°C), with a mean rise from baseline of 9.8°C. The mean peak temperature recorded from the outflow fluid from the wand was 71.6°C (65.6-77.6°C), with a mean rise from baseline of 49.4°C., Conclusion: High temperatures were noted in the outflow fluid from the wand; however, this was not evident in the subacromial bursa itself. Use of room temperature inflow fluid, maintenance of flow through the bursa, and avoidance of prolonged uninterrupted use of the wand all appear to ensure that safe temperatures are maintained in the subacromial bursa not only in the laboratory but also in a clinical setting., (Copyright © 2012 Journal of Shoulder and Elbow Surgery Board of Trustees. Published by Mosby, Inc. All rights reserved.)

Meniscal healing especially in the inner avascular region has always been a major challenge. In this study we investigated the potential for platelet derived growth factor-AB (PDGF-AB) to promote meniscal tissue regeneration in the inner (avascular), middle, and outer (vascular) zones of the meniscus. Various concentrations of PDGF-AB were tested on sheep meniscal cell cultures. We used the radioactive thymidine uptake assay to assess cell proliferation, and the radioactive sulphur and proline uptake assays and Blyscan assay to assess matrix formation. In general, PDGF-AB stimulated both cell proliferation and matrix formation by cells from all meniscal zones. PDGF-AB at a concentration of 100 ng/ml increased cell proliferation and matrix formation by eight and four fold respectively, by fibrochondrocytes cultured from all meniscal zones (p<0.001). These results indicate that fibrochondrocytes present within the avascular region of the meniscus have the ability to proliferate and form new matrix when exposed to anabolic cytokines such as PDGF-AB.

Fractures of the distal humerus are routinely treated by open reduction and internal fixation in an attempt to retain a painless, stable and functional joint. However, results of fixation, even with advances in plate technology, are still dependent on screw purchase and bone quality. Reported results, over the past decade, now support consideration of primary total elbow arthroplasty, in cases of highly comminuted distal humeral fractures, especially in the elderly who have low physical demands, or in those who have significant pre-existing inflammatory joint disease resulting in marked joint destruction.

Apoptosis induced by the death-inducing ligand FasL (CD95L) is a major mechanism of cell death. Trophoblast cells express the Fas receptor yet survive in an environment that is rich in the ligand. We report that basal nitric oxide (NO) production is responsible for the resistance of trophoblasts to FasL-induced apoptosis. In this study we demonstrate that basal NO production resulted in the inhibition of receptor clustering following ligand binding. In addition NO also protected cells through the selective nitrosylation, and inhibition, of protein kinase Cepsilon (PKCepsilon) but not PKCalpha. In the absence of NO production PKCepsilon interacted with, and phosphorylated, the anti-apoptotic protein cFLIP. The interaction is predominantly with the short form of cFLIP and its phosphorylation reduces its recruitment to the death-inducing signaling complex (DISC) that is formed following binding of a death-inducing ligand to its receptor. Inhibition of cFLIP recruitment to the DISC leads to increased activation of caspase 8 and subsequently to apoptosis. Inhibition of PKCepsilon using siRNA significantly reversed the sensitivity to apoptosis induced by inhibition of NO synthesis suggesting that NO-mediated inhibition of PKCepsilon plays an important role in the regulation of Fas-induced apoptosis.

Excessive apoptosis of trophoblast cells is thought to be a contributing factor in complications of pregnancy such as pre-eclampsia. Hepatocyte growth factor (HGF) inhibits apoptosis in trophoblasts and we have investigated the signalling pathways through which this anti-apoptotic effect is mediated. Treatment of cells with HGF led to rapid phosphorylation of Akt while an Akt inhibitor blocked the protective effect of HGF. Glycogen synthase kinase-3beta (GSK-3beta) was found to be one of the downstream targets of Akt. HGF treatment inactivated GSK-3beta which in turn led to the activation of the transcription factor beta-catenin. Pharmacological inhibition of GSK-3beta, independently of HGF treatment, strongly increased both beta-catenin activity and cell survival, suggesting that beta-catenin alone has a pronounced anti-apoptotic effect. We also found that both HGF treatment and pharmacological activation of beta-catenin leads to increased expression of inducible nitric oxide synthase (iNOS). We suggest that the Akt mediated activation of beta-catenin leads to inhibition of trophoblast apoptosis following increased expression of iNOS.

Objective: To assess the effectiveness of a systematic examination of the ulnar collateral ligament (UCL) of the thumb metacarpophalangeal joint (MCPJ) prior to and post infiltration of local anaesthetic., Methods: During the study period from 24 October 2001 to 22 February 2002, 51 patients with clinical signs suggestive of UCL injuries were identified prospectively from initial ED attendances and attendances at a subsequent review clinic. Patients were formally assessed a mean of 6.6 days post injury. A single ED Senior House Officer carried out examination before and after direct infiltration of local anaesthetic around the site of injury. Stress radiography was also performed as the 'gold standard' diagnostic test of UCL instability., Results: Forty-seven patients were enrolled in the study. When reviewed by the single observer, examination prior to and post local anaesthetic infiltration revealed a degree of joint stability in 28% (95% CI 16-43%) and 98% (95% CI 88-100%) cases, respectively, compared to the gold standard. Post infiltration, this technique had a specificity of 100% (95% CI 94-100%) and a sensitivity of 87.5% (95% CI 74-95%) (P < 0.001). Stress radiography offered additional information in one patient. A total of eight patients previously underdiagnosed in the ED were found to have unstable thumb MCPJs., Conclusion: This simple technique improves assessment of suspected UCL injuries approximately 1 week post injury. Further studies are indicated to determine its effectiveness in the ED immediately post injury.

We report two cases of extensor pollicis longus tendon tethering following K-wire insertion to treat unstable distal radius fractures, an unusual complication. In both cases, extensor pollicis longus function returned with conservative management. The structures considered "at risk" during K-wire insertion are described, and the common complications are discussed. Operative approaches to minimise soft tissue damage during K-wire insertion are reviewed. This case report is the first to demonstrate the potential for ultrasound scanning to aid in the diagnosis of extensor pollicis longus tethering.

Background: Meniscal tears situated within the inner avascular region do not heal despite suturing. New approaches need to be developed to augment surgical repair., Hypothesis: To demonstrate that basic fibroblast growth factor, used as a single agent or in combination with serum, stimulates the activity of fibrochondrocytes by enhancing proliferation and extracellular matrix synthesis in all meniscal zones, including the inner (avascular) zone of the meniscus., Study Design: Controlled laboratory study., Methods: Monolayer cell cultures were prepared from the inner, middle, and outer zones of the lateral meniscus. Various concentrations of basic fibroblast growth factor were used in the presence or absence of 10% fetal calf serum. The authors measured the uptake of radiolabeled thymidine to assess cell proliferation and radioactive sulfur and proline to assess extracellular matrix formation., Results: Overall, basic fibroblast growth factor-stimulated cells from all meniscal zones to proliferate and to form new extra-cellular matrix (P <.05). The basic fibroblast growth factor (in the absence of serum) increased DNA formation and protein synthesis by cells from the inner meniscal zone by 7- and 15-fold, respectively (P <.001)., Conclusions: These results indicate that meniscal cells and, more important, cells from the avascular zone are capable of responding favorably to the addition of basic fibroblast growth factor by expressing their intrinsic potential to proliferate and generate new extracellular matrix., Clinical Relevance: The results suggest that it may be possible to augment surgical repair of the meniscus in the future.

Objective: Identifying sites on the TSH-receptor that are involved in the pathological stimulation of the thyroid by autoantibodies in Graves' disease would aid the development of new therapies. We tested a series of monoclonal antibodies that recognize the native receptor for their ability to inhibit stimulation of the receptor in vitro., Patients and Methods: Heterologous cells expressing the recombinant human TSH-receptor were stimulated with TSH or serum samples from 13 Graves' disease patients or the MRC Long-Acting Thyroid Stimulator standard B (LATS-B) and their cAMP responses measured. The effect on this stimulation of various doses of purified monoclonal antibodies with defined epitopes was determined., Results: Antibodies against one epitope (residues 381-384) inhibited TSH-stimulated cyclic adenosine monophosphate (cAMP) production (1 microg/ml causing 50% inhibition of the response to 100 microU/ml TSH) and also inhibited cAMP production induced by sera from approximately 40% (6/14) of Graves' disease patients, including the MRC LATS-B standard., Conclusions: Residues 381-384 of the human TSH-receptor are important in the physiological and pathological stimulation of the thyroid. This opens the possibility of more specific therapy of some Graves' disease patients by agents directed against this epitope.

Background: The cAMP response of porcine thyrocytes to the immunoglobulin (Ig) fraction from Graves' sera is increased if these fractions are prepared with higher than usual concentrations of polyethylene glycol (PEG; 22.5% rather than 13.5%), leading to the suggestion that additional factors might exist in serum which influence the ability of autoantibodies to stimulate thyroid cells., Methods: We characterised the stimulatory activity of fractions prepared by differential PEG precipitation of Graves' sera, using heterologous eukaryotic cells expressing recombinant human thyrotrophin (TSH) receptor., Results: We found no evidence that material soluble in 13.5% PEG but precipitated by 22.5% PEG was stimulatory either on its own or in combination with the immunoglobulin-containing material precipitated by 13.5% PEG. Indeed, the stimulatory effect was reproduced by simply including low concentrations of PEG (1-4%) in the diluted sera from the majority of Graves' patients (12/18 tested) added to the target cells. Intriguingly, PEG had no effect on basal levels, with normal sera or stimulation by thyrotrophin., Conclusions: The increase in stimulation reported when using immunoglobulins prepared with higher concentrations of PEG is attributable to a direct effect of the extra PEG (which had not been removed from the preparations) during the stimulation of the cells. Because the effect is observed with recombinant heterologous cells, it must be caused by interaction between PEG and the autoantibodies and/or the receptor-it cannot involve any other thyroid-specific molecule, although an involvement of other molecules widely distributed on many cell types is possible.

Apoptosis is thought to play an important regulatory role in placental development and inappropriate trophoblast apoptosis has been implicated in complications of pregnancy such as pre-eclampsia. Here we show that apoptosis of a human extravillous trophoblast-derived cell line (SGHPL-4) can be regulated by nitric oxide (NO). Nitric oxide produced exogenously by the addition of NO donors was able to delay or inhibit apoptosis induced by a combination of tumour necrosis factor alpha and actinomycin D and to suppress the activity of caspase 3. Treatment with hepatocyte growth factor (HGF) stimulated expression of the inducible isoform of NO synthase and was also able to protect SGHPL-4 cells from caspase 3 activation and apoptosis. The inhibition of basal NO production with NO synthase inhibitors was shown to sensitise cells to apoptotic stimuli and to reduce the level of endogenous caspase 3 nitrosylation. The anti-apoptotic effects of NO in these extravillous trophoblast cells appear to be mediated through the production of cyclic GMP as inhibitors of soluble guanylate cyclase inhibited the protective effect of both HGF and NO donors.

Graves disease is directly caused by thyroid-stimulating autoantibodies (TSAb's) that activate the thyrotropin receptor (TSHR). We observed upon flow cytometry using intact cells that a mouse mAb (3BD10) recognized the TSHR ectodomain with a glycosidylphosphatidylinositol (ECD-GPI) anchor approximately tenfold better than the same ectodomain on the wild-type TSHR, despite the far higher level of expression of the latter. The 3BD10 epitope contains the N-terminal cysteine cluster critical for TSAb action. Consequently, we hypothesized and confirmed that TSAb (but not thyrotropin-blocking autoantibodies [TBAb's]) also poorly recognize the wild-type TSHR relative to the ECD-GPI. Despite poor recognition by TSAb of the holoreceptor, soluble TSHR A subunits (known to be shed from surface TSHR) fully neutralized autoantibody-binding activity. These data indicate that the epitope(s) for TSAb's, but not for TBAb's, are partially sterically hindered on the holoreceptor by the plasma membrane, the serpentine region of the TSHR, or by TSHR dimerization. However, the TSAb epitope on the soluble A subunit is freely accessible. This observation, as well as other evidence, supports the concept that A subunit shedding either initiates or amplifies the autoimmune response to the TSHR, thereby causing Graves disease in genetically susceptible individuals.