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Objectives: To explore patient experiences, understanding and perceptions of analgesia following major lower limb amputation., Design: Qualitative interview study, conducted as part of a randomised controlled feasibility trial., Setting: Participants were recruited from two general hospitals in South Wales., Participants: Interview participants were patients enrolled in PLACEMENT (Perineural Local Anaesthetic Catheter aftEr Major lowEr limb amputatioN Trial): a randomised controlled feasibility trial comparing the use of perineural catheter (PNC) versus standard care for postoperative pain relief following major lower limb amputation. PLACEMENT participants who completed 5-day postoperative follow-up, were able and willing to participate in a face-to-face interview, and had consented to be contacted, were eligible to take part in the qualitative study. A total of 20 interviews were conducted with 14 participants: 10 male and 4 female., Methods: Semi-structured, face-to-face interviews were conducted with participants over two time points: (1) up to 1 month and (2) at least 6 months following amputation. Interviews were audio-recorded, transcribed verbatim and analysed using a framework approach., Results: Interviews revealed unanticipated benefits of PNC usage for postoperative pain relief. Participants valued the localised and continuous nature of this mode of analgesia in comparison to opioids. Concerns about opioid dependence and side effects of pain relief medication were raised by participants in both treatment groups, with some reporting trying to limit their intake of analgesics., Conclusions: Findings suggest routine placement of a PNC following major lower limb amputation could reduce postoperative pain, particularly for patient groups at risk of postoperative delirium. This method of analgesic delivery also has the potential to reduce preoperative anxiety, alleviate the burden of pain management and minimise opioid use. Future research could further examine the comparison between patient-controlled analgesia and continuous analgesia in relation to patient anxiety and satisfaction with pain management., Trial Registration Number: ISRCTN: 85710690; EudraCT: 2016-003544-37., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Accurate prediction of outcomes following surgery with high morbidity and mortality rates is essential for informed shared decision-making between patients and clinicians. It is unknown how accurately healthcare professionals predict outcomes following major lower-limb amputation (MLLA). Several MLLA outcome-prediction tools have been developed. These could be valuable in clinical practice, but most require validation in independent cohorts before routine clinical use can be recommended. The primary aim of this study is to evaluate the accuracy of healthcare professionals' predictions of outcomes in adult patients undergoing MLLA for complications of chronic limb-threatening ischaemia (CLTI) or diabetes. Secondary aims include the validation of existing outcome-prediction tools., Method: This study is an international, multicentre prospective observational study including adult patients undergoing a primary MLLA for CLTI or diabetes. Healthcare professionals' accuracy in predicting outcomes at 30-days (death, morbidity and MLLA revision) and 1-year (death, MLLA revision and ambulation) will be evaluated. Sixteen existing outcome-prediction tools specific to MLLA will be examined for validity. Data collection began on 1 October 2020; the end of follow-up will be 1 May 2022. The C-statistic, Hosmer-Lemeshow test, reclassification tables and Brier score will be used to evaluate the predictive performance of healthcare professionals and prediction tools, respectively., Study Registration and Dissemination: This study will be registered locally at each centre in accordance with local policies before commencing data collection, overseen by local clinician leads. Results will be disseminated to all centres, and any subsequent presentation(s) and/or publication(s) will follow a collaborative co-authorship model., (© The Author(s) 2021. Published by Oxford University Press on behalf of BJS Society Ltd.)

Objective: Controlling pain after major lower limb amputation (MLLA) is of critical importance to patients and clinicians. The aim of this systematic review and meta-analysis was to assess the effect of perineural catheters (PNCs) on post-operative pain, post-operative morphine requirement, in-hospital mortality, long term phantom limb pain, and chronic stump pain., Methods: A systematic review using PubMed, EMBASE via OVID and the Cochrane library from database inception (1946) to 20 October 2020 was performed according to PRISMA guidelines. Studies involving patients undergoing MLLA which reported on post-operative morphine requirement, pain scores, in-hospital mortality, phantom limb pain (PLP), and chronic stump pain were included. Studies comparing PNC use with epidural or wound site local anaesthetic infusions were excluded. Outcome data were extracted from individual studies and meta-analysis was performed using a random effects (Mantel-Haenszel) model for dichotomous data using an odds ratio (OR) summary statistic with 95% confidence intervals (CI), and with an inverse variance random effects model for continuous data using a standardised mean difference (SMD) summary statistic with 95% CIs. Sensitivity analyses were performed for post-operative pain scores and post-operative morphine requirement. Study quality was assessed using the Downs and Black score, and outcomes were assessed using the GRADE tool., Results: Ten studies reporting on 731 patients were included, with 350 patients receiving a PNC and 381 receiving standard care. PNC use is associated with a reduction in post-operative pain (SMD -0.30, 95% CI -0.58 - -0.01, p = .040, I 2  = 54%, GRADE quality of evidence: low) and post-operative morphine requirements (SMD -0.63, 95% CI -1.03 - -0.23, p = .002, I 2  = 75%, GRADE quality of evidence: moderate), although the effect of PNC on reduced post-operative morphine requirements is lost on sensitivity analysis of randomised trials only (p = .40). No demonstrable effect was found on in-hospital mortality, PLP, or chronic stump pain (GRADE quality of evidence: low)., Conclusion: PNC use in amputees is associated with a significant reduction in post-operative pain scores and post-operative morphine requirements, although this latter finding is lost on sensitivity analysis of randomised trials only., (Crown Copyright © 2021. Published by Elsevier B.V. All rights reserved.)

Objective: This study aimed to develop and internally validate risk prediction models for predicting groin wound surgical site infections (SSIs) following arterial intervention and to evaluate the utility of existing risk prediction models for this outcome., Methods: Data from the Groin wound Infection after Vascular Exposure (GIVE) multicentre cohort study were used. The GIVE study prospectively enrolled 1 039 consecutive patients undergoing an arterial procedure through 1 339 groin incisions. An overall SSI rate of 8.6% per groin incision, and a deep/organ space SSI rate of 3.8%, were reported. Eight independent predictors of all SSIs, and four independent predictors of deep/organ space SSIs were included in the development and internal validation of two risk prediction models. A systematic search of the literature was conducted to identify relevant risk prediction models for their evaluation., Results: The "GIVE SSI risk prediction model" ("GIVE SSI model") and the "GIVE deep/organ space SSI risk prediction model" ("deep SSI model") had adequate discrimination (C statistic 0.735 and 0.720, respectively). Three other groin incision SSI risk prediction models were identified; both GIVE risk prediction models significantly outperformed these other risk models in this cohort (C statistic 0.618 - 0.629; p < .050 for inferior discrimination in all cases)., Conclusion: Two models were created and internally validated that performed acceptably in predicting "all" and "deep" groin SSIs, outperforming current existing risk prediction models in this cohort. Future studies should aim to externally validate the GIVE models., (Copyright © 2021 European Society for Vascular Surgery. Published by Elsevier B.V. All rights reserved.)

Objective: The decision to undertake a major lower limb amputation can be complex. This review evaluates the performance of risk prediction tools in estimating mortality, morbidity, and other outcomes following amputation., Methods: A systematic review was performed following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. The MEDLINE, Embase, and Cochrane databases were searched to identify studies reporting on risk prediction tools that predict outcomes following amputation. Outcome measures included the accuracy of the risk tool in predicting a range of post-operative complications, including mortality (both short and long term), peri-operative morbidity, need for re-amputation, and ambulation success. A narrative synthesis was performed in accordance with the Guidance on the Conduct of Narrative Synthesis In Systematic Reviews., Results: The search identified 518 database records. Twelve observational studies, evaluating 13 risk prediction tools in a total cohort of 61 099 amputations, were included. One study performed external validation of an existing risk prediction tool, while all other studies developed novel tools or modified pre-existing generic calculators. Two studies conducted external validation of the novel/modified tools. Nine tools provided risk estimations for mortality, two tools provided predictions for post-operative morbidity, two for likelihood of ambulation, and one for re-amputation to the same or higher level. Most mortality prediction tools demonstrated acceptable discrimination performance with C statistic values ranging from 0.65 to 0.81. Tools estimating the risk of post-operative complications (0.65 - 0.74) and necessity for re-amputation (0.72) also performed acceptably. The Blatchford Allman Russell tool demonstrated outstanding discrimination for predicting functional mobility outcomes post-amputation (0.94). Overall, most studies were at high risk of bias with poor external validity., Conclusion: This review identified several risk prediction tools that demonstrate acceptable to outstanding discrimination for objectively predicting an array of important post-operative outcomes. However, the methodological quality of some studies was poor, external validation studies are generally lacking, and there are no tools predicting other important outcomes, especially quality of life., Competing Interests: Conflicts of interest Daniel Norvell and Joseph Czerniecki were involved in the development of the AMPREDICT tools,(18)(,)(22)(,)(26) and Christopher Twine and Emma Thomas-Jones developed UKAmpRisk.(23) Ryan A. Preece, Nafi Dilaver, Cherry-Ann Waldron, Philip Pallmann, Emma Thomas-Jones, Brenig L. Gwilym, Christopher P. Twine, and David C. Bosanquet are currently part of the team running PERCEIVE.(33), (Copyright © 2021 European Society for Vascular Surgery. All rights reserved.)

Objective: Groin incision surgical site infections (SSIs) following arterial surgery are common and are a source of considerable morbidity. This review evaluates interventions and adjuncts delivered immediately before, during, or after skin closure, to prevent SSIs in patients undergoing arterial interventions involving a groin incision., Data Sources: MEDLINE, EMBASE, and CENTRAL databases were searched., Review Methods: This review was undertaken according to established international reporting guidelines and was registered prospectively with the International prospective register of systematic reviews (CRD42020185170). The MEDLINE, EMBASE, and CENTRAL databases were searched using pre-defined search terms without date restriction. Randomised controlled trials (RCTs) and observational studies recruiting patients with non-infected groin incisions for arterial exposure were included; SSI rates and other outcomes were captured. Interventions reported in two or more studies were subjected to meta-analysis., Results: The search identified 1 532 articles. Seventeen RCTs and seven observational studies, reporting on 3 747 patients undergoing 4 130 groin incisions were included. A total of seven interventions and nine outcomes were reported upon. Prophylactic closed incision negative pressure wound therapy (ciNPWT) reduced groin SSIs compared with standard dressings (odds ratio [OR] 0.34, 95% CI 0.23 - 0.51; p < .001, GRADE strength of evidence: moderate). Local antibiotics did not reduce groin SSIs (OR 0.60 95% CI 0.30 - 1.21 p = .15, GRADE strength: low). Subcuticular sutures (vs. transdermal sutures or clips) reduced groin SSI rates (OR 0.33, 95% CI 0.17 - 0.65, p = .001, GRADE strength: low). Wound drains, platelet rich plasma, fibrin glue, and silver alginate dressings did not show any significant effect on SSI rates., Conclusion: There is evidence that ciNPWT and subcuticular sutures reduce groin SSI in patients undergoing arterial vascular interventions involving a groin incision. Local antibiotics did not reduce groin wound SSI, although the strength of this evidence is lower. No other interventions demonstrated a significant effect., (Copyright © 2020 European Society for Vascular Surgery. Published by Elsevier B.V. All rights reserved.)

Background: Neuromuscular electrical stimulator (NMES) devices increase blood flow to the lower limb by a process of intermittent muscular contraction initiated by a transdermal stimulus to the common peroneal nerve. However, its effects on localized microvascular blood supply to lower limb wounds are unknown. This study is a single-center open label study measuring the effect of neuromuscular stimulation of the common peroneal nerve on the microvascular blood flow within the wound bed of arterial leg ulcers., Methods: Eights patients with ischemic lower limb wounds had an NMES (geko™) applied to the common peroneal nerve. Baseline and intervention analysis of blood flow to the wound bed and edge was performed using Laser Speckle Contrast Imaging. Mean flow (flux) and pulse amplitude (pulsatility) were measured., Results: Stimulation of the common peroneal nerve with the NMES resulted in a significantly increased flux and pulsatility in both the wound bed and the wound edge in all 8 patients., Conclusions: Neuromuscular electrical stimulation immediately increases microcirculatory blood flow to the wound bed and edge in patients with ischemic lower limb wounds. These data may provide mechanistic insight into the clinical efficacy of NMES in healing wounds. www.clinicaltrials.gov NCT03186560., (Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.)

Objective: Every year, thousands of patients with peripheral vascular disease undergo major lower limb amputation. Despite this, evidence for optimal management is weak. Core outcome sets capture consensus on the most important outcomes for a patient group to improve the consistency and quality of research. The aim was to define short and medium term core outcome sets for studies involving patients undergoing major lower limb amputation., Methods: A systematic review of the literature and focus groups involving patients, carers, and healthcare professionals were used to derive a list of potential outcomes. Findings informed a three round online Delphi consensus process, where outcomes were rated for both short and medium term studies. The results of the Delphi process were discussed at a face to face consensus meeting, and recommendations were made for each core outcome set., Results: A systematic review revealed 45 themes to carry forward to the consensus survey. These were supplemented by a further five from focus groups. The consensus survey received responses from 123 participants in round one, and 91 individuals completed all three rounds. In the final round, nine outcomes were rated as "core" for short term studies and a further nine for medium term studies. Wound infection and healing were rated as "core" for both short and medium term studies. Outcomes related to mortality, quality of life, communication, and additional healthcare needs were also rated as "core" for short term studies. In medium term studies, outcomes related to quality of life, mobility, and social integration/independence were rated as "core". The face to face stakeholder meeting ratified inclusion of all outcomes from the Delphi and suggested that deterioration of the other leg and psychological morbidity should also be reported for both short and medium term studies., Conclusion: Consensus was established on 11 core outcomes for short and medium term studies. It is recommended that all future studies involving patients undergoing major lower limb amputation should report these outcomes., (Copyright © 2020 European Society for Vascular Surgery. Published by Elsevier B.V. All rights reserved.)

Objective: To compare outcomes between long posterior flap (LPF) and skew flap (SF) amputation over a 13 year period., Methods: This was a retrospective observational cohort study. Consecutive patients undergoing a LPF or SF below knee amputation (BKA) over a 13 year period at one hospital were identified. Both techniques were performed regularly, depending on tissue loss and surgeon preference. The primary outcome was surgical revision of any kind. Secondary outcomes included revision to above knee amputation (AKA), length of hospital stay (LOS), and mortality. A smaller cohort of patients who were alive and unilateral below knee amputees were contacted to ascertain prosthetic use and functional status., Results: In total, 242 BKAs were performed in 212 patients (125 LPF and 117 SF; median follow up 25.8 months). Outcomes for the two groups were equivalent for surgical revision of any kind (27 LPF vs. 31 SF; p = .37), revision to an AKA (18 LPF vs. 14 SF; p = .58), LOS (29 days for LPF vs. 28 days for SF; p = .83), and median survival (23.9 months for LPF vs. 28.8 months for SF; p = .89). Multivariable analysis found amputation type had no effect on any outcome. Functional scores from a smaller cohort of 40 unilateral amputees who were contactable demonstrated improved outcomes with the LPF vs. the SF (p = .038)., Conclusion: Both techniques appear equivalent for rates of surgical residual limb failure. Functional outcomes may be better with the LPF., (Copyright © 2020 European Society for Vascular Surgery. Published by Elsevier B.V. All rights reserved.)

Background: The accuracy with which surgeons can predict outcomes following surgery has not been explored in a systematic way. The aim of this review was to determine how accurately a surgeon's 'gut feeling' or perception of risk correlates with patient outcomes and available risk scoring systems., Methods: A systematic review was undertaken in accordance with PRISMA guidelines. A narrative synthesis was performed in accordance with the Guidance on the Conduct of Narrative Synthesis In Systematic Reviews. Studies comparing surgeons' preoperative or postoperative assessment of patient outcomes were included. Studies that made comparisons with risk scoring tools were also included. Outcomes evaluated were postoperative mortality, general and operation-specific morbidity and long-term outcomes., Results: Twenty-seven studies comprising 20 898 patients undergoing general, gastrointestinal, cardiothoracic, orthopaedic, vascular, urology, endocrine and neurosurgical operations were included. Surgeons consistently overpredicted mortality rates and were outperformed by existing risk scoring tools in six of seven studies comparing area under receiver operating characteristic (ROC) curves (AUC). Surgeons' prediction of general morbidity was good, and was equivalent to, or better than, pre-existing risk prediction models. Long-term outcomes were poorly predicted by surgeons, with AUC values ranging from 0·51 to 0·75. Four of five studies found postoperative risk estimates to be more accurate than those made before surgery., Conclusion: Surgeons consistently overestimate mortality risk and are outperformed by pre-existing tools; prediction of longer-term outcomes is also poor. Surgeons should consider the use of risk prediction tools when available to inform clinical decision-making., (© 2019 The Authors. BJS Open published by John Wiley & Sons Ltd on behalf of BJS Society Ltd.)

Objectives: To determine the feasibility of undertaking a randomised controlled effectiveness trial evaluating the use of a perineural catheter (PNC) after major lower limb amputation with postoperative pain as the primary outcome., Design: Randomised controlled feasibility trial., Setting: Two vascular Centres in South Wales, UK., Participants: 50 patients scheduled for major lower limb amputation (below or above knee) for complications of peripheral vascular disease., Interventions: The treatment arm received a PNC placed adjacent to the sciatic or tibial nerve at the time of surgery, with continuous infusion of levobupivacaine hydrochloride 0.125% for up to 5 days. The control arm received neither local anaesthetic nor PNC. Both arms received usual perioperative anaesthesia and postoperative analgesia., Primary and Secondary Outcome Measures: The primary outcomes were the proportion of eligible patients who were randomised and the proportion of recruited patients who provided primary effectiveness outcome data. Secondary outcomes were: the proportion of recruited patients reaching 2 and 6 month follow-up and supplying pain data; identification of key cost drivers; development of an economic analysis framework for a future effectiveness trial; identification of barriers to recruitment and site set-up; and identification of the best way to measure postoperative pain., Results: Seventy-six of 103 screened patients were deemed eligible over a 10 month period. Fifty (64.5%) of these patients were randomised, with one excluded in the perioperative period. Forty-five (91.3%) of 49 recruited patients provided enough pain scores on a 4-point verbal rating scale to allow primary effectiveness outcome evaluation. Attrition rates were high; 18 patients supplied data at 6 month follow-up. Costs were dominated by length of hospital stay. Patients and healthcare professionals reported that trial processes were acceptable., Conclusions: Recruitment of patients into a trial comparing PNC use to usual care after major lower limb amputation with postoperative pain measured on a 4-point verbal rating scale is feasible. Evaluation of longer-term symptoms is difficult., Trial Registration Number: ISRCTN: 85 710 690. EudraCT: 2016-003544-37., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Introduction: Surgical site infections (SSIs) following groin incision for arterial exposure are commonplace and a significant cause of morbidity and mortality following major arterial surgery. Published incidence varies considerably. The primary aim of GIVE will be to compare individual units' practice with established guidelines from The National Institute for Health and Care Excellence (NICE). Secondary aims will be to describe the contemporary rate of SSI in patients undergoing groin incision for arterial exposure, to identify risk factors for groin wound infection, to examine the value of published tools in the prediction of SSI, to identify areas of equipoise which could be examined in future efficacy/effectiveness trials and to compare UK SSI rates with international centres., Methods and Analysis: This international, multicentre, prospective observational study will be delivered via the Vascular and Endovascular Research Network (VERN). Participating centres will identify all patients undergoing clean emergency or elective groin incision(s) for arterial intervention during a consecutive 3-month period. Follow up data will be captured at 90 days after surgery. SSIs will be defined according to the Centres for Disease Control and Prevention (CDC) criteria. Data will be gathered centrally using an anonymised electronic data collection tool or secure email transfer., Ethics and Dissemination: This study will be registered as a clinical audit at all participating UK centres; research ethics approval is not required. National leads will oversee the appropriate registration and approvals in countries outside the UK as required. Site specific reports of SSI rates will be provided to each participating centre. Study results will be disseminated locally at each site, publicised on social media and submitted for peer-reviewed publication., (© 2019 The Authors.)

Background: Chronic venous leg ulcers pose a significant burden to healthcare systems, and predicting wound healing is challenging. The aim of this study was to develop a genetic test to evaluate the propensity of a chronic ulcer to heal., Methods: Sequential refinement and testing of a gene expression signature was conducted using three distinct cohorts of human wound tissue. The expression of candidate genes was screened using a cohort of acute and chronic wound tissue and normal skin with quantitative transcript analysis. Genes showing significant expression differences were combined and examined, using receiver operating characteristic (ROC) curve analysis, in a controlled prospective study of patients with venous leg ulcers. A refined gene signature was evaluated using a prospective, blinded study of consecutive patients with venous ulcers., Results: The initial gene signature, comprising 25 genes, could identify the outcome (healing versus non-healing) of chronic venous leg ulcers (area under the curve (AUC) 0·84, 95 per cent c.i. 0·73 to 0·94). Subsequent refinement resulted in a final 14-gene signature (WD14), which performed equally well (AUC 0·88, 0·80 to 0·97). When examined in a prospective blinded study, the WD14 signature could also identify wounds likely to demonstrate signs of healing (AUC 0·73, 0·62 to 0·84)., Conclusion: A gene signature can identify people with chronic venous leg ulcers that are unlikely to heal., (© 2019 BJS Society Ltd Published by John Wiley & Sons Ltd.)

Objective: To explain the angiosome concept and explore the practical application of the angiosome literature to a clinical scenario, in this case a tibial angioplasty for critical ischaemia., Methods: Clinical vignette with explanation of the decisions made and subsequent clinical results based on the theory of the angiosome concept and the literature on angiosomal revascularisation; in this case the results of our group's recent update to a systematic review and meta-analysis., Results: Endovascular combined or direct angiosomal revascularisation if superior to indirect revascularisation. This was borne out in the clinical scenario, where an indirect peroneal reperfusion of the AT angiosome resulted in major amputation. Open surgery is less dependent on the angiosome concept. The presence of adequate collateralisation into a foot arch seems to be the most important factor predicting success of indirect revascularisation. The evidence for both suffers from selection bias and many of the findings in the literature are wholly due to selection bias., Conclusion: The angiosome concept is useful during both open and endovascular tibial revascularisation. However, the runoff in the foot is critical to success and may not follow the 'classic' angiosome model in diabetes., (Copyright © 2018 European Society for Vascular Surgery. Published by Elsevier B.V. All rights reserved.)

Background: The importance of the angiosome concept in tibial artery revascularisation remains controversial. The aim of this review was to assess the outcomes of direct revascularisation (revascularisation to the angiosome of tissue loss; DR) versus indirect revascularisation (IR) in infrapopliteal arteries., Methods: A previously conducted systematic review was updated according to PRISMA guidelines. Studies comparing DR with IR by both endovascular and surgical means for patients with localised tissue loss were included. Meta-analyses were performed to assess the effect of DR versus IR on wound healing (total and time to healing), limb salvage, mortality, and re-intervention rates, with multiple sensitivity analyses. Outcome data quality was determined using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) tool., Results: Seven studies (2278 limbs) were identified in the updated search, which when combined with the previous search resulted in 22 studies, comprising 4146 limbs, being included. Wound healing rates (odds ratio [OR] 0.51; 95% CI 0.39-0.68, p < 0.001), time to wound healing (standard mean difference [SMD] -1.70; 95% CI -3.34 to -0.07, p = .04) and limb salvage (OR 0.37; 95% CI 0.24-0.58, p < .0001) were significantly better with DR compared with IR. Sensitivity analyses were concordant with the primary analysis for these outcomes, with the exception of the effect of wound healing rates between DR and IR, which was lost on sensitivity analysis for bypass surgery. Mode of revascularisation had no effect on mortality or on re-intervention rates. GRADE outcomes were very low., Conclusion: DR of the tibial vessels appears to result in improved wound healing and limb salvage rates compared with IR, with no effect on mortality or re-intervention rates. For surgical revascularisation the importance of DR appears to be lost for wound healing. When possible, these low quality data suggests DR should be undertaken in preference to IR., (Crown Copyright © 2018. Published by Elsevier B.V. All rights reserved.)

Competing Interests: Conflict of interest: The author(s) declared no potential conflicts of interest with respect to the research, authorship and/or publication of this article.

Background: Significant stenoses in arteriovenous fistulae (AVFs) or arteriovenous grafts (AVGs) with limitation of flow and dialysis inadequacy should prompt consideration for fistuloplasty. We sought to identify fistulae, lesions, and patient-specific variables, which predict for outcomes after fistuloplasty., Methods: Data were extracted retrospectively from a renal access database from 2011 to 2016 of patients undergoing fistuloplasty. Demographics, comorbidities, outcomes of intervention, and flow rates documented on preintervention and postintervention duplex were collected. Secondary analysis of factors associated with postfistuloplasty flow rates of >600 mL/min, previously shown to be predictive of not requiring future intervention, was performed., Results: Of 204 attempted fistuloplasties, 176 were completed. One hundred forty (79.5%) were native AVFs and 34 (19.3%), AVGs (no data for 2). Median stenosis treated was 75%, with a majority (43.8%) in the proximal outflow vein. Flow rate on duplex after fistuloplasty was significantly better in AVFs (mean improvement 189.2 mL/min) than that in AVGs (mean improvement 51.8 mL/min; P = 0.034). Greatest flow improvement occurred for needling site stenotic lesions compared with other locations (from anastomosis to central vein) but was not significant. Brachio-brachial or brachio-axillary AVGs did significantly (P < 0.05) worse than all other fistulae types. The presence of hypertension was predicted for postfistuloplasty flow rate of >600 mL/min., Conclusions: Flow rates after fistuloplasty vary depending on the type of fistula treated and the presence of hypertension. Knowledge of this can lead to better patient selection and counseling for fistuloplasty., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Objectives: New and re-designed stent grafts for endovascular aortic aneurysm repair (EVAR) are released regularly. Manufacturers use data from registries to assess stent graft performance, but little is known about the ability of such registries to detect rates of clinically relevant complications. The aim of this paper was to perform a systematic review and meta-analysis to determine pooled failure rates for EVAR stent grafts, to define an acceptable non-inferiority limit for these devices, and then to calculate the number of patients needed for a new device to achieve non-inferiority against published devices., Data Sources and Review Methods: MEDLINE and EMBASE were searched for studies reporting outcomes of specific EVAR grafts being used for intact infrarenal abdominal aortic aneurysms, from inception to November 2016. Meta-regression was performed to pool data and calculate the patient numbers needed to detect non-inferiority of a future graft performance. An expert consensus was performed to define adequate standards for device safety., Results: One hundred and forty-seven moderate quality papers involving 27,058 patients were included. Multiple outcomes were pooled. Of these, the estimated rate (±standard error) of overall endoleak (excluding Type II) at 2 years was 5.7 ± 0.6%. The pooled re-intervention rate was 11.1 ± 0.7% at 2 years. There were differences in pooled endoleak rates between different stent graft types. Expert consensus defined non-inferiority as better performance than the worst performing 25% of stent grafts. The most popular outcome in the expert consensus was cumulative endoleak rate (excluding Type II). The number of patients who would need to be enrolled in a registry to demonstrate non-inferiority at this level was 525. Only two of 147 included studies achieved this. The second most popular choice in the expert consensus was re-intervention rate; 492 patients are required to demonstrate this., Conclusions: Five hundred and twenty-five patients need to be entered into a registry to demonstrate non-inferiority to previous stent grafts. Almost all previous publications have captured lower patient numbers. With performance varying between devices, and new devices being introduced regularly, there is an urgent need to capture higher quality long-term data on EVAR stent grafts., (Copyright © 2017 European Society for Vascular Surgery. Published by Elsevier Ltd. All rights reserved.)

Background: Pain after major lower limb amputation for peripheral arterial disease (PAD) is a significant problem. A perineural catheter (PNC) can be placed adjacent to the major nerve at the time of amputation with a continuous local anaesthetic infusion given postoperatively to try and reduce pain. Although low-quality observational data suggest that PNC usage reduces postoperative opioid requirements, there are limited data regarding its effect on pain. The aim of PLACEMENT is to explore the feasibility of running an effectiveness trial to assess the impact of a PNC with continuous local anaesthetic infusion, inserted at the time of amputation, on short and medium-term postoperative outcomes., Methods/design: Fifty patients undergoing a major lower limb amputation (below or above the knee) for PAD will be recruited from two centres. Patients will be randomised in a 1:1 ratio to receive standard postoperative analgesia, with or without insertion of a PNC and local anaesthetic infusion for the first 5 postoperative days. Outcome data will be captured for the first 5 days, including pain scores (primary outcome, captured three times a day), opioid use, nausea or vomiting, itching, dizziness and complications. Patients will be contacted 2 and 6 months after surgery to assess quality of life, phantom limb pain, chronic stump pain and total healthcare costs. Semi-structured interviews will be conducted with at least 10 patients (dependent on saturation of analytic themes on preliminary coding) purposefully sampled to achieve variation in site and study arm. Interviews will explore patients' perception of post-amputation pain and its treatment, and experience of study processes. Semi-structured interviews with 5-10 health professionals will explore feasibility, fidelity, and acceptability of the study. Data from this pilot will be used to assess feasibility of, and estimate parameters to calculate the sample size for an effectiveness trial. Full ethical approval has been granted (Wales Research Ethics Committee 3 reference number 16/WA/0353)., Discussion: PLACEMENT will be the first study to explore the feasibility of running an effectiveness trial on PNC usage for postoperative pain in amputees, and provide parameters to calculate the appropriate sample size for this study., Trial Registration: ISRCTN.com, ISRCTN85710690 . Registered on 21 October 2016. European Clinical Trials Database (EudraCT), 2016-003544-37. Registered on 24 August 2016.

Background: The development of a standardised reporting set is important to ensure that research is directed towards the most important outcomes and that data is comparable. To ensure validity, the set must be agreed by a consensus of stakeholders including patients, healthcare professionals and lay representatives. There is currently no agreed core outcome set for patients undergoing major lower limb amputation for peripheral arterial disease (PAD) for either short- or medium-term research outcomes. By developing these sets we aim to rationalise future trial outcomes, facilitate meta-analysis and improve the quality and applicability of amputation research., Methods/design: We will undertake a comprehensive systematic review of studies of patients undergoing major lower limb amputation for PAD. Data regarding all primary and secondary outcomes reported in relevant studies will be extracted and summarised as outcome domains. We will then undertake focus groups with key stakeholders (patients, carers, health and social care workers) to collect qualitative data to identify the main short- and medium-term research outcomes for patients undergoing major lower limb amputation. Results of the systematic review and focus groups will be combined to create a comprehensive list of potential key outcomes. Stakeholders (patients, researchers and health and social care workers) will then be polled to determine which of the outcomes are considered to be important in a general context using a three-phase Delphi process. After preliminary analysis, results will be presented at a face-to-face meeting of key stakeholders for discussion and voting on the final set of core outcomes. This project is being run in parallel with a feasibility trial assessing perineural catheters in patients undergoing lower limb amputation (the PLACEMENT trial). Full ethical approval has been granted for the study (Wales REC 3 reference number 16/WA/0353)., Discussion: Core outcome sets will be developed for short- and medium-term outcomes of research involving patients undergoing major lower limb amputation for PAD. This will help with the design of future trials and facilitate meta-analyses of trial data., Trial Registration: PROSPERO: CRD42017059329 . Registered on 30 March 2017., Comet: 975 . Registered on 5 April 2017.

Psoriasin (S100A7) is an 11-kDa small calcium binding protein initially isolated from psoriatic skin lesions. It belongs to the S100 family of proteins which play an important role in a range of cell functions including proliferation, differentiation, migration and apoptosis. Aberrant Psoriasin expression has been implicated in a range of cancers and is often associated with poor prognosis. This study examined the role of Psoriasin on pancreatic cancer cell functions and the implication in progression of the disease. Expression of Psoriasin was determined in a cohort of pancreatic tissues comprised of 126 pancreatic tumours and 114 adjacent non-tumour pancreatic tissues. Knockdown and overexpression of Psoriasin in pancreatic cancer cells was performed using specifically constructed plasmids, which either had anti-Psoriasin ribozyme transgene or the full length human Psoriasin coding sequence. Psoriasin knockdown and overexpression was verified using conventional RT-PCR and qPCR. The effect of manipulating Psoriasin expression on pancreatic cancer cell functions was assessed using several in vitro cell function assays. Local invasive pancreatic cancers extended beyond the pancreas expressed higher levels of Psoriasin transcripts compared with the cancers confined to the pancreas. Primary tumours with distant metastases exhibited a reduced expression of Psoriasin. Psoriasin overexpression cell lines exhibited significantly increased growth and migration compared to control cells. In addition, Psoriasin overexpression resulted in increased pancreatic cancer cell invasion which was associated with upregulation of matrix metalloproteinase-2 (MMP-2) and MMP-9. Overexpression of Psoriasin also promoted aggregation and survival of pancreatic cancer cells when they lost anchorage. Taken together, higher expression of Psoriasin was associated with local invasion in pancreatic cancers. Psoriasin expression is associated with pancreatic cancer cell growth, migration, cell-matrix adhesion, and invasion via regulation of MMPs. As such, the proposed implications of Psoriasin in invasion, disease progression and as a potential therapeutic target warrant further investigation.

Objective: Endovascular abdominal aortic aneurysm repair (EVAR) sometimes requires internal iliac artery (IIA) coverage to achieve a landing zone in the external iliac artery. The aim of this study was to determine complication rates following IIA exclusion., Materials and Methods: A systematic review of key journals was undertaken from January 1980 to April 2016. Studies detailing occlusion (using coils or plugs) or coverage of the IIA with outcome data were included. Weighted means were calculated for continuous variables. Meta-analysis was performed when comparative data were available. Quality was assessed using the GRADE system., Results: Sixty-one non-randomised studies (2671 patients; 2748 IIAs) were analysed. Fifteen per cent of EVARs require IIA sacrifice. Buttock claudication (BC) occurred in 27.9% of patients, although 48.0% resolved after 21.8 months. BC rates were 32.6% with coils, 23.8% with plugs, and 12.9% with coverage alone, and less with unilateral (vs. bilateral) IIA treatment (OR 0.57, 95% CI 0.36-0.91). More proximal coil placement resulted in lower rates of BC (OR 0.12, 95% CI 0.03-0.48). Erectile dysfunction occurred in 10.2% of males, with higher rates after coiling. Type II endoleaks were more frequent after covering alone; however re-interventions were rare. Significant ischaemic events (bowel/gluteal/spinal ischaemia) were very rare. Plugs were quicker to place and required less radiation (p < .001) than coils. GRADE scoring was very low for all outcomes., Conclusion: Overall the quality of reported data on IIA sacrifice is poor. Buttock claudication and erectile dysfunction occurred frequently after IIA sacrifice. Where both options are technically possible, plugs could be considered preferential to coils, and placed as proximally in the IIA as possible., (Copyright © 2017. Published by Elsevier Ltd.)

Introduction: Infra-popliteal angioplasty continues to be widely performed with minimal evidence to guide practice. Endovascular device selection is contentious and there is even uncertainty over which artery to treat for optimum reperfusion. Direct reperfusion (DR) targets the artery supplying the ischaemic tissue. Indirect reperfusion (IR) targets an artery supplying collaterals to the ischaemic area. Our unit practice for the last eight years has been to attempt to open all tibial arteries at the time of angioplasty. When successful, this results in both direct and indirect; or combined reperfusion (CR). The aim was to review the outcomes of CR and compare them with DR or IR alone., Methods: An eight year retrospective review from a single unit of all infra-popliteal angioplasties was undertaken. Wound healing, limb salvage, amputation-free and overall survival data as well as re-intervention rates were captured for all patients. Subgroup analysis for diabetics was undertaken. Kaplan Meier curves are presented for survival outcomes. All odds and hazard ratios (HR) and p values were corrected for bias from confounders using multivariate analysis., Results: 250 procedures were performed: 22 (9%) were CR; 115 (46%) DR and 113 (45%) IR. Amputation-free survival (HR 0.504, p = 0.039) and re-intervention and amputation-free survival (HR 0.414, p = 0.005) were significantly improved in patients undergoing CR compared to IR. Wound healing was similarly affected by reperfusion strategy (OR = 0.35, p = 0.047). Effects of CR over IR were similar when only diabetic patients were considered., Conclusions: Combined revascularisation can only be achieved in approximately 10% of patients. However, when successful, it results in significant improvements in wound healing and amputation-free survival over simple indirect reperfusion techniques.

While the overwhelming majority of wounds heal rapidly, a significant proportion fail to progress through the wound-healing process. These resultant chronic wounds cause considerable morbidity and are costly to treat. Wound bed preparation, summarised by the TIME (Tissue, Inflammation/infection, Moisture imbalance, Epithelial edge advancement) concept, is a systematic approach for assessing chronic wounds. Each of these components needs to be addressed and optimised to improve the chances of successful wound closure. We present an up-to-date literature review of the most important recent aspects of wound bed preparation. While there are many novel therapies that are available to the treating clinician, often, there are limited data on which to assess their clinical value, and a lack of appreciation for adequate wound bed preparation needed before expensive therapy is used to heal a wound., (© 2016 Medicalhelplines.com Inc and John Wiley & Sons Ltd.)

Chronic intractable pain is a common problem in severe pancreatic disease. Bilateral thoracoscopic splanchnotomy, a thoracoscopic neurotomy of the splanchnic nerves, is rarely performed but may provide significant pain relief in these patients. We present a safe strategy that uses prone positioning and two thoracoscopic ports for either hemithorax, permitting easy exposure and simple dissection of the greater and lesser splanchnic nerves. In our experience, this technique provides excellent pain relief with a minimal postoperative stay and few postoperative adverse events. This intervention has the potential to reduce dependency on opioid agents and improve quality of life in carefully selected patients., (Copyright © 2016 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Heel ulceration, most frequently the result of prolonged pressure because of patient immobility, can range from the trivial to the life threatening. Whilst the vast majority of heel pressure ulcers (PUs) are superficial and involve the skin (stages I and II) or underlying fat (stage III), between 10% and 20% will involve deeper tissues, either muscle, tendon or bone (stage IV). These stage IV heel PUs represent a major health and economic burden and can be difficult to treat. The worst outcomes are seen in those with large ulcers, compromised peripheral arterial supply, osteomyelitis and associated comorbidities. Whilst the mainstay of management of stage I-III heel pressure ulceration centres on offloading and appropriate wound care, successful healing in stage IV PUs is often only possible with surgical intervention. Such intervention includes simple debridement, partial or total calcanectomy, arterial revascularisation in the context of coexisting peripheral vascular disease or using free tissue flaps. Amputation may be required for failed surgical intervention, or as a definitive first-line procedure in certain high-risk or poor prognosis patient groups. This review provides an overview of heel PUs, alongside a comprehensive literature review detailing the surgical interventions available when managing such patients., (© 2015 Medicalhelplines.com Inc and John Wiley & Sons Ltd.)

Coral reef aorta is a rare condition characterised by extreme calcific growths affecting the juxta and suprarenal aorta. It can cause symptoms due to visceral ischaemia, lower limb hypoperfusion, and distal embolisation. We present a case of a 61-year-old man with unresponsive hypertension, who was found to have an occluded right renal artery, and an extensive coral reef aorta with a marked pressure gradient across the lesion. Renal hypoperfusion secondary to aortic coral reef aorta was thought to be the cause for his hypertension. Endovascular placement of a balloon expandable uncovered stent resolved his hypertension within one month, with no adverse effects noted at subsequent follow-up. Endovascular treatment of coral reef aorta is technically possible and avoids a major vascular procedure., (© The Author(s) 2014.)

Background: The incidence of incisional hernias (IHs) following midline abdominal incisions is difficult to estimate. Furthermore recent analyses have reported inconsistent findings on the superiority of absorbable versus non-absorbable sutures., Objective: To estimate the mean IH rate following midline laparotomy from the published literature, to identify variables that predict IH rates and to analyse whether the type of suture (absorbable versus non-absorbable) affects IH rates., Methods: We undertook a systematic review according to PRISMA guidelines. We sought randomised trials and observational studies including patients undergoing midline incisions with standard suture closure. Papers describing two or more arms suitable for inclusion had data abstracted independently for each arm., Results: Fifty-six papers, describing 83 separate groups comprising 14,618 patients, met the inclusion criteria. The prevalence of IHs after midline incision was 12.8% (range: 0 to 35.6%) at a weighted mean of 23.7 months. The estimated risk of undergoing IH repair after midline laparotomy was 5.2%. Two meta-regression analyses (A and B) each identified seven characteristics associated with increased IH rate: one patient variable (higher age), two surgical variables (surgery for AAA and either surgery for obesity surgery (model A) or using an upper midline incision (model B)), two inclusion criteria (including patients with previous laparotomies and those with previous IHs), and two circumstantial variables (later year of publication and specifying an exact significance level). There was no significant difference in IH rate between absorbable and non-absorbable sutures either alone or in conjunction with either regression analysis., Conclusions: The IH rate estimated by pooling the published literature is 12.8% after about two years. Seven factors account for the large variation in IH rates across groups. However there is no evidence that suture type has an intrinsic effect on IH rates.

Objective: The aim of this systematic review and meta-analysis was to evaluate the effects of using an intraoperatively placed perineural catheter (PNC) with a postoperative local anaesthetic infusion on immediate and long-term outcomes after lower limb amputation., Methods: A systematic review of key electronic journal databases was undertaken from inception to January 2015. Studies comparing PNC use with either a control, or no PNC, were included. Meta-analysis was performed for postoperative opioid use, pain scores, mortality, and long-term incidence of stump and phantom limb pain. Sensitivity analysis was performed for opioid use. Quality of evidence was assessed using the GRADE system., Results: Seven studies reporting on 416 patients undergoing lower limb amputation with PNC usage (n = 199) or not (n = 217) were included. Approximately 60% were transtibial amputations PNC use reduced postoperative opioid consumption (standardised mean difference: -0.59, 95% CI -1.10 to -0.07, p = .03), maintained on sensitivity analysis for large (p = .03) and high-quality (p = .003) studies, but was marginally lost (p = .06) on studies enrolling patients with peripheral arterial disease only. PNC treatment did not affect postoperative pain scores (p = .48), in-hospital mortality (p = .77), phantom limb pain (p = .28) or stump pain (p = .37). GRADE quality of evidence for all outcomes was very low., Conclusion: There is poor-quality evidence that PNC usage significantly reduces opioid consumption following lower limb amputation, without affecting other short- or long-term outcomes. Well-performed randomised studies are required., (Copyright © 2015 European Society for Vascular Surgery. Published by Elsevier Ltd. All rights reserved.)

Hepatocyte growth factor-like protein (HGFl) and its receptor, Recepteur d'Origine Nantais (RON), have been implicated in the development of wound chronicity. HGFl and RON expression was detected in acute wound tissue, chronic wound tissue and in normal skin using quantitative polymerase chain reaction (Q-PCR). HGFl and RON expression was also assessed in chronic healing and chronic non-healing wound tissues using Q-PCR and immunohistochemical staining. Expression was similarly detected in the HaCaT immortalized human keratinocyte cell line using reverse transcription polymerase chain reaction (RT-PCR). rhHGFl was used to assess the impact of this molecule on HaCaT cell functionality using in vitro growth assays and electric cell-substrate impendence sensing (ECIS) migration assays. HGFl and RON transcript expression were significantly increased in acute wound tissue compared to chronic wound tissue and were also elevated, though non-significantly, in comparison to normal skin. Minimal expression was seen in both healing and non-healing chronic wounds. Treatment of HaCaT cells with rhHGFl had no effect on growth rates but did enhance cell migration. This effect was abolished by the addition of a phospholipase C gamma (PLCγ) small molecule inhibitor. The increased expression of HGFl and RON in acute, healing wounds and the pro-migratory effect of HGFl in an in vitro human keratinocyte model, may indicate a role for HGFl in active wound healing.

Purpose: The aim of this study was to identify significant factors relating to fistula survival and create an easy-to-use scoring system for predicting fistula patency rates., Methods: A total of 276 consecutive radio-cephalic forearm fistulae created in a single tertiary vascular unit were identified retrospectively. Numerous patient- and fistula-related demographics were noted. Cox regression analysis was used to identify significant factors predictive of reduced fistula patency rates, and significant variables weighted according to their hazard ratio., Results: Five significant factors were identified: ipsilateral Central venous access, Age >73 years, anastomosed Vein <2.2 mm, previous lower limb Angioplasty and absent intra-operative Thrill (1 point for first three variables, 2 points for the latter two). The CAVeA2T2 score (maximum 7 points) significantly predicted for reduced fistula patency (p = 0.001) and a reduced rate of successful dialysis (p = 0.001). Fistulae with CAVeA2T2 scores ≥2 had 6 week and 1 year patency rates significantly below pooled published rates. Without scoring for thrill, that is in the pre-operative setting, the scoring system remained significant at all stages., Conclusion: The CAVeA2T2 scoring system is a potential scoring system for predicting fistula patency rates and the likelihood of dialysing through a fistula. Further studies and/or external validation is required in the context of methodological limitations. How to manage patients with a high CAVeA2T2 score is unknown.

Motility is a requirement for a number of biological processes, including embryonic development, neuronal development, immune responses, cancer progression and wound healing. Specific to wound healing is the migration of endothelial cells, fibroblasts and other key cellular players into the wound space. Aberrations in wound healing can result in either chronic wounds or abnormally healed wounds. The protein 4.1R, ezrin, radixin, moesin (FERM) superfamily consists of over 40 proteins all containing a three lobed N-terminal FERM domain which binds a variety of cell-membrane associated proteins and lipids. The C-terminal ends of these proteins typically contain an actin-binding domain (ABD). These proteins therefore mediate the linkage between the cell membrane and the actin cytoskeleton, and are involved in cellular movements and migration. Certain FERM proteins have been shown to promote cancer metastasis via this very mechanism. Herein we review the effects of a number of FERM proteins on wound healing and cancer. We show how these proteins typically aid wound healing through their effects on increasing cellular migration and movements, but also typically promote metastasis in cancer. We conclude that FERM proteins play important roles in cellular migration, with markedly different outcomes in the context of cancer and wound healing.

Objective: The aim of this systematic review was to evaluate outcomes of direct revascularisation (DR) versus indirect revascularisation (IR) of infrapopliteal arteries to the affected angiosome for critical limb ischaemia. Both open and endovascular techniques were included., Methods: A systematic review of key electronic journal databases was undertaken from inception to 22 March 2014. Studies comparing DR versus IR in patients with localised tissue loss were included. Meta-analysis was performed for wound healing, limb salvage, mortality, and re-intervention rates, with numerous sensitivity analyses. Quality of evidence was assessed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) system., Results: Fifteen cohort studies reporting on 1,868 individual limbs were included (endovascular revascularisation, 1,284 limbs; surgical revascularisation, 508 limbs; both methods, 76 limbs). GRADE quality of evidence was low or very low for all outcomes. DR resulted in improved wound healing rates compared with IR (odds ratio [OR] 0.40, 95% confidence interval [CI] 0.29-0.54) and improved limb salvage rates (OR 0.24, 95% CI 0.13-0.45), although this latter effect was lost on high-quality study sensitivity analysis. Wound healing and limb salvage was improved for both open and endovascular intervention. There was no effect on mortality (OR 0.77, 95% CI 0.50-1.19) or reintervention rates (OR: 0.44, 95% CI 0.10-1.88)., Conclusion: DR of the tibial vessels appears to result in improved wound healing and limb salvage rates compared with IR, with no effect on mortality or reintervention rates. However, the quality of evidence on which these conclusions are based on is low., (Copyright © 2014 European Society for Vascular Surgery. Published by Elsevier Ltd. All rights reserved.)

Multiple factors affect the likelihood of a wound healing. One of these factors, wound duration, is well known to be related to healing rates, with numerous publications showing that older wounds are less likely to heal. However, disentangling the effect of this factor on wound healing rates is complex. Is this simply an observation of the obvious; wounds of longer duration will by definition be harder to heal? Or does time represent an independent factor, implying that should treatments be given earlier in the disease process, better outcomes may result? This review summarizes the available evidence of the effects of wound duration on healing rates and examines potential biological aberrations identified in chronic wounds, which may be significant in making chronic wounds difficult to heal. Wounds of longer duration are associated with excessive inflammation, fibroblast senescence, and alterations in wound bed flora, which appears to have a temporal relationship. Early and aggressive treatment of ulcers that fail to respond to standard care may well aid in reducing the burden of wounds that become chronic., (© 2014 by the Wound Healing Society.)

Background: Multiple factors have been shown to delay dermal wound healing. These resultant wounds pose a significant problem in terms of morbidity and healthcare spend. Recently, an increasing volume of research has focused on the molecular perturbations underlying non-healing wounds., Objectives: This study investigates the effect of a novel cancer promoter, Ehm2, in wound healing. Ehm2 belongs to the FERM family of proteins, known to be involved in membrane-cytoskeletal interactions, and has been shown to promote cancer metastasis in melanoma, prostate cancer and breast cancer., Methods: Ehm2 mRNA levels were analysed using qRT-PCR, standardised to GAPDH, from either acute or chronic wounds, and normal skin. IHC analysis was also undertaken from wound edge biopsies. An anti-Ehm2 transgene was created and transfected into the HaCaT cell line. The effect of Ehm2 knockdown on migration, adhesion, growth, cell cycle progression and apoptosis was analysed using standard laboratory methods. Western Blot analysis was used to investigate potential downstream protein interactions., Results: Ehm2 is expressed nearly three times higher in acute wound tissues, compared to chronic wound tissues. Increased Ehm2 expression is found in wounds undergoing healing, especially at the leading wound edge. In vitro, Ehm2 knockdown reduces cellular adhesion, migration and motility, without affecting growth, cell cycle and apoptosis. Finally, Ehm2 knockdown results in reduced NWasp protein expression., Conclusion: These results suggest Ehm2 may be an important player in the wound healing process, and show that Ehm2 knockdown downregulates the expression of NWasp, through which it may have its effect on cellular migration., (Copyright © 2013 Japanese Society for Investigative Dermatology. Published by Elsevier Ireland Ltd. All rights reserved.)