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Surgical site infections represent a considerable burden for healthcare systems. To obtain a consensus on the impact and future clinical and economic needs regarding SSI management in an era of multidrug resistance. A modified Delphi method was used to obtain consensus among experts from five European countries. The Delphi questionnaire was assembled by a steering committee, verified by a panel of experts and administered to 90 experts in 8 different surgical specialities (Abdominal, Cancer, Cardiac, General surgery, Orthopaedic, Thoracic, Transplant and Vascular and three other specialities (infectious disease, internal medicine microbiology). Respondents (n = 52) reached consensus on 62/73 items including that resistant pathogens are an increasing matter of concern and increase both treatment complexity and the length of hospital stay. There was strong positive consensus on the cost-effectiveness of early discharge (ED) programs, improvement of quality of life with ED and association between increased length of stay and economic burden to the hospital. However, established ED protocols were not widely available in their hospitals. Respondents expressed a positive consensus on the usefulness of antibiotics that allow ED. Surgeons are aware of their responsibility in an interdisciplinary team for the treatment of SSI, and of the impact of multidrug-resistant bacteria in the context of SSI. Reducing the length of hospital stays by applying ED protocols and implementing new treatment alternatives is crucial to reduce harm to patients and costs for the hospital., (© 2021. The Author(s).)

Objective: The goal of any topical formulation is efficient transdermal delivery of its active components. However, delivery of compounds can be problematic with penetration through tough layers of fibrotic dermal scar tissue. Approach: We propose a new approach combining high-performance liquid chromatography (HPLC) and Raman spectroscopy (RS) using a topical of unknown composition against a well-known antiscar topical (as control). Results: Positive detection of compounds within the treatment topical using both techniques was validated with mass spectrometry. RS detected conformational structural changes; the 1,655/1,446 cm -1 ratio estimating collagen content significantly decreased ( p  < 0.05) over weeks 4, 12, and 16 compared with day 0. The amide I band, known to represent collagen and protein in skin, shifted from 1,667 to 1,656 cm -1 , which may represent a change from β-sheets in elastin to α-helices in collagen. Confirmatory elastin immunohistochemistry decreased compared with day 0, conversely the collagen I/III ratio increased in the same samples by week 12 ( p  < 0.05, and p  < 0.0001, respectively), in keeping with normal scar formation. Optical coherence tomography attenuation coefficient representing collagen deposition was significantly decreased at week 4 compared with day 0 and increased at week 16 ( p  < 0.05). Innovation: This study provides a platform for further research on the simultaneous evaluation of the effects of compounds in cutaneous scarring by RS and HPLC, and identifies a role for RS in the therapeutic evaluation and theranostic management of skin scarring. Conclusions: RS can provide noninvasive information on the effects of topicals on scar pathogenesis and structural composition, validated by other analytical techniques.

Background: Transcatheter aortic valve implantation (TAVI) is most commonly performed via the femoral approach. Small caliber ilio-femoral arteries, severe calcification and tortuosity are often prohibitive reasons for TAVI via the femoral approach. Mid-aortic syndrome is a rare condition describing congenital or acquired coarctation of the abdominal aorta., Case Summary: To the best of our knowledge, this case report describes the world's first TAVI in a patient with mid-aortic syndrome with challenging vascular access that would preclude conventional TAVI access routes. A 76-year-old woman with intermittent claudication, underwent work-up for axillo-bifemoral bypass, underwent a TAVI for incidental severe asymptomatic severe aortic stenosis via right common carotid TAVI facilitated by innominate artery angioplasty achieved vascular access for TAVI. Percutaneous coronary intervention to a right coronary artery vein graft was simultaneously performed via a left brachial artery cut down., Discussion: We demonstrate that complex angioplasty to coronary artery bypass grafts and the innominate artery alongside TAVI via a variety of arterial access sites is both safe and feasible., (© The Author(s) 2020. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Profiling skin microbiome and metabolome has been utilised to gain further insight into wound healing processes. The aims of this multi-part temporal study in 11 volunteers were to analytically profile the dynamic wound tissue and headspace metabolome and sequence microbial communities in acute wound healing at days 0, 7, 14, 21 and 28, and to investigate their relationship to wound healing, using non-invasive quantitative devices. Metabolites were obtained using tissue extraction, sorbent and polydimethylsiloxane patches and analysed using GCMS. PCA of wound tissue metabolome clearly separated time points with 10 metabolites of 346 being involved in separation. Analysis of variance-simultaneous component analysis identified a statistical difference between the wound headspace metabolome, sites (P = 0.0024) and time points (P<0.0001), with 10 out of the 129 metabolites measured involved with this separation between sites and time points. A reciprocal relationship between Staphylococcus spp. and Propionibacterium spp. was observed at day 21 (P<0.05) with a statistical correlation between collagen and Propionibacterium (r = 0.417; P = 0.038) and Staphylococcus (r = -0.434; P = 0.03). Procrustes analysis showed a statistically significant similarity between wound headspace and tissue metabolome with non-invasive wound devices. This exploratory study demonstrates the temporal and dynamic nature of acute wound metabolome and microbiome presenting a novel class of biomarkers that correspond to wound healing, with further confirmatory studies now necessary., Competing Interests: The authors have declared that no competing interests exist.

Background: Epigallocatechin-3-gallate (EGCG), a polyphenol, influences cutaneous wound healing because of its antiangiogenic, anti-inflammatory, and antioxidant properties. We previously showed the role of EGCG in scarring in ex vivo human scar models. Here, we evaluate direct application of topical EGCG compared with zonal priming, a unique concept in the immediate treatment of the zone of injury at the time of wounding before scar formation., Trial Design: Double-blind randomized controlled trial., Methods: We assessed EGCG application compared with placebo over 1-6 weeks in scars created in 62 human volunteers using quantitative noninvasive devices, immunohistochemical analysis, mRNA sequencing, and quantitative real-time reverse transcriptase-PCR of tissue biopsy samples., Results: EGCG reduced mast cells at weeks 1-3, as evidenced by gene and protein analyses (P ≤ 0.01). M2 macrophages were increased with EGCG compared with placebo. EGCG application by zonal priming significantly down-regulated VEGFA and CD31 at week 1 and at 1-2 weeks after direct application (P ≤ 0.01). Direct EGCG application also reduced scar thickness at weeks 1-3 (P = 0.001) and increased scar elasticity at week 4 (P = 0.01). Increased hydration was evident both noninvasively and by increased hyaluronic acid levels (P < 0.01) at week 3., Conclusions: We show the beneficial role of both zonal priming and direct EGCG application in scar therapy with positive effects on scar thickness, erythema, hydration, and elasticity. Trial register: International standard randomized controlled trial, registration number ISRCTN 18643079; July 16, 2018., (Copyright © 2019 The Authors. Published by Elsevier Inc. All rights reserved.)

Objective: Many topicals claim an efficacious role in skin scar management with limited evidence. Our aim is to present a clear format for functional testing of a skin scarring ointment, using noninvasive and invasive measurements, categorizing findings under the physiological, structural, and mechanical parameters of a scar. Approach: A double-blinded, randomized volunteer research study of 45 subjects receiving an ointment composing of natural ingredients against a widely used antiscarring topical used as a positive control with temporal sequential punch biopsies (up to 16 weeks) was evaluated using noninvasive quantitative devices and validated by gene and protein studies. Results: Outcome measures included physiological, mechanical, and structural features of scars. Significant non-invasive findings included an increase in skin hydration ( p  < 0.05) at week (W) 4, 8, and 12, and elasticity (W16; p  = 0.009). These findings were validated by immunohistochemistry (IHC) and quantitative real-time PCR (qRT-PCR). Hyaluronic acid IHC (W4 p  = 0.014, W12 p  = 0.034, and W16 p  = 0.042), qRT-PCR (W16 p  = 0.049); Collagen I (W16 p  = 0.034, and 0.049) IHC and qRT-PCR, respectively. Collagen III qRT-PCR (W12 p  = 0.035, and W16 p  = 0.32); elastin IHC (W12 p  = 0.044); and fibronectin IHC (W4 p  = 0.009, W12 p  = 0.038, and W16 p = 0.026). Innovation: Utilizing this model allows for quantitative, objective evaluation of any topical, where previously there has been a paucity of relevant methods to evaluate their effect. Conclusions: The positive effect of a topical formulation with an unknown mechanism of action on early cutaneous scar maturation over progressive sequential time points is now evidenced using noninvasive and invasive techniques with the findings categorized on the basis of scarring parameters., Competing Interests: R.A.K. is an employee of Julphar Gulf Pharmaceutical Industries, UAE. For R.B., M.B., P.F., and A.B., no competing financial interests exist. The content of this article was expressly written by the authors listed. No ghostwriters were used to write this article., (Copyright 2019, Mary Ann Liebert, Inc., publishers.)

Management of biofilm infections relies on time-consuming laboratory techniques and monitoring treatment by subjective clinical evaluations. Due to these limitations, there is a need to explore alternative strategies. The aims of this study were to assess the feasibility of using volatile organic compound (VOC) biomarkers to monitor treatment response and measure anti-biofilm efficacy of electrical stimulation (ES) in vitro and in human cutaneous wound biofilm models. Staphylococcus aureus (MSSA) and Pseudomonas aeruginosa (PA) biofilms were exposed to ES, ciprofloxacin, or both, with efficacy assessed and quantified by fluorescence staining, enumeration, metabolic assays, and biomass quantification; VOCs were measured by gas chromatography-mass spectrometry. In vitro MSSA and PA and ex vivo PA biofilms exposed to ES showed significantly reduced bacterial viability, metabolic activity, and biomass compared to controls (p < 0.05). There was significant variation in the relative abundance of VOCs in in vitro MSSA and PA and in ex vivo PA biofilms exposed to ES and antibiotic (p < 0.05). 2-methyl-1-propanol was associated with MSSA viability (R = 0.93, p < 0.05), biomass (R = 0.97, p < 0.05), and metabolic activity (R = 0.93, p < 0.05) and 3-methyl-1-butanol was associated with PA biomass (R = 0.93, p < 0.05). We showed that ES and VOC biomarkers are possible options for alternative nonpharmacological antimicrobial management of biofilms and noninvasive monitoring of wound infection treatment responses, respectively., (© 2018 by the Wound Healing Society.)

Biofilms are major contributors to delayed wound healing and there is a need for clinically relevant experimental models to assess theranostics. Microorganisms release volatile organic compounds (VOCs) and the ability to identify these in infected cutaneous wounds could lead to efficient non-invasive diagnosis. The aims here were to develop and assess bacterial biofilm formation and identify their VOC profiles in an in vitro model and validate in human ex vivo incisional and excisional cutaneous wound models. Biofilm development was assessed using multiple microscopy techniques with biofilm-forming deficient controls and quantified using metabolic and biomass assays; and VOC production measured by gas chromatography-mass spectrometry. The production of most VOCs was affected by biofilm development and model used. Some VOCs were specific either for planktonic or biofilm growth. The relative abundance of some VOCs was significantly increased or decreased by biofilm growth phase (P < 0.05). Some Staphylococcus aureus and Pseudomonas aeruginosa VOCs correlated with biofilm metabolic activity and biomass (R ≤ -0.5; ≥0.5). We present for the first time bacterial biofilm formation in human ex vivo cutaneous wound models and their specific VOC profiles. These models provide a vehicle for human skin-relevant biofilm studies and VOC detection has potential clinical translatability in efficient non-invasive diagnosis of wound infection.

Chronic cutaneous wound infections and surgical site infections (SSIs) present a huge burden on the healthcare system and can lead to increased morbidity and mortality. Current diagnostic methods of identifying and confirming infection involve culture-based and molecular methods. Both techniques are time-consuming and delays commonly lead to untargeted empirical treatment. An ideal diagnostic method would be noninvasive and highly sensitive and detect pathogenic organisms with a high degree of accuracy to allow targeted treatment. Volatile organic compounds (VOCs) are a diverse group of carbon-based molecules produced and released by humans and microorganisms. VOC detection has the potential in aiding cutaneous wound infection diagnostics using noninvasive and time-efficient methods. This review provides a comprehensive update on VOCs produced and emitted by bacteria commonly associated with chronic wounds and SSIs. VOC sampling has the advantage of being painless, time-efficient, noninvasive, and reproducible. VOCs emitted by these organisms are diverse. In vitro studies have identified potential signature volatile profiles, which can be used in detecting these microorganisms. Combining these profiles with volatile profiles emitted from acute, chronic and surgical wounds in vivo could potentially allow identification of bacterial-specific VOCs. VOC detection has the potential for a relatively inexpensive, portable, noninvasive, and reliable clinical diagnostic tool, which could be used in detecting cutaneous wound infections and guiding their optimal management., (© 2017 by the Wound Healing Society.)

Background: Surgical lower extremity revascularisation (LER) can lead to poor outcomes that include delayed hospital discharge, in-hospital mortality, major amputations and readmissions. The aim of this study was to identify pre-operative predictors associated with these poor clinical outcomes., Materials and Methods: All patients (n = 635; mean age 69; male 67.4%) who underwent surgical LER over a 5 year period in a single tertiary vascular institution were identified. Patients considered to have suffered a poor outcome (Group A) included all in-hospital mortality and major amputations, delayed discharges with a length of stay (LOS) over one standard deviation above the mean or any readmission under any specialty within 12 months. Group A included 247 patients (38.9%) and the good outcome group included the remaining 388 patients (61.1%) from which a sample of 99 patients were selected as controls (Group B)., Results: Mean LOS for the entire study group was 14.4 ± 17.5 days, 12 month readmission rate was 29.1% and in-hospital mortality and major amputation rate was 2.7% and 1.4%, respectively. Pre-admission residence other than own home (OR 9.0; 95% CI 1.2-70.1; P = 0.036), atherosclerotic disease burden (OR 2.2; 95% CI 1.3-3.8; P = 0.003) and tissue loss (OR 3.0; 95% CI 1.6-5.3; P < 0.001) were identified as independent, statistically significant pre-operative predictors of poor outcome. Following discharge, group B patients had a significantly higher rate of amputation free survival and graft infection free survival (P < 0.001) compared to group A., Conclusion: Recognition of pre-operative predictors of poor outcome should inform case selection and identify high risk patients requiring intensive perioperative optimisation and post discharge follow up., (Copyright © 2017 IJS Publishing Group Ltd. Published by Elsevier Ltd. All rights reserved.)

Infection contributes significantly to delayed cutaneous wound healing, which impacts patient care. External application of electrical stimulation (ES) has beneficial effects on wound repair and regeneration. The majority of studies to date have explored ES in relation to planktonic microorganisms, yet evidence indicates that bacteria in chronic wounds reside as antibiotic-resistant polymicrobial biofilms, which contribute to impairing wound healing. Culture-independent sequencing techniques have revolutionized our understanding of the skin microbiome and allowed a more accurate determination of microbial taxa and their relative abundance in wounds allowing a greater understanding of the host-microbial interface. Future studies combining the fields of ES, biofilm and microbiome research are necessary to fully elucidate the use of ES in the management of wound infection.

We evaluated our experience following the introduction of a percutaneous endovascular aneurysm repair (pEVAR) first approach using Perclose Proglide assessing efficacy, complications, and identification of factors that could predict failure. A retrospective cohort study on patients over a 2-year period following the introduction of a pEVAR first approach was performed. The primary end point was defined as successful deployment and access site hemostasis. Percutaneous EVAR was technically successful in 41 (77.4%) of 53 patients and 83 (86.5%) of 96 access sites. Factors associated with failure were smaller common femoral artery (CFA) diameter ( P = .045) and CFA circumferential calcification of greater than 50% ( P = .0001). The incidence of access site infection was significantly higher in the failure group ( P = .008) as was procedure duration ( P = .026). Percutaneous EVAR first approach must be introduced with caution. Percutaneous EVAR failure occurs more often in patients with unfavorable access site anatomy. Success rate can be improved with careful patient selection.

Current gold standard lower extremity cutaneous wound management is not always effective. Cutaneous wounds generate a "current of injury" which is directly involved in wound healing processes. Application of exogenous electrical stimulation has been hypothesised to imitate the natural electric current that occurs in cutaneous wounds. The aim of this extensive review was to provide a detailed update on the variety of electrical stimulation modalities used in the management of lower extremity wounds. Several different waveforms and delivery methods of electrical stimulation have been used. Pulsed current appears superior to other electrical modalities available. The majority of studies support the beneficial effects of pulsed current over conservative management of lower extremity cutaneous wounds. Although it appears to have no benefit over causal surgical intervention, it is a treatment option which could be utilised in those patients unsuitable for surgery. Other waveforms and modalities appear promising; however, they still lack large trial data to recommend a firm conclusion with regards to their use. Current studies also vary in quantity, quality and protocol across the different modalities. The ideal electrical stimulation device needs to be non-invasive, portable and cost-effective and provides minimal interference with patients' daily life. Further studies are necessary to establish the ideal electrical stimulation modality, parameters, method of delivery and duration of treatment. The development and implementation of newer devices in the management of acute and chronic wounds provides an exciting direction in the field of electrotherapy., (© 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)