Value of clinical, ultrasonographic and MRI signs as diagnostic differentiators of non-benign lipomatous tumours.

Suspicion of malignant change within a lipoma is a common and increasing workload within the UK Sarcoma multidisciplinary team (MDT) network, and a source of considerable patient anxiety. Currently, there is no lipoma-specific data, with regard to which clinical or radiographic features predict non-benign histology, or calculate an odds-ratio specific to a lipomatous lesion being non-benign. We performed a 9-year, double-blind, unmatched cohort study, comparing post-operative histology outcomes (benign versus non-benign) versus 15 signs across three domains: Clinical (size of tumour, depth, growth noticed by patient, previous lipoma, patient felt pain), Ultrasonographic (size, depth, vascularity, heterogenous features, septae) and MRI (size, depth, vascularity, heterogenous features, septae, complete fat signal suppression). Receiver operating characteristic (ROC) analysis, odds ratios and binary logistic regression analysis was performed double-blind. When each sign is considered independently, (ROC analysis, followed by binary logistic regression) only Ultrasound depth is a significant predictor (p = 0.044) of a histologically non-benign lipoma. Ultrasonographically determined vascularity and septation were not statistically significant predictors. None of the clinical signs were statistically significant (p > 0.05). Of the MRI signs none was statistically significant (p > 0.05). However, heterogeneous MRI features fared better than MRI depth. Ultrasound signs (Pseudo R-Square = 0.105) are more predictive of the post-operation histology outcome than Clinical signs (Pseudo R-Square = 0.082) or MRI tests (Pseudo R-Square = 0.052) Ultrasound and Clinical tests combined (Pseudo R-Square = 0.147) are more predictive of the post-operation histology outcome than MRI tests (Pseudo R-Square = 0.052). This work challenges the traditional perception of "red-flag" signs when applied to lipomatous tumours. We provide accurate data upon which an informed choice can be made, and provides a robust bases for expedited risk/benefit. The importance of an experienced and cohesive MDT network is emphasised.

Cutaneous laser surgery for secondary burn reconstruction: Cost benefit analysis.

Thermal disease presents a major burden to individual patient morbidity, healthcare cost as well as to over all economy. Burns also also represent a significant per-patient utlilisation of finite healthcare resources. Secondary complications in these patients, such as multiple drug resistant organisms, may have a devastating effect. Laser surgery has recently come of age as an optimal tool in the secondary reconstruction of burn injury, that is able to simultaneously address significant sheet scar tightness, hypertrophic, atrophic, and keloid complications, pruritus, microstomia, ectropion, skin graft honeycombing, and improve range of movement whilst reducing the risk of infection to <1%. Yet, cutaneous laser surgery is often underutilised due to the perceived concerns about the sustainability of a new service with relatively high startup cost. We present a dual methodology to explore this concern: an evidence-based background review of the last 5 years of current best evidence, and a 22-year cost-analysis comparison at an established, high volume UK Centre of reconstructive surgery. We report that fiscal viability for laser surgery services for secondary burn reconstruction is supported by: level 2 (one systematic review) level 4 evidence (2 studies) and level 5 evidence (expert reports). Evidence over 22 years from an established super-regional NHS laser centre shows that introduction of this service led to sustained and substantial cost saving, producing excellent surgical results at a fraction of the cost of traditional surgery. Analysis of the potential dollar-effect of these advantages to the general population supports state investment in expertise and capital equipment as a medium to long-term cost saving strategy, which may also aid re-integrating patients into the workforce making a meaningful contribution to the economy.

New Developments for Fractional Co2 Resurfacing for Skin Rejuvenation and Scar Reduction.

Fractional CO2 procedures are an established, safe and effective armamentarium for managing skin rejuvenation and scarring. Very short-pulse-duration devices offer a very high ablated volume/ablated surface ratio, inducing a controlled thermal damage. With this kind of device, each procedure can be customized on the features of the skin of each patient. The same device can be used to treat severe burn scars. With a very deep fractional procedure on a scar tissue, immediate relaxation of the tension and retraction forces may be obtained, and downstream, improvements are related more to the activation of a molecular cascade. The authors review the state-of-the-art, in the use of fractioned CO2 laser technology for aesthetic and scar remodelling indications.

Chromophores in operative surgery: Current practice and rationalized development.

BACKGROUND: Chromophore-containing molecules feature extensively in surgical practice, with synthetic dyes gaining popularity over endogenous optical adjuncts. New applications for chromophores in diagnostics and operative treatment exploit unique chemical structures suited for illuminating target tissues beyond the visual spectrum, ranging from ultraviolet (UV) to near-infrared (NIR). This review outlines the rationale for surgical chromophore application, the weaknesses and risks in each class of these compounds, and areas of foreseeable potential for employment of specialized contrast agents. METHOD: An English-language literature search applied the following Boolean Search String: "dye OR Lake OR Stain OR chromophore" AND "tox$ OR terato* OR carcino$ OR Allerg$ OR surg$ OR clinic" using EMBASE, PUBMED, PUBMED central and OVIDSp, with back-referencing through Web of Knowledge™. RESULTS: Based on the primary literature, this study proposes a surgically relevant classification system of chromophores in current use, which facilitates risk/benefit consideration for the surgeon who employs them, and which facilitates clinically oriented development. CONCLUSIONS: The next stage of development for optically active surgical adjuncts must address practical constraints whilst minimizing risks of adverse effects. Exploiting the technology's full potential also requires improvements in the usefulness of imagery equipment.

Measuring coagulation in burns: an evidence-based systematic review.

INTRODUCTION: Dynamic monitoring of coagulation is important to predict both haemorrhagic and thrombotic complications and to guide blood product administration. Reducing blood loss and tailoring blood product administration may improve patient outcome and reduce mortality associated with transfusion. The current literature lacks a systematic, critical appraisal of current best evidence on which clinical decisions may be based. OBJECTIVES: Establishing the role of different coagulation markers in burn patients, diagnosing coagulopathy, tailoring blood product administration and indicating prognosis. METHODS: Literature during 2004-2017 from the Cochrane Library, PubMed, Scopus, Medline and Embase was reviewed. Eligibility criteria included randomised controlled trials, systematic reviews, multi-/single-centre study and meta-analyses. Keywords searched were 'burns', 'blood coagulation disorders', 'rotem', 'blood coagulation' and 'thromboelastography'. The PRISMA flow system was used for stratification and the CASP framework for appraisal of the studies retrieved. RESULTS: In total, 13 articles were included after inclusion/exclusion criteria had been applied to the initial 79 studies retrieved. Hypercoagulation increases in proportion to the severity of thermal injury. Whole blood testing, using thrombelastography (TEG) and rotation thromboelastometry (ROTEM), was superior to standard plasma based tests, including prothrombin time (PT) and activated partial thromboplastin time (APTT) at detecting burn-related coagulopathies. CONCLUSIONS: Routine laboratory markers such as PT/APTT are poor indicators of coagulation status in burns patients. Viscoelastic tests, such as TEG and ROTEM, are efficient, fast and have a potential use in the management of burn patients; however, strong evidence is lacking. This review highlights the need for more randomised controlled trials, to guide future practice.

Polymer therapeutics in surgery: the next frontier.

Polymer therapeutics is a successful branch of nanomedicine, which is now established in several facets of everyday practice. However, to our knowledge, no literature regarding the application of the underpinning principles, general safety, and potential of this versatile class to the perioperative patient has been published. This study provides an overview of polymer therapeutics applied to clinical surgery, including the evolution of this demand-oriented scientific field, cutting-edge concepts, its implications, and limitations, illustrated by products already in clinical use and promising ones in development. In particular, the effect of design of polymer therapeutics on biophysical and biochemical properties, the potential for targeted delivery, smart release, and safety are addressed. Emphasis is made on principles, giving examples in salient areas of demand in current surgical practice. Exposure of the practising surgeon to this versatile class is crucial to evaluate and maximise the benefits that this established field presents and to attract a new generation of clinician-scientists with the necessary knowledge mix to drive highly successful innovation.

Development and validation of an in vitro pharmacokinetic/pharmacodynamic model to test the antibacterial efficacy of antibiotic polymer conjugates.

This study describes the use of a novel, two-compartment, static dialysis bag model to study the release, diffusion, and antibacterial activity of a novel, bioresponsive dextrin-colistin polymer conjugate against multidrug resistant (MDR) wild-type Acinetobacter baumannii. In this model, colistin sulfate, at its MIC, produced a rapid and extensive drop in viable bacterial counts (<2 log10 CFU/ml at 4 h); however, a marked recovery was observed thereafter, with regrowth equivalent to that of control by 48 h. In contrast, dextrin-colistin conjugate, at its MIC, suppressed bacterial growth for up to 48 h, with 3 log10 CFU/ml lower bacterial counts after 48 h than those of controls. Doubling the concentration of dextrin-colistin conjugate (to 2× MIC) led to an initial bacterial killing of 3 log10 CFU/ml at 8 h, with a similar regrowth profile to 1× MIC treatment thereafter. The addition of colistin sulfate (1× MIC) to dextrin-colistin conjugate (1× MIC) resulted in undetectable bacterial counts after 4 h, followed by suppressed bacterial growth (3.5 log10 CFU/ml lower than that of control at 48 h). Incubation of dextrin-colistin conjugates with infected wound exudate from a series of burn patients (n = 6) revealed an increasing concentration of unmasked colistin in the outer compartment (OC) over time (up to 86.3% of the initial dose at 48 h), confirming that colistin would be liberated from the conjugate by endogenous α-amylase within the wound environment. These studies confirm the utility of this model system to simulate the pharmacokinetics of colistin formation in humans administered dextrin-colistin conjugates and further supports the development of antibiotic polymer conjugates in the treatment of MDR infections.

Gram negative wound infection in hospitalised adult burn patients--systematic review and metanalysis-.

BACKGROUND: Gram negative infection is a major determinant of morbidity and survival. Traditional teaching suggests that burn wound infections in different centres are caused by differing sets of causative organisms. This study established whether Gram-negative burn wound isolates associated to clinical wound infection differ between burn centres. METHODS: Studies investigating adult hospitalised patients (2000-2010) were critically appraised and qualified to a levels of evidence hierarchy. The contribution of bacterial pathogen type, and burn centre to the variance in standardised incidence of Gram-negative burn wound infection was analysed using two-way analysis of variance. PRIMARY FINDINGS: Pseudomonas aeruginosa, Klebsiella pneumoniae, Acinetobacter baumanni, Enterobacter spp., Proteus spp. and Escherichia coli emerged as the commonest Gram-negative burn wound pathogens. Individual pathogens' incidence did not differ significantly between burn centres (F (4, 20) = 1.1, p = 0.3797; r2 = 9.84). INTERPRETATION: Gram-negative infections predominate in burn surgery. This study is the first to establish that burn wound infections do not differ significantly between burn centres. It is the first study to report the pathogens responsible for the majority of Gram-negative infections in these patients. Whilst burn wound infection is not exclusive to these bacteria, it is hoped that reporting the presence of this group of common Gram-negative "target organisms" facilitate clinical practice and target research towards a defined clinical demand.

The enhanced permeability retention effect: a new paradigm for drug targeting in infection.

Multidrug-resistant, Gram-negative infection is a major global determinant of morbidity, mortality and cost of care. The advent of nanomedicine has enabled tailored engineering of macromolecular constructs, permitting increasingly selective targeting, alteration of volume of distribution and activity/toxicity. Macromolecules tend to passively and preferentially accumulate at sites of enhanced vascular permeability and are then retained. This enhanced permeability and retention (EPR) effect, whilst recognized as a major breakthrough in anti-tumoral targeting, has not yet been fully exploited in infection. Shared pathophysiological pathways in both cancer and infection are evident and a number of novel nanomedicines have shown promise in selective, passive, size-mediated targeting to infection. This review describes the similarities and parallels in pathophysiological pathways at molecular, cellular and circulatory levels between inflammation/infection and cancer therapy, where use of this principle has been established.

Colistin in burn intensive care: back to the future?

Colistin is a venerable antibiotic whose fortunes have been revived by its excellent activity, the diminishing output of novel clinically effective antibiotics and the increasing importance of MDR infection in burn surgery, both in the civilian and military arenas. This review synthesizes current evidence on the usage of colistin in burn surgery including the structure-activity relationship; dosing, pharmacokinetics/pharmacodynamic (PK/PD), analytic methods, resistance and current research efforts into the redevelopment of this antibiotic, to distil recommendations for future research and clinical efficacy.

Colistin past and future: a bibliographic analysis.

OBJECTIVE: Colistin is a venerable drug that has found renewed interest because of multidrug resistance (MDR) and the shortfall of effective antibiotics. We present a synthesis of publication trends on MDR infection, colistin, and its adverse events, as a measure of the medical-academic community's interest, to inform current redevelopment strategies. DESIGN: This was a multidatabase electronic search over 50 years with back- and forward-referencing through Web of Knowledge. Studies were grouped into MDR, colistin, and adverse events and were plotted in 5-year clusters. RESULTS: Three periods could be mapped with distinct literature trends: A, 1940 to 1975; B, 1975 to 2000; and C, post-2000. Period A was characterized by increasing publications, soon followed by adverse-effect-themed publications. Period B reported a sharp publication decline; and period C reported a sharp increase in interest, mirroring the exponential increase in MDR literature. Period B predated standardized modern pharmacologic requirements. Period C coincided with novel drug development techniques. DISCUSSION: Two current trends (period C) were identified. Optimization of the current formulation may have been influenced by period B. Current research efforts within this trend include pharmacokinetic/pharmacodynamic analysis, purification, formulation, and resistance surveillance. The second trend involved colistin's redevelopment by tailored chemical reengineering to produce novel and patentable chemical entities, with an interdisciplinary approach emphasis. It is hoped that an analysis of the interplay between historical trends and current redevelopment strategies of this colistin case study may highlight strategies to stoke the drying antibiotic pipeline.

The efficacy of medicinal leeches in plastic and reconstructive surgery: a systematic review of 277 reported clinical cases.

BACKGROUND: Although there are numerous case reports and small case series describing the experiences of leech therapy in various circumstances, there are relatively few large studies evaluating the effectiveness of leeching to relieve venous congestion. The therapeutic value of leeching is illustrated by these reports but the current literature lacks a cohesive summary of previous experiences. METHODS: An electronic search of PubMed, the Cochrane library and the Centre for Reviews and Dissemination between 1966 and 2009 was used to retrieve human studies published in the English language evaluating outcomes following leech therapy. The "success" and "failure" of leech therapy were the primary outcome measures and secondary outcomes included complications, number of leeches used, pharmacological adjuncts and blood transfusion requirements. RESULTS: In total, out of 461 articles, 394 articles met the exclusion criteria. The 67 included papers reported on 277 cases of leech use with an age range of 2-81 years and a male to female ratio of almost 2:1. The overall reported "success" rate following leech therapy was 77.98% (216/277). In terms of secondary outcome measures, 49.75% of cases (N = 101) required blood transfusions, 79.05% received antibiotics (N = 166) and 54.29% received concomitant anticoagulant therapy. The overall complication rate was 21.8%. CONCLUSION: In the absence of robust randomized controlled trials on which the evidence may be based, this synthesis of current best evidence guides clinicians during the process of consenting patients and using leeches in their practice.

Chemical and mechanical alternatives to leech therapy: a systematic review and critical appraisal.

Although leech therapy is a well-established, effective method of relieving venous congestion, it is associated with complications such as wound infection and leech migration. To minimize these risks, efforts to reproduce their effects have been developed and investigated. A search string using (chemical OR mechanical OR alternative) AND (Leeches OR HIRUDO MEDICINALIS) in Boolean format was used across the major electronic databases to cover the past 10 years. Selected references were subsequently validated against critical appraisal frameworks and classified and evaluated against a framework of hierarchies of evidence. Out of 95 retrieved studies, 25 articles were selected after content appraisal. Of these, 12 articles were methodologically and statistically robust. The heterogeneity noted in the studies precluded meta-analysis of the results. The studies infer evidence at Grade B level that current device prototypes show proof of concept by providing suction and chemical anticoagulation following a surgically created wound. Although progress had been made to replicate leech action, there are still areas to address in future research. This article represents the current state of play in clinical translation of these concepts, providing efficacious devices without the drawbacks of traditional leech therapy.

Emerging gram-negative infections in burn wounds.

Gram-negative infection remains a major contributor to morbidity, mortality, and cost of care. In the absence of comparative multinational epidemiological studies specific to burn patients, we sought to review literature trends in emerging Gram-negative burn wound infections within the past 60 years. Mapping trends in these organisms, although in a minority compared with the six "ESKAPE" pathogens currently being targeted by the Infectious Diseases Society of North America, would identify pathogens of increasing concern to burn physicians in the near future and develop patient profiles that may predict susceptibility to infection. Aeromonas hydrophila infection was identified as the emerging pathogen of note, constituting 76% of the identified publications. A. hydrophila constituted 96% of Aeromonas spp. isolates (mortality 10.7%). The following patient profile indicated predisposition to Aeromonas infection: mean age (mean 33.7 years, range 17 ≤ R ≤ 80, SD = 15.6); TBSA (mean 41.1%, range 8% ≤ R ≤ 80%, SD = 15.2); full-thickness skin burns (mean 27.7%, range 3% ≤ R ≤ 60%, SD = 16.6); and a male predominance (81.3%). Other pathogens included Stenotrophomonas maltophilia Vibrio spp., Chryseobacterium spp., Alcaligenes xylosoxidans, and Cedecia lapigei. Arresting the thermal injury by untreated water was the common predisposing factor. These emerging infections clearly constitute a minority of Gram-negative bacterial infections in burn patients at present. However, these are the infections most likely to pose significant clinical challenge because of the high prevalence of multidrug resistance, rapid acquisition of multidrug resistance, high mortality, and ubiquity in the natural environment. This article therefore presents a rationale for understanding and recognizing the role of these emerging infections in burn patients.

Pyogenic granuloma as a surrogate indicator of deep seated foreign bodies: a case report.

Although pyogenic granulomas are often clinically associated with foreign bodies or recurrent traumatic injury, this association is not well documented. We report a case of a recurrent, intractable pyogenic granuloma due to a missed foreign body. An extensive search retrieved no previous literature reporting this association. This lack of evidence bases may hinder the hand surgeon from extending the wound incision and thorough exploration. Recurrent pyogenic granulomas should lead the hand surgeon to entertain the possibility of a missed foreign body.

Fluid resuscitation in adults with severe burns at risk of secondary abdominal compartment syndrome--an evidence based systematic review.

BACKGROUND: Secondary abdominal compartment syndrome (sACS) in adults with severe burns is commonly unsuspected, can be rapidly fatal and seriously compromises the reliability of urine output as an indicator of perfusion and resuscitation status. Current literature lacks an exhaustive, evidence-based review critically appraising all retrieved literature on which clinical decisions may be based. METHODS: The evidence on three inter-related concepts was evaluated: fluid-volume management and its contribution to sACS; the role of urinary bladder pressure monitoring; and awareness of the burns community to sACS. Literature published over the last ten years across the major databases was retrieved, and the search strategy was fully reported to reduce the retrieval bias ubiquitous in previous literature. Each article was individually appraised and classified into a framework of evidence, enabling the formulation of specific, graded recommendations. RESULTS: Current best evidence supports recommendations to reduce fluid-volume administered through use of colloids or hypertonic saline especially if the projected resuscitation volume surpasses a 'volume ceiling'. Continuous intra-vesical monitoring is recommended: to guide fluid resuscitation for early diagnosis of sACS; and as a guide to reliability of urine output as indicator of organ perfusion. A priming volume of 75 cm(3) or less is recommended. CONCLUSION: Fluid resuscitation volume is causative to sACS, especially once a predetermined maxima is reached. Continuous intra-vesical pressure monitoring is a cheap, reliable, user-friendly monitoring method recommended in high-risk patients. Poor awareness among the burns community requires urgent dissemination of evidence based information.