ABSTRACT
Background: Traumatic and thermal injuries result in a state of systemic immune suppression, yet the mechanisms that underlie its development are poorly understood. Released from injured muscle and lysed red blood cells, heme is a damage associated molecular pattern with potent immune modulatory properties. Here, we measured plasma concentrations of total heme in over 200 traumatic and thermally-injured patients in order to examine its relationship with clinical outcomes and post-injury immune suppression. Methods: Blood samples were collected from 98 burns (≥15% total body surface area) and 147 traumatically-injured (injury severity score ≥8) patients across the ultra-early (≤1 hour) and acute (4-72 hours) post-injury settings. Pro-inflammatory cytokine production by lipopolysaccharide (LPS) challenged whole blood leukocytes was studied, and plasma concentrations of total heme, and its scavengers haptoglobin, hemopexin and albumin measured, alongside the expression of heme-oxygenase-1 (HO-1) in peripheral blood mononuclear cells (PBMCs). LPS-induced tumour necrosis factor-alpha (TNF-α) production by THP-1 cells and monocytes following in vitro heme treatment was also examined. Results: Burns and traumatic injury resulted in significantly elevated plasma concentrations of heme, which coincided with reduced levels of hemopexin and albumin, and correlated positively with circulating levels of pro and anti-inflammatory cytokines. PBMCs isolated from trauma patients 4-12 and 48-72 hours post-injury exhibited increased HO-1 gene expression. Non-survivors of burn injury and patients who developed sepsis, presented on day 1 with significantly elevated heme levels, with a difference of 6.5 µM in heme concentrations corresponding to a relative 52% increase in the odds of post-burn mortality. On day 1 post-burn, heme levels were negatively associated with ex vivo LPS-induced TNF-α and interleukin-6 production by whole blood leukocytes. THP-1 cells and monocytes pre-treated with heme exhibited significantly reduced TNF-α production following LPS stimulation. This impairment was associated with decreased gene transcription, reduced activation of extracellular signal-regulated kinase 1/2 and an impaired glycolytic response. Conclusions: Major injury results in elevated plasma concentrations of total heme that may contribute to the development of endotoxin tolerance and increase the risk of poor clinical outcomes. Restoration of the heme scavenging system could be a therapeutic approach by which to improve immune function post-injury.
Subject(s)
Burns , Heme , Humans , Heme/metabolism , Burns/blood , Burns/immunology , Male , Adult , Female , Middle Aged , Cytokines/blood , Wounds and Injuries/immunology , Wounds and Injuries/blood , Young Adult , Aged , THP-1 Cells , Leukocytes, Mononuclear/metabolism , Leukocytes, Mononuclear/immunology , Biomarkers/blood , Lipopolysaccharides , Heme Oxygenase-1/bloodABSTRACT
BACKGROUND: Burn damage to skin often results in scarring; however in some individuals the failure of normal wound-healing processes results in excessive scar tissue formation, termed 'hypertrophic scarring'. The most commonly used method for the prevention and treatment of hypertrophic scarring is pressure-garment therapy (PGT). PGT is considered standard care globally; however, there is continued uncertainty around its effectiveness. OBJECTIVES: To evaluate the benefits and harms of pressure-garment therapy for the prevention of hypertrophic scarring after burn injury. SEARCH METHODS: We used standard, extensive Cochrane search methods. We searched CENTRAL, MEDLINE, Embase, two other databases, and two trials registers on 8 June 2023 with reference checking, citation searching, and contact with study authors to identify additional studies. SELECTION CRITERIA: We included randomised controlled trials (RCTs) comparing PGT (alone or in combination with other scar-management therapies) with scar management therapies not including PGT, or comparing different PGT pressures or different types of PGT. DATA COLLECTION AND ANALYSIS: At least two review authors independently selected trials for inclusion using predetermined inclusion criteria, extracted data, and assessed risk of bias using the Cochrane RoB 1 tool. We assessed the certainty of evidence using GRADE. MAIN RESULTS: We included 15 studies in this review (1179 participants), 14 of which (1057 participants) presented useable data. The sample size of included studies ranged from 17 to 159 participants. Most studies included both adults and children. Eight studies compared a pressure garment (with or without another scar management therapy) with scar management therapy alone, five studies compared the same pressure garment at a higher pressure versus a lower pressure, and two studies compared two different types of pressure garments. Studies used a variety of pressure garments (e.g. in-house manufactured or a commercial brand). Types of scar management therapies included were lanolin massage, topical silicone gel, silicone sheet/dressing, and heparin sodium ointment. Meta-analysis was not possible as there was significant clinical and methodological heterogeneity between studies. Main outcome measures were scar improvement assessed using the Vancouver Scar Scale (VSS) or the Patient and Observer Scar Assessment Scale (POSAS) (or both), pain, pruritus, quality of life, adverse events, and adherence to therapy. Studies additionally reported a further 14 outcomes, mostly individual scar parameters, some of which contributed to global scores on the VSS or POSAS. The amount of evidence for each individual outcome was limited. Most studies had a short follow-up, which may have affected results as the full effect of any therapy on scar healing may not be seen until around 18 months. PGT versus no treatment/lanolin We included five studies (378 participants). The evidence is very uncertain on whether PGT improves scars as assessed by the VSS compared with no treatment/lanolin. The evidence is also very uncertain for pain, pruritus, adverse events, and adherence. No study used the POSAS or assessed quality of life. One additional study (122 participants) did not report useable data. PGT versus silicone We included three studies (359 participants). The evidence is very uncertain on the effect of PGT compared with silicone, as assessed by the VSS and POSAS. The evidence is also very uncertain for pain, pruritus, quality of life, adverse events, adherence, and other scar parameters. It is possible that silicone may result in fewer adverse events or better adherence compared with PGT but this was also based on very low-certainty evidence. PGT plus silicone versus no treatment/lanolin We included two studies (200 participants). The evidence is very uncertain on whether PGT plus silicone improves scars as assessed by the VSS compared with no treatment/lanolin. The evidence is also very uncertain for pain, pruritus, and adverse events. No study used the POSAS or assessed quality of life or adherence. PGT plus silicone versus silicone We included three studies (359 participants). The evidence is very uncertain on the effect of PGT plus silicone compared with silicone, as assessed by the VSS and POSAS. The evidence is also very uncertain for pain, pruritus, quality of life, adverse events, and adherence. PGT plus scar management therapy including silicone versus scar management therapy including silicone We included one study (88 participants). The evidence is very uncertain on the effect of PGT plus scar management therapy including silicone versus scar management therapy including silicone, as assessed by the VSS and POSAS. The evidence is also very uncertain for pain, pruritus, quality of life, adverse events, and adherence. High-pressure versus low-pressure garments We included five studies (262 participants). The evidence is very uncertain on the effect of high pressure versus low pressure PGT on adverse events and adherence. No study used the VSS or the POSAS or assessed pain, pruritus, or quality of life. Different types of PGT (Caroskin Tricot + an adhesive silicone gel sheet versus Gecko Nanoplast (silicone gel bandage)) We included one study (60 participants). The evidence is very uncertain on the effect of Caroskin Tricot versus Gecko Nanoplast on the POSAS, pain, pruritus, and adverse events. The study did not use the VSS or assess quality of life or adherence. Different types of pressure garments (Jobst versus Tubigrip) We included one study (110 participants). The evidence is very uncertain on the adherence to either Jobst or Tubigrip. This study did not report any other outcomes. AUTHORS' CONCLUSIONS: There is insufficient evidence to recommend using either PGT or an alternative for preventing hypertrophic scarring after burn injury. PGT is already commonly used in practice and it is possible that continuing to do so may provide some benefit to some people. However, until more evidence becomes available, it may be appropriate to allow patient preference to guide therapy.
Subject(s)
Burns , Cicatrix , Adult , Child , Humans , Cicatrix/etiology , Cicatrix/prevention & control , Lanolin , Silicone Gels/therapeutic use , Burns/complications , Burns/therapy , Pain , Pruritus/etiology , Pruritus/prevention & controlABSTRACT
AIM: The study aims to identify whether factors such as time to initiation of laser therapy following scar formation, type of laser used, laser treatment interval and presence of complications influence burn scar outcomes in adults, by meta-analysis of previous studies. METHODS: A literature search was conducted in May 2022 in seven databases to select studies on the effects of laser therapy in adult hypertrophic burn scars. The study protocol was registered with PROSPERO (CRD42022347836). RESULTS: Eleven studies were included in the meta-analysis, with a total of 491 patients. Laser therapy significantly improved overall VSS/POSAS, vascularity, pliability, pigmentation and scar height of burn scars. Vascularity improvement was greater when laser therapy was performed >12 months (-1.50 [95%CI = -2.58;-0.42], p = 0.01) compared to <12 months after injury (-0.39 [95%CI = -0.68; -0.10], p = 0.01), the same was true for scar height ((-1.36 [95%CI = -2.07; -0.66], p<0.001) vs (-0.56 [95%CI = -0.70; -0.42], p<0.001)). Pulse dye laser (-4.35 [95%CI = -6.83; -1.86], p<0.001) gave a greater reduction in VSS/POSAS scores compared to non-ablative (-1.52 [95%CI = -2.24; -0.83], p<0.001) and ablative lasers (-0.95 [95%CI = -1.31; -0.59], p<0.001). CONCLUSION: Efficacy of laser therapy is influenced by the time lapse after injury, the type of laser used and the interval between laser treatments. Significant heterogeneity was observed among studies, suggesting the need to explore other factors that may affect scar outcomes.
ABSTRACT
BACKGROUND: Burn injuries are the fourth most common type of trauma and are associated with substantial morbidity and mortality. The impact of burn injury is clinically significant as burn injuries often give rise to exuberant scarring. Hypertrophic scarring (HTS) is a particular concern as up to 70% of burns patients develop HTS. Laser therapy is used for treating HTS and has shown positive clinical outcomes, although the mechanisms remain unclear limiting approaches to improve its effectiveness. Emerging evidence has shown that fibroblasts and senescent cells are important modifiers of scarring. This study aims to investigate the cellular kinetics in HTS after laser therapy, with a focus on the association of scar reduction with the presence of senescent cells. METHODS: We will conduct a multicentre, intra-patient, single-blinded, randomised controlled longitudinal pilot study with parallel assignments to achieve this objective. 60 participants will be recruited to receive 3 interventional ablative fractional CO2 laser treatments over a 12-month period. Each participant will have two scars randomly allocated to receive either laser treatment or standard care. Biopsies will be obtained from laser-treated, scarred-no treatment and non-scarred tissues for immune-histological staining to investigate the longitudinal kinetics of p16INK4A+-senescent cells and fibroblast subpopulations (CD90+/Thy1+ and αSMA+). Combined subjective scar assessments including Modified Vancouver Scar Scale, Patient and Observer Scar Assessment Scale and Brisbane Burn Scar Impact Profile; and objective assessment tools including 3D-Vectra-H1 photography, DermaScan® Cortex, Cutometer® and ColoriMeter®DSMIII will be used to evaluate clinical outcomes. These will then be used to investigate the association between senescent cells and scar reduction after laser therapy. This study will also collect blood samples to explore the systemic biomarkers associated with the response to laser therapy. DISCUSSION: This study will provide an improved understanding of mechanisms potentially mediating scar reduction with laser treatment, which will enable better designs of laser treatment regimens for those living with HTS. TRIAL REGISTRATION: ClinicalTrials.gov: NCT04736251.
Subject(s)
Cicatrix, Hypertrophic , Lasers, Gas , Low-Level Light Therapy , Humans , Pilot Projects , Lasers, Gas/therapeutic use , Prospective Studies , Cicatrix, Hypertrophic/radiotherapy , Carbon Dioxide , Randomized Controlled Trials as Topic , Multicenter Studies as Topic , Observational Studies as TopicABSTRACT
INTRODUCTION: Burn-induced changes in the phenotype and function of neutrophils, cells which provide front-line protection against rapidly dividing bacterial infections, are emerging as potential biomarkers for the early prediction of sepsis. In a longitudinal study of adult burns patients, we recently demonstrated that a combined measurement of neutrophil phagocytic capacity, immature granulocyte (IG) count and plasma cell-free DNA (cfDNA) levels on the day of injury gave good discriminatory power for the prediction of later sepsis development. However, limited by a small sample size, single-centre design and focus on adult burns patients, these biomarkers require prospective validation in a larger patient cohort. The Scientific Investigation of the Biological Pathways Following Thermal Injury-2 study aims to prospectively validate neutrophil phagocytic activity, IG count and plasma cfDNA levels as early prognostic biomarkers of sepsis in thermally injured adult and paediatric patients. METHODS AND ANALYSIS: This multicentre, longitudinal, observational cohort study will enrol 245 paediatric and adult patients with moderate to severe burns within 24 hours of injury. Blood samples will be obtained at 19 postinjury time points (days 1-14, day 28, months 3, 6, 12 and 24) and analysed for neutrophil phagocytic activity, IG count and cfDNA levels. Patients will be screened daily for sepsis using the 2007 American Burn Association diagnostic criteria for sepsis. In addition, daily multiple organ dysfunction syndrome and Sequential Organ Failure Assessment Scores will be recorded relationships between neutrophil phagocytic activity, IG count and plasma cfDNA levels on day 1 of injury and the development of sepsis will be examined using logistic regression models. ETHICS AND DISSEMINATION: This study received ethics approval from the West Midlands, Coventry and Warwickshire Research Ethics Committee (REC reference:16/WM/0217). Findings will be presented at national and international conferences, and submitted for publication in peer-reviewed journals. TRIAL REGISTRATION NUMBER: NCT04693442.
Subject(s)
Burns , Sepsis , Adult , Child , Cohort Studies , Humans , Longitudinal Studies , Multicenter Studies as Topic , Neutrophils , Observational Studies as Topic , Prospective Studies , Sepsis/diagnosisABSTRACT
BACKGROUND: The early diagnosis of infection or sepsis in burns are important for patient care. Globally, a large number of burn centres advocate quantitative cultures of wound biopsies for patient management, since there is assumed to be a direct link between the bioburden of a burn wound and the risk of microbial invasion. Given the conflicting study findings in this area, a systematic review was warranted. METHODS: Bibliographic databases were searched with no language restrictions to August 2015. Study selection, data extraction and risk of bias assessment were performed in duplicate using pre-defined criteria. Substantial heterogeneity precluded quantitative synthesis, and findings were described narratively, sub-grouped by clinical question. RESULTS: Twenty six laboratory and/or clinical studies were included. Substantial heterogeneity hampered comparisons across studies and interpretation of findings. Limited evidence suggests that (i) more than one quantitative microbiology sample is required to obtain reliable estimates of bacterial load; (ii) biopsies are more sensitive than swabs in diagnosing or predicting sepsis; (iii) high bacterial loads may predict worse clinical outcomes, and (iv) both quantitative and semi-quantitative culture reports need to be interpreted with caution and in the context of other clinical risk factors. CONCLUSION: The evidence base for the utility and reliability of quantitative microbiology for diagnosing or predicting clinical outcomes in burns patients is limited and often poorly reported. Consequently future research is warranted.
Subject(s)
Burns/microbiology , Wound Infection/diagnosis , Bacterial Load/methods , Biopsy , Humans , Reproducibility of Results , Sepsis/diagnosisABSTRACT
This review gives an updated overview on keratinocyte transplantation in burn wounds concentrating on application methods and future therapeutic cell delivery options with a special interest in hydrogels and spray devices for cell delivery. To achieve faster re-epithelialisation of burn wounds, the original autologous keratinocyte culture and transplantation technique was introduced over 3 decades ago. Application types of keratinocytes transplantation have improved from cell sheets to single-cell solutions delivered with a spray system. However, further enhancement of cell culture, cell viability and function in vivo, cell carrier and cell delivery systems remain themes of interest. Hydrogels such as chitosan, alginate, fibrin and collagen are frequently used in burn wound care and have advantageous characteristics as cell carriers. Future approaches of keratinocyte transplantation involve spray devices, but optimisation of application technique and carrier type is necessary.
Subject(s)
Burns/therapy , Keratinocytes/transplantation , Wound Healing , Burns/physiopathology , HumansABSTRACT
OBJECTIVE: The aim of this study was to measure neutrophil function longitudinally following burn injury and to examine the relationship between neutrophil dysfunction and sepsis. BACKGROUND: Sepsis prevalence and its associated mortality is high following burn injury, and sepsis diagnosis is complicated by the ongoing inflammatory response. Previous studies have suggested that neutrophil dysfunction may underlie high infection rates and sepsis postburn; however, neutrophil dysfunction has not been thoroughly characterized over time in burns patients. METHODS: Neutrophil phagocytosis, oxidative burst capacity, and neutrophil extracellular trap (NET) generation (NETosis) were measured from 1 day to up to 1 year postburn injury in 63 patients with major burns (≥15% total body surface area). In addition, immature granulocyte (IG) count, plasma cell-free DNA (cfDNA), and plasma citrullinated histone H3 (Cit H3) levels were measured. RESULTS: Neutrophil function was reduced for 28 days postburn injury and to a greater degree in patients who developed sepsis, which was also characterized by elevated IG counts. Plasma cfDNA and Cit-H3, a specific marker of NETosis, were elevated during septic episodes. The combination of neutrophil phagocytic capacity, plasma cfDNA levels, and IG count at day 1 postinjury gave good discriminatory power for the identification of septic patients. CONCLUSION: Neutrophil function, IG count, and plasma cfDNA levels show potential as biomarkers for the prediction/early diagnosis of sepsis postburn injury and neutrophil dysfunction may actively contribute to the development of sepsis. Targeting neutrophil dysfunction and IG release may be a viable therapeutic intervention to help reduce the incidence of nosocomial infections and sepsis postburn.
Subject(s)
Burns/complications , DNA/blood , Granulocytes , Neutrophils/physiology , Sepsis/diagnosis , Biomarkers/blood , Cross Infection/diagnosis , Histones/blood , Humans , Leukocyte Count , Phagocytosis , Prospective Studies , Respiratory BurstABSTRACT
This study analyzed cone beam computed tomography (CBCT) records. Radiographic image analysis included: (1) the width and height of the palatal vault, and diameter and location of the incisive foramen; (2) the potential block graft dimensions and their correlation to arch dimensions; (3) the potential graft size and its variation by sex. CBCT scans of 76 patients were included, 42 from female patients and 34 from male patients (mean age 42.3 years). The mean palatal width was 35.2±3.4 mm, while the mean palatal height was 15.2±2.9 mm. The mean diameter of the incisive foramen was 3.1±1.3. mm. The mean potential osteotomy diameter was 7.8±1.5 mm. The mean osteotomy length varied according to site: central incisor region, 5.9±2.0 mm; lateral incisor region, 5.2±2.1 mm; canine region, 4.7±1.9 mm; premolar region, 4.1±1.7 mm. A positive correlation was observed between the osteotomy diameter and the palatal width: a greater osteotomy length was obtained from the more anterior teeth position. Males presented significantly greater osteotomy diameter and length compared to females. The palate represents a potential site for the harvest of autogenous bone block grafts for the reconstruction of ridge defects.
Subject(s)
Bone Transplantation , Cone-Beam Computed Tomography , Palate, Hard/diagnostic imaging , Adult , Female , Humans , Imaging, Three-Dimensional , Male , Middle Aged , Osteotomy , Palate, Hard/surgery , Radiographic Image Interpretation, Computer-AssistedABSTRACT
BACKGROUND: Sepsis from burn injuries can result from colonisation of burn wounds, especially in large surface area burns. Reducing bacterial infection will reduce morbidity and mortality, and mortality for severe burns can be as high as 15 %. There are various quantitative and semi-quantitative techniques to monitor bacterial load on wounds. In the UK, burn wounds are typically monitored for the presence or absence of bacteria through the collection and culture of swabs, but no absolute count is obtained. Quantitative burn wound culture provides a measure of bacterial count and is gaining increased popularity in some countries. It is however more resource intensive, and evidence for its utility appears to be inconsistent. This systematic review therefore aims to assess the evidence on the utility and reliability of different quantitative microbiology techniques in terms of diagnosing or predicting clinical outcomes. METHODS/DESIGN: Standard systematic review methods aimed at minimising bias will be employed for study identification, selection and data extraction. Bibliographic databases and ongoing trial registers will be searched and conference abstracts screened. Studies will be eligible if they are prospective studies or systematic reviews of burn patients (any age) for whom quantitative microbiology has been performed, whether it is compared to another method. Quality assessment will be based on quality assessment tools for diagnostic and prognostic studies and tailored to the review as necessary. Synthesis is likely to be primarily narrative, but meta-analysis may be considered where clinical and methodological homogeneity exists. DISCUSSION: Given the increasing use of quantitative methods, this is a timely systematic review, which will attempt to clarify the evidence base. As far as the authors are aware, it will be the first to address this topic. TRIAL REGISTRATION: PROSPERO, CRD42015023903.
Subject(s)
Bacterial Infections/diagnosis , Bacterial Infections/prevention & control , Bacterial Load , Burns/microbiology , Burns/therapy , Bacterial Infections/complications , Colony Count, Microbial , Humans , Research Design , Sepsis/microbiology , Systematic Reviews as TopicABSTRACT
INTRODUCTION: Localised infections, and burn wound sepsis are key concerns in the treatment of burns patients, and prevention of colonisation largely relies on biocides. Acetic acid has been shown to have good antibacterial activity against various planktonic organisms, however data is limited on efficacy, and few studies have been performed on biofilms. OBJECTIVES: We sought to investigate the antibacterial activity of acetic acid against important burn wound colonising organisms growing planktonically and as biofilms. METHODS: Laboratory experiments were performed to test the ability of acetic acid to inhibit growth of pathogens, inhibit the formation of biofilms, and eradicate pre-formed biofilms. RESULTS: Twenty-nine isolates of common wound-infecting pathogens were tested. Acetic acid was antibacterial against planktonic growth, with an minimum inhibitory concentration of 0.16-0.31% for all isolates, and was also able to prevent formation of biofilms (at 0.31%). Eradication of mature biofilms was observed for all isolates after three hours of exposure. CONCLUSIONS: This study provides evidence that acetic acid can inhibit growth of key burn wound pathogens when used at very dilute concentrations. Owing to current concerns of the reducing efficacy of systemic antibiotics, this novel biocide application offers great promise as a cheap and effective measure to treat infections in burns patients.
Subject(s)
Acetic Acid/pharmacology , Bacteria/drug effects , Biofilms/drug effects , Burns/microbiology , Disinfectants/pharmacology , Bacteria/isolation & purification , Bacteria/pathogenicity , Cross Infection/microbiology , Drug Evaluation, Preclinical , Humans , Microbial Sensitivity Tests , Time Factors , Wound Infection/prevention & controlABSTRACT
UNLABELLED: Antimicrobial medicated dressings (AMD) are often used to reduce bacterial infection of burns and other wounds. However, there is limited literature regarding comparative efficacies to inform effective clinical decision making. OBJECTIVES: Following on from a previous study where we demonstrated good antibiofilm properties of acetic acid (AA), we assessed and compared the in vitro anti-biofilm activity of a range of AMDs and non-AMDs to AA. METHODS: Laboratory experiments determined the ability of a range of eleven commercial AMD, two nAMD, and AA, to prevent the formation of biofilms of a panel of four isolates of Pseudomonas aeruginosa and Acinetobacter baumannii. RESULTS: There is a large variation in ability of different dressings to inhibit biofilm formation, seen between dressings that contain the same, and those that contain other antimicrobial agents. The best performing AMD were Mepilex(®) Ag and Acticoat. AA consistently prevented biofilm formation. CONCLUSIONS: Large variation exists in the ability of AMD to prevent biofilm formation and colonisation of wounds. A standardised in vitro methodology should be developed for external parties to examine and compare the efficacies of commercially available AMDs, along with robust clinical randomised controlled trials. This is essential for informed clinical decision-making and optimal patient management.
Subject(s)
Acinetobacter baumannii/drug effects , Anti-Bacterial Agents/pharmacology , Bandages , Biofilms/drug effects , Burns/therapy , Pseudomonas aeruginosa/drug effects , Acetic Acid/pharmacology , Acetic Acid/therapeutic use , Acinetobacter Infections/prevention & control , Acinetobacter baumannii/growth & development , Anti-Bacterial Agents/therapeutic use , Biofilms/growth & development , Burns/microbiology , Chlorhexidine/pharmacology , Chlorhexidine/therapeutic use , Honey , In Vitro Techniques , Iodine/pharmacology , Iodine/therapeutic use , Microbial Sensitivity Tests , Polyesters/therapeutic use , Polyethylenes/therapeutic use , Pseudomonas Infections/prevention & control , Pseudomonas aeruginosa/growth & development , Silver/pharmacology , Silver/therapeutic use , Wound Infection/prevention & controlABSTRACT
OBJECTIVES: Pseudomonas aeruginosa is a common nosocomial pathogen responsible for significant morbidity and mortality internationally. Patients may become colonised or infected with P. aeruginosa after exposure to contaminated sources within the hospital environment. The aim of this study was to determine whether whole-genome sequencing (WGS) can be used to determine the source in a cohort of burns patients at high risk of P. aeruginosa acquisition. STUDY DESIGN: An observational prospective cohort study. SETTING: Burns care ward and critical care ward in the UK. PARTICIPANTS: Patients with >7% total burns by surface area were recruited into the study. METHODS: All patients were screened for P. aeruginosa on admission and samples taken from their immediate environment, including water. Screening patients who subsequently developed a positive P. aeruginosa microbiology result were subject to enhanced environmental surveillance. All isolates of P. aeruginosa were genome sequenced. Sequence analysis looked at similarity and relatedness between isolates. RESULTS: WGS for 141 P. aeruginosa isolates were obtained from patients, hospital water and the ward environment. Phylogenetic analysis revealed eight distinct clades, with a single clade representing the majority of environmental isolates in the burns unit. Isolates from three patients had identical genotypes compared with water isolates from the same room. There was clear clustering of water isolates by room and outlet, allowing the source of acquisitions to be unambiguously identified. Whole-genome shotgun sequencing of biofilm DNA extracted from a thermostatic mixer valve revealed this was the source of a P. aeruginosa subpopulation previously detected in water. In the remaining two cases there was no clear link to the hospital environment. CONCLUSIONS: This study reveals that WGS can be used for source tracking of P. aeruginosa in a hospital setting, and that acquisitions can be traced to a specific source within a hospital ward.
Subject(s)
Cross Infection/microbiology , Pseudomonas Infections/microbiology , Pseudomonas aeruginosa/genetics , Adult , Female , Genome, Bacterial , Genome-Wide Association Study , Hospitals , Humans , Male , Prospective StudiesABSTRACT
BACKGROUND: Although commercial skin substitutes are widely available, its use remains challenging at surgery and postoperatively. The high cost is also prohibitive. We designed and characterized a scaffold for dermal replacement, using advanced nanocomposite materials, which are known to have unique nanoscale features that enhance cellular behavior. METHODS: A bilayered scaffold was developed using the nanocomposite, polyhedral oligomeric silsesquioxane, incorporated into poly(caprolactone-urea)urethane, resulting in a mechanically robust bioabsorbable polymer; forming the inner layer, which was designed with a range of porosities. The removable outer layer contained nanosilver. Tensile testing, surface tension, permeability, and scanning electron microscopy were performed. Optimal pore morphology for cellular proliferation was elucidated through adipose tissue-derived stem cell culture and a cell viability assay. All tests were repeated on Integra Dermal Regeneration Template. RESULTS: The physical construct was easy to handle and clinically applicable. Macroporosity and permeability of scaffolds was demonstrated, confirmed by scanning electron microscopy. Both tensile strength and surface tension were comparable with skin; outer layer demonstrated hydrophobicity and inner layer showed hydrophilicity. Cell assay confirmed cellular proliferation onto the scaffold, comparable with Integra. CONCLUSIONS: We demonstrate that a porous bilayered dermal scaffold could form the basis of a new generation of skin substitute that is both mechanically robust and harbors the ability for enhancing cell regeneration.
Subject(s)
Organosilicon Compounds/chemistry , Skin , Tissue Scaffolds , Adipose Tissue/ultrastructure , Biomechanical Phenomena , Cell Survival , Humans , L-Lactate Dehydrogenase/ultrastructure , Microscopy, Electron, Scanning , Nanocomposites/ultrastructure , Skin/ultrastructure , Skin, Artificial , Stem Cells/ultrastructureABSTRACT
INTRODUCTION: Hydrotherapy is widely used in burns management however there are risks associated with its use, in particular cross-infection. Data regarding indications and techniques in common use is deficient. This study aimed to investigate hydrotherapy practices in the UK and Ireland. METHODS: A survey of the hydrotherapy practice of major burn care providers was performed by e mail and where necessary, follow up telephone contact. RESULTS: The survey included 28 burn care providers. 27 reported using hydrotherapy. Only 11 (41%) had defined indication criteria with 4 (15%) implementing a specific protocol. Variations in hydrotherapy practice were seen. CONCLUSION: Hydrotherapy is used nationwide, however considerable variation in practice exists. One area worthy of further consideration is the need for appropriate standards of infection control.
Subject(s)
Burns/rehabilitation , Cross Infection/prevention & control , Hydrotherapy/methods , Infection Control/methods , Practice Patterns, Physicians'/statistics & numerical data , Wound Infection/prevention & control , Humans , Ireland , Patient Selection , United KingdomABSTRACT
Burn injuries are one of the most common and devastating afflictions on the human body. In this article we look back at how the treatment of burns has evolved over the centuries from a primarily topical therapy consisting of weird and wonderful topical concoctions in ancient times to one that spans multiple scientific fields of topical therapy, antibiotics, fluid resuscitation, skin excision and grafting, respiratory and metabolic care and nutrition. Most major advances in burn care occurred in the last 50 years, spurred on by wars and great fires. The use of systemic antibiotics and topical silver therapy greatly reduced sepsis related mortality. This along with the advent of antiseptic surgical techniques, burn depth classification and skin grafting allowed the excision and coverage of full-thickness burns which resulted in greatly improved survival rates. Advancements in the methods of assessing the surface area of burns paved way for more accurate fluid resuscitation, minimising the effects of shock and avoiding fluid over-loading. The introduction of metabolic care, nutritional support and care of inhalational injuries further improved the outcome of burn patients. We also briefly discuss some future directions in burn care such as the use of cell and pharmalogical therapies.
ABSTRACT
Despite widespread use of wound dressings containing silver, few studies have investigated patients' serum silver levels. An earlier study of Acticoat use in small burns showed transient elevations of serum silver. The aim of this study was to examine the serum silver profile when Acticoat is used in major burns. A prospective study of 6 patients with burns greater than 20% total body surface area (TBSA). All burn wounds, including grafted and non-grafted areas and skin graft donor sites, were dressed with Acticoat or Acticoat Absorbent. Patients' serum silver levels, biochemistry and haematology were examined before, during and after the application of the silver dressings. The median total wound size (including donor sites) was 46.1% TBSA. The median maximum serum silver level recorded, 200.3 µg/L, reached at a median of 9.5 days following initial silver dressing application. This decreased to a median of 164.8 µg/L at the end of the treatment period and to a median of 8.2 µg/L at the end of follow-up. One adverse event, partial skin graft loss was thought to be dressing related. In this small study, serum silver levels were elevated but remained similar to that reported following the use of silver sulfadiazine. This study confirmed our view that Acticoat is safe to use on patients with burns, even when they are extensive.
Subject(s)
Anti-Infective Agents, Local/therapeutic use , Bandages , Burns/therapy , Polyesters/therapeutic use , Polyethylenes/therapeutic use , Silver/blood , Adult , Burns/blood , Female , Humans , Male , Middle Aged , Prospective Studies , Silver/pharmacokinetics , Young AdultABSTRACT
INTRODUCTION: Helicopter emergency medical services play a valuable role in the transfer of critically ill patients. This paper reviews the role of air ambulance services in the provision of regional burns care and suggests guidelines for their use. METHODS: A retrospective review of patients treated at the Midlands Adult Burns Centre over a 3-year period. RESULTS: 27 adult burns patients were transported by air ambulance during the study period. Patients were aged 19-89 years (average 41.3 years) with an estimated burn size of 5-70% TBSA. Distance travelled was 11-79 miles (average 41.2 miles). All patients were appropriately referred to the burns centre according to national referral guidelines but in 7 cases (26%) it was felt that transport by air ambulance was not clinically indicated and land transfer would have been safe and appropriate. CONCLUSION: Air ambulances offer a fast and effective means of transferring patients to a regional burns centre in selected cases. There is limited data for the beneficial effects of helicopters and survival benefit is seen only in the most severely injured patients. We suggest criteria for the use of air ambulances in burns patients in order to maximise the benefit and reduce unnecessary flights.
Subject(s)
Air Ambulances/statistics & numerical data , Needs Assessment , Transportation of Patients , Adult , Aged , Aged, 80 and over , Air Ambulances/standards , Female , Guidelines as Topic , Humans , Male , Middle Aged , Retrospective Studies , Transportation of Patients/standards , United Kingdom , Utilization Review , Young AdultABSTRACT
BACKGROUND: The use of topical negative pressure (TNP) dressings with dermal regeneration template (DRT), Integra, has improved outcomes and simplified aftercare. Previous clinical studies have suggested accelerated vascularisation; with a reduction in the duration of the 1st stage after the application of Integra, from 2 to 4 weeks to as little as 4 days, but with no histological evidence. However, histological studies, without TNP, have shown that vascularisation occurs between the second and the fourth week. This study set out to examine histologically the rate of DRT neovascularisation when combined with TNP. METHODS: Eight patients with nine reconstruction sites were enlisted. Unmeshed Integra and fibrin sealant to promote adherence were used. TNP was applied for the duration between the 1st and the 2nd stages. Patients underwent serial biopsies on days 7, 14, 21 and 28 post-application. The biopsies were stained with H&E and endothelial markers CD31 and CD34. Template vascularisation was assessed as a percentage of the template depth in which patent, canalised vascular channels could be demonstrated. RESULTS: The median percentage of the template depth which demonstrated canalised channels was 0%, 20%, 61% and 80% for days, 7, 14, 21 and 28, respectively. CONCLUSION: The application of TNP dressings to dermal templates can reduce shearing forces, restrict seroma and haematoma formation, simplify wound care and improve patient tolerance. However, this study could not demonstrate that TNP accelerates neovascularisation as verified by the presence of histologically patent vascular channels.