Naiem Moiemen

Seeking the source of Pseudomonas aeruginosa infections in a recently opened hospital: an observational study using whole-genome sequencing

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.

Long-Term Clinical and Histological Analysis of Integra Dermal Regeneration Template

Background: This study looked at clinical and histological outcomes of patients treated with Integra more than 2 years earlier. Although previous studies have investigated the short-term clinical and histological results, there have been no studies to investigate longer-term changes. Methods: Fourteen patients (23 sites) were assessed. Patients used a visual analogue scale to score characteristics of their scars. Objective evaluation of the reconstructions was carried out using the Cutometer MPA580. Punch biopsy specimens of the sites were stained and labeled immunohistochemically with S100, CD31, and CD34 antisera. Results: The highest scoring category by patients was softness (median, +45 percent). The lowest score was sweating, which all patients scored 0. The median Cutometer readings ranged from 39 to 52 percent of the control values. Histological examination showed three patterns of collagen arrangement; parallel arrangement was found in over 60 percent of specimens. Elastic fibers were identified in all specimens; however, all were of abnormal morphology. The majority of specimens showed evidence of nerve fiber regeneration although confined to the mid- or lower reticular dermis. There was no regeneration of skin adnexa. Conclusions: This study showed significant improvements in patient-assessed mobility, softness, and appearance. Collagen and elastic fibrin were present in all specimens, nerve fiber regeneration was limited to the mid- or lower reticular dermis, and adnexal structures were absent. The typical wrinkled appearance of mature Integra reconstruction cannot be said to be entirely due to a lack of elastic fibers.

Neutrophil Dysfunction, Immature Granulocytes, and Cell-free Dna are Early Biomarkers of Sepsis in Burn-injured Patients: A Prospective Observational Cohort Study

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.

Topical negative pressure therapy: Does it accelerate neovascularisation within the dermal regeneration template, Integra? A prospective histological in vivo study

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.

Hydroxyethylstarch supplementation in burn resuscitation—A prospective randomised controlled trial

INTRODUCTION Hydroxyethylstarches (HES) are thought to be beneficial in trauma and major surgery management, due to their volume expansion and anti-inflammatory properties. This study examined the use of 6% (HES) in burn resuscitation. METHODS 26 adult patients with burns exceeding 15% total body surface area (TBSA) were randomised to either crystalloid (Hartmanns solution) or a colloid-supplemented resuscitation regime, where 1/3 of the crystalloid-predicted requirement was replaced by 6% HES. RESULTS There was no difference in age, gender or TBSA between the two groups. The median (95% CI) fluid volume/%TBSA received in the first 24 h was 307 ml and 263 ml for the crystalloid only and HES-supplemented group respectively (p=0.0234, Mann-Whitney). Body weight gain within the first 24 h after injury was significantly lower in the HES-supplemented group 2.5 kg versus 1.4 kg respectively (p=0.0039). The median (95% CI) serum C-reactive protein at 48 h after injury was 210 (167-257) and 128 (74-145) mg/L for the crystalloid only and HES-supplemented group respectively (p=0.0001). Albumin-creatinine ratio per % burn (ACR, a marker of capillary leak) was lower in the HES-supplemented group at 12h after burn (p=0.0310). CONCLUSIONS Patients treated with HES-supplemented resuscitation required less fluid, showed less interstitial oedema and a dampened inflammatory response compared to patients receiving isotonic crystalloid alone.

ISBI PRACTICE GUIDELINES FOR BURN CARE

Practice guidelines (PGs) are recommendations for diagnosis and treatment of diseases and injuries, and are designed to define optimal evaluation and management. The first PGs for burn care addressed the issues encountered in developed countries, lacking consideration for circumstances in resource-limited settings (RLS). Thus, the mission of the 2014-2016 committee established by the International Society for Burn Injury (ISBI) was to create PGs for burn care to improve the care of burn patients in both RLS and resource-abundant settings. An important component of this effort is to communicate a consensus opinion on recommendations for burn care for different aspects of burn management. An additional goal is to reduce costs by outlining effective and efficient recommendations for management of medical problems specific to burn care. These recommendations are supported by the best research evidence, as well as by expert opinion. Although our vision was the creation of clinical guidelines that could be applicable in RLS, the ISBI PGs for Burn Care have been written to address the needs of burn specialists everywhere in the world.

Air ambulance transfer of adult patients to a UK regional burns centre: Who needs to fly?

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.

Proposing “The Burns Suite” as a Novel Simulation Tool for Advancing the Delivery of Burns Education

Educational theory highlights the importance of contextualized simulation for effective learning. We explored this concept in a burns scenario in a novel, low-cost, high-fidelity, portable, immersive simulation environment (referred to as distributed simulation). This contextualized simulation/distributed simulation combination was named “The Burns Suite” (TBS). A pediatric burn resuscitation scenario was selected after high trainee demand. It was designed on Advanced Trauma and Life Support and Emergency Management of Severe Burns principles and refined using expert opinion through cognitive task analysis. TBS contained “realism” props, briefed nurses, and a simulated patient. Novices and experts were recruited. Five-point Likert-type questionnaires were developed for face and content validity. Cronbach’s &agr; was calculated for scale reliability. Semistructured interviews captured responses for qualitative thematic analysis allowing for data triangulation. Twelve participants completed TBS scenario. Mean face and content validity ratings were high (4.6 and 4.5, respectively; range, 4–5). The internal consistency of questions was high. Qualitative data analysis revealed that participants felt 1) the experience was “real” and they were “able to behave as if in a real resuscitation environment,” and 2) TBS “addressed what Advanced Trauma and Life Support and Emergency Management of Severe Burns didn’t” (including the efficacy of incorporating nontechnical skills). TBS provides a novel, effective simulation tool to significantly advance the delivery of burns education. Recreating clinical challenge is crucial to optimize simulation training. This low-cost approach also has major implications for surgical education, particularly during increasing financial austerity. Alternative scenarios and/or procedures can be recreated within TBS, providing a diverse educational immersive simulation experience.

Using "The Burns Suite" as a Novel High Fidelity Simulation Tool for Interprofessional and Teamwork Training.

Educational theory highlights the importance of contextualized simulation for effective learning. The authors recently published the concept of “The Burns Suite” (TBS) as a novel tool to advance the delivery of burns education for residents/clinicians. Effectively, TBS represents a low-cost, high-fidelity, portable, immersive simulation environment. Recently, simulation-based team training (SBTT) has been advocated as a means to improve interprofessional practice. The authors aimed to explore the role of TBS in SBTT. A realistic pediatric burn resuscitation scenario was designed based on “advanced trauma and life support” and “emergency management of severe burns” principles, refined utilizing expert opinion through cognitive task analysis. The focus of this analysis was on nontechnical and interpersonal skills of clinicians and nurses within the scenario, mirroring what happens in real life. Five-point Likert-type questionnaires were developed for face and content validity. Cronbach’s alpha was calculated for scale reliability. Semistructured interviews captured responses for qualitative thematic analysis allowing for data triangulation. Twenty-two participants completed TBS resuscitation scenario. Mean face and content validity ratings were high (4.4 and 4.7 respectively; range 4–5). The internal consistency of questions was high. Qualitative data analysis revealed two new themes. Participants reported that the experience felt particularly authentic because the simulation had high psychological and social fidelity, and there was a demand for such a facility to be made available to improve nontechnical skills and interprofessional relations. TBS provides a realistic, novel tool for SBTT, addressing both nontechnical and interprofessional team skills. Recreating clinical challenge is crucial to optimize SBTT. With a better understanding of the theories underpinning simulation and interprofessional education, future simulation scenarios can be designed to provide unique educational experiences whereby team members will learn with and from other specialties and professions in a safe, controlled environment.

Controllable degradation kinetics of POSS nanoparticle-integrated poly(ε-caprolactone urea)urethane elastomers for tissue engineering applications.

Biodegradable elastomers are a popular choice for tissue engineering scaffolds, particularly in mechanically challenging settings (e.g. the skin). As the optimal rate of scaffold degradation depends on the tissue type to be regenerated, next-generation scaffolds must demonstrate tuneable degradation patterns. Previous investigations mainly focussed on the integration of more or less hydrolysable components to modulate degradation rates. In this study, however, the objective was to develop and synthesize a family of novel biodegradable polyurethanes (PUs) based on a poly(ε-caprolactone urea)urethane backbone integrating polyhedral oligomeric silsesquioxane (POSS-PCLU) with varying amounts of hard segments (24%, 28% and 33% (w/v)) in order to investigate the influence of hard segment chemistry on the degradation rate and profile. PUs lacking POSS nanoparticles served to prove the important function of POSS in maintaining the mechanical structures of the PU scaffolds before, during and after degradation. Mechanical testing of degraded samples revealed hard segment-dependent modulation of the materials’ viscoelastic properties, which was attributable to (i) degradation-induced changes in the PU crystallinity and (ii) either the presence or absence of POSS. In conclusion, this study presents a facile method of controlling degradation profiles of PU scaffolds used in tissue engineering applications.