A systematic review and meta-analysis of 30-day readmission rates following burns.

INTRODUCTION: Unplanned hospital readmissions in surgical areas account for high costs and have become an area of focus for health care providers and insurance companies. The aim of this systematic review is to identify the rate and common reasons for unplanned 30-day readmission following burns. METHODS: This study was performed following the PRISMA guidelines. Pubmed, Web of Science and CENTRAL databases were searched for publications without date or language restrictions. Extracted outcomes included 30-day readmission rate and reasons for readmission. Pooled 30-day readmission rate was estimated from weighted individual study estimates using random-effect models. Pooled estimates for risk factors are reported as odds ratios (ORs) and 95% confidence intervals (CIs). RESULTS: A total of eight studies were included into qualitative analysis and six (four adults, two children) into quantitative analysis. The overall readmission rate was 7.4% (95% CI 4.1-10.7) in adults and 2.7% (95% CI 2.2-3.2) in children. Based on two studies in 112,312 adult burn patients, burn size greater than 20% total body surface area (TBSA) was not a significant predictor of readmission rate (OR 1.75, 95% CI 0.64-4.75; NS). The most common reasons were infection/sepsis, wound healing complications, and pain in both adults and children. DISCUSSION: Unplanned readmissions following burns are generally low and appear more common in adults than in pediatric patients. However, only few studies are reporting on 30-day readmission rates following burns. Evidence is limited to support a significant association between greater burn size and higher readmission rates. Since cost effectiveness and utilized hospital capacity are becoming an area of focus for improvement in health care, future studies should assess the risk factors of unplanned readmission following burns. Follow-up assessments and outpatient resources, even if not underlined by this data, could reduce readmission rates. SYSTEMATIC REVIEW REGISTRATION: PROSPERO: CRD42019117649.

[Wnt signaling in cutaneous wound healing]. / Wnt-Signalwege bei kutaner Wundheilung.

Human skin is an efficient barrier that protects the organism from noxious substances. Wounds destroy this barrier. Wound healing is a phased physiological regeneration of the destroyed tissue that ideally leads to occlusion of a wound, in particular by regeneration of connective tissue and capillaries. The Wnt signaling pathway is a highly conserved signal transduction cascade across the animal kingdom that controls basic cellular interactions in multicellular organisms. Accordingly, through the Wnt signaling path many processes, e. g. as the balance between proliferation and differentiation or apoptosis, coordinated. Wnt signaling is activated by a wound and participates in each subsequent phase of the healing process, beginning with inflammatory control and programmed cell death, to the mobilization of stem cells within the wound. Endogenous Wnt signaling is an attractive therapeutic approach to assist in the repair of skin wounds, as the complex mechanisms of the Wnt signaling pathway have become increasingly understood over the years. This review summarizes current data to clarify the role of Wnt signaling in the wound healing process of the skin.

Continuous pH monitoring in wounds using a composite indicator dressing - A feasibility study.

PURPOSE: Modern burn care strives for new means to guarantee optimised wound healing. Several studies have shown a correlation between the pH value in a (burn) wound and successful wound healing. A multitude of devices to monitor pH is available, all requiring direct wound contact and removal of the dressing for pH monitoring. The aim of this feasibility study was to create a sterile and easy to handle method for pH monitoring while simultaneously using an advanced wound dressing. MATERIALS AND METHODS: Dressing sheets of biotechnologically generated nanofibrillar cellulose (epicitehydro) were chemically functionalised with the indicator dye GJM-534. pH-donors with increasing pH were subsequently applied to the created indicator dressing. To investigate temporal resolution and continuous monitoring we used circular pH-donors with different pH (7 and 10) and decreasing diameters that were placed on another dressing sheet. Clinically relevant spatial resolution was checked by a wound bed simulation with small areas (8 mm) of higher pH (10) on a field of lower pH (7) and vice versa. RESULTS: The indicator dressing showed a gradual colouring from yellow to dark orange with increasing pH in steps of 0.3. After conversion of digital pictures to greyscale values, a sigmoidal distribution with a pKa-value of 8.4 was obtained. A ring-like pattern with alternating colour change corresponding to the pH was observed in the continuous monitoring experiment and the wound bed simulation delivered excellent local resolution. CONCLUSION: Since the pH of a (burn) wound can have a significant influence on wound healing, a pH indicator was successfully linked to an advanced, temporary, alloplastic wound dressing material. We were able to show the possibility of pH monitoring by the dressing itself. Additional testing, including studies with large case numbers for optimisation are necessary before clinical implementation.

[Antibiotic treatment of infections in burn patients - a systematic review]. / Antibiotikatherapie von Infektionen bei Verbrennungspatienten ­ Eine systematische Übersichtsarbeit.

BACKGROUND: Due to the loss of the natural skin barrier function with reduced immune competence as a result of a plasma loss and the numerous intensive care interventions, burn patients are particularly at risk for infection. STUDY DESIGN: systematic review METHODS: A systematic review of German and English literature between 1990 and 2018 analyzes the epidemiological and diagnostic aspects as well as the therapeutic use of antibiotics in infections of burn patients in clinical trials. RESULTS: A total number of 53 randomized controlled clinical trials met the inclusion criteria. Various types / forms of application of antibiotic prophylaxis in burn wounds were investigated: topically, systemically (generally), systemically (perioperatively), nonabsorbable antibiotics (= selective intestinal decontamination), locally (inhaled) and all forms of administration versus control. Early postburn prophylaxis was studied in low-severity patients (six studies) and severe burn patients (seven studies). Antimicrobial prophylaxis has shown no effectiveness in the prevention of toxic shock syndrome in low grade burns, but can be useful in patients with severe burns in need for mechanical ventilation. Perioperative prophylaxis has been studied in ten studies. CONCLUSION: The benefit of long-term systemic antibiotic prophylaxis in the majority of burn patients is not evident. Mild infections in stable clinical conditions should be closely monitored, while in severe infections, international sepsis guidelines and the Tarragona principle are recommended.

A tribute to Cicero Parker Meek.

Cicero Parker Meek (1914-1979) was working as a general practitioner at the Aiken County Hospital in South Carolina, USA, and had a special interest in the treatment of burn patients. The procedure first presented in 1958 by Meek for a device-based expansion of split-skin (micrografting), which was invented before the mesh technique, is a milestone in the history of burns surgery. The method was forgotten until well into the 90s of the last century, and was only readopted and improved by no longer identifiable physicians at the Red Cross Hospital in Beverwijk. The Meek translation procedure was subsequently modified through the innovations of Kreis and Raff. With increased survival of massively burned patients, mesh grafting fell short of requirements. Mesh grafts of 1:9 expansion are difficult to handle and are vulnerable to dislodgement on the wound bed. Kreis and Raff showed in 1994 that 1:9 expanded mesh grafts did not achieve a true 1:9 expansion on the wound surface, in contrast to 1:9 expanded Meek grafts. Thus Meek grafts provided a highly effective autograft expansion in very large burns. Cicero Parker Meek was an exceptional person in the history of burn therapy.

[Keloid and hypertrophic scar treatment modalities. An update]. / Therapie von hypertrophen Narben und Keloiden. Ein Update.

Over the past two decades the treatment of hypertrophic scars and keloids has seen substantial changes due to the evolution of current and establishment of new conservative and surgical methods. This review gives an overview of the current research with respect to the multifactorial etiology and pathophysiology of keloids and hypertrophic scars, discusses conservative surgical treatment options and provides an outlook on novel treatment strategies.

Pre-clinical evaluation of liposomal gene transfer to improve dermal and epidermal regeneration.

Liposomal gene transfer effectively enhances dermal and epidermal regeneration in burned rodents. To advance this treatment to clinical studies, we investigated the efficacy of liposomal gene transfer in a clinically relevant porcine wound model. Mimicking the clinical scenario, six female Yorkshire pigs (40-50 kg) received up to 12 burns of 50 cm(2) area that were fully excised and covered with skin autograft meshed at 4:1 ratio 24 h post-burn. Animals received control injections (empty liposomes), liposomes (DMRIE-C) containing 1 mg LacZ-cDNA, or liposomes (DMRIE-C) with 1 mg of platelet-derived growth factor (PDGF)-cDNA, or the naked PDGF gene. Serial biopsies were taken from different wound sites at multiple time points up to 12 days post-wounding. Transfection efficacy and transfection rate of LacZ and localization of beta-gal were determined by immunohistochemical and immunofluorescent techniques. RT-PCR and multiplex protein analysis (ELISA) were used to measure levels of growth factor mRNA transcribed and growth factor protein translated. Wound re-epithelialization and graft adhesion was evaluated using planimetric analysis and clinical scores. We found that peak transfection of liposomal beta-galactosidase occurred on day 2, with a fluorescence increase of 154% to baseline (P<0.001). Transfection intensity dropped to 115% above baseline on day 4 (P<0.001) and 109% on day 7. Immunohistochemistry showed a maximum transfection rate of 34% of cells in wound tissue. Gene transfer of liposomal PDGF-cDNA resulted in increased PDGF-mRNA and protein expression on days 2 and 4, and accelerated wound re-epithlialization as well as graft adhesion on day 9 (P<0.05). In this study, we showed that liposomal cDNA gene transfer is possible in a porcine wound model, and by using PDGF-cDNA we further showed that dermal and epidermal regeneration can be improved. These data indicate that liposomal gene transfer can be a new therapeutic approach to improve wound healing in humans.

Gene therapy in wound healing: present status and future directions.

Gene therapy was traditionally considered a treatment modality for patients with congenital defects of key metabolic functions or late-stage malignancies. The realization that gene therapy applications were much vaster has opened up endless opportunities for therapeutic genetic manipulations, especially in the skin and external wounds. Cutaneous wound healing is a complicated, multistep process with numerous mediators that act in a network of activation and inhibition processes. Gene delivery in this environment poses a particular challenge. Numerous models of gene delivery have been developed, including naked DNA application, viral transfection, high-pressure injection, liposomal delivery, and more. Of the various methods for gene transfer, cationic cholesterol-containing liposomal constructs are emerging as a method with great potential for non-viral gene transfer in the wound. This article aims to review the research on gene therapy in wound healing and possible future directions in this exciting field.

Depolarization affects the binding properties of muscarinic acetylcholine receptors and their interaction with proteins of the exocytic apparatus.

Membrane depolarization is the signal that triggers release of neurotransmitter from nerve terminals. As a result of depolarization, voltage-dependent Ca(2+) channels open, level of intracellular Ca(2+) increases. and release of neurotransmitter commences. Previous study had shown that in rat brain synaptosomes, muscarinic acetylcholine (ACh) receptors (mAChRs) interact with soluble NSF attachment protein receptor proteins of the exocytic machinery in a voltage-dependent manner. It was suggested that this interaction might control the rapid, synchronous release of acetylcholine. The present study investigates the mechanism for such a voltage-dependent interaction. Here we show that depolarization shifts mAChRs, specifically the m2 receptor subtype, to a low affinity state toward its agonists. At resting potential, mAChRs are in a high affinity state (K(d) of approximately 20 nM) and they shift to a low affinity state (K(d) of tens of microM) upon membrane depolarization. In addition, interaction between m2 receptor subtype and the exocytic machinery increases with receptor occupancy. Both phenomena are independent of Ca(2+) influx. We propose that these results may explain control of ACh release from nerve terminals. At resting potential the exocytic machinery is clamped due to its interaction with the occupied mAChR and depolarization relieves this interaction. This, together with Ca(2+) influx, enables release of ACh to commence.

Expression and localization of muscarinic receptors in P19-derived neurons.

The muscarinic acetylcholine receptors are important in a variety of physiological processes such as induction of secretion from various glands and regulation of pacemaker activity, muscle tone, and neurotransmission. To date, the muscarinic receptor family includes five members (designated m1-m5), of which m1-m4 are abundant in brain and in peripheral tissues, and m5 is found exclusively in brain, and even there at very low levels. The expression of m1-m5 receptor subtypes was studied in neurons derived from the murine embryonal carcinoma cell line P19. These cells serve as a model system for differentiation and maturation of neurons resembling CNS neurons. Our results show that P19 neurons express mainly the m2, m3, and m5 subtypes. Low levels of m1 receptors are also detected and m4 subtype is practically absent. Furthermore, muscarinic receptors in P19 neurons are functional in activating second messenger signaling pathways. The localization of m2 receptors is predominantly presynaptic, whereas the m5 subtype is mainly postsynaptic. Consequently, P19 cells provide a model system for the study of pre- and postsynaptic muscarinic acetylcholine-receptor subtypes in a proper neuronal context. This is particularly valid for the rare m5 receptors.