Early Autocalibrated Arterial Waveform Analysis for the Management of Burn Shock-A Cohort Study.

Adequate fluid therapy is crucial for resuscitation after major burns. To adapt this to individual patient demands, standard is adjustment of volume to laboratory parameters and values of enhanced hemodynamic monitoring. To implement calibrated parameters, patients must have reached the intensive care unit (ICU). The aim of this study was, to evaluate the use of an auto-calibrated enhanced hemodynamic monitoring device to improve fluid management before admission to ICU. We used PulsioflexProAqt® (Getinge) during initial treatment and burn shock resuscitation. Analysis was performed regarding time of measurement, volume management, organ dysfunction, and mortality. We conducted a monocentre, prospective cohort study of 20 severely burned patients, >20% total body surface area (TBSA), receiving monitoring immediately after admission. We compared to 57 patients, matched in terms of TBSA, age, sex, and existence of inhalation injury out of a retrospective control group, who received standard care. Hemodynamic measurement with autocalibrated monitoring started significantly earlier: 3.75(2.67-6.0) hours (h) after trauma in the study group versus 13.6(8.1-17.5) h in the control group (P < .001). Study group received less fluid after 6 h: 1.7(1.2-2.2) versus 2.3(1.6-2.8) ml/TBSA%/kg, P = .043 and 12 h: 3.0(2.5-4.0) versus 4.2(3.1-5.0) ml/TBSA%/kg, P = .047. Dosage of norepinephrine was higher after 18 h in the study group: 0.20(0.12-0.3) versus 0.08(0.02-0.18) µg/kg/min, P = .014. The study group showed no adult respiratory distress syndrome versus 21% in the control group, P = .031. There was no difference in other organ failures, organ replacement therapy, and mortality. The use of auto-calibrated enhanced hemodynamic monitoring is a fast and feasible way to guide early fluid therapy after burn trauma. It reduces the time to reach information about patient's volume capacity. Management of fluid application changed to a more restrictive fluid use in the early period of burn shock and led to a reduction of pulmonary complications.

A TRP channel trio mediates acute noxious heat sensing.

Acute pain represents a crucial alarm signal to protect us from injury. Whereas the nociceptive neurons that convey pain signals were described more than a century ago, the molecular sensors that detect noxious thermal or mechanical insults have yet to be fully identified. Here we show that acute noxious heat sensing in mice depends on a triad of transient receptor potential (TRP) ion channels: TRPM3, TRPV1, and TRPA1. We found that robust somatosensory heat responsiveness at the cellular and behavioural levels is observed only if at least one of these TRP channels is functional. However, combined genetic or pharmacological elimination of all three channels largely and selectively prevents heat responses in both isolated sensory neurons and rapidly firing C and Aδ sensory nerve fibres that innervate the skin. Strikingly, Trpv1-/-Trpm3-/-Trpa1-/- triple knockout (TKO) mice lack the acute withdrawal response to noxious heat that is necessary to avoid burn injury, while showing normal nociceptive responses to cold or mechanical stimuli and a preserved preference for moderate temperatures. These findings indicate that the initiation of the acute heat-evoked pain response in sensory nerve endings relies on three functionally redundant TRP channels, representing a fault-tolerant mechanism to avoid burn injury.

Modeling Burn Progression Using Comb Burns: The Impact of Thermal Contact Duration on Model Outcomes.

BACKGROUND: Burn progression is a phenomenon that remains poorly characterized. The mechanisms of burn conversion are not completely understood, and consequently, both predictive diagnostic tools and interventions are limited. The rat comb burn model is a commonly used approach to study horizontal burn conversion. However, there is significant variability in how the model is performed. Skin contact duration, comb device heating method, comb heating duration, amount of pressure applied, the weight of the comb, and associated depth of burn are all variables that are heterogeneous in studies utilizing the model. MATERIALS AND METHODS: Here, contact duration was examined to determine the impact the duration of burn delivery has on the conversion of interspaces in this model. Data from multiple experiments consisting of 10, 15, 20, 30, 40, and 45 s comb burns were compiled and assessed. Burns were made using combs heated in a 100°C dry bath and then monitored for 2 d. Interspace viability was assessed by digital and laser doppler imaging and biopsy procurement. RESULTS: Laser Doppler Imaging and viable interspace measurements showed that as burn duration increased, the percentage of the viable interspace and interspace perfusion decreased. Additionally, a contact time of 30 s or greater was required to result in 100% interspace conversion. CONCLUSIONS: These results demonstrate a need to better characterize and potentially standardize the rat comb burn model to reduce variation and maintain it as a valuable tool for controlled studies of the pathophysiology of burn wound progression.

Insulin Modulates Myogenesis and Muscle Atrophy Resulting From Skin Scald Burn in Young Male Rats.

BACKGROUND: Burn injuries (BIs) due to scalding are one of the most common accidents among children. BIs greater than 40% of total body surface area are considered extensive and result in local and systemic response. We sought to assess morphological and myogenic mechanisms through both short- and long-term intensive insulin therapies that affect the skeletal muscle after extensive skin BI in young rats. MATERIALS AND METHODS: Wistar rats aged 21 d were distributed into four groups: control (C), control with insulin (C + I), scald burn injury (SI), and SI with insulin (SI + I). The SI groups were submitted to a 45% total body surface area burn, and the C + I and SI + I groups received insulin (5 UI/Kg/d) for 4 or 14 d. Glucose tolerance and the homeostatic model assessment of insulin resistance index were determined. Gastrocnemius muscles were analyzed for histopathological, morphometric, and immunohistochemical myogenic parameters (Pax7, MyoD, and MyoG); in addition, the expression of genes related to muscle atrophy (MuRF1 and MAFbx) and its regulation (IGF-1) were also assessed. RESULTS: Short-term treatment with insulin favored muscle regeneration by primary myogenesis and decreased muscle atrophy in animals with BIs, whereas the long-term treatment modulated myogenesis by increasing the MyoD protein. Both treatments improved histopathological parameters and secondary myogenesis by increasing the MyoG protein. CONCLUSIONS: Treatment with insulin benefits myogenic parameters during regeneration and modulates MuRF1, an important mediator of muscle atrophy.

The development of a tool to predict temperature-exposure of incinerated teeth using colourimetric and hydroxyapatite crystal size data.

This study presents a novel tool to predict temperature-exposure of incinerated pig teeth as a proxy for understanding impacts of fire on human teeth. Previous studies on the estimation of temperature-exposure of skeletal elements have been limited to that of heat-exposed bone. This predictive tool was developed using a multinomial regression model of colourimetric and hydroxyapatite crystal size variables using data obtained from unheated pig teeth and teeth incinerated at 300 °C, 600 °C, 800 °C and 1000 °C. An additional variable based on the observed appearance of the tooth was included in the tool. This enables the tooth to be classified as definitely burnt (600 °C-1000 °C) or uncertain (27 °C/300 °C). As a result, the model predicting the temperature-exposure of the incinerated teeth had an accuracy of 95%. This tool is a holistic, robust and reliable approach to estimate temperature of heat-exposed pig teeth, with high accuracy, and may act as a valuable proxy to estimate heat exposure for human teeth in forensic casework.

Physical plasma therapy accelerates wound re-epithelialisation and enhances extracellular matrix formation in cutaneous skin grafts.

Skin grafting is a surgical method of cutaneous reconstruction, which provides volumetric replacement in wounds unable to heal by primary intention. Clinically, full-thickness skin grafts (FTSGs) are placed in aesthetically sensitive and mechanically demanding areas such as the hands, face, and neck. Complete or partial graft failure is the primary complication associated with this surgical procedure. Strategies aimed at improving the rate of skin graft integration will reduce the incidence of graft failure. Cold atmospheric plasma (CAP) is an emerging technology offering innovative clinical applications. The aim of this study was to test the therapeutic potential of CAP to improve wound healing and skin graft integration into the recipient site. In vitro models that mimic wound healing were used to investigate the ability of CAP to enhance cellular migration, a key factor in cutaneous tissue repair. We demonstrated that CAP enhanced the migration of epidermal keratinocytes and dermal fibroblasts. This increased cellular migration was possibly induced by the low dose of reactive oxygen and nitrogen species produced by CAP. Using a mouse model of burn wound reconstructed with a full-thickness skin graft, we showed that wounds treated with CAP healed faster than did control wounds. Immunohistochemical wound analysis showed that CAP treatment enhanced the expression of the dermal-epidermal junction components, which are vital for successful skin graft integration. CAP treatment was characterised by increased levels of Tgfbr1 mRNA and collagen I protein in vivo, suggesting enhanced wound maturity and extracellular matrix deposition. Mechanistically, we show that CAP induced the activation of the canonical SMAD-dependent TGF-ß1 pathway in primary human dermal fibroblasts, which may explain the increased collagen I synthesis in vitro. These studies revealed that CAP improved wound repair and skin graft integration via mechanisms involving extracellular matrix formation. CAP offers a novel approach for treating cutaneous wounds and skin grafts. © 2020 The Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

Elevated Plasma Concentrations of Syndecan-1 Do Not Correlate With Increased Capillary Leakage of 20% Albumin.

BACKGROUND: Preclinical experiments show that an inflammatory reaction causes degradation of the endothelial glycocalyx layer and accelerated capillary leakage of albumin and fluid. The hypothesis in the present study was that elevated plasma concentrations of glycocalyx degradation products are associated with greater capillary leakage in humans. METHODS: This open clinical trial involved administration of an intravenous infusion of 20% albumin at 3 mL/kg over 30 minutes to 15 postburn patients who showed an activated inflammatory response. Blood samples and urine were collected for 300 minutes. The plasma concentrations of 2 biomarkers of glycocalyx degradation-syndecan-1 and heparan sulfate-were measured at 0, 60, and 300 minutes and compared to the capillary leakage of albumin and fluid obtained by mass balance calculations and population kinetic analysis. RESULTS: Patients were studied at 7 days (median) after a burn injury that covered 15% (maximum 48%) of the body surface area. The median plasma syndecan-1 concentration was 71 (25th-75th percentiles, 41-185) ng/mL. The 2 patients with highest values showed 2279 and 2395 ng/mL (normal 15 ng/mL). Heparan sulfate concentrations averaged 915 (673-1539) ng/mL. The infused amount of albumin was 57 (48-62) g, and 6.3 (5.1-7.7)% of that leaked from the plasma per hour.Linear correlation analysis of the relationship between the 10logarithm of the mean syndecan-1 and the albumin leakage showed a slope coefficient of -1.3 (95% confidence interval [CI], -3.6 to 1.0) and a correlation coefficient of -0.33 (P = .24). The kinetic analysis revealed that syndecan-1 served as a statistically significant covariate to the albumin leakage, but the relationship was inverse (power exponent -0.78, 95% CI, -1.50 to -0.05; P < .02). Heparan sulfate levels did not correlate with the capillary leakage of albumin or fluid in any of the analyses. CONCLUSIONS: A raised plasma concentration of syndecan-1 alone cannot be extrapolated to indicate increased capillary leakage of albumin and fluid.

Effects of Virtual Reality and Task-Oriented Training on Hand Function and Activity Performance in Pediatric Hand Burns: A Randomized Controlled Trial.

OBJECTIVE: To assess the efficacy of a motion-sensing, hands-free gaming device and task-oriented training (TOT) programs on improving hand function, activity performance, and satisfaction in pediatric hand burns. DESIGN: A randomized controlled trial. SETTING: Outpatient rehabilitation center. PARTICIPANTS: Fifty children with deep partial-thickness or full-thickness hand burns. (N=50; mean age, 10.70±1.64y; range, 7-14y) INTERVENTIONS: Children were randomized into 1 of the following 3 groups: the motion-sensing, hands-free gaming device group that used interactive video games plus traditional rehabilitation (TR); the TOT group that used real materials plus TR; and the control group that only received TR, all groups received the interventions 3 days per week for 8 weeks. MAIN OUTCOME MEASURES: We assessed the children at the baseline and after 8 weeks of intervention. The primary outcome measures were the Jebsen-Taylor Hand Function Test, Duruoz Hand Index (DHI), and Canadian Occupational Performance Measure (COPM). The secondary outcome measures were range of motion (ROM) of the digits, grip strength, and pinch strengths (tip, palmer, and lateral pinch). RESULTS: There was a significant increase in all measurements of the motion-sensing, hands-free gaming device and TOT groups compared with that of the control group postintervention (P<.05). There was no significant change in Jebsen-Taylor Hand Function Test, COPM performance, ROM, grip strength, and tip and lateral pinch strengths between the motion-sensing, hands-free gaming device group and TOT group (P>.05), whereas there was a significant increase in DHI, COPM satisfaction, and palmer pinch strength (P<.05) in the motion-sensing, hands-free gaming device group compared with the TOT group postintervention. CONCLUSIONS: The motion-sensing, hands-free gaming device and TOT programs resulted in significant improvement in hand function, activity performance and satisfaction, ROM of the digits, grip strength, and pinch strengths in pediatric hand burns compared with the traditional hand rehabilitation.

Recent Applications of Virtual Reality for the Management of Pain in Burn and Pediatric Patients.

PURPOSE OF REVIEW: Virtual reality, via integration of immersive visual and auditory modalities, offers an innovative approach to pain management. The purpose of this review is to investigate the clinical application of virutal reality as an adjunct analgesic to standard of care, particularly in pediatric and burn patients. RECENT FINDINGS: Although relatively new, virtual reality has been successfully implemented in a wide range of clinical scenarios for educational, diagnostic, and therapeutic purposes. Most recent literature supports the use of this adjunct analgesic in reducing pain intensity for pediatric and burn patients undergoing acute, painful procedures. This summative review demonstrates the efficacy of virtual reality in altering pain perception by decreasing pain and increasing functionality among pediatric and burn patients. However, large, multi-center randomized controlled trials are still warranted to generalize these findings to more diverse patient demographics and medical scenarios.

Development of a Topical Insulin Polymeric Nanoformulation for Skin Burn Regeneration: An Experimental Approach.

Insulin is a peptide hormone with many physiological functions, besides its use in diabetes treatment. An important role of insulin is related to the wound healing process-however, insulin itself is too sensitive to the external environment requiring the protective of a nanocarrier. Polymer-based nanoparticles can protect, deliver, and retain the protein in the target area. This study aims to produce and characterize a topical treatment for wound healing consisting of insulin-loaded poly-DL-lactide/glycolide (PLGA) nanoparticles. Insulin-loaded nanoparticles present a mean size of approximately 500 nm and neutral surface charge. Spherical shaped nanoparticles are observed by scanning electron microscopy and confirmed by atomic force microscopy. SDS-PAGE and circular dichroism analysis demonstrated that insulin preserved its integrity and secondary structure after the encapsulation process. In vitro release studies suggested a controlled release profile. Safety of the formulation was confirmed using cell lines, and cell viability was concentration and time-dependent. Preliminary safety in vivo assays also revealed promising results.

Keratin-Alginate Sponges Support Healing of Partial-Thickness Burns.

Deep partial-thickness burns damage most of the dermis and can cause severe pain, scarring, and mortality if left untreated. This study serves to evaluate the effectiveness of crosslinked keratin-alginate composite sponges as dermal substitutes for deep partial-thickness burns. Crosslinked keratin-alginate sponges were tested for the ability to support human dermal fibroblasts in vitro and to support the closure and healing of partial-thickness burn wounds in Sus scrofa pigs. Keratin-alginate composite sponges supported the enhanced proliferation of human dermal fibroblasts compared to alginate-only sponges and exhibited decreased contraction in vitro when compared to keratin only sponges. As dermal substitutes in vivo, the sponges supported the expression of keratin 14, alpha-smooth muscle actin, and collagen IV within wound sites, comparable to collagen sponges. Keratin-alginate composite sponges supported the regeneration of basement membranes in the wounds more than in collagen-treated wounds and non-grafted controls, suggesting the subsequent development of pathological scar tissues may be minimized. Results from this study indicate that crosslinked keratin-alginate sponges are suitable alternative dermal substitutes for clinical applications in wound healing and skin regeneration.

The Effect of Betulin Diphosphate in Wound Dressings of Bacterial Cellulose-ZnO NPs on Platelet Aggregation and the Activity of Oxidoreductases Regulated by NAD(P)+/NAD(P)H-Balance in Burns on Rats.

The inhibition of platelet aggregation, and the activity of oxidoreductases and microhemocirculation in a burn wound on the treatment of burns with wound dressings based on bacterial nanocellulose (BC)-zinc oxide nanoparticles (ZnO NPs)-betulin diphosphate (BDP) were studied. The control of the treatment by BC-ZnO NPs-BDP on burned rats by the noninvasive DLF method showed an increase in perfusion and the respiratory component in wavelet spectra, characterizing an improvement in oxygen saturation in the wound. The study on the volunteers' blood found the inhibition of ADP-induced platelet aggregation by 30-90%. Disaggregation depends on the dose under the action of the ionized form of BDP and ZnO NPs-BDP in a phosphate buffer; it was reversible and had two waves. It was shown on rats that the specific activity of LDHreverse and LDHdirect (control-intact animals) on day 21 of treatment increased by 11-38% and 23%, respectively. The LDHreverse/LDHdirect ratio increased at BC-ZnO NPs-BDP treatment, which characterizes efficient NAD+ regeneration. AlDH activity increased significantly in the first 10 days by 70-170%, reflecting the effectiveness of the enzyme and NAD+ in utilizing toxic aldehydes at this stage of burn disease. The activities of GR and G6PDH using NADP(H) were increased with BC-ZnO NPs-BDP treatment.

The History and Development of Hyperbaric Oxygenation (HBO) in Thermal Burn Injury.

Background and Objectives: Hyperbaric oxygenation (HBO) denotes breathing of 100% oxygen under elevated ambient pressure. Since the initiation of HBO for burns in 1965, abundant experimental and clinical work has been done. Despite many undisputedly positive and only a few controversial results on the efficacy of adjunctive HBO for burn injury, the method has not yet been established in clinical routine. Materials and Methods: We did a retrospective analysis of the literature according to PRISMA-guidelines, from the very beginning of HBO for burns up to present, trying to elucidate the question why HBO is still sidelined in the treatment of burn injury. Results: Forty-seven publications (32 animal experiments, four trials in human volunteers and 11 clinical studies) fulfilled the inclusion criteria. Except four investigators who found little or no beneficial action, all were able to demonstrate positive effects of HBO, most of them describing less edema, improved healing, less infection or bacterial growth and most recently, reduction of post-burn pain. Secondary enlargement of burn was prevented, as microvascular perfusion could be preserved, and cells were kept viable. The application of HBO, however, concerning pressure, duration, frequency and number of treatment sessions, varied considerably. Authors of large clinical studies underscored the intricate measures required when administering HBO in severe burns. Conclusions: HBO unquestionably has a positive impact on the pathophysiological mechanisms, and hence on the healing and course of burns. The few negative results are most likely due to peculiarities in the administration of HBO and possibly also to interactions when delivering the treatment to severely ill patients. Well-designed studies are needed to definitively assess its clinical value as an adjunctive treatment focusing on relevant outcome criteria such as wound healing time, complications, length of hospital stay, mortality and scar quality, while also defining optimal HBO dosage and timing.

Role of caveolin-1 in epidermal stem cells during burn wound healing in rats.

Local transplantation of stem cells has therapeutic effects on skin damage but cannot provide satisfactory wound healing. Studies on the mechanisms underlying the therapeutic effects of stem cells on skin wound healing will be needed. Hence, in the present study, we explored the role of Caveolin-1 in epidermal stem cells (EpiSCs) in the modulation of wound healing. We first isolated EpiSCs from mouse skin tissues and established stable EpiSCs with overexpression of Caveolin-1 using a lentiviral construct. We then evaluated the epidermal growth factor (EGF)-induced cell proliferation ability using cell counting Kit-8 (CCK-8) assay and assessed EpiSC pluripotency by examining Nanog mRNA levels in EpiSCs. Furthermore, we treated mice with skin burn injury using EpiSCs with overexpression of Caveolin-1. Histological examinations were conducted to evaluate re-epithelialization, wound scores, cell proliferation and capillary density in wounds. We found that overexpression of Caveolin-1 in EpiSCs promoted EGF-induced cell proliferation ability and increased wound closure in a mouse model of skin burn injury. Histological evaluation demonstrated that overexpression of Caveolin-1 in EpiSCs promoted re-epithelialization in wounds, enhanced cellularity, and increased vasculature, as well as increased wound scores. Taken together, our results suggested that Caveolin-1 expression in the EpiSCs play a critical role in the regulation of EpiSC proliferation ability and alteration of EpiSC proliferation ability may be an effective approach in promoting EpiSC-based therapy in skin wound healing.

Mechanism of pulmonary immunosuppression: extrapulmonary burn injury suppresses bacterial endotoxin-induced pulmonary neutrophil recruitment and neutrophil extracellular trap (NET) formation.

Pulmonary immunosuppression often occurs after burn injury (BI). However, the reasons for BI-induced pulmonary immunosuppression are not clearly understood. Neutrophil recruitment and neutrophil extracellular trap (NET) formation (NETosis) are important components of a robust pulmonary immune response, and we hypothesized that pulmonary inflammation and NETosis are defective after BI. To test this hypothesis, we established a mouse model with intranasal LPS instillation in the presence or absence of BI (15% of body surface burn) and determined the degree of immune cell infiltration, NETosis, and the cytokine levels in the airways and blood on d 2. Presence of LPS recruited monocytes and large numbers of neutrophils to the airways and induced NETosis (citrullinated histone H3, DNA, myeloperoxidase). By contrast, BI significantly reduced LPS-mediated leukocyte recruitment and NETosis. This BI-induced immunosuppression is attributable to the reduction of chemokine (C-C motif) ligand (CCL) 2 (monocyte chemoattractant protein 1) and CCL3 (macrophage inflammatory protein 1α). BI also suppressed LPS-induced increase in IL-17A, IL-17C, and IL-17E/IL-25 levels in the airways. Therefore, BI-mediated reduction in leukocyte recruitment and NETosis in the lungs are attributable to these cytokines. Regulating the levels of some of these key cytokines represents a potential therapeutic option for mitigating BI-mediated pulmonary immunosuppression.-Sakuma, M., Khan, M. A. S., Yasuhara, S., Martyn, J. A., Palaniyar, N. Mechanism of pulmonary immunosuppression: extrapulmonary burn injury suppresses bacterial endotoxin-induced pulmonary neutrophil recruitment and neutrophil extracellular trap (NET) formation.

Validity of thermography for measuring burn wound healing potential.

Accurate assessment of burn wound depth and the associated healing potential is vital in determining the need for surgical treatment in burns. Infrared thermography measures the temperature of the burn wound noninvasively, thereby providing indirect information on its blood flow. Previous research demonstrated that a small, low-priced, handheld thermal imager has an excellent reliability, but a moderate validity for measuring burn wound healing potential. A new and more sensitive version of this convenient device has become available. The aim of this study was to evaluate the validity of thermography for measuring burn wound healing potential, compared to Laser Doppler Imaging (LDI) as a reference standard. Thermal images and LDI scans were obtained from burn wounds between 2 and 5 days postburn. Temperature differences between burned and nonburned skin (ΔT) were calculated. To evaluate validity, ΔT values were compared to the healing potential categories assessed by LDI. Two receiver operating characteristic curves were created and two ΔT cutoff values were calculated to illustrate the ability to discriminate between burn wounds that heal in a time period of less than 14 days, between 14 and 21 days, and more than 21 days. Between June and October 2018, 43 burn wounds in 32 patients were measured. ΔT cutoff values of 0.6°C (sensitivity 68%, specificity 95%) and -2.3°C (sensitivity 30%, specificity 95%) were calculated to discriminate between burn wounds that heal in <14 and ≥14 days, and burn wound that heal in ≤21 and >21 days, respectively. This study shows a good validity of the feasible thermal imager for the assessment of burn wound healing potential. Therefore, we consider it a promising technique to be used for triage in local hospitals and general practices, and as a valuable addition to clinical evaluation in burn centers.

Expression profile and bioinformatics analysis of circular RNA in intestinal mucosal injury and repair after severe burns.

Circular RNA (circRNA) is a novel noncoding RNA that is mostly found in humans and animals. Although the flux of circRNA research has increased in recent years, its precise function is still unclear. Some studies demonstrate that circRNAs can function as microRNA (miRNA) sponges involved in the regulation of competitive endogenous RNAs networks and play a crucial role in many biological processes. Other studies show that circRNAs play multiple biological roles in gastrointestinal diseases. However, the expression characteristics and function of circRNA in intestinal mucosal injury and repair after severe burn have not been reported. This study aims to screen differentially expressed circRNAs in intestinal mucosal injury and repair after severe burns and understand their underlying mechanisms. To test our hypothesis that circRNA may play a role in promoting repair in intestinal mucosa injury after severe burns, we collected the intestinal tissues of three severely burned mice and three pseudo-scalded mice and evaluated the expression of circRNAs via microarray analysis. Quantitative real-time polymerase chain reaction was also used to validate the circRNA microarray data by selecting six based on different multiples, original values, and p values. The host genes of all differentially expressed circRNAs and the downstream target genes of six selected DEcircRNAs were identified by Gene Ontology and the Kyoto Encyclopedia of Genes and Genomes pathway analysis. Meanwhile, we also created a circRNA-miRNA-mRNA network to predict the role and function of circRNAs in intestinal mucosal injury and repair after severe burns.

Acute kidney injury in burn patients admitted to the intensive care unit: a systematic review and meta-analysis.

BACKGROUND: Acute kidney injury (AKI) is a common complication in burn patients admitted to the intensive care unit (ICU) associated with increased morbidity and mortality. Our primary aim was to review incidence, risk factors, and outcomes of AKI in burn patients admitted to the ICU. Secondary aims were to review the use of renal replacement therapy (RRT) and impact on health care costs. METHODS: We conducted a systematic search in PubMed, UpToDate, and NICE through 3 December 2018. All reviews in Cochrane Database of Systematic Reviews except protocols were added to the PubMed search. We searched for studies on AKI according to Risk, Injury, Failure, Loss of kidney function, and End-stage kidney disease (RIFLE); Acute Kidney Injury Network (AKIN); and/or Kidney Disease: Improving Global Outcomes (KDIGO) criteria in burn patients admitted to the ICU. We collected data on AKI incidence, risk factors, use of RRT, renal recovery, length of stay (LOS), mortality, and health care costs. RESULTS: We included 33 observational studies comprising 8200 patients. Overall study quality, scored according to the Newcastle-Ottawa scale, was moderate. Random effect model meta-analysis revealed that the incidence of AKI among burn patients in the ICU was 38 (30-46) %. Patients with AKI were almost evenly distributed in the mild, moderate, and severe AKI subgroups. RRT was used in 12 (8-16) % of all patients. Risk factors for AKI were high age, chronic hypertension, diabetes mellitus, high Total Body Surface Area percent burnt, high Abbreviated Burn Severity Index score, inhalation injury, rhabdomyolysis, surgery, high Acute Physiology and Chronic Health Evaluation II score, high Sequential Organ Failure Assessment score, sepsis, and mechanical ventilation. AKI patients had 8.6 (4.0-13.2) days longer ICU LOS and higher mortality than non-AKI patients, OR 11.3 (7.3-17.4). Few studies reported renal recovery, and no study reported health care costs. CONCLUSIONS: AKI occurred in 38% of burn patients admitted to the ICU, and 12% of all patients received RRT. Presence of AKI was associated with increased LOS and mortality. TRIAL REGISTRATION: PROSPERO (CRD42017060420).

Circulating dipeptidyl peptidase-3 at admission is associated with circulatory failure, acute kidney injury and death in severely ill burn patients.

BACKGROUND: Dipeptidyl peptidase-3 (DPP3) is a metallopeptidase which cleaves bioactive peptides, notably angiotensin II, and is involved in inflammation regulation. DPP3 has been proposed to be a myocardial depressant factor and to be involved in circulatory failure in acute illnesses, possibly due to angiotensin II cleavage. In this study, we evaluated the association between plasmatic DPP3 level and outcome (mortality and hemodynamic failure) in severely ill burn patients. METHODS: In this biomarker analysis of a prospective cohort study, we included severely ill adult burn patients in two tertiary burn intensive care units. DPP3 was measured at admission (DPP3admin) and 3 days after. The primary endpoint was 90-day mortality. Secondary endpoints were hemodynamic failure and acute kidney injury (AKI). RESULTS: One hundred and eleven consecutive patients were enrolled. The median age was 48 (32.5-63) years, with a median total body surface area burned of 35% (25-53.5) and Abbreviated Burn Severity Index (ABSI) of 8 (7-11). Ninety-day mortality was 32%. The median DPP3admin was significantly higher in non-survivors versus survivors (53.3 ng/mL [IQR 28.8-103.5] versus 27.1 ng/mL [IQR 19.4-38.9]; p < 0.0001). Patients with a sustained elevated DPP3 had an increased risk of death compared to patients with high DPP3admin but decreased levels on day 3. Patients with circulatory failure had higher DPP3admin (39.2 ng/mL [IQR 25.9-76.1] versus 28.4 ng/mL [IQR 19.8-39.6]; p = 0.001) as well as patients with AKI (49.7 ng/mL [IQR 30.3-87.3] versus 27.6 ng/mL [IQR 19.4-41.4]; p = 0.001). DPP3admin added prognostic value on top of ABSI (added chi2 12.2, p = 0.0005), Sequential Organ Failure Assessment (SOFA) score at admission (added chi2 4.9, p = 0.0268), and plasma lactate at admission (added chi2 6.9, p = 0.0086) to predict circulatory failure within the first 48 h. CONCLUSIONS: Plasma DPP3 concentration at admission was associated with an increased risk of death, circulatory failure, and AKI in severely burned patients. Whether DPP3 plasma levels could identify patients who would respond to alternative hemodynamic support strategies, such as intravenous angiotensin II, should be explored.

Plasma volume expansion and capillary leakage of 20% albumin in burned patients and volunteers.

BACKGROUND: Burn injury is associated with a long-standing inflammatory reaction. The use of albumin solutions for plasma volume support is controversial because of concerns of increased capillary leakage, which could aggravate the commonly seen interstitial oedema. METHODS: In the present open controlled clinical trial, an intravenous infusion of 20% albumin at 3 mL/kg was given over 30 min to 15 burn patients and 15 healthy volunteers. Blood samples and urine were collected for 5 h. Plasma dilution, plasma albumin and colloid osmotic pressure were compared. Mass balance calculations were used to estimate plasma volume expansion and capillary leakage of fluid and albumin. RESULTS: The patients were studied between 4 and 14 (median, 7) days after the burn injury, which spread over 7-48% (median, 15%) of the total body surface area. The albumin solution expanded the plasma volume by almost 15%, equivalent to twice the infused volume, in both groups. The urinary excretion exceeded the infused volume by a factor of 2.5. Capillary leakage of albumin occurred at a rate of 3.4 ± 1.5 g/h in burn patients and 3.7 ± 1.6 g/h in the volunteers (P = 0.61), which corresponded to 2.4 ± 1.0% and 2.5 ± 1.2% per hour of the intravascular pool (P = 0.85). The median half-life of the plasma volume expansion was 5.9 (25th-75th percentiles 2.7-11.7) h in the burn patients and 6.9 (3.4-8.5) h in the volunteers (P = 0.56). CONCLUSIONS: Albumin 20% was an effective volume expander in patients at 1 week post-burn. No relevant differences were found between burn patients and healthy volunteers. TRIAL REGISTRATION: EudraCT 2016-000996-26 on May 31, 2016.