Disruption of bone and skeletal muscle in severe burns

Severe burn injury triggers the body＇s nonspecific adaptive responses to acute insult, including the systemic inflammatory and stress responses, as well as the sympathetic response to immobilization. These responses trigger inflammatory bone resorption followed by glucocorticoid-induced apoptosis of osteoblasts and probably osteocytes. Because these patients are catabolic, they suffer concomitant muscle wasting and negative nitrogen balance. The use of anabolic agents such as recombinant human growth hormone and oxandrolone results in improved bone mineral content and muscle strength after approximately I year. Use of bisphosphonates within the first 10 days of a severe burn completely blocks the resorptive bone loss and has the added advantage of appearing to preserve muscle protein from excessive breakdown. The mechanism for the protective effect on muscle is not currently known. However, if the effect of bisphosphonates on muscle can be confirmed, it raises the possibility that bone communicates with muscle.

Prevention and treatment of gastrointestinal dysfunction following severe burns: A summary of recent 30-year clinical experience

AIM： To sum up the recent 30-year experience in the prevention and treatment of gastrointestinal dysfunction in severe burn patients, and propose practicable guidelines for the prevention and treatment of gastrointestinal （GI） dysfunction. METHODS： From 1980 to 2007, a total of 219 patients with large area and extraordinarily large area burns （LAB） were admitted, who were classified into three stages according the therapeutic protocols used at the time： Stage 1 from 1980 to 1989, stage 2 from 1990 to 1995, and stage 3 from 1996 to 2007. The occurrence and mortality of GI dysfunction in patients of the three stages were calculated and the main causes were analyzed. RESULTS： The occurrence of stress ulcer in patients with LAB was 8.6% in stage 1, which was significantly Dower than that in stage 1 （P 〈 0.05）. No massive hemorrhage from severe stress ulcer and enterogenic infections occurred in stages 2 and 3. The occurrence of abdominal distension and stress ulcer and the mortality in stage 3 patients with extraordinarily LAB was 7.1%, 21.4% and 28.5%, respectively, which were significantly lower than those in stage 1 patients （P 〈 0.05 or P 〈 0.01）, and the occurrence of stress ulcer was also significantly lower than that in stage 2 patients （P 〈 0.05）. CONCLUSION： Comprehensive fluid resuscitation, early excision of necrotic tissue, staged food ingestion, and administration of specific nutrients are essential strategies for preventing gastrointestinal complications and lowering mortality in severely burned patients.

Long-term medical treatment of patients with severe burns at exposed sites

BACKGROUND Body parts such as the face and hands are highly exposed during daily life and burns may accumulate in these areas.In addition,residual wounds,scar hyperplasia and contracture often exist in the late stage of a deep burn in these areas,which may affect patients’appearance,movements,and mental health.However,inadequate attention has been paid to this issue which can result in problems,such as difficulty in healing,possibility of carcinoma,chronic pain and a heavy mental burden.AIM To investigate the long-term medical treatment of patients with severe burns at exposed sites following a mass burn casualty event.METHODS A retrospective analysis of 13 patients with severe burns at exposed sites was performed to determine their respective long-term medical treatment.A combined wound dressing scheme consisting of traditional Chinese and Western medicine was introduced to repair residual wounds.Active and passive functional exercises with massage,Chinese herbal baths and compression fixation were proposed to ameliorate the condition of the hands.A combination of physical,chemical and photoelectrical measures was adopted for anti-scar treatment.A psychological intervention and recovery guide was provided which corresponded to the patients’psychological status.RESULTS Compared to patients who did not simultaneously receive the same treatment,patients who underwent systematic treatment recovered with a lower woundinfection rate(P<0.05),a shorter healing time(13.6±3.2 d)compared with(19.1±3.5 d)and more bearable pain during wound dressing at three days,one week and two weeks after a Chinese herbal bath(P<0.05).Satisfactory results were achieved with regard to restored function of patients’joints and blood supply to nerve endings,closure of the eyelids and the size of mouth opening tended to be normal,and only 7.1%of patients were diagnosed with severe scar hyperplasia and contracture deformity compared with 30.7%in the control group.In addition,the color,thickness,vascular distribution and softness score of the scars improved(P<0.01),and the effects of the psychological intervention was remarkable as shown by the Self-Rating Anxiety Scale and Self-Rating Depression Scale.CONCLUSION A better prognosis can be achieved in patients in the late stage of a burn with active residual wound repair,limb functional exercise,anti-scar and psychological rehabilitation.

Extracorporeal membrane oxygenation combined with continuous renal replacement therapy for the treatment of severe burns:current status and challenges

Severe burns often cause various systemic complications and multiple organ dysfunction syndrome,which is the main cause of death.The lungs and kidneys are vulnerable organs in patients with multiple organ dysfunction syndrome after burns.Extracorporeal membrane oxygenation(ECMO)and continuous renal replacement therapy(CRRT)have been gradually applied in clinical practice and are beneficial for severe burn patients with refractory respiratory failure or renal dysfunction.However,the literature on ECMO combined with CRRT for the treatment of severe burns is limited.Here,we focus on the current status of ECMO combined with CRRT for the treatment of severe burns and the associated challenges,including the timing of treatment,nutrition support,heparinization and wound management,catheter-related infection and drug dosing in CRRT.With the advancement of medical technology,ECMO combined with CRRT will be further optimized to improve the outcomes of patients with severe burns.

Neutrophil-derived heparin binding protein triggers vascular leakage and synergizes with myeloperoxidase at the early stage of severe burns(With video)

Background:Burn shock caused by vascular leakage is one of the main causes of high mortality in severe burn injury.However,the pathophysiological mechanism of vascular leakage is still unclear.The purpose of this study was to explore the molecular mechanism of vascular leakage in the early stage of severe burn and provide a new target for the treatment of severe burns.Methods:Neutrophils were isolated from human peripheral blood by magnetic beads sorting.ELISA was used to detect neutrophil-derived granule proteins and glycocalyx injury products in plasma.The vascular leakage and neutrophil movement were assessed by in vivo laser confocal imaging in mice,and high-quality video were provided.Adhesion-related molecules were investigated by qRT-PCR.The damage to glycocalyx of mice vascular endothelial cellswas observed by transmission electron microscope and scanning electron microscope.Proteomic analysis,flow cytometry and immunofluorescence were used to further study the relationship between human peripheral blood neutrophil-derived hypochlorite(HOCl)and CD44 of human vascular endothelial cells.Results:In this study,we found that rapidly increasing activated neutrophils secrete heparin binding protein(HBP)andmyeloperoxidase(MPO)after severe burn injury.Increased HBP triggers vascular leakage with synergy of MPO,results in systemic edema and burn shock.Furthermore,we found that the MPO catalytic product HOCl but not MPO triggers CD44 extracellular domain shedding from vascular endothelial cells to damage the glycocalyx.Damage to the glycocalyx results in firm adhesion of neutrophils and increases vascular leakage.However,MPO inhibitors partially protect the glycocalyx of vascular endothelial cells.The combination of HBP and MPO inhibitors markedly reduces vascular leakage and systemic edema in the early stage of severe burns.Conclusions:Taken together,these data reveal that neutrophil-derived HBP and MPO play an important synergies role in triggering vascular leakage at the early stage of severe burns.Targeted intervention in these two biomolecules may introduce new strategies for helping to reduce large amount of fluid loss and subsequent burn shock.

CircRNA_Maml2 promotes the proliferation and migration of intestinal epithelial cells after severe burns by regulating the miR-93-3p/FZD7/Wnt/β-catenin pathway

Background:Circular RNA(circRNA)plays key regulatory roles in the development of many diseases.However the biological functions and potential molecular mechanisms of circRNA in the injury and repair of intestinal mucosa in mice after severe burns are yet to be elucidated.Methods:Cell counting kit-8(CCK-8),5-ethynyl-2-deoxyuridine(EdU),wound healing and transwell assays were used to detect cell proliferation and migration ability.Real-time quantitative PCR was used to identify the expression of circRNA,microRNA and messenger RNA.Nuclear and cytoplas-mic separation experiments were employed to perceive the location of circRNA_Maml2.Finally,in vitro and in vivo experiments were conducted to study the repairing effect of circRNA_Maml2 on the intestinal mucosa of mice after severe burns.Results:When compared with the control group,the expression of circRNA_Maml2 was sig-nificantly reduced in the severe burn group.Furthermore,overexpression of circRNA_Maml2 promoted the proliferation and migration of CT26.wt cells in vivo and the repair of damaged intestinal mucosa in vitro.CircRNA_Maml2 acted as a sponge adsorption molecule for miR-93-3p to enhance the expression of frizzled class receptor 7 and activate the downstream Wnt/β-catenin pathway,thereby promoting the repair of the intestinal mucosa.Conclusions:Our findings demonstrate that circRNA_Maml2 regulates the miR-93-3p/FZD7/Wnt/β-catenin pathway and promotes the repair of damaged intestinal mucosa.Hence,circRNA_Maml2 is a potential therapeutic target to promote intestinal mucosal repair.

Gastrointestinal dysfunction is associated with mortality in severe burn patients:a 10-year retrospective observational study from South China

Background:Data on severe and extensive burns in China are limited,as is data on the prevalence of a range of related gastrointestinal(GI)disorders[such as stress ulcers,delayed defecation,opioid-related bowel immotility,and abdominal compartment syndrome(ACS)].We present a multicentre analysis of coincident GI dysfunction and its effect on burn-related mortality.Methods:This retrospective analysis was conducted on patients with severe[≥20%total burn surface area(TBSA)]and extensive(>50%TBSA or>25%full-thickness TBSA)burns admitted to three university teaching institutions in China between January 1,2011 and December 31,2020.Both 30-and 90-day mortality were assessed by collating demographic data,burn causes,admission TBSA,%full-thickness TBSA,Baux score,Abbreviated Burn Severity Index(ABSI)score,and Sequential Organ Failure Assessment(SOFA)score,shock at admission and the presence of an inhalation injury.GI dysfunction included abdominal distension,nausea/vomiting,diarrhoea/constipation,GI ulcer/haemorrhage,paralytic ileus,feeding intolerance and ACS.Surgeries,length of intensive care unit(ICU)stay,pain control[in morphine milligram equivalents(MME)]and overall length of hospital stay(LOHS)were recorded.Results:We analyzed 328 patients[75.6%male,mean age:(41.6±13.6)years]with a median TBSA of 62.0%(41.0%–80.0%);256(78.0%)patients presented with extensive burns.The 90-day mortality was 23.2%(76/328),with 64(84.2%)of these deaths occurring within 30 d and 25(32.9%)occurring within 7 d.GI dysfunction was experienced by 45.4%of patients and had a significant effect on 90-day mortality[odds ratio(OR)=14.070,95%confidence interval(CI)5.886–38.290,P<0.001].Multivariate analysis showed that GI dysfunction was associated with admission SOFA score and%full-thickness TBSA.Overall,88.2%(67/76)of deceased patients had GI dysfunction[hazard ratio(HR)for death of GI dysfunction=5.951],with a survival advantage for functional disorders(diarrhoea,constipation,or nausea/vomiting)over GI ulcer/haemorrhage(P<0.001).Conclusion:Patients with severe burns have an unfavourable prognosis,as nearly one-fifth died within 90 d.Half of our patients had comorbidities related to GI dysfunction,among which GI ulcers and haemorrhages were independently correlated with 90-day mortality.More attention should be given to severe burn patients with GI dysfunction.

Study on integrated treatment of severe burn in batch patients

Objective:To explore the burn treatment and first aid flow mode in batch patients.Methods:A retrospective analysis was performed on the treatment experience of 10 or more patients in the group burn accident admitted to the Third Affiliated Hospital of Inner Mongolia Medical University from 2008 to 2020,in order to acquire the general information(e.g.,age,sex[male and female],injury causes and factors,total burn surface area,inhalation injury and compound injury),the time when each first-aid rescue team was in place;the reception time of the triage group;specialist rescue start time;treatment process and treatment outcome in patients with severe burns,such as the establishment time of deep venous access.Results:67 cases(n=68)of patients were cured and the curative ratio was 98.5%.The average time from the rescue order of the commander-in-chief to the placement of each medical group was 8.8 minutes,the average reception time of the triage group was 4.5 minutes,the average specialist rescue start time was 18.6 minutes,and the average establishment time of deep vein access for patients with severe burns was about 11.3 minutes.Conclusions:Scientific and reasonable pre-hospital emergency triage and treatment for burn patients can be achieved by implementing integrated treatment.

Prospective study and validation of early warning marker discovery based on integrating multi-omics analysis in severe burn patients with sepsis

Background:Early detection,timely diagnosis and rapid response are essential for case management and precautions of burn-associated sepsis.However,studies on indicators for early warning and intervention have rarely been conducted.This study was performed to better understand the pathophysiological changes and targets for prevention of severe burn injuries.Methods:We conducted a multi-center,prospective multi-omics study,including genomics,microRNAomics,proteomics and single-cell transcriptomics,in 60 patients with severe burn injuries.A mouse model of severe burn injuries was also constructed to verify the early warning ability and therapeutic effects of potential markers.Results:Through genomic analysis,we identified seven important susceptibility genes(DNAH11,LAMA2,ABCA2,ZFAND4,CEP290,MUC20 and ENTPD1)in patients with severe burn injuries complicated with sepsis.Through plasma miRNAomics studies,we identified four miRNAs(hsamiR-16-5p,hsa-miR-185-5p,hsa-miR-451a and hsa-miR-423-5p)that may serve as early warning markers of burn-associated sepsis.A proteomic study indicated the changes in abundance of major proteins at different time points after severe burn injury and revealed the candidate early warning markers S100A8 and SERPINA10.In addition,the proteomic analysis indicated that neutrophils play an important role in the pathogenesis of severe burn injuries,as also supported by findings from single-cell transcriptome sequencing of neutrophils.Through further studies on severely burned mice,we determined that S100A8 is also a potential early therapeutic target for severe burn injuries,beyond being an early warning indicator.Conclusions:Our multi-omics study identified seven susceptibility genes,four miRNAs and two proteins as early warning markers for severe burn-associated sepsis.In severe burn-associated sepsis,the protein S100A8 has both warning and therapeutic effects.

Pre-fire aboveground biomass, estimated from LiDAR, spectral and field inventory data, as a major driver of burn severity in maritime pine (Pinus pinaster) ecosystems

Background:The characterization of surface and canopy fuel loadings in fire-prone pine ecosystems is critical for understanding fire behavior and anticipating the most harmful ecological effects of fire.Nevertheless,the joint consideration of both overstory and understory strata in burn severity assessments is often dismissed.The aim of this work was to assess the role of total,overstory and understory pre-fire aboveground biomass(AGB),estimated by means of airborne Light Detection and Ranging(LiDAR)and Landsat data,as drivers of burn severity in a megafire occurred in a pine ecosystem dominated by Pinus pinaster Ait.in the western Mediterranean Basin.Results:Total and overstory AGB were more accurately estimated(R^(2) equal to 0.72 and 0.68,respectively)from LiDAR and spectral data than understory AGB(R^(2)=0.26).Density and height percentile LiDAR metrics for several strata were found to be important predictors of AGB.Burn severity responded markedly and non-linearly to total(R^(2)=0.60)and overstory(R ^(2)=0.53)AGB,whereas the relationship with understory AGB was weaker(R ^(2)=0.21).Nevertheless,the overstory plus understory AGB contribution led to the highest ability to predict burn severity(RMSE=122.46 in dNBR scale),instead of the joint consideration as total AGB(RMSE=158.41).Conclusions:This study novelty evaluated the potential of pre-fire AGB,as a vegetation biophysical property derived from LiDAR,spectral and field plot inventory data,for predicting burn severity,separating the contri-bution of the fuel loads in the understory and overstory strata in Pinus pinaster stands.The evidenced relationships between burn severity and pre-fire AGB distribution in Pinus pinaster stands would allow the implementation of threshold criteria to support decision making in fuel treatments designed to minimize crown fire hazard.

Wildfire severity alters soil microbial exoenzyme production and fungal abundances in the southern Appalachian Mountains

Climate change has increased drought frequency and duration that are exacerbated by increased temperatures globally.This effect has,and will continue,to increase fire occurrence across many regions of North America.In the southern Appalachian Mountains,wildfires with high burn severity occurred in 2016due to increased drought and human activity.To investigate the effects of burn severity on soil physicochemical properties,microbial extracellular enzyme production,and microbial abundances in a temperate region,surface soils(0-15 cm)were collected from two sites(the Great Smoky Mountains National Park in Tennessee and the Nantahala National Forest in North Carolina,USA)spanning lightly,moderately,and severely burned areas,accompanied by adjacent unburned locations that act as controls.The soil samples were collected at three time points between 2017 and 2019(i.e.,0.5,1,and 2.5 years post-fire)among burn severity plots.Total hydrolytic enzyme production varied over time,with severe burn plots having significantly lower enzyme production at 2.5years post-fire.Individual enzymes varied among burn severities and across time post-fire.Light burn plots showed greater carbon-specific(β-glucosidase andβ-xylosidase)and phosphorus-specific(acid phosphatase)enzyme activities at 0.5 years post-fire,but this effect was transient.At 2.5 years post-fire,theβ-xylosidase and acid phosphatase activities were lower in severe or moderate burn plots relative to the controls.In contrast,the activity of nitrogen-specific enzyme leucyl aminopeptidase was the lowest in severe burn plots at 0.5 years post-fire,but was the lowest in light burn plots at 2.5 years post-fire.The fungi:bacteria ratio declined with burn severity,indicating that fungi are sensitive or less resilient to high burn severity during recovery.These results suggest that wildfires alter trajectories for soil microbial structure and function within a 2.5-year timeframe,which potentially has long-term impacts on biogeochemical cycling.

3D bioprinting of integral ADSCs-NO hydrogel scaffolds to promote severe burn wound healing

Severe burns are challenging to heal and result in significant death throughout the world.Adiposederived mesenchymal stem cells(ADSCs)have emerged as a promising treatment for fullthickness burn healing but are impeded by their low viability and efficiency after grafting in vivo.Nitric oxide(NO)is beneficial in promoting stem cell bioactivity,but whether it can function effectively in vivo is still largely unknown.In this study,we bioprinted an efficient biological scaffold loaded with ADSCs and NO(3D-ADSCs/NO)to evaluate its biological efficacy in promoting severe burn wound healing.The integral 3D-ADSCs/NO hydrogel scaffolds were constructed via 3D bioprinting.Our results shown that 3D-ADSCs/NO can enhance the migration and angiogenesis of Human Umbilical Vein Endothelial Cells(HUVECs).Burn wound healing experiments in mice revealed that 3D-ADSCs/NO accelerated the wound healing by promoting faster epithelialization and collagen deposition.Notably,immunohistochemistry of CD31 suggested an increase in neovascularization,supported by the upregulation of vascular endothelial growth factor(VEGF)mRNA in ADSCs in the 3D biosystem.These findings indicated that 3D-ADSC/NO hydrogel scaffold can promote severe burn wound healing through increased neovascularization via the VEGF signalling pathway.This scaffold may be considered a promising strategy for healing severe burns.

Spatial pattern analysis of post-fire damages in the Menderes District of Turkey

Forest fires,whether caused naturally or by human activity can have disastrous effects on the environment.Turkey,located in the Mediterranean climate zone,experiences hundreds of forest fires every year.Over the past two decades,these fires have destroyed approximately 308000 ha of forest area,threatening the sustainability of its ecosystem.This study analyzes the forest fire that occurred in the Menderes region of Izmir on July 1,2017,by using pre-and post-fire Sentinel 2(10 m and 20 m)and Landsat 8(30 m)satellite images,MODIS and VIIRS fire radiative power(FRP)data(1000 m and 375 m,respectively),and reference data obtained from a field study.Hence,image processing techniques integrated with the Geographic Information System(GIS)database were applied to a satellite image data set to monitor,analyze,and map the effects of the forest fire.The results show that the land surface temperature(LST)of the burned forest area increased from 1 to 11°C.A high correlation(R=0.81)between LST and burn severity was also determined.The burned areas were calculated using two different classification methods,and their accuracy was compared with the reference data.According to the accuracy assessment,the Sentinel(10 m)image classification gave the best result(96.43%for Maximum Likelihood,and 99.56%for Support Vector Machine).The relationship between topographical/forest parameters,burn severity and disturbance index was evaluated for spatial pattern distribution.According to the results,the areas having canopy closure between 71%–100%and slope above 35%had the highest burn incidence.As a final step,a spatial correlation analysis was performed to evaluate the effectiveness of MODIS and VIIRS FRP data in the postfire analysis.A high correlation was found between FRPslope,and FRP-burn severity(0.96 and 0.88,respectively).

An automatic procedure for generating burn severity maps from the satellite images-derived spectral indices

Fire,especially wildfire,which can be considered as one of the main threats to vegetation cover and animals’life,has attracted lots of attention from environmental researchers.To better manage the fire crisis and take the necessary measures to compensate for its damages,it is essential to have detailed information about the burn severity levels.Accordingly,satellite images and their spectral indices have been widely considered in the literature as powerful tools in producing burn severity information.Despite the efficiency of the previously proposed methods,the necessity of ground reference data for their thresholding step faces them with serious challenges.To address this problem,in this study,an automatic procedure based on the change-point analysis is presented for thresholding differenced normalized burn ratio(dNBR)and its another version,dNBR2.In this procedure,a mean-shift based change-point analysis is performed on the dNBR and dNBR2 images for classifying them into burn severity levels.Experiments,conducted on some parts of Alaska and California in the United States,illustrated the high efficiency of the proposed method.Moreover,as an applied experiment,the severity of the fires,occurred in 2020 in the Khaeiz protected area in Iran,was estimated and compared with local reports.