Synchronous carcinoma and sarcoma in a burn scar: a treatment conundrum.

Marjolijn's ulcer is a malignant ulcer in a burn scar. Types of malignancy are squamous cell carcinoma, basal cell carcinoma and malignant melanoma. Soft tissue sarcoma case reports indicate only one type of cancer. We present a patient in her 60s with a 10-year-old burn scar developing a biopsy-proven squamous cell carcinoma on the lateral aspect of the left thigh with metastatic superficial inguinal node. A wide excision and grafting of ulcer with ilioinguinal dissection done on left side. On the 12th postoperative day 2, subcutaneous swellings adjacent to the grafted area developed, on biopsy revealed to be pleomorphic sarcoma. PET CT scan revealed tumour deposits in the muscles of the left lower limb, liver and lung. There are no case reports of synchronous carcinoma and sarcoma in a burn scar. The case is reported for its rarity and the decision-making dilemma.

Current Approaches to Wound Repair in Burns: How far Have we Come From Cover to Close? A Narrative Review.

Burn injuries are a significant global health concern, with more than 11 million people requiring medical intervention each year and approximately 180,000 deaths annually. Despite progress in health and social care, burn injuries continue to result in socioeconomic burdens for victims and their families. The management of severe burn injuries involves preventing and treating burn shock and promoting skin repair through a two-step procedure of covering and closing the wound. Currently, split-thickness/full-thickness skin autografts are the gold standard for permanent skin substitution. However, deep burns treated with split-thickness skin autografts may contract, leading to functional and appearance issues. Conversely, defects treated with full-thickness skin autografts often result in more satisfactory function and appearance. The development of tissue-engineered dermal templates has further expanded the scope of wound repair, providing scar reductive and regenerative properties that have extended their use to reconstructive surgical interventions. Although their interactions with the wound microenvironment are not fully understood, these templates have shown potential in local infection control. This narrative review discusses the current state of wound repair in burn injuries, focusing on the progress made from wound cover to wound closure and local infection control. Advancements in technology and therapies hold promise for improving the outcomes for burn injury patients. Understanding the underlying mechanisms of wound repair and tissue regeneration may provide new insights for developing more effective treatments in the future.

Topical Noneuphoric Phytocannabinoid Elixir 14 Reduces Inflammation and Mitigates Burn Progression.

INTRODUCTION: Thermal injuries are caused by exposure to a wide variety of agents including heat, electricity, radiation, chemicals, and friction. Early intervention can decrease injury severity by preventing excess inflammation and mitigating burn wound progression for improved healing outcomes. Previous studies have demonstrated that cannabinoids can trigger anti-inflammatory responses and promote wound closure. Therefore, the purpose of this study was to investigate whether a topical application of Noneuphoric Phytocannabinoid Elixir 14 (NEPE14) containing a full complement of phytocannabinoids (< 0.3% delta-9-tetrahydrocannabinol or cannabidiol) and other phytochemicals would mitigate burn wound progression in the treatment of deep partial-thickness burn wounds. METHODS: Deep partial-thickness burns were created on the dorsum of four anesthetized pigs and treated with NEPE14, Vehicle control, Silverlon, or gauze. The burns were assessed on postburn days 4, 7, and 14. Assessments consisted of digital photographs, Laser-Speckle imagery (blood perfusion), MolecuLight imagery (qualitative bacterial load), and biopsies for histology and immunohistochemistry (interleukin six and tumor necrosis factor-α). RESULTS: Topical treatment with NEPE14 significantly (P < 0.001) decreased inflammation (interleukin six and tumor necrosis factor-α) in comparison to control groups. It was also demonstrated that the reduction in inflammation led to mitigation of burn wound progression. In terms of wound healing and presence of bacteria, no statistically significant differences were observed. CONCLUSIONS: Topical treatment of deep partial-thickness burns with NEPE14 decreased wound inflammation and mitigated burn wound progression in comparison to control treatments.

Quantitative color analysis of burned bone to predict DNA quantity, quality, and genotyping success.

Badly burned skeletal remains are commonly submitted to forensic laboratories for victim identification via DNA analysis methods. Burned skeletal remains present many challenges for DNA analysis as they can contain low amounts of DNA which can also be damaged and degraded, resulting in partial or no STR profiles. Therefore, a simple, but effective screening method that identifies which samples may provide the most successful STR or mtDNA typing results for identification would enable forensic laboratories to save time, money, and resources. One metric that can be used and a screening method is the color of burned bone, as bone color changes with exposure to fire as temperature and length of exposure increase. This research developed a quantitative screening method based on the surface color of burned bone. The different visual bone colors (light brown, dark brown, black, gray, and white) were quantified using the Commission on Illumination L*a*b color space. These values were then compared to DNA yield, STR, and mtDNA profile completeness to identify whether the L*a*b values can predict genotyping success. A Bayesian network was constructed to determine the probability of STR typing success, given a set of L*a*b values. Results demonstrated that samples with an a* value greater than or equal to one and b* value greater than eight (light brown and dark brown burned samples) were the most predictive of STR typing success and mtDNA typing success. A decision tree for processing burned bones was constructed based on the color value thresholds.

Re-recognition of the role of roughness in keloid assessment.

BACKGROUND: Under visual observation, keloids are more rough than normal skin. This roughness may be used to assess the activity and severity of keloids but lacks the support of objective and accurate evidence. The purpose of this study was to verify the role of roughness in the development of keloids and to clarify the advantage of roughness in the comprehensive assessment of keloids. METHODS: Patients with keloids who attended Peking Union Medical College Hospital were recruited. Keloids were classified into progressive, stable, and atrophic stages based on the change in size over the past year and blood perfusion. The keloids were evaluated using the Vancouver Scar Scale (VSS) and the Patient and Observer Scar Assessment Scale (POSAS). The roughnesses of the keloid and normal skin were measured using the Phaseshift Rapid In vivo Measurement Of the Skin (PRIMOS), and blood perfusion was measured using laser speckle contrast imaging (LSCI). RESULTS: Thirty-three patients with a total of 81 keloids were included. The surface roughness values Sa, Sq, and Sz of the keloid region were 243.70 (143.85-328.05), 316.20 (179.85-475.20), and 1708.20 (1098.30-4087.20), respectively, which were 4.87, 4.80, and 3.08 times higher than those of normal skin. There were significant differences in roughness among the different keloid stages. A significantly strong correlation between roughness and other assessed indices was found. CONCLUSIONS: Roughness as a morphological characteristic is of great value in the evaluation of keloids. It is recommended as an important examination for keloids.

Tripterine Inhibits Proliferation and Promotes Apoptosis of Keloid Fibroblasts by Targeting ROS/JNK Signaling.

Keloids are benign skin tumors characterized by excessive fibroblast proliferation and collagen deposition. The current treatment of keloids with hormone drug injection, surgical excision, radiotherapy, physical compression, laser therapy, cryotherapy often have unsatisfactory outcomes. The phytochemical compounds have shown great potential in treating keloids. Tripterine, a natural triterpene derived from the traditional Chinese medicine Thunder God Vine (Tripterygium wilfordii), was previously reported to exhibit an anti-scarring bioactivity in mouse embryonic fibroblast NIH/3T3 cells. Accordingly, our study was dedicated to explore its role in regulating the pathological phenotypes of keloid fibroblasts. Human keloid fibroblasts were treated with tripterine (0-10 µM) for 24 hours. Cell viability, proliferation, migration, apoptosis, and extracellular matrix (ECM) deposition were determined by CCK-8, EdU, wound healing, Transwell, flow cytometry, western blotting, and RT-qPCR assays. The effects of tripterine treatment on reactive oxygen species (ROS) generation and JNK activation in keloid fibroblasts were assessed by DCFH-DA staining and western blotting analysis. Tripterine at the concentrations higher than 4 µM attenuated the viability of human keloid fibroblasts in a dose-dependent manner. Treatment with tripterine (4, 6, and 8 µM) dose-dependently inhibited cell proliferation and migration, promoted cell apoptosis, reduced α-SMA, Col1, and Fn expression, induced ROS production, and enhanced JNK phosphorylation in keloid fibroblasts. Collectively, tripterine ameliorates the pathological characteristics of keloid fibroblasts that are associated with keloidformation and growth by inducing ROS generation and activating JNK signalingpathway.

Iterative refinement of a histologic algorithm for burn depth categorization based on 798 consecutive burn wound biopsies.

INTRODUCTION: Our group previously reported a burn biopsy algorithm (BBA-V1) for categorizing burn wound depth. Here, we sought to promulgate a newer, simpler version of the BBA (BBA-V2). METHODS: Burn wounds undergoing excision underwent 4 mm biopsies procured every 25 cm2. Serial still photos were obtained at enrollment and at excision intraoperatively. Burn wounds assessed as likely to heal by 21 days were imaged within 72 h of injury and at 21 days. A sample of 798 burn wound biopsies were classified by both BBAV1 and BBAV2 algorithms. For nonoperative burn wounds, the proportion of healing versus nonhealing pixels at 21 days after injury were compared. RESULTS: The 798 biopsies were classified by BBAV1 as 24% SPT, 47% DPT, 28% FT and by BBAV2 as 3% SPT, 67% DPT, and 30% FT (p < 0.0001). Overall, the proportion of biopsies whose wound reclassification changed from a nonoperative to operative pathway was 21% (95% CI: 18-24%). Nonoperative wounds judged at injury as being SPT contained 12.8 million pixels. Repeat 21-day imaging revealed 11.3 million healed pixels (accuracy = 89.6% (95% CI: 89.59-89.62)). CONCLUSIONS: BBA-V2 was associated with a significantly higher concordance with visual assessment for burn wounds clinically judged as deep partial and full thickness.

Use of adipose derived stem cells accelerates the healing process in third-degree burns.

INTRODUCTION: Burns are defined as a traumatic injury, usually of thermal origin, that affects the epithelial and adjacent tissue and is classified according to the depth reached. Tissue repair involved in this type of injury is often a challenge both due to its severity and the multiplicity of complications. Regenerative medicine has focused on the use of low-level laser photobiomodulation therapy (LLLT) and adipose-derived stem cells (ADSC), especially in the early stages of the process, to promote better healing and shorten repair time. Therefore, aim of this study was to evaluate the action of LLLT (660 nm) and ADSC in the repair process of burned skin tissue and investigate the association of the techniques (LLLT and ADSC). MATERIALS AND METHODS: An in vivo study was carried out using 96 rats (Wister) with a scald burn model at a temperature of 95ºC, exposing the animal's back for 14 s. Animals were randomized into seven groups and three periods, five, 14 and 21 days. The groups included GC: Control group, ADSC-: Group treated with CD49d negative cells, ADSC+ : Group treated with positive CD49d cells, CULT: Group treated with conventional isolation cells, LLLT: Group treated only with LLLT Low Power Laser, ADSC-LLLT: Group treated with CD49d negative cells and LLLT. ADSC+LLLT: Group treated with positive CD49d cells and LLLT. The groups treated with LLLT (660 nm; 5 J/cm2) received irradiation three times a week, on alternate days for five, 14 and 21 days, according to the time of biopsy. ADSC-treated groups received one to three applications of the cells in a total volume of 1000 µL starting soon after the surgical debridement of the burn. Photographic monitoring was carried out at 5, 14 and 21 days after the beginning of the experiment to assess the degree of lesion contraction. Macroscopic, morphometric and histopathological analyzes were performed. RESULTS: We showed significant re-epithelialization as well as an improvement in the healing process in the ADSC+, LLLT and ADSC+LLLT groups. We observed effects in the reduction of the inflammatory phase, increase in angiogenesis, decrease in oedema, greater collagen deposition, and better organization of the extracellular matrix compared to the other treatments. Moreover, the immunomagnetic separation of ADSC cells through the expression of the CD49d protein proved to be a useful means to obtain a more homogeneous population of cells with a role in tissue regeneration compared to the ADSC- and CULT groups. CONCLUSION: In conclusion, the association of ADSC+ with LLLT was effective in accelerating the burn repair process, stimulating cell proliferation and formation of more normal skin tissue.

Rete ridges are decreased in dyschromic burn hypertrophic scar: A histological study.

Dyschromic hypertrophic scar (HTS) is a common sequelae of burn injury, however, its mechanism has not been elucidated. This work is a histological study of these scars with a focus on rete ridges. Rete ridges are important for normal skin physiology, and their absence or presence may hold mechanistic significance in post-burn HTS dyschromia. It was posited that hyper-, and hypo-pigmented areas of scars have different numbers of rete ridges. Subjects with dyschromic burn hypertrophic scar were prospectively enrolled (n = 44). Punch biopsies of hyper-, hypo-, and normally pigmented scar and skin were collected. Biopsies were paraffin embedded, sectioned, stained with H&E, and imaged. The number of rete ridges were investigated. Burn hypertrophic scars that healed without autografts were first investigated. The number of rete ridges was higher in normal skin compared to HTS that was either hypo- (p < 0.01) or hyper-pigmented (p < 0.001). This difference was similar despite scar pigmentation phenotype (p = 0.8687). Autografted hyper-pigmented scars had higher rete ridge ratio compared to non-autografted hyper-pigmented HTS (p < 0.0001). Burn hypertrophihc scars have fewer rete ridges than normal skin. This finding may explain the decreased epidermal adherence to underlying dermis associated with hypertrophic scars. Though, contrary to our hypothesis, no direct link between the extent of dyschromia and rete ridge quantity was observed, the differences in normal skin and hypertrophic scar may lead to further understanding of dyschromic scars.

Ubiquitin-specific peptidase 11 promotes development of keloid derived fibroblasts by de-ubiquitinating TGF-ß receptorII.

BACKGROUND: Keloid scars occur as a result of abnormal wound healing caused by trauma or inflammation of the skin. The progression of keloids is dependent on genetic and environmental influences. The incidence is more prevalent in people with darker skin tones (African, Asian and Hispanic origin). Studies have demonstrated that transforming growth factor (TGF) ß/Smad signalling has an essential function in keloid as well as that USP11 could modulate the activation of TGFß/Smad signalling and impact the progression of the fibrotic disease. Nonetheless, the potential mechanisms of USP11 in keloid were still unclear. The authors postulated that USP11 up-regulates and augments the ability of proliferation, invasion, migration and collagen deposition of keloid-derived fibroblasts (KFBs) through deubiquitinating TGF-ß receptor II (TßRII). METHODS: Fibroblast cells were isolated from keloid scars in vitro. Lentivirus infection was utilized to knockdown and over-express the USP11 in KFBs. Influence of USP11 on proliferation, invasion and migration of KFBs, and expression level of TßRII, Smad2, Smad3, α-SMA, collagen1 and collagen3 were assayed by CCK8, scratching, transwell, Western blot and real-time quantitative polymerase chain reaction. The interactions between USP11 and TßRII were examined using ubiquitination assays and co-immunoprecipitation. To further confirm the role of USP11 in keloid growth, we performed animal experiments. RESULTS: Results show that down-regulated USP11 markedly suppressed the ability of proliferation, invasion and migration of keloid derived-fibroblasts in vitro and reduce the expression of TßRII, Smad2, Smad3, αSMA, collagen1 and collagen3. In addition, over-expression of USP11 demonstrated the contrary tendency. Ubiquitination experiments and co-immunoprecipitation demonstrated that USP11 was interacting with TßRII and deubiquitinated TßRII. Interferences with USP11 inhibited growth of keloid in vivo. Additionally, we have verified that knockdown of USP11 has no significant effect on normal skin fibroblasts. CONCLUSION: USP11 elevates the ability of proliferation, collagen deposition, invasion and migration of keloid-derived fibroblasts by deubiquitinating TßRII.

Maximizing wound coverage in full-thickness skin defects: A randomized-controlled trial of autologous skin cell suspension and widely meshed autograft versus standard autografting.

BACKGROUND: Traumatic insults, infection, and surgical procedures can leave skin defects that are not amenable to primary closure. Split-thickness skin grafting (STSG) is frequently used to achieve closure of these wounds. Although effective, STSG can be associated with donor site morbidity, compounding the burden of illness in patients undergoing soft tissue reconstruction procedures. With an expansion ratio of 1:80, autologous skin cell suspension (ASCS) has been demonstrated to significantly decrease donor skin requirements compared with traditional STSG in burn injuries. We hypothesized that the clinical performance of ASCS would be similar for soft tissue reconstruction of nonburn wounds. METHODS: A multicenter, within-patient, evaluator-blinded, randomized-controlled trial was conducted of 65 patients with acute, nonthermal, full-thickness skin defects requiring autografting. For each patient, two treatment areas were randomly assigned to concurrently receive a predefined standard-of-care meshed STSG (control) or ASCS + more widely meshed STSG (ASCS+STSG). Coprimary endpoints were noninferiority of ASCS+STSG for complete treatment area closure by Week 8, and superiority for relative reduction in donor skin area. RESULTS: At 8 weeks, complete closure was observed for 58% of control areas compared with 65% of ASCS+STSG areas (p = 0.005), establishing noninferiority of ASCS+STSG. On average, 27.4% less donor skin was required with ASCS+ STSG, establishing superiority over control (p < 0.001). Clinical healing (≥95% reepithelialization) was achieved in 87% and 85% of Control and ASCS+STSG areas, respectively, at 8 weeks. The treatment approaches had similar long-term scarring outcomes and safety profiles, with no unanticipated events and no serious ASCS device-related events. CONCLUSION: ASCS+STSG represents a clinically effective and safe solution to reduce the amount of skin required to achieve definitive closure of full-thickness defects without compromising healing, scarring, or safety outcomes. This can lead to reduced donor site morbidity and potentially decreased cost associated with patient care.Clincaltrials.gov identifier: NCT04091672. LEVEL OF EVIDENCE: Therapeutic/Care Management; Level I.

Preclinical study of experimental burns treated with photobiomodulation and Human Amniotic Membrane, both isolated and associated / Estudo pré-clínico de queimaduras experimentais tratadas com fotobiomodulação e membrana amniótica humana, isoladas e associadas / Estudio preclínico de quemaduras experimentales tratadas con fotobiomodulación y membrana amniótica humana, solas y combinadas

Abstract Objective: to evaluate the effect of photobiomodulation with low-level 660 nm laser alone or associated with Human Amniotic Membrane in the repair of partial-thickness burns in rats. Method: an experimental study conducted with 48 male Wistar rats, randomized into four groups: Control, Human Amniotic Membrane, Low-Level Laser Therapy, and Low-Level Laser Therapy associated with Human Amniotic Membrane. The histopathological characteristics of the skin samples were analyzed 7 and 14 days after the burn. The data obtained were submitted to the Kolmogorov-Smirnov and Mann-Whitney tests. Results: the histological analysis of the burn injuries showed a decrease in inflammation (p<0.0001) and an increase in proliferation of fibroblasts (p<0.0001) mainly at 7 days in all treatments related to the control group. At 14 days, the greater effectiveness in accelerating the healing process was significant (p<0.0001) in the Low-Level Laser Therapy group associated with the Human Amniotic Membrane. Conclusion: the association of photobiomodulation therapies with the Human Amniotic Membrane allowed verifying a reduction in the healing process time of the experimental lesions, stimulating its proposal as a treatment protocol in partial-thickness burns.

Resumo Objetivo: avaliar o efeito da fotobiomodulação com laser de baixa intensidade 660 nm isoladamente ou associada à membrana amniótica humana no reparo de queimaduras de espessura parcial em ratos. Método: estudo experimental com 48 ratos Wistar machos, randomizados em quatro grupos: Controle, Membrana Amniótica Humana, Terapia a Laser de Baixa Intensidade e Terapia a Laser de Baixa Intensidade associado à Membrana Amniótica Humana. As características histopatológicas das amostras de pele foram analisadas aos 7 e 14 dias após a queimadura. Os dados obtidos foram submetidos aos testes de Kolmogorov-Smirnov e Mann Whitney. Resultados: a análise histológica das lesões por queimadura mostrou a diminuição da inflamação (p <0,0001) e aumento da proliferação de fibroblastos (p <0,0001), principalmente nos 7 dias em todos os tratamentos relacionados ao grupo controle. Aos 14 dias, a maior efetividade na aceleração do processo cicatricial foi significativa (p<0,0001) no grupo Terapia a Laser de Baixa Intensidade associado à Membrana Amniótica Humana. Conclusão: a associação das terapias de fotobiomodulação à membrana amniótica humana permitiu comprovar redução no tempo do processo cicatricial das lesões experimentais, estimulando sua proposição como protocolo de tratamento em queimaduras de espessura parcial.

Resumen Objetivo: evaluar el efecto de la fotobiomodulación con láser de baja intensidad 660 nm de sola o combinada con la membrana amniótica humana en la reparación de quemaduras de espesor parcial en ratas. Método: estudio experimental con 48 ratas Wistar macho, aleatorizadas en cuatro grupos: Control, Membrana Amniótica Humana, Terapia con Láser de Baja Intensidad y Terapia con Láser de Baja Intensidad combinada con la Membrana Amniótica Humana. Las características histopatológicas de las muestras de piel fueron analizadas a los 7 y 14 días después de la quemadura. Los datos obtenidos fueron sometidos a las pruebas de Kolmogorov-Smirnov y Mann-Whitney. Resultados: el análisis histológico de las lesiones por quemadura mostró una disminución de la inflamación (p <0,0001) y un aumento de la proliferación de fibroblastos (p <0,0001) principalmente a los 7 días en todos los tratamientos en comparación con el grupo control; a los 14 días, en el grupo de Terapia con Láser de Baja Intensidad combinada con la Membrana Amniótica Humana la mayor efectividad en la aceleración del proceso de cicatrización fue significativa (p<0,0001). Conclusión: la asociación de terapias de fotobiomodulación con la membrana amniótica humana permitió comprobar que hubo una reducción en el tiempo del proceso de cicatrización de lesiones experimentales, lo cual favorece que se proponga como protocolo de tratamiento en quemaduras de espesor parcial.

Biomimetic nanoparticles of platelet membranes carrying bFGF and VEGFA genes promote deep burn wound healing.

INTRODUCTION: The treatment of burn wounds, especially deep burn wounds, remains a major clinical challenge. Growth factors such as basic fibroblast growth factor (bFGF) and vascular endothelial growth factor A (VEGFA) show great potential in promoting the healing of damaged tissues. This study explored wound healing following targeted delivery of bFGF and VEGFA genes into deep burn wounds through a novel platelet membrane-coated nanoparticle (PM@gene-NP) complex delivery system. METHODS: First, bFGF and VEGFA genes were inserted into plasmid (pEGFP-N1) vectors. Subsequently, the assembled plasmids were loaded onto nanoparticles to form gene-loaded nanoparticle complexes, which were then wrapped with extracted platelet membrane, fully simulating the characteristics of platelets, in order to actively target sites of inflammatory damage. After administration of PM@gene-NP complexes through the tail vein of rats, a series of experiments were conducted to evaluate wound healing. RESULTS: The PM@gene-NP complexes effectively targeted the burn sites. After the administration of the PM@gene-NP complexes, the rats exhibited increased blood flow in the burn wounds, which also healed faster than control groups. Histological results showed fewer inflammatory cells in the burned skin tissue after treatment. After the wounds healed, the production of hair follicles, sebaceous glands and other skin accessories in the skin tissue increased. CONCLUSION: Our results showed that the PM@gene-NP complexes can effectively deliver gene therapy to the injured area, and this delivery system should be considered as a potential method for treating deep burns.

[Research advances on mental disorders in patients with extensive burns].

Extensive burns can cause nonnegligible acute and chronic damage to central nervous system of patients. The damage of central nervous system may have a profound impact on patients, including neurobehavioral changes such as post-traumatic stress disorder, depression, anxiety, and sleep disorder. These changes may persist after injury, greatly affecting patients' integration into society and return to work. This paper systematically reviewed the clinical manifestations, pathogenesis, and current intervention methods of mental disorders in patients with extensive burns, aiming to provide a basis for further understanding, prevention, and treatment of patients with mental disorders after burns.

Intravenous Autologous Bone Marrow-derived Mesenchymal Stromal Cells Delay Acute Respiratory Distress Syndrome in Swine.

Rationale: Early post injury mitigation strategies in ARDS are in short supply. Treatments with allogeneic stromal cells are administered after ARDS develops, require specialized expertise and equipment, and to date have shown limited benefit. Objectives: Assess the efficacy of immediate post injury intravenous administration of autologous or allogeneic bone marrow-derived mesenchymal stromal cells (MSCs) for the treatment of acute respiratory distress syndrome (ARDS) due to smoke inhalation and burns. Methods: Yorkshire swine (n = 32, 44.3 ± 0.5 kg) underwent intravenous anesthesia, placement of lines, severe smoke inhalation, and 40% total body surface area flame burns, followed by 72 hours of around-the-clock ICU care. Mechanical ventilation, fluids, pressors, bronchoscopic cast removal, daily lung computed tomography scans, and arterial blood assays were performed. After injury and 24 and 48 hours later, animals were randomized to receive autologous concentrated bone marrow aspirate (n = 10; 3 × 106 white blood cells and a mean of 56.6 × 106 platelets per dose), allogeneic MSCs (n = 10; 6.1 × 106 MSCs per dose) harvested from healthy donor swine, or no treatment in injured control animals (n = 12). Measurements and Main Results: The intravenous administration of MSCs after injury and at 24 and 48 hours delayed the onset of ARDS in swine treated with autologous MSCs (48 ± 10 h) versus control animals (14 ± 2 h) (P = 0.004), reduced ARDS severity at 24 (P < 0.001) and 48 (P = 0.003) hours, and demonstrated visibly diminished consolidation on computed tomography (not significant). Mortality at 72 hours was 1 in 10 (10%) in the autologous group, 5 in 10 (50%) in the allogeneic group, and 6 in 12 (50%) in injured control animals (not significant). Both autologous and allogeneic MSCs suppressed systemic concentrations of TNF-α (tumor necrosis factor-α). Conclusions: The intravenous administration of three doses of freshly processed autologous bone marrow-derived MSCs delays ARDS development and reduces its severity in swine. Bedside retrieval and administration of autologous MSCs in swine is feasible and may be a viable injury mitigation strategy for ARDS.

Lipopolysaccharide induces skin scarring through the TLR4/Myd88 inflammatory signaling pathway in dermal fibroblasts.

Skin scarring is a frequent complication of the wound healing process. Bacterial contamination and prolonged inflammation in wounds are thought to play significant roles during scar formation, but little is known about their specific mechanisms of action. In this study, hypertrophic scar derived fibroblasts (HSFs) and paired normal skin derived fibroblasts (NSFs) were used to evaluate the effects of lipopolysaccharide (LPS) on inflammation-induced skin scarring and explore the inflammation-mediated mechanism of activity of LPS on dermal fibroblasts. LPS was found to significantly upregulate the expression of the proinflammatory molecules TLR4, Myd88, TRAF6, and p65, and the fibrosis-related proteins Col I, Col III, and α-SMA, in NSFs. Blocking Myd88 expression with T6167923 downregulated the expression of Col I, Col III, and α-SMA, whereas activating Myd88 expression with CL075 significantly upregulated their expression in LPS-treated NSFs. LPS was found to delay wound healing and increase skin scarring in cell and mouse models. These results showed that LPS could induce scar formation through the TLR4/Myd88 signaling pathway in dermal fibroblasts, suggesting that the downregulation of excessive inflammation in wound tissues inhibits skin scarring and improves scar appearance.

Skeletal muscle wasting after burn is regulated by a decrease in anabolic signaling in the early flow phase.

Following burns a sustained catabolic stress response is activated, resulting in skeletal muscle wasting. A better understanding of the underlying mechanisms of postburn skeletal muscle wasting is essential for the development of preventive and/or therapeutic strategies. Six weeks old female rats underwent a sham, 10% or 40% total body surface area scald burn. Ten days post-injury, severely burned animals gained significantly less weight compared to sham treated and minor burned animals, reflected in a significantly lower ratio of muscle to total body weight for Soleus (SOL) and Extensor Digitorum Longus (EDL) in the severely burned group. Postburn, total fiber number was significantly lower in EDL, while in SOL the amount of type1 fibers significantly increased and type2 fibers significantly decreased. No signs of mitochondrial dysfunction (COX/SDH) or apoptosis (caspase-3) were found. In SOL and EDL, eEF2 and pAKT expression was significantly lower after severe burn. MURF1,2,3 and Atrogin-1 was significantly higher in SOL, whilst in EDL MURF1,2,3 was significantly lower postburn. In both muscles, FOXO3A was significantly lower postburn. This study identified postburn changes in muscle anthropomorphology and proteins involved in pathways regulating protein synthesis and breakdown, with more pronounced catabolic effects in SOL.

Preoperative expectations, postoperative satisfaction and patient directed priorities for clinical burn research.

INTRODUCTION: Burn patients receiving split thickness skin grafting are left with scarring and chronically dysfunctional grafted skin. Given evidence that patients' preoperative expectations mediate postoperative outcomes and satisfaction, we described burn patients' experience, expectations, and satisfaction with their skin graft, their views towards a cell based clinical trial to improve their graft and identified graft outcome measures for use in future studies. METHODS: Data were collected via questionnaires preoperatively, one, and three months postoperatively. Longitudinal analyses assessed change over time. RESULTS: Expectations of graft function were consistent pre- and postoperatively. Expectations of graft appearance showed significant decrease over time (ß1 = -0.290, p = 0.008). Significant improvements in skin function (ß1 = 0.579, p = 0.000) and appearance (ß1 = 0.247, p = 0.025) at the wound site during recovery were observed. Patients noted great difference between grafted and normal skin. Patient satisfaction with their graft did not change significantly over time. Patients were willing to participate in a cell based clinical trial to improve graft symptomology and prioritized improvements in scarring, redness, sensation, and elasticity. CONCLUSIONS: Outcome measures in trials advancing skin grafting should reflect chronic, patient prioritized limitations. We recommend preoperative educational interventions for burn patients receiving grafting to improve postoperative satisfaction.

Fibrosis in burns: an overview of mechanisms and therapies.

Scar development remains a common occurrence and a major healthcare challenge affecting the lives of millions of patients annually. Severe injuries to the skin, such as burns can lead to pathological wound healing patterns, often characterized by dermal fibrosis or excessive scarring, and chronic inflammation. The two most common forms of fibrotic diseases following burn trauma are hypertrophic scars (HSCs) and keloids, which severely impact the patient's quality of life. Although the cellular and molecular mechanisms are similar, HSC and keloids have several distinct differences. In this review, we discuss the different forms of fibrosis that occur postburn injury, emphasizing how the extent of burn influences scar development. Moreover, we highlight how a systemic response induced by a burn injury drives wound fibrosis, including both the role of the inflammatory response, as well as the fate of fibroblast during skin healing. Finally, we list potential therapeutics aimed at alleviating pathological scar formation. An understanding of the mechanisms of postburn fibrosis will allow us to effectively move studies from bench to bedside.

Ethanol exacerbates pulmonary complications after burn injury in mice, regardless of frequency of ethanol exposures.

Burn injuries are associated with significant morbidity and mortality, and lungs are the most common organ to fail. Interestingly, patients with alcohol intoxication at the time of burn have worse clinical outcomes, including pulmonary complications. Using a clinically relevant murine model, we have previously reported that episodic ethanol exposure before burn exacerbated lung inflammation. Specifically, intoxicated burned mice had worsened pulmonary responses, including increased leukocyte infiltration and heightened levels of CXCL1 and IL-6. Herein, we examined whether a single binge ethanol exposure before scald burn injury yields similar pulmonary responses. C57BL/6 male mice were given ethanol (1.2 g/kg) 30 min before a 15 % total body surface area burn. These mice were compared to a second cohort given episodic ethanol binge for a total of 6 days (3 days ethanol, 4 days rest, 3 days ethanol) prior to burn injury. 24 h after burn, histopathological examination of lungs were performed. In addition, survival, and levels of infiltrating leukocytes, CXCL1, and IL-6 were quantified. Episodic and single ethanol exposure before burn decreased survival compared to burn only mice and sham vehicle mice, respectively (p < 0.05). However, no difference in survival was observed between burned mice with single and episodic ethanol binge. Examination of H&E-stained lung sections revealed that regardless of ethanol binge frequency, intoxication prior to burn worsened pulmonary inflammation, evidenced by elevated granulocyte accumulation and congestion, relative to burned mice without any ethanol exposure. Levels of infiltrating granulocyte in the lungs were significantly higher in burned mice with both episodic and single ethanol intoxication, compared to burn injury only (p < 0.05). In addition, there was no difference in the granulocyte count between single and ethanol binge mice with burn injury. Neutrophil chemoattractant CXCL1 levels in the lung were similarly increased following single and episodic ethanol exposure prior to burn compared to burn alone (22-fold and 26-fold respectively, p < 0.05). Lastly, we assessed pulmonary IL-6, which revealed that irrespective of frequency, ethanol exposure combined with burn injury raised pro-inflammatory cytokine IL-6 in the lungs relative to burn mice. Again, we did not find any difference in the amount of IL-6 in lungs of burned mice with single and episodic ethanol intoxication. Taken altogether, these data demonstrate that both single and episodic exposure to ethanol prior to burn injury similarly worsens pulmonary inflammation. These results suggest that ethanol-induced exacerbation of the pulmonary responses to burn injury is due to presence of ethanol at the time of injury rather than longer-term effects of ethanol exposure.