Oral glutamine dipeptide or oral glutamine free amino acid reduces burned injury progression in rats / O dipeptídeo de glutamina oral ou aminoácido livre de glutamina oral reduz a progressão da lesão por queimadura em ratos

Abstract This study was carried out to evaluate the effect of Glutamine, as a dipeptide or a free amino acid form, on the progression of burn injuries in rats. Thirty male Wistar rats were burned with a comb metal plate heated in boiling water (98 °C) for three minutes, creating four rectangular full-thickness burn areas separated by three unburned interspaces (zone of stasis) in both dorsum sides. The animals were randomized into three groups (n=10): saline solution (G1-Control) and treated groups that orally received Glutamine as dipeptide (G2-Dip) or free amino acid (G3-FreeAA). Two and seven days after burn injury, lesions were photographed for unburned interspaces necrosis evolution assessment. Seven days after injury, glutathione seric was measured and histopathological analysis was performed. By photographs, there was a significant reduction in necrosis progression in G3-Free-AA between days two and seven. Histopathological analysis at day 7 showed a significantly higher stasis zone without necrosis and a higher number of fibroblasts in G2-Dip and G3-FreeAA compared with G1-Control. Also, glutathione serum dosage was higher in G2-Dip. The plasmatic glutathione levels were higher in the G2-Dip than the G1-Control, and there was a trend to higher levels in G3-FreeAA. The reduction in histological lesions, greater production of fibroblasts, and greater amounts of glutathione may have benefited the evolution of burn necrosis, which showed greater preservation of interspaces.

Resumo Este estudo foi realizado para avaliar o efeito da Glutamina, como um dipeptídeo ou forma de aminoácido livre, na progressão de queimaduras em ratos. Trinta ratos Wistar machos foram queimados com um pente de metal aquecido em água fervente (98 °C) por três minutos, criando quatro áreas retangulares queimadas separadas por três interesespaços não queimados (zona de estase) em ambos os lados do dorso. Os animais foram randomizados em três grupos (n = 10): solução salina (G1-Controle) e grupos tratados que receberam glutamina via oral como dipeptídeo (G2-Dip) ou aminoácido livre (G3-FreeAA). Dois e sete dias após a queimadura, as lesões foram fotografadas para avaliação da evolução da necrose entre os espaços não queimados. Sete dias após a lesão, foi dosada a glutationa sérica e realizada análise histopatológica. Pelas fotografias, houve uma redução significativa na progressão da necrose no G3-Free-AA entre os dias dois e sete. A análise histopatológica no dia 7 mostrou uma zona de estase significativamente maior sem necrose e número mais elevado de fibroblastos em G2-Dip e G3-FreeAA em comparação com G1-Controle. Os níveis plasmáticos de glutationa foram maiores no G2-Dip em relação ao G1-Controle, e houve tendência a níveis mais elevados no G3-FreeAA. A redução das lesões histológicas, maior produção de fibroblastos, maior quantidade de glutationa podem ter beneficiado a evolução da necrose da queimadura, que mostrou maior preservação dos interespaços.

Antibacterial activity of ethanolic extracts of Plantago major leaves against Pseudomonas aeruginosa from burn infections.

INTRODUCTION: The use of herbal extracts is increasing because of the increase in bacterial resistance to conventional antibiotics. Plantago major is frequently used in traditional medicine because of its medicinal properties. The aim of the current study was to assess the antibacterial efficacy of an ethanolic extract of P. major leaves against Pseudomonas aeruginosa isolated from burn infections. METHODOLOGY: One hundred and twenty burn samples were collected from hospitalized patients at the Burn Hospital in Duhok city. The bacterium was identified using Gram stain, colony morphology, biochemical tests and selective differential media. Antibacterial activity of P. major leaves was assessed by using an ethanolic extract in serial dilutions of 100, 75, 50, 25, and 10 % and disc diffusion assay. Antibiotic susceptibility testing was also performed by disk diffusion using Muller-Hinton agar medium. RESULTS: Different concentrations of the ethanolic extract of P. major leaves exhibited different zones of inhibition against P. aeruginosa from 9.93 mm to 22.18 mm in diameter. The inhibition zone increased as the concentration of the extract increased. The 100% ethanolic extract had the greatest inhibitory effect, inhibiting bacteria in the zone of 22.18 mm diameter. This bacterium showed a high level of resistance to the antibiotics used. CONCLUSIONS: This study demonstrated that herbal extracts could be used as a combination therapy with antibiotics and chemical drugs in the elimination of bacterial growth. Further investigations and future experiments, need to be carried out before recommending use of herbal extracts.

Deep Eutectic Liquids as a Topical Vehicle for Tadalafil: Characterisation and Potential Wound Healing and Antimicrobial Activity.

Deep eutectic solvents (DESs) and ionic liquids (ILs) offer novel opportunities for several pharmaceutical applications. Their tunable properties offer control over their design and applications. Choline chloride (CC)-based DESs (referred to as Type III eutectics) offer superior advantages for various pharmaceutical and therapeutic applications. Here, CC-based DESs of tadalafil (TDF), a selective phosphodiesterase type 5 (PDE-5) enzyme inhibitor, were designed for implementation in wound healing. The adopted approach provides formulations for the topical application of TDF, hence avoiding systemic exposure. To this end, the DESs were chosen based on their suitability for topical application. Then, DES formulations of TDF were prepared, yielding a tremendous increase in the equilibrium solubility of TDF. Lidocaine (LDC) was included in the formulation with TDF to provide a local anaesthetic effect, forming F01. The addition of propylene glycol (PG) to the formulation was attempted to reduce the viscosity, forming F02. The formulations were fully characterised using NMR, FTIR and DCS techniques. According to the obtained characterisation results, the drugs were soluble in the DES with no detectable degradation. Our results demonstrated the utility of F01 in wound healing in vivo using cut wound and burn wound models. Significant retraction of the cut wound area was observed within three weeks of the application of F01 when compared with DES. Furthermore, the utilisation of F01 resulted in less scarring of the burn wounds than any other group including the positive control, thus rendering it a candidate formula for burn dressing formulations. We demonstrated that the slower healing process associated with F01 resulted in less scarring potential. Lastly, the antimicrobial activity of the DES formulations was demonstrated against a panel of fungi and bacterial strains, thus providing a unique wound healing process via simultaneous prevention of wound infection. In conclusion, this work presents the design and application of a topical vehicle for TDF with novel biomedical applications.

Preclinical study of experimental burns treated with photobiomodulation and Human Amniotic Membrane, both isolated and associated.

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.

[A prospective study on application of human umbilical cord mesenchymal stem cells combined with autologous Meek microskin transplantation in patients with extensive burns].

Objective: To investigate the effects of human umbilical cord mesenchymal stem cells (hUCMSCs) combined with autologous Meek microskin transplantation on patients with extensive burns. Methods: The prospective self-controlled study was conducted. From May 2019 to June 2022, 16 patients with extensive burns admitted to the 990th Hospital of PLA Joint Logistics Support Force met the inclusion criteria, while 3 patients were excluded according to the exclusion criteria, and 13 patients were finally selected, including 10 males and 3 females, aged 24-61 (42±13) years. A total of 20 trial areas (40 wounds, with area of 10 cm×10 cm in each wound) were selected. Two adjacent wounds in each trial area were divided into hUCMSC+gel group applied with hyaluronic acid gel containing hUCMSCs and gel only group applied with hyaluronic acid gel only according to the random number table, with 20 wounds in each group. Afterwards the wounds in two groups were transplanted with autologous Meek microskin grafts with an extension ratio of 1∶6. In 2, 3, and 4 weeks post operation, the wound healing was observed, the wound healing rate was calculated, and the wound healing time was recorded. The specimen of wound secretion was collected for microorganism culture if there was purulent secretion on the wound post operation. In 3, 6, and 12 months post operation, the scar hyperplasia in wound was assessed using the Vancouver scar scale (VSS). In 3 months post operation, the wound tissue was collected for hematoxylin-eosin (HE) staining to observe the morphological changes and for immunohistochemical staining to observe the positive expressions of Ki67 and vimentin and to count the number of positive cells. Data were statistically analyzed with paired samples t test and Bonferronni correction. Results: In 2, 3, and 4 weeks post operation, the wound healing rates in hUCMSC+gel group were (80±11)%, (84±12)%, and (92±9)%, respectively, which were significantly higher than (67±18)%, (74±21)%, and (84±16)% in gel only group (with t values of 4.01, 3.52, and 3.66, respectively, P<0.05). The wound healing time in hUCMSC+gel group was (31±11) d, which was significantly shorter than (36±13) d in gel only group (t=-3.68, P<0.05). The microbiological culture of the postoperative wound secretion specimens from the adjacent wounds in 2 groups was identical, with negative results in 4 trial areas and positive results in 16 trial areas. In 3, 6, and 12 months post operation, the VSS scores of wounds in gel only group were 7.8±1.9, 6.7±2.1, and 5.4±1.6, which were significantly higher than 6.8±1.8, 5.6±1.6, and 4.0±1.4 in hUCMSC+gel group, respectively (with t values of -4.79, -4.37, and -5.47, respectively, P<0.05). In 3 months post operation, HE staining showed an increase in epidermal layer thickness and epidermal crest in wound in hUCMSC+gel group compared with those in gel only group, and immunohistochemical staining showed a significant increase in the number of Ki67 positive cells in wound in hUCMSC+gel group compared with those in gel only group (t=4.39, P<0.05), with no statistically significant difference in the number of vimentin positive cells in wound between the 2 groups (P>0.05). Conclusions: The application of hyaluronic acid gel containing hUCMSCs to the wound is simple to perform and is therefore a preferable route. Topical application of hUCMSCs can promote healing of the autologous Meek microskin grafted area in patients with extensive burns, shorten wound healing time, and alleviate scar hyperplasia. The above effects may be related to the increased epidermal thickness and epidermal crest, and active cell proliferation.

Burn Wound Healing Effect of a Sterilized Traditional Formulation of Boswellia carteri vs. Silver Sulfadiazine Cream 1% in Patients Presenting Second-degree Burn Wounds: A Randomized, Double-blind Clinical Trial.

Background: Burn wounds rank among the most serious healthcare issues. Many studies reported the effectiveness of natural products in the wound-healing process. The present study compared the effects of a standardized herbal formulation derived from Boswellia carteri (B. carteri) and silver sulfadiazine (SSD) cream 1% on the healing of burn wounds. Methods: This randomized double-blind clinical trial was conducted at Shiraz Burn Hospital (Shiraz, Iran) between July 2012 to August 2013. A sterilized formulation comprising B. carteri 40% was prepared. 54 second-degree burn patients of both sexes with age ranges of 20 to 60 were invited to participate in this double-blind, randomized clinical trial. They were randomly divided into two groups and given either the Boswellia formulation or SSD cream. The healing index was determined based on the wound area assessment using the planimetry technique. The Kaplan-Meier survival analysis was used to assess the primary outcome, which was the amount of time until complete healing. Results: The trial was completed by 17 patients from the SSD group and 15 patients from the Boswellia group. During the study period, both groups showed a progressive healing trend. The mean (95% CI) healing time in the SSD group was 10.94 (9.03-12.85) days and 10.73 (9.23-12.23) days in the Boswellia group (P=0.71), indicating no significant difference. On the 17th day, the healing index of all patients in the Boswellia group reached 1. Conclusion: Boswellia topical formulation had a burn wound healing effect comparable to that of the standard SSD 1% treatment. Based on the findings of this study, the likelihood of contact dermatitis with Boswellia should be taken into consideration.

Nutrition after severe burn injury.

PURPOSE OF REVIEW: Severe burn injury causes significant metabolic changes and demands that make nutritional support particularly important. Feeding the severe burn patient is a real challenge in regard to the specific needs and the clinical constraints. This review aims to challenge the existing recommendations in the light of the few recently published data on nutritional support in burn patients. RECENT FINDINGS: Some key macro- and micro-nutrients have been recently studied in severe burn patients. Repletion, complementation or supplementation of omega-3 fatty acids, vitamin C, vitamin D, antioxidant micronutrients may be promising from a physiologic perspective, but evidence of benefits on hard outcomes is still weak due to the studies' design. On the contrary, the anticipated positive effects of glutamine on the time to discharge, mortality and bacteremias have been disproved in the largest randomized controlled trial investigating glutamine supplementation in burns. An individualized approach in term of nutrients quantity and quality may proof highly valuable and needs to be validated in adequate trials. The combination of nutrition and physical exercises is another studied strategy that could improve muscle outcomes. SUMMARY: Due to the low number of clinical trials focused on severe burn injury, most often including limited number of patients, developing new evidence-based guidelines is challenging. More high-quality trials are needed to improve the existing recommendations in the very next future.

Biodegradable temporising matrix: use of negative pressure wound therapy shows a significantly higher success rate.

OBJECTIVE: The purpose of this case series was to evaluate the efficacy of a synthetic biodegradable temporising matrix (BTM; PolyNovo Biomaterials Pty Ltd, Australia) and compare the outcome of BTM patients with and without negative pressure wound therapy (NPWT). METHOD: A retrospective chart review was conducted on patients admitted with deep full-thickness burns, traumatic or complex wound injuries treated with BTM. Electronic medical records and images were evaluated by a team of clinical professionals. Endpoints included: the measure of successful BTM integration; and comparison between patients treated with and without NPWT. Additional measures were BTM total surface area, BTM sites, timeliness of BTM application and any complications. RESULTS: A total of 28 patients were evaluated and 23 (82.1%) demonstrated overall successful BTM integration. Patients treated with BTM in conjunction with NPWT (n=16) demonstrated a significantly higher (p=0.046) integration rate compared to patients treated without NPWT (n=12) (93.8% versus 58.3%, respectively). Patients treated with BTM with NPWT continued to successfully integrate and sustain favourable outcomes despite the presence of severe infection or the development of haematomas. CONCLUSION: A significantly higher integration rate was demonstrated when BTM was used in conjunction with NPWT. The results of this study further support the efficacy of successful integration of BTM as a replacement for tissue loss in the treatment of deep, full-thickness burns, traumatic and complex wound injuries, and particularly favourable outcomes with the use of NPWT. To the best of our knowledge, this is the first reported case series comparing the clinical outcomes of BTM with and without the use of NPWT.

Novel recombinant endolysin ointment with broad antimicrobial activity against methicillin-resistant Staphylococcus aureus isolated from wounds and burns.

The major problem in the management of burn wounds is infections. Methicillin-resistant Staphylococcus aureus (MRSA) is one of the major causes of infection in burn wounds. Antibiotic-resistant bacteria around the world have become a major therapeutic challenge. Bacteriophages and their lysin are suggested as an antimicrobial alternative agent. The approach of this study was to evaluate the potential of recombinant phage lysin ointment efficacy in MRSA burn wound infection in vitro. Whole genome sequencing was performed to the three isolated bacteriophages by ABM, USA using Illumina next-generation sequencing (NGS) technology. De novo assembly and genetic analysis carried out. Expression of lysin genes was performed by cloning using Escherichia coli JM109. Lysin protein extraction and purification was performed before and after cloning using precipitation by ammonium sulfate, dialysis, and gel filtration chromatography. Dose-dependent assay and time-kill curve experiment was performed for 2 lysins showed that recombinant lysin 2 functions more than its non-recombinant lysins 2 with the same concentration of 0.5 µg/mL. Both lysins' ointment was prepared and compared with commercial ointments. 62 (78.4%) out of 79 wounds a burns swabs were detected as S. aureus and S methicillin-resistant S. aureus (MRSA) rate was determined to be 29 (46.8%) in total, while 33 isolates (53.2%) determined as methicillin-sensitive S. aureus (MSSA). According to the antibiotic susceptibility test results, all S. aureus isolates were identified as sensitive against vancomycin, ceftaroline, and linezolid. Results shows one lysogenic bacteriophage and three distinct lytic specific S. aureus bacteriophage were isolated from sewage. For each of the three samples, a single contig was possible to be obtained. Sample BP-SA2 had the best coverage, and the contig was slightly longer than the other bacteriophages. In addition, BLAST search identified Staphylococcus bacteriophage vB-SscM-1 (accession KX171212.1) as the closest match to the public database. Finally, the gene annotation was checked, and two potential lysin genes were identified. Besides the two ends, there are only 4 SNPs between the three genomes. It should be noted that the two lysin genes from the genomes have no SNPs, and are identical across the three genomes. It can be seen that the three bacteriophages (BP-SA1), (BP-SA 2), and (BP-SA3) form their own tight cluster. It can be seen that (BP-SA 2) is more closely related to Staphylococcus bacteriophage vB-SscM-1 genome and most noticeable 5' region of S5 and vB-SscM-1 are now located at 3' end of vB-Sau-Clo6. The investigation of the two lysin genes in (BP-SA 2) by whole genome sequencing showed that there is some homology with vB-SscM-1; although the first gene is annotated as hypothetical protein, the second gene is annotated as amidase. The same two lysin genes are identified in all three bacteriophage genomes by the RAST. The putative protein sequences of the discovered phage lysin was analyzed using protein search with UniProt/Swiss-Prot database, and all matches suggest that the putative protein of the discovered phage lysin is a real endolysin. The three samples of bacteriophage were harboring both (Lysin 1 and lysin 2) genes were amplified. Afterward, 2-lysin genes were cloned successfully; for the dose-dependent assay, the same incubation time of recombinant lysins and its two non-recombinant lysins with the bacteria for 30 min. It is found that the bactericidal activity of these groups increased in correlation with their concentrations. For the time-kill curve experiment, it showed that Recombinant lysin 2 functions more than its non-recombinant lysins 2 with the same concentration of 0.5 µg/mL. Both lysins' ointments have potential activity against S. aureus isolates more than mupirocin and have a similar activity with Fusidic acid through applying 10 µL from lysin 1 ointment, lysin 2 ointment, mupirocin ointment 2%, and Fusidic acid cream 2%. In vitro lytic spectrum analysis revealed that 100% (29/29) tested S. aureus were sensitive. One dose of lysin ointment resulted in a reduction of 3.3 log units in the number of bacteria (from an initial count of 2 × 105 CFU/mg) at 18 hours compared with one dose of mupirocin, PBS, or Aquaphor. Specifically, this study provides evidence that the application of lysin ointment has significant potential as an alternative strategy for MRSA infections.

["Leverage pry-off method" for effective prevention of thermal injury during microwave ablation of benign thyroid nodules].

OBJECTIVE: To assess the safety and efficacy of"leverage pry-off method"for preventing thermal injury during microwave ablation of benign thyroid nodules. METHODS: From July, 2017 to September, 2019, a total of 348 patients with benign thyroid nodules underwent ultrasound-guided microwave ablation. For protecting from thermal injury during the ablation, "hydrodissection technique" was used in 174 of the patients (admitted from July, 2017 to August, 2018) and "leverage pry-off method" in the other 174 patients (admitted from September, 2018 to September, 2019). All the patients were followed up for 1 to 12 months after the operation for observation of severe complications and nodular residues. RESULTS: Ultrasound-guided microwave ablation was completed in all the 348 patients. The most common severe complication associated with the ablation was voice change, occurring in 3 cases (1.7%) in "hydrodissection technique" group and in 4 (2.3%) in the "leverage pry-off method" group, showing no significant difference between the two groups (P>0.05). During the follow-up, no significant difference was found in the rate of nodular residues between the "hydrodissection technique" group and "hydrodissection technique" group (9.8% vs 10.9% (P>0.05). CONCLUSIONS: The "leverage pry-off method" is simple and effective for preventing thermal injury during microwave ablation of benign thyroid nodules.

The effects of dexmedetomidine on early acute kidney injury in severely burned rats.

OBJECTIVE: Burns are a global medical and economic problem. In addition to high costs, the lengthy therapeutic process and the emotional trauma experienced by patients and their families indirectly worsen the socioeconomic damage caused. Kidney failure observed after burns is highly correlated with mortality. MATERIALS AND METHODS: Twenty-eight male Sprague-Dawley rats (age four months, weight 250-350 g) were included in the study. They were randomly assigned into four groups consisting of seven rats each with similar mean weights. Group 1 (n=7) represented the healthy control group (C), Group 2 (n=7) the Sham+dexmedetomidine (DEX) 100 mcg/kg (three doses) (S+DEX100) group, Group 3 (n=7) the 30% Burn (B), and Group 4 (n=7) the 30% Burn+DEX 100 mcg/kg/day group (B+DEX100) (three doses). Thiobarbituric acid reactive substances (TBARS), total thiol (TT), interleukin-1 (IL-1) and tumor necrosis factor-α (TNF-α) values in kidney tissues were investigated biochemically, and histopathological analyses were also performed. Nuclear factor κB (NF-κB)/p65 was measured using immunohistochemistry, and the TUNEL assay was applied to indicate apoptotic tubular epithelial cells. RESULTS: TBARS, IL-1, and TNF-α in kidney tissues decreased in the B+DEX100 group compared to the 30% burn group, while total thiol values increased. Histopathologically, atypical glomeruli, particularly necrotic tubules, and inflammation in peritubular areas decreased in the B+DEX100 group compared to the 30% burn group. In addition, apoptotic tubular epithelial cells exhibiting TUNEL positivity and tubular epithelial cells exhibiting NF-кß/p65 positivity also decreased in the B+DEX100 group compared to the 30% burn group. CONCLUSIONS: Dexmedetomidine reduced apoptotic activity in rats and exhibited anti-inflammatory antioxidant effects in the burn model in this study.

[Meta-analysis of the effects of xenogeneic acellular dermal matrix dressings in the treatment of wounds in burn patients].

Objective: To evaluate the efficacy and safety of xenogeneic acellular dermal matrix (ADM) dressings for the treatment of wounds in burn patients. Methods: The meta-analysis method was adopted. Databases including Chinese Journal Full-text Database, Wanfang Database, VIP Database, and Chinese Biomedical Database were retrieved with the search terms in Chinese version of ", , , " and PubMed, Embase, Web of Science, and Cochrane Library were retrieved with the search terms in English version of "xenogeneic acellular dermal matrix, dressing, burn wound, burn" to obtain the publicly published randomized controlled trials on the efficacy of xenogeneic ADM dressings for the treatment of wounds in burn patients from the establishment of each database to December 2021. The outcome indexes included wound healing time, ratio of scar hyperplasia, Vancouver scar scale (VSS) score, ratio of complications, ratio of skin grafting, and ratio of bacteria detection. Rev Man 5.3 and Stata 14.0 statistical softwares were used to conduct a meta-analysis of eligible studies. Results: A total of 1 596 burn patients from 16 studies were included, including 835 patients in experimental group who received xenogeneic ADM dressings therapy and 761 patients in control group who received other methods therapy. The bias risk of all the 16 included studies was uncertain. Compared with those in control group, patients in experimental group had significantly shorter wound healing time, lower VSS scores (with standardized mean differences of -2.50 and -3.10, 95% confidence intervals of -3.02--1.98 and -4.87--1.34, respectively, P values both <0.05), and lower ratios of scar hyperplasia, complications, skin grafting, and bacteria detection (with relative risks of 0.58, 0.23, 0.32, and 0.27, 95% confidence intervals of 0.43-0.80, 0.14-0.37, 0.15-0.67, and 0.11-0.69, respectively, P<0.05). Subgroup analysis showed that the difference of intervention measures in control group might be the source of heterogeneity in wound healing time. There was no publication bias in ratio of scar hyperplasia (P≥0.05), while there was publication bias in wound healing time, VSS score, and ratio of complications (P<0.05). Conclusions: Xenogeneic ADM dressings can shorten the wound healing time of burn patients, reduce the VSS score and the ratios of scar hyperplasia, complications, skin grafting, and bacteria detection.

Acute kidney injury in burns in the intensive care unit: A retrospective research.

BACKGROUND: Acute kidney injury (AKI) is one of the common complications, associated with high mortality and morbidity in patients with burn injuries. This study aimed to determine the frequency of AKI development, its affective factors, and mortality rates according to kidney disease improving global outcomes (KDIGO) criteria in the burn patients. METHODS: The study included patients who are hospitalized for at least 48 h and aged >18 years, whereas patients with a renal transplant, chronic renal failure, undergoing hemodialysis, <18 years of age, with a glomerular filtration rate of <15 on admission, and toxic epidermal necrolysis was excluded from the study. KDIGO criteria were used to evaluate the occurrence of AKI. Burn mech-anism, total body surface area, inhalation injury respiratory tract burn, fluid replacement at 72 h with Parkland Formula, mechanical ventilator support, inotrope/vasopressor support, intensive care unit, lenght of stay, mortality, abbreviated burn severity index (ABSI), acute physiology, and chronic health evaluation II (APACHE II) ve Sequential organ failure assessment (SOFA) were recorded. RESULTS: A total of 48 patients were included in our study, of which 26 (54.2%) developed AKI (+), whereas 22 (45.8%) did not (-). The mean total burn surface area was 47.30% in the AKI (+) group and 19.88% in the AKI (-) group. Mean scores of ABSI, II (APACHE II), and SOFA, the mechanical ventilation and inotrope/vasopressor support and the presence of sepsis were significantly higher in the AKI (+). No mortality was determined in the AKI (-) group, whereas 34.6% in the AKI (+) group which was significantly high. CONCLUSION: AKI was related to high morbidity and mortality in patients with burns. Using KDIGOs, classification in daily fol-low-up is useful in early diagnosis.

Uso de plata metálica y ácido hialurónico en paciente varón con quemadura de segundo grado / Use of metallic silver and hyaluronic acid in a male patient with a second degree burn

Dentro de las quemaduras que se producen en el ámbito domiciliario, una de las más frecuentes es la quemadura por aceite hirviendo; en este caso presentamos un paciente varón con quemadura de segundo grado superficial en la mano derecha con afectación del dorso de la mano, dedos y palma.Pasadas 24 horas de la primera cura es remitido a nuestra consulta por aparición de ampollas; a partir de ahí, el paciente es tratado exclusivamente en nuestra consulta hasta la resolución del proceso.El caso se soluciona llegando a una total curación con el uso de plata metálica combinada con ácido hialurónico en forma de spray, lo que agiliza y acorta el tiempo dedicado a las curas y consigue que el paciente apenas tenga dolor durante las mismas.La eficacia y la facilidad de aplicación de este nuevo apósito en spray, nos proporciona una nueva forma de tratamiento de quemaduras, sobre todo si estas se producen en zonas con pliegues complejos para su abordaje. (AU)

One of the most frequent accidents involving burns at home is burning oneself with cooking oil. In this article, we present the case of a male patient with a superficial second-degree burn on the right hand affecting the back of the hand, the fingers, and the palm.Twenty-four hours after the first treatment, he was referred to our office due to the appearance of blisters; from then on, the patient was treated exclusively in our office until the burn was healed.The patient was fully healed with metallic silver combined with hyaluronic acid in the form of spray, which shortens the time spent on the cures and ensures that the patient experiences little pain during the treatment.The efficacy and ease of application of this new spray-on plaster provides us with a new way of treating burns, especially if they occur in areas with complex folds that make them difficult to reach. (AU)

Skin-Fat Composite Grafts for Reconstructing Large Full-Thickness Skin Defects.

BACKGROUND: The uppermost layer of subcutaneous tissue has a rich vascular network, the subdermal plexus and multiple perforating vessels in the interlobular septa. When skin-fat composite grafts (SFCGs) include this uppermost layer, they can be readily vascularized to enhance survival. The authors describe their clinical experience with large SFCG transplantations. METHODS: This retrospective study included patients who underwent SFCG transplantation for large, full-thickness skin defects, formed after burn scar contracture or contraction deformity excision. The recipient tissue bed was prepared by retaining the deepest layer of scar tissue or reticular dermis to preserve the interlobular septa, subdermal plexus, and ascending arterioles above the subcutaneous tissue. The SFCG was prepared by trimming fat lobules and preserving the interlobular septa and vessels to form a 1- to 4-mm-thick base of subdermal fat tissue. The trimmed SFCG was placed onto the defective tissue and secured with a tie-over dressing. RESULTS: Among 86 grafts, 76 (88.4%) survived completely (sizes, 6 to 161 cm 2 ; mean surface area, 68.7cm 2 ). Focal skin sloughing or graft loss occurred in 10 cases. These events were followed by spontaneous healing in eight cases. Focal hypertrophic scars formed in six cases. In 15 cases, hyperpigmentation occurred, but improved gradually. Most transplantations achieved satisfactory pliability (93.0%), contour (90.7%), and color (88.4%). CONCLUSIONS: SFCGs survived better than expected with minimal complications, probably because of the preservation of rich vascular networks in both the recipient and SFCG tissues. Therefore, SFCG transplantation may be a good option for reconstructing full-thickness skin defects with a large surface area. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, IV.

Extracorporeal life support in pediatric burn care: A systematic review.

A systematic review of the role of extracorporeal life support (ECLS) in pediatric patients with burn and smoke inhalation injury was undertaken. A systematic search of the literature according to a specific combination of keywords to ascertain the effectiveness of this treatment strategy was conducted. A total of 14 articles out of 266 were considered suitable for the analysis in pediatric patients. The PICOS approach and PRISMA flow chart were followed for the purpose of this review. Despite the limited number of studies on the subject, ECMO in burn and smoke inhalation injury provides an additional level of support in pediatric patients leading to positive outcomes. V-V ECMO demonstrated the best overall survival of all configurations, with similar outcomes to non-burned patients. Prolonged mechanical ventilation prior to ECMO decreases survival and increases mortality by 12% with each additional day off ECMO. Good outcomes have been described for scald burns, dressing changes, and pre-ECMO cardiac arrest.

Wound Pain as a Determinant of Function in Patients Hospitalised for Burns.

Burn wounds most often occur on visible parts of the body. They therefore cause fear of disfigurement and rejection by those around them. In addition, they cause pain. The main aim of this study was to analyse factors affecting the functioning of patients hospitalised for burns. The study included 57 patients hospitalised for burns. Each person was surveyed twice: on day seven after admission and on the day of discharge from the hospital. The following research tools were used: a personal questionnaire to collect clinical data and the scales of the Katz Activities of Daily Living (ADL), the short-form McGill Pain Questionnaire (SF-MPQ), the Beck Depression Inventory (BDI) and the Satisfaction with Appearance Scale (SWAP). On the discharge day, compared to day 7, there was an improvement in the patient's level of functioning in all areas analysed. Pain intensity (p < 0.0001), depression (p < 0.0001) and dissatisfaction with appearance (p = 0.0239) decreased significantly. Improvements in daily functioning were also obtained (p < 0.0001). Multiple regression was performed to estimate the effect of selected variables on patients' level of functioning. Burn area (p = 0.0126), pain level (questionnaire part B: p = 0.0004 and questionnaire part C: p = 0.0208) and gender (p = 0.0413) had a significant impact on the level of daily functioning. Pain complaints are the most crucial predictor affecting the functional status and depression levels in burn wound patients. Increased levels of depression promote dissatisfaction with one's appearance.

Resolvin D1 attenuates mechanical allodynia after burn injury: Involvement of spinal glia, p38 mitogen-activated protein kinase, and brain-derived neurotrophic factor/tropomyosin-related kinase B signaling.

Resolvin D1 (RvD1) suppresses inflammatory, postoperative, and neuropathic pain. The present study assessed the roles and mechanisms of RvD1 in mechanical allodynia after burn injury. A rat model of burn injury was established for analyses, and RvD1 was injected intraperitoneally. Pain behavior and the expression levels of spinal dorsal horn Iba-1 (microglia marker), GFAP (astrocyte marker), p-p38 mitogen-activated protein kinase (MAPK), brain-derived neurotrophic factor (BDNF), and tropomyosin-related kinase B (TrkB) were detected by behavioral and immunocytochemical assays. The results showed that RvD1 attenuated mechanical allodynia after burn injury, prevented microglial and astroglial activation, and downregulated p-p38 MAPK in microglia and BDNF/TrkB following burn injury. Similarly, inhibition of p38 MAPK and BDNF/TrkB signaling attenuated mechanical allodynia after burn injury. In addition, inhibition of p38 MAPK prevented spinal microglial activation and downregulated BDNF/TrkB following burn injury. Furthermore, inhibition of BDNF/TrkB signaling prevented spinal microglial activation and downregulated p-p38 MAPK within spinal microglia. Taken together, this study demonstrated that RvD1 might attenuate mechanical allodynia after burn injury by inhibiting spinal cord glial activation, microglial p38 MAPK, and BDNF/TrkB signaling in the spinal dorsal horn.

NUCLEAR FACTOR-ERYTHROID-2-RELATED FACTOR REGULATES SYSTEMIC AND PULMONARY BARRIER FUNCTION AND IMMUNE PROGRAMMING AFTER BURN AND INHALATION INJURY.

ABSTRACT: Major burn injury is associated with systemic hyperinflammatory and oxidative stresses that encompass the wound, vascular, and pulmonary systems that contribute to complications and poor outcomes. These stresses are exacerbated if there is a combined burn and inhalation (B+I) injury, which leads to increases in morbidity and mortality. Nuclear factor-erythroid-2-related factor (NRF2) is a transcription factor that functions to maintain homeostasis during stress, in part by modulating inflammation and oxidative injury. We hypothesized that the NRF2-mediated homeostasis after burn alone and combined B-I injury is insufficient, but that pharmacological activation of the NRF2 pathway has the potential to reduce/reverse acute hyper inflammatory responses. We found that, after burn and B+I injury, Nrf2 -/- mice have higher mortality and exhibit greater pulmonary edema, vascular permeability, and exacerbated pulmonary and systemic proinflammatory responses compared with injured wild-type (WT) controls. Transcriptome analysis of lung tissue revealed specific Nrf2 -dependent dysregulated immune pathways after injury. In WT mice, we observed that B+I injury induces cytosolic, but not nuclear, accumulation of NRF2 protein in the lung microenvironment compared with sham-injured controls. Bardoxolone methyl (CDDO-Me)-containing microparticles (CDDO-MPs) were developed that allow for dilution in saline and stable release of CDDO-Me. When delivered intraperitoneally into mice 1 hour after B+I injury, CDDO-MPs significantly reduced mortality and cytokine dysfunction compared with untreated B-I animals. These data implicate the role of NRF2 regulation of pulmonary and systemic immune dysfunction after burn and B+I injury, and also a deficiency in controlling immune dysregulation. Selectively activating the NRF2 pathway may improve clinical outcomes in burn and B+I patients.

DIAGNOSTIC VALUE OF MITOCHONDRIAL DNA AND PERIPHERAL BLOOD MONONUCLEAR CELL RESPIROMETRY FOR BURN-RELATED SEPSIS.

ABSTRACT: Background: Sepsis is the leading cause of mortality among burn patients that survive acute resuscitation. Clinical criteria have poor diagnostic value for burn-induced sepsis, making it difficult to diagnose. Protein biomarkers (e.g., procalcitonin) have been examined with limited success. We aimed to explore other biomarkers related to mitochondria (mitochondrial DNA [mtDNA]) and mitochondrial function of peripheral blood mononuclear cells (PBMCs) for sepsis diagnosis in burn patients. Methods: We conducted a follow-up analysis of a single center, prospective observational study of subjects (n = 10 healthy volunteers, n = 24 burn patients) to examine the diagnostic value of mtDNA and PBMC respirometry. Patients were enrolled regardless of sepsis status and followed longitudinally. Patient samples were classified as septic or not based on empiric clinical criteria. Isolated PBMCs were loaded into a high-resolution respirometer, and circulating mtDNA was measured with a PCR-based assay. Sequential Organ Failure Assessment (SOFA) criteria were also compared. Results: The SOFA criteria comparing septic versus before/nonseptic patients revealed significantly higher heart rate ( P = 0.012) and lower mean arterial pressure ( P = 0.039) in burn sepsis. MtDNA was significantly elevated in septic burn patients compared with healthy volunteers ( P < 0.0001) and nonseptic patients ( P < 0.0001), with no significant difference between healthy volunteers and nonseptic burn patients ( P = 0.187). The area under the ROC curve (AUC) for mtDNA was 0.685 (95% confidence interval = 0.50-0.86). For PBMC respirometry, burn patients exhibited increased routine and maximal respiration potential compared with healthy volunteers. However, no difference was found between nonseptic and septic patient samples. A subanalysis revealed a significant mortality difference in PBMC respirometry after sepsis diagnosis, wherein survivors had higher routine respiration ( P = 0.003) and maximal respiration ( P = 0.011) compared with nonsurvivors. Conclusion: Our findings reveal that mtDNA may have diagnostic value for burn sepsis, whereas PBMC respirometry is nonspecifically elevated in burns, but may have value in mortality prognosis. A larger, multisite study is warranted for further validity of the diagnostic value of mtDNA and PBMC respirometry as biomarkers for prognosis of sepsis and outcomes in burn patients.