Photoactivated rose bengal mitigates a fibrotic phenotype and improves cutaneous wound healing in full-thickness injuries.

Healing of deep cutaneous wounds often results in detrimental sequelae, including painful and debilitating scars. Current therapies for full-thickness injuries that target specific phases of wound healing have moderate success; however, full resolution remains incomplete and negative consequences persist if skin homeostasis is not achieved. Photoactivated molecules can modulate cellular responses by generating reactive oxygen species and may provide a novel therapeutic option to improve wound healing. In the current study, we investigated the effects of Rose bengal (RB) dye in a preclinical model of full-thickness cutaneous injury. Monochromatic green light activates RB to generate ROS in the presence of oxygen, subsequently crosslinking collagen fibrils. In in vitro studies, we show that photoactivated RB is well tolerated by epidermal keratinocytes and dermal fibroblasts and can mitigate fibrotic signalling by downregulating collagen production. In a murine model of full-thickness injury, topically-applied and photoactivated RB closed wounds faster than control and vehicle treatments and showed significantly improved wound healing outcomes, including enhanced early granulation, better collagen organisation and increased vascularity in the presence of protracted tissue ROS. These data support an overall improved cutaneous wound healing profile after RB phototherapy and warrant further investigations into this versatile molecule.

Genital Burns Are Associated with Worse Psychosocial and Physical Outcomes.

Genital burns are unique and complex injuries that impact patients physically and emotionally. This study investigates the specific impact of genital burns on psychosocial and physical outcomes. A retrospective cohort study was conducted using the TriNetX database, encompassing over 117 million patients from U.S. healthcare institutions. Patients with genital burns were identified and categorized into sub-cohorts based on TBSA and burn degree. Propensity score matching and cohort balancing were performed based on age, gender, race, and ethnicity. Outcomes were analyzed both short-term (1 month) and long-term (5 years), focusing on psychiatric and physical aspects. This study identified 3,496 genital burn patients over a 15-year period. Analyses revealed that genital burns significantly increased short-term risk of death (RR: 2.8), anxiety (RR: 2.656), hospitalization (RR: 2.167), and any anxiety, PTSD, or depression (RR: 2.363), and long-term risk of death (RR: 1.658) and pruritus (RR: 1.58) (all p<0.05). Interestingly, genital burn patients showed a lower risk of chronic joint pain compared to other burn injuries (RR: 0.815) (p<0.05). These results occurred independently of the extent of TBSA. Genital burns have a distinctive impact on patients, leading to higher rates of certain psychiatric morbidities and physical complications. This study highlights the need for tailored care and consideration of the unique challenges faced by patients with genital burns, both in the immediate aftermath and in the long term. Understanding the specific impacts of genital burns is vital for healthcare practitioners to develop care strategies and better support for patients recovering from such injuries.

Metformin is associated with reduced risk of mortality and morbidity in burn patients compared to insulin.

PURPOSE: The standard of care for burned patients experiencing hyperglycemia associated with the hypermetabolic response is insulin therapy. Insulin treatment predisposes burn patients to hypoglycemia, which increases morbidity and mortality. Metformin has been suggested as an alternative to insulin therapy for glycemic control in burn patients given its safety profile, but further research is warranted. This study investigated whether metformin use in burn patients is associated with improved glycemic control and morbidity/mortality outcomes compared to insulin use alone. MATERIALS AND METHODS: Using the TriNetX database, we conducted a retrospective study of burned patients who were administered insulin, metformin, or both within one week of injury. Demographic, comorbidity, and burn severity information were collected. Patients were categorized by treatment type, propensity score-matched, and compared for the following outcomes within 3 months: hyperglycemia, hypoglycemia, sepsis, lactic acidosis, and death. Statistical significance was set a priori at p ≤ 0.05. RESULTS: The insulin cohort was at increased risk for all outcomes (all p < 0.0001) compared to the metformin cohort, and an increased risk for sepsis, lactic acidosis, and death (all p ≤ 0.0002) compared to the insulin/metformin combination cohort. When compared to the metformin cohort, the combination cohort was at increased risk for all outcomes (all p ≤ 0.0107) except death. CONCLUSIONS: Treatment with metformin after burn is associated with a reduced risk of morbidity and mortality compared to insulin. The combination of insulin and metformin is no more effective in reducing the risk of hyperglycemia and hypoglycemia than insulin alone but is less effective than metformin alone.

Elevated Cardiac Troponin I Level Associated to Cardiac Dysfunction in Burned Patients.

Severely burned patients often develop cardiac dysfunction and heart failure. The purpose of this retrospective study is to evaluate the role of cardiac troponin I (cTI) and its association to patients with burns. Patients deidentified data were collected from a national database in May 2023. Adult patients with burns who had cTnI lab counted were enrolled in this study. Patients were grouped by the cTnI mean level within 72 h including patients with elevated cTnI levels at >0.3 ng/mL (n = 2188 patients) and patients with nonelevated cTnI level (<0.04 ng/mL) (n = 3200). The cohorts were further stratified by less than 20% TBSA mild burn population and >20% TBSA severe burn population to replicate the severity of burns. The 30-day incidences of acute myocardial infarction (MI), sepsis, and mortality were investigated after the cohorts were propensity-matching balanced. The odds ratios (ORs) with 95% CI for MI were (9.829/7.081-13.645), sepsis (1.527/1.269-1.959), and mortality (2.586/2.110-3.170), respectively (P < .05). The groups that were further stratified into mild burn and severe burn had the following results: The mild burn ORs and 95% CI for MI was (6.237/3.986-9.785), sepsis (1.603/1.132-2.270), and mortality was (2.298/1.629-3.242). The severe burn cohort had ORs and 95% CI for MI (3.145/1.469-6.732), sepsis (0.993/0.555-1.777), and mortality (2.934/1.924-4.475). In conclusion, the patients with earlier elevated cTnI levels had worse outcomes of MI and mortality in both severe and mild burns.

THE RISKS OF FIRST ONSET PRIMARY HYPERTENSION DIAGNOSIS IN THERMAL-INJURED PATIENTS.

ABSTRACT: Introduction: Hypertension is a prevalent condition in the United States and leads to an increased risk of developing various comorbidities. However, the impact of new-onset hypertension after severe burns on patient outcomes is not known. We posit that hypertension onset after severe burn is associated with increased risk of developing comorbidities and mortality. Methods: Using the TriNetX database, burned patients diagnosed with essential hypertension after injury were compared with those who did not develop hypertension; neither had prior hypertension. Each cohort was grouped by sex, percent total body surface area (TBSA) burned, and age, then propensity matched for sex, race, ethnicity, and laboratory values. Outcomes assessed were acute kidney injury (AKI), hyperglycemia, heart failure, myocardial infarction (MI), and death. Results: Those diagnosed with hypertension after severe burn were 4.9 times more likely to develop AKI, 3.6 times for hyperglycemia, 5.3 times for heart failure, 4.7 times for acute MI, and 1.5 times for mortality. Sex analysis shows that men were at greater risk for AKI (1.5 times), heart failure (1.1 times), and death (1.4 times). Women were 1.3 times more likely to develop hyperglycemia. Percent TBSA burned grouping showed increased risk for all outcomes with increasing severity. Age grouping indicated an elevated risk of developing AKI, heart failure, acute MI, and death. Conclusion: New-onset hypertension diagnosis in severely burned patients is associated with acute kidney injury, heart failure, acute MI, and death. Overall, males, older patients, and those with a higher % TBSA burned are at a higher risk of developing these comorbidities.

The Utilisation of INR to identify coagulopathy in burn patients.

Studies conflict on the significance of burn-induced coagulopathy. We posit that burn-induced coagulopathy is associated with injury severity in burns. Our purpose was to characterize coagulopathy profiles in burns and determine relationships between % total burn surface area (TBSA) burned and coagulopathy using the International Normalized Ratio (INR). Burned patients with INR values were identified in the TriNetX database and analyzed by %TBSA burned. Patients with history of transfusions, chronic hepatic failure, and those on anticoagulant medications were excluded. Interquartile ranges for INR in the burned study population were 1.2 (1.0-1.4). An INR of ≥ 1.5 was used to represent those with burn-induced coagulopathy as it fell outside the 3rd quartile. The population was stratified into subgroups using INR levels <1.5 or ≥1.5 on the day of injury. Data are average ± SD analyzed using chi-square; p < .05 was considered significant. There were 7,364 burned patients identified with INR <1.5, and 635 had INR ≥1.5. Comparing TBSA burned groups, burn-induced coagulopathy significantly increased in those with ≥20% TBSA; p = .048 at 20-29% TBSA, p = .0005 at 30-39% TBSA, and p < .0001 for 40% TBSA and above. Age played a significant factor with average age for those with burn-induced coagulopathy 59 ± 21.5 years and 46 ± 21.8 for those without (p < .0001). After matching for age, TBSA, and demographics, the risk of 28 day-mortality was higher in those with burn-induced coagulopathy compared to those without (risk difference 20.9%, p < .0001) and the odd ratio with 95% CI is 4.45 (3.399-5.825). Investigation of conditions associated with burn-induced coagulopathy showed the effect of heart diseases to be significant; 53% of patients with burn-induced coagulopathy had hypertension (p < .0001). Burn-induced coagulopathy increases with %TBSA burned. The information gained firmly reflects a link between %TBSA and burn-induced coagulopathy, which could be useful in prognosis and treatment decisions.

Post-traumatic stress disorder in burn patients - A large database analysis.

INTRODUCTION: Post-traumatic stress disorder (PTSD) afflicts a significant portion of burn patients. This study aims to analyze the morbidity, prevalence, and treatment of PTSD in the burn population. METHODS: Using the TriNetX database, we identified burned patients > 18 years of age without (A) or with (B) a PTSD diagnosis. Patients were then stratified by percent of total body surface area (TBSA) burned. Morbidity and mortality was analyzed in each cohort. Prevalence and pharmacologic treatments for PTSD were analyzed from 2002 to 2022. RESULTS: PTSD incidence increased from 2.4% (n = 2281) in patients with < 10% to 3.1% (n = 542) in 10-30%, 7.4% (n = 285) in 30-59%, and 5.3% (n = 90) in > 60% TBSA burned. In patients with < 60% TBSA burned, PTSD diagnosis increased the risk of depression (p = <0.0003) and anxiety (p = <0.0001). In those with < 30% TBSA burned, PTSD diagnosis also increased risk of insomnia (p = <0.0001) and pruritus (p = 0.0211 for TBSA <10% and 0.0059 for TBSA 10-29%). PTSD diagnosis was associated with a decreased risk of mortality in patients with > 30% TBSA burned (p = 0.0179 for TBSA 30-59% and p = 0.0089 for TBSA >60%). From 2002 to 2022, the prevalence of PTSD in all burn patients was relatively stable between 2.2% and 3.2%. We found an increase in the use of serotonergic agents and prazosin for the treatment of PTSD during this timeframe. CONCLUSION: PTSD is not uncommon in the burn population, and those with burns and concomitant PTSD have an increased risk of morbidity. Screening and preventative measures to reduce morbidity and early implementation of care in burned patients with PTSD are indicated.

A retrospective analysis of mortality risk and immunosuppressive therapy for Stevens-Johnson Syndrome and toxic epidermal necrolysis syndrome using the TriNetX research network.

Stevens-Johnson Syndrome (SJS) and Toxic Epidermal Necrolysis (TEN) exist on a spectrum of autoimmune conditions which cause epidermal detachment and keratinocyte necrosis. Due to the rare incidence of these conditions, a dramatic heterogeneity in treatment algorithms exists. To better appreciate pharmacologic immunosuppressive therapies' impact on survival, the authors queried a multi-institutional data network. Data for this study was extracted from TriNetX Research Network, a platform that contains ICD-9/ICD-10 coding data from a consortium of international healthcare organizations. Seventy-one institutions were queried to identify adult patients diagnosed with SJS, TEN or SJS-TEN Overlap. Cohorts were created based on the therapy received: systemic steroids (SS), diphenhydramine (DH), cyclosporine (CS), intravenous immunoglobulin (IVIG), tumor necrosis factor alpha inhibitors (TNFαi), or a combination of treatments. Cohorts were then propensity matched with patients who received supportive care. Patients who only received one of the above treatments showed no significant reduction in 90-day mortality. Patients who received CS or IVIG as part of their multitherapy showed a significantly increased risk of death when compared to supportive care (CS: RR = 1.583, 95% CI [1.119, 2.240]; IVIG: RR = 2.132, 95% CI [1.485, 3.059]). Despite their frequent utilization, this study's analysis suggests that none of these therapies confer significant 90-day mortality survival over supportive care alone. These results highlight the heterogeneity of therapies and emphasize the need for critical prospective appraisal of their outcomes in SJS and TEN.

Patterns of antibiotic administration in patients with burn injuries: A TriNetX study.

BACKGROUND: In the advent of increasing antibiotic resistance, several studies sought to determine antibiotic prescription trends; however, no pattern has been firmly identified particularly for the burned population. We performed a query of burned patients in a large established database to understand differences in antibiotic use related to patient-specific factors. METHODS: Burned patients with systemic antibiotics given within 7 days of injury were identified on the TriNetX database. The patient population was stratified by age, 1-year time intervals of antibiotic prescription from 2004 to 2019, time of antibiotic prescription in 1-day intervals after injury, and % TBSA burned in 10% intervals ranging from < 10% to > 90%. Data were analyzed using χ2 with p < 0.05 considered significant. Pearson coefficients (r2) values were used to correlate differences in antibiotic prescription between age groups and to changes over time. RESULTS: Stratification by age revealed higher use of antibiotics in older burned patients compared to younger patients. Surprisingly, 87.6% of burn patients of those who received antibiotic therapy was on the day of injury. Penicillins and beta-lactam antimicrobials were used most often at a frequency of 64%. No statistically significant differences in rates of antibiotic therapy were observed in burned patients when stratified by %TBSA burned. CONCLUSIONS: The study elucidates current patterns of antibiotic use in burn care in the United States, allowing for improved understanding of both past and present patterns of antibiotic prescription.

Comparing the Effectiveness of Glucocorticoids in Preventing Hypertrophic Scar Diagnosis in Burn Patients.

Background and Objectives: The prevalence of hypertrophic scarring after a burn is approximately 70%. Despite advances in burn management, there is currently no gold standard treatment to reduce or prevent its occurrence. Glucocorticoids are frequently given to patients early after burns for other therapeutic purposes and have been shown to induce scar regression. Therefore, the purpose of the present work is to determine the incidence of hypertrophic scar diagnosis in burn patients who were administered glucocorticoid treatment using TriNetX, a large patient database. Materials and Methods: Patients diagnosed with hypertrophic scarring, hypertrophic disorders of the skin, or scar conditions and fibrosis of the skin after burn injury were identified in the TriNetX database. The glucocorticoids investigated include hydrocortisone, methylprednisolone, dexamethasone, triamcinolone, and prednisone. Patients were stratified into three groups based on total body surface area (TBSA) burned: 0-19%, 20-39%, and 40-100%. The risk ratio was evaluated for burn patients who received varying glucocorticoids after injury based on TBSA burned. Additionally, treatment pathways, time of treatment, and treatment purity pathways were evaluated. Results: In patients with a 0-19% TBSA burn, methylprednisolone showed a decreased risk of developing hypertrophic scar diagnosis. In those with a 20-39% TBSA burn or 40-100% TBSA burn, dexamethasone showed an increased risk of developing hypertrophic scar diagnosis. Additionally, dexamethasone was the most commonly administered glucocorticoid for burn patients and was most likely to be administered earlier after burn injury, comparatively. Conclusions: Methylprednisolone was associated with reduced hypertrophic scar diagnosis in burn patients independent of TBSA burn. While glucocorticoids are one of the mainstay treatments for hypertrophic scarring, further studies are needed to determine early therapeutic interventions that will reduce the potential for hypertrophic scar development in burn patients.

Opioid prescription and opioid disorders in burns: A large database analysis from 1990 to 2019.

BACKGROUND: Opioids remain crucial in the management of burn pain. A comprehensive analysis of opioid use in burns and their complications has not been investigated. METHODS: Data were collected from TriNetX, a large multicenter database with de-identified patient information. The population included patients prescribed opioids on or following burn injury from January 1st, 1990, to December 31st, 2019. Opioid prescription use was analyzed after cohort stratification by decades: 1990-1999, 2000-2009, and 2010-2019. Outcomes for opioid-related disorders, opioid dependence, opioid abuse, intentional self-harm, and mental and behavioral disorders from psychoactive substance use were investigated. RESULTS: Hydrocodone was the most frequently prescribed opioid in 1990-1999 and 2000-2009, with oxycodone taking the lead in 2010-2019 (p < 0.0001). During 1990-1999, patients had a decreased risk of recorded opioid-related disorders (RR=0.52), opioid dependence (RR=0.46), opioid abuse (RR=0.55), mental and behavioral disorders (RR=0.88), and intentional self-harm (RR=0.37) when compared to 2000-2009. A comparison of the 2000-2009-2010-2019 cohorts showed an increased risk of recorded opioid-related disorders (RR= 1.91), opioid dependence (RR=1.56), opioid abuse (RR=1.67), mental and behavioral disorders (RR =1.73), and intentional self-harm (RR=2.02). CONCLUSIONS: The risk of opioid-related disorders has nearly doubled since the year 2000 warranting precautions when prescribing pain medications to burn patients.

Pre-existing skin diseases as predictors of post-burn pruritus.

BACKGROUND: Post-burn pruritus (PBP) has been shown to adversely affect burn patients' quality of life. However, the predictors of PBP are not known. We hypothesize a pre-existing pruritic skin diagnosis is associated with an increased risk of adverse outcomes following a burn injury. METHODS: This retrospective study utilized data from the TriNetX electronic health record. Burn patients with a history of a pruritic skin disorder were compared to patients without a diagnosed skin disorder and the occurrence of pruritus was compared between the two cohorts. RESULTS: Patients with pre-existing skin conditions were more likely to develop PBP. The risk of PBP was highest 1 year after injury. Stratification by percent TBSA burned, gender, race, and age showed an increased risk of PBP for females, Caucasians, older patients, and those with large burns. CONCLUSION: A pre-existing pruritic skin diagnosis is highly associated with developing pruritus following a burn injury.

Early wound excision within three days decreases risks of wound infection and death in burned patients.

INTRODUCTION: In lieu of limited studies on the timing of burn wound eschar excision for burns, a more comprehensive analysis is indicated to determine the effects of early wound excision following burns. This study aims to address the outcomes of early wound excision in burn patients. METHODS: Data collection were from TriNetX research database. Three groups of burn patients were stratified by the number of days in which they received burn wound excision within 14 days of injury. Five outcomes were observed: death, wound infection, sepsis, myocardial contractile dysfunction, and blood transfusion. Risk and incidence of various health outcomes were compared between the groups after propensity-matching age, sex, ethnicity, race and burn size using a z-test with p < 0.05 considered significant. RESULTS: We identified 6158 burn patients with wound excision within 14 days of injury, the majority of whom (60.1%) received burn wound excision between 0 and 3 days after burn. 72.5% of patients had burns covering less than 20% of total body surface area. After propensity matching, we found a significantly lower risk of mortality in those who received burn wound excision within the first three days (3.84%) as compared to 8-14 days after burn (6.09%) (p < 0.05). Moreover, we found a decreased risk of wound infection in patients with burn wound excision within 0-3 days (37.84%) compared to those 4-7 days (42.48%) (p < 0.05). No statistical difference was detected in propensity-matched groups for myocardial contractile dysfunction, blood transfusion, or sepsis. In addition, the risk of hypertrophic scaring significantly decreased when wound excision was performed within 0-3 days (22% within 0-3 days, 28% within 4-7 days, p < 0.05). CONCLUSION: Burn wound excision within 3 days of injury is beneficial when comparing to later treatment between 4 and 14 days, which results in a significantly lowered risk of mortality and infection in burn patient.

Impact of pre-burn statin use on metabolic and cardiovascular disorders.

INTRODUCTION: Statins are among the most widely prescribed medications with proven effectiveness in patients with hyperlipidemia and atherosclerotic cardiovascular diseases. We investigated the relationship between statin use, metabolic and cardiovascular outcomes after burn. METHODS: We utilized data from the TriNetX electronic health database. Burn patients with prior statin use were compared to patients without prior use and analyzed the occurrence of metabolic and cardiovascular disorders. RESULTS: Prior statin use burn patients were 1.33 times as likely to develop hyperglycemia, 1.20 times for cardiac arrhythmia, 1.70 times for coronary artery disease (CAD), 1.10 times for sepsis, and 0.80 times for death. High percent TBSA burn, male sex, and lipophilic statin use were associated with higher odds of outcome development. CONCLUSION: Prior statin use in severely burned patients is associated with an increased risk of developing hyperglycemia, arrhythmias, and CAD, with higher odds in males, higher TBSA burn, and lipophilic statin users.

C-reactive protein elevation is associated with increased morbidity and mortality in elderly burned patients.

BACKGROUND: C-reactive protein (CRP) is an acute-phase protein produced in response to inflammation after traumatic injury. We posit that C-reactive protein (CRP) is reliable in predicting morbidity and mortality following severe burn. In this study, we explored the relationship between serum CRP values and clinical outcomes in the severely burned. METHODS: Using the Research Network within the TriNetX database, we queried de-identified burn patient data across the United States and enrolled 36,556 burn patients with reported CRP values from 2006 to 2020. RESULTS: Circulating CRP levels were elevated significantly in patients ≥60 years as well as in males and African Americans (p < 0.05). CRP levels reached the zenith on the first day after burn, and were highest when burn size reached 60% total body surface area (TBSA). After bisecting the data at 10 mg/L of CRP, we compared clinical findings between patient groups (n = 16,284/18,647 in high/low CRP levels). The risk of patient death doubled in the high CRP group from 4.687% to 9.313%, with higher incidences of sepsis, skin infection, and myocardial infarction (p < 0.05). Moreover, mortality increased from 0.9% to 1.926% in those younger than 20 years when comparing the low and high CRP groups, whereas mortality significantly increased from 8.84% to 15.818% in those ≥60 years old (p < 0.05). Both elderly and paediatric groups had significant increases in the diagnosis of sepsis-associated with increased CRP expression. However, incidences of skin infection, pneumonia, and acute kidney injury increased significantly only in the elderly group (p < 0.05). CONCLUSION: Elevated CRP expression is common in burn patients. The factor of age influenced the association of CRP expression to clinical outcomes.

Skeletal muscle transcriptome is affected by age in severely burned mice.

Severe burn results in muscle wasting affecting quality of life in both children and adults. Biologic metabolic profiles are noticeably distinctive in childhood. We posit that muscle gene expression profiles are differentially regulated in response to severe burns in young animals. Twelve C57BL6 male mice, including young (5 weeks-old) and adults (11 weeks-old), received either scald burn, or sham procedure. Mouse muscle tissue was harvested 24 h later for Next Generation Sequence analysis. Our results showed 662 downregulated and 450 upregulated genes in gastrocnemius of young mice compared to adults without injury. After injury, we found 74/75 downregulated genes and 107/128 upregulated genes in both burned groups compared to respective uninjured age groups. VEGFA-VEGFR2, focal adhesion, and nuclear receptor meta-pathways were the top 3 gene pathways undergoing a differential change in response to age. Of note, the proteasome degradation pathway showed the most similar changes in both adult and young burned animals. This study demonstrates the characteristic profile of gene expression in skeletal muscle in young and adult burned mice. Prominent age effects were revealed in transcriptional levels with increased alterations of genes, miRNAs, pathways, and interactions.

Therapeutic Strategies to Reduce Burn Wound Conversion.

Burn wound conversion refers to the phenomenon whereby superficial burns that appear to retain the ability to spontaneously heal, convert later into deeper wounds in need of excision. While no current treatment can definitively stop burn wound conversion, attempts to slow tissue damage remain unsatisfactory, justifying the need for new therapeutic interventions. To attenuate burn wound conversion, various studies have targeted at least one of the molecular mechanisms underlying burn wound conversion, including ischemia, inflammation, apoptosis, autophagy, generation of reactive oxygen species, hypothermia, and wound rehydration. However, therapeutic strategies that can target various mechanisms involved in burn wound conversion are still lacking. This review highlights the pathophysiology of burn wound conversion and focuses on recent studies that have turned to the novel use of biologics such as mesenchymal stem cells, biomaterials, and immune regulators to mitigate wound conversion. Future research should investigate mechanistic pathways, side effects, safety, and efficacy of these different treatments before translation into clinical studies.

Galunisertib Exerts Antifibrotic Effects on TGF-ß-Induced Fibroproliferative Dermal Fibroblasts.

Dermal fibroblasts in pathological scars secrete constitutively elevated levels of TGF-ß, signaling the transcription of fibrotic genes via activin-like kinase 5 (ALK5). In the present study, we examine the antifibrotic effects of galunisertib, a small-molecule inhibitor of ALK5, on fibroproliferative dermal fibroblasts in an in vitro model of wound healing. We induced fibrosis in human dermal fibroblasts with exogenous TGF-ß and performed cellular proliferation assays after treatment with varying concentrations of galunisertib. Dermal fibroblast proliferation was diminished to homeostatic levels without cytotoxicity at concentrations as high as 10 µM. An in vitro scratch assay revealed that galunisertib significantly enhanced cellular migration and in vitro wound closure beginning 24 h post-injury. A gene expression analysis demonstrated a significant attenuation of fibrotic gene expression, including collagen-1a, alpha-smooth muscle actin, fibronectin, and connective tissue growth factor, with increased expression of the antifibrotic genes MMP1 and decorin. Protein synthesis assays confirmed drug activity and corroborated the transcription findings. In summary, galunisertib simultaneously exerts antifibrotic effects on dermal fibroblasts while enhancing rates of in vitro wound closure. Galunisertib has already completed phase II clinical trials for cancer therapy with minimal adverse effects and is a promising candidate for the treatment and prevention of pathological cutaneous scars.

Higher risk of acute kidney injury and death with rhabdomyolysis in severely burned patients.

BACKGROUND: Rhabdomyolysis is a severe condition responsible for up to 10% of acute kidney injury (AKI) cases. Severely burned patients are susceptible to developing both rhabdomyolysis and acute kidney injury, but whether burned patients with rhabdomyolysis are at greater risk of acute kidney injury compared to non-burned patients with rhabdomyolysis is unclear. METHODS: TriNetX, a clinical research platform, was used to obtain electronic medical record information in 3 patient cohorts over the recent 20-year period. Cohort 1 included burn patients who developed rhabdomyolysis, cohort 2 were those who developed rhabdomyolysis due to non-burn causes, and cohort 3 included burn patients who did not develop rhabdomyolysis. Matching was performed to balance demographics and comorbidities for each cohort. Cohorts were then compared for the development of acute kidney injury and death. RESULTS: We found 84 of 111 patients in cohort 1 (75.676%), 56 of 111 patients in cohort 2 (50.45%), and 18 of 111 patients in cohort 3 (16.216%) developed acute kidney injury within 5 days. The odds ratio for developing acute kidney injury for burned patients compared to non-burned patients with rhabdomyolysis was 3.056 with a 95% confidence interval of 1.726 to 5.41 (P < .05), and between burned patients with and without rhabdomyolysis was 16.074 with a 95% confidence interval of 8.263 to 31.268 (P < .05). The incidence of death within 1 year was also significantly higher in cohort 1 (48%) than the other cohorts (9% and 14%, respectively) (P < .05). CONCLUSION: The risk of acute kidney injury and mortality in severely burned patients with rhabdomyolysis is significantly increased compared to matched non-burn patients with rhabdomyolysis or burned patients without rhabdomyolysis.

Role of Exosomes in Dermal Wound Healing: A Systematic Review.

Cell-based therapy imparts its therapeutic effects through soluble GFs and vesicular bodies such as exosomes. A systematic review with a meta-analysis of preclinical studies was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses and the modified Stroke Therapy Academic Industry Roundtable guidelines to identify exosomes as an archetype biological therapy for dermal wound healing and to provide guidelines for the concentrations to be used in preclinical studies. A total of 51 rodent studies were included in the systematic review and 9 were included in the meta-analysis section. Three independent reviewers cross-screened eligibility and selected studies for quality assessment from 3,064 published studies on exosomes and wound healing. The mean quality scores for all studies were 5.08 ± 0.752 and 5.11 ± 1.13 for systematic review and meta-analysis, respectively. Exosome effects were reported to have the highest efficacy at 7 days (OR = 1.82, 95% confidence interval = 0.69‒2.95) than at 14 days (OR = 2.29, 95% confidence interval = 0.01‒4.56) after administration. Exosomes were reported to regulate all phases of skin wound healing, mostly by the actions of circulating microRNA. The outcome of this review may be used to guide preclinical and clinical studies on the role of exosomes in wound healing.