FireSync EMS: A Novel Mobile Application for Burn Surface Area Calculation.

The percent total body surface area burned is a critical determinant of the required level of care, initial management, and prognosis in burn patients. The current gold standard for estimating this measurement, the Lund-Browder chart, requires familiarity with its construction and may not be practical for use by first responders in the field. In this study, we present a novel burn surface area calculator mobile application developed for first responders and validate its accuracy. Infant, pediatric, and adult manikins were fabricated with eight simulated burns of varying sizes and distributions. 42 pre-clinical medical students and firefighters were tasked with estimating the total body surface area of each burn using both the FireSync-EMS app and Lund-Browder chart. Univariate analysis and mixed-effects linear regression modeling were performed to compare the accuracy of both methods in relation to user experience, manikin size, and burn size. FireSync-EMS significantly reduced overestimation bias (0.11%, SD 2.33 versus 0.91%, SD 4.12, p = 0.002), particularly for burns on child-size manikins (p < 0.001) and burns involving <10% (p = 0.005) and >20% (p = 0.030) total body surface area. Multivariable modeling revealed that the Lund-Browder chart was an independent determinant of the magnitude of estimation error, with a 1.19 times multiplicative effect relative to FireSyncEMS (p < 0.001). Participants overwhelmingly found FireSync-EMS easier, more intuitive, faster, and preferable (p < 0.001 for all). FireSync-EMS may be an easier, faster, and more accurate alternative to the Lund-Browder chart for estimation of the total body surface area burned.

Navigating Scar Care: An Evaluation of Scar Treatment Patient Education Materials.

While patient education materials (PEMs) across various specialties have been reported as being too difficult to read, the quality and understandability of PEMs related to scar management have not been assessed. In this study, we report the breadth of scar management interventions and readability of online PEMs authored by academic societies and university hospitals. Websites of academic medical societies and university hospitals with scar revision PEMs were assessed for relevance. PEM readability was assessed via Flesch Reading Ease, Flesch-Kincaid Grade Level, and Gunning-Fox Index scores. Understandability and actionability were evaluated using the Patient Education Material Assessment Tool (PEMAT). A total of 26 scar revision PEMs met the inclusion criteria. The most commonly mentioned scar management interventions were scar revision surgery (73%) and laser scar revision (70%), with minimal emphasis on non-invasive methods like scar massage or sun protection. Readability analysis yielded a mean Flesch reading level of 8.8. Overall PEMAT understandability of online scar treatment PEMs was moderate, with a median of 76.0% (IQR 71.5 - 80.5%). PEMs from all specialties and institution types were lacking in actionability, with median actionability of 40.8% (IQR 38.1-60.0%). Online scar revision PEMs included a wide breadth of scar management interventions, however the least costly interventions of sun protection and scar massage were not commonly included. PEMs for scar management could be improved by simplifying language, including visual aids, and including checklists or specific steps patients can take to take action on scar management interventions.

Analyzing Burn-Related Content on Social Media Platforms: A Study of Creator Types, Content Focus, and Engagement Metrics.

Social media offers a readily available, cost-effective way for medical experts to disseminate knowledge and shape public health outcomes but also allows for the spread of misinformation. This study aims to analyze burn-related material on social media by creator, content type, and engagement. Facebook, TikTok, and X (formerly Twitter) were queried with the following search terms: "burn," "burn injury," "burn recovery," and "burn treatment." Identified accounts were then manually screened for relevance. Year of creation and engagement metrics were collected. Accounts were categorized by content and creator type. Data was reported using descriptive statistics and visualized graphically to explore trends. Our search yielded 434 profiles, 234 of which met inclusion criteria. TikTok had the most engagement at a median of 43,500 followers per account, with 38.3% of accounts focusing on individual experiences of burn survivors primarily on personal accounts (48.3%). In contrast, content on Facebook was related to promotion of medical services (36.9%), where the most represented creator type was medical centers (33.6%). Nonprofits made up 40.4% of accounts on Twitter/X and more than a third of the content focused on patient advocacy, support, or burn prevention (36.5%). Important topics like burn education, prevention, and social support are lacking on major social media platforms. Engagement from burn care organizations and burn experts on social media is necessary. The findings of this study may guide advocates in the burn community on where and how to disseminate information in social media.

Surgical Management of Diabetic Foot Burns is Associated with Poor Outcomes: A Systematic Review and Meta-Analysis.

There is no consensus for the optimal management of diabetic foot burn injuries. Here, we systematically identify studies reporting on diabetic foot burns and evaluate outcomes among patients managed operatively versus non-operatively. PubMed, Embase, and Web of Science were searched. Screening was performed by independent reviewers. Primary research studies with English full texts published between 1980 to 2023 that discussed outcomes of foot burns in adults with diabetes were included and critically appraised using validated tools. Results are presented using descriptive statistics of aggregated data. The search yielded 2,402 non-duplicate papers, of which 35 met inclusion criteria. Nine papers were included for meta-analysis, including seven retrospective comparative analyses, one cross-sectional study, and one retrospective chart review. There were 1798 diabetic foot burn patients. Mean age was 58.2 years (SD 4.12) and 73.1% (n = 1,314) were male. A total of 15.7% (n = 283) of patients were surgically managed, including debridement (3.7%, n = 66), grafting (8.2%, n = 147), flap (0.2%, n = 3), and primary amputation (7.1%, n = 127). Secondary amputation rate, defined as amputation following initial surgery, was 4.9%, (n = 14). The overall amputation rate was 7.8% (n = 141). Other complications included infection (4.0%, n = 72), osteomyelitis (1.9%, n = 34), and graft failure (8.2%, n = 12). One study reported functional status at last visit. Diabetic foot burns are highly morbid. The surgical management of these complex injuries is high risk, as amputation results in poorer quality of life and functional outcomes.

Prominin-1 promotes restitution of the murine extrahepatic biliary luminal epithelium following cholestatic liver injury.

BACKGROUND AND AIMS: Restitution of the extrahepatic biliary luminal epithelium in cholangiopathies is poorly understood. Prominin-1 (Prom1) is a key component of epithelial ciliary body of stem/progenitor cells. Given that intrahepatic Prom1-expressing progenitor cells undergo cholangiocyte differentiation, we hypothesized that Prom1 may promote restitution of the extrahepatic bile duct (EHBD) epithelium following injury. APPROACH AND RESULTS: Utilizing various murine biliary injury models, we identified Prom1-expressing cells in the peribiliary glands of the EHBD. These Prom1-expressing cells are progenitor cells which give rise to cholangiocytes as part of the normal maintenance of the EHBD epithelium. Following injury, these cells proliferate significantly more rapidly to re-populate the biliary luminal epithelium. Null mutation of Prom1 leads to significantly >10-fold dilated peribiliary glands following rhesus rotavirus-mediated biliary injury. Cultured organoids derived from Prom1 knockout mice are comprised of biliary progenitor cells with altered apical-basal cellular polarity, significantly fewer and shorter cilia, and decreased organoid proliferation dynamics consistent with impaired cell motility. CONCLUSIONS: We, therefore, conclude that Prom1 is involved in biliary epithelial restitution following biliary injury in part through its role in supporting cell polarity.

TWEAK/FN14 promotes profibrogenic pathway activation in Prominin-1-expressing hepatic progenitor cells in biliary atresia.

BACKGROUND AND AIMS: Biliary atresia (BA), a congenital cholestatic liver disease, commonly culminates in end-stage liver disease. We previously demonstrated in BA that Prominin-1 ( Prom1 )-expressing hepatic progenitor cells (HPCs) expand within regions of developing fibrosis, giving rise to cholangiocytes within biliary ductular reactions. Null mutation of Prom1 or ablation of cells expressing Prom1 significantly diminishes fibrogenesis. FN14, the receptor for TNF-like weak inducer of apoptosis (TWEAK), is expressed by HPCs. TWEAK/FN14 signaling promotes fibrosis in multiple organ systems. Therefore, we hypothesized that TWEAK/FN14 signaling mediates Prom1 -expressing HPC proliferation leading to profibrogenic ductular reactions in BA. APPROACH AND RESULTS: The experimental mouse model of BA mediated by perinatal rhesus rotavirus (RRV) infection resulted in increased co-expression of Fn14 in Prom1 -expressing HPCs within regions of ductular reactions. FN14 antagonist L524-0366 decreased ductular reactions, biliary fibrosis and periportal fibroblast activation in RRV injury. L524-0366 inhibition also demonstrated loss of downstream noncanonical NF-kB signaling expression in RRV injury. Murine HPC organoids demonstrated accelerated organoid growth and proliferation when treated with recombinant TWEAK. Increased organoid proliferation with recombinant TWEAK was lost when also treated with L524-0366. Analysis of a large publicly available RNA sequencing database of BA and normal control patients revealed significant increases in expression of PROM1 , FN14 , and genes downstream of TNF signaling and noncanonical NF-κB signaling pathways in BA infants. Infants who failed to achieve bile drainage after hepatoportoenterostomy had higher relative levels of FN14 expression. CONCLUSION: TWEAK/FN14 signaling activation in Prom1 -expressing HPCs contributes to proliferation of profibrogenic ductular reactions in BA.

Prominin-1-expressing hepatic progenitor cells induce fibrogenesis in murine cholestatic liver injury.

Cholestatic liver injury is associated with intrahepatic biliary fibrosis, which can progress to cirrhosis. Resident hepatic progenitor cells (HPCs) expressing Prominin-1 (Prom1 or CD133) become activated and participate in the expansion of cholangiocytes known as the ductular reaction. Previously, we demonstrated that in biliary atresia, Prom1(+) HPCs are present within developing fibrosis and that null mutation of Prom1 significantly abrogates fibrogenesis. Here, we hypothesized that these activated Prom1-expressing HPCs promote fibrogenesis in cholestatic liver injury. Using Prom1CreERT2-nLacZ/+ ;Rosa26Lsl-GFP/+ mice, we traced the fate of Prom1-expressing HPCs in the growth of the neonatal and adult livers and in biliary fibrosis induced by bile duct ligation (BDL). Prom1-expressing cell lineage labeling with Green Fluorescent Protein (GFP) on postnatal day 1 exhibited an expanded population as well as bipotent differentiation potential toward both hepatocytes and cholangiocytes at postnatal day 35. However, in the adult liver, they lost hepatocyte differentiation potential. Upon cholestatic liver injury, adult Prom1-expressing HPCs gave rise to both PROM1(+) and PROM1(-) cholangiocytes contributing to ductular reaction without hepatocyte or myofibroblast differentiation. RNA-sequencing analysis of GFP(+) Prom1-expressing HPC lineage revealed a persistent cholangiocyte phenotype and evidence of Transforming Growth Factor-ß pathway activation. When Prom1-expressing cells were ablated with induced Diphtheria toxin in Prom1CreERT-nLacZ/+ ;Rosa26DTA/+ mice, we observed a decrease in ductular reactions and biliary fibrosis typically present in BDL as well as decreased expression of numerous fibrogenic gene markers. Our data indicate that Prom1-expressing HPCs promote biliary fibrosis associated with activation of myofibroblasts in cholestatic liver injury.

Helical antimicrobial peptides assemble into protofibril scaffolds that present ordered dsDNA to TLR9.

Amphiphilicity in ɑ-helical antimicrobial peptides (AMPs) is recognized as a signature of potential membrane activity. Some AMPs are also strongly immunomodulatory: LL37-DNA complexes potently amplify Toll-like receptor 9 (TLR9) activation in immune cells and exacerbate autoimmune diseases. The rules governing this proinflammatory activity of AMPs are unknown. Here we examine the supramolecular structures formed between DNA and three prototypical AMPs using small angle X-ray scattering and molecular modeling. We correlate these structures to their ability to activate TLR9 and show that a key criterion is the AMP's ability to assemble into superhelical protofibril scaffolds. These structures enforce spatially-periodic DNA organization in nanocrystalline immunocomplexes that trigger strong recognition by TLR9, which is conventionally known to bind single DNA ligands. We demonstrate that we can "knock in" this ability for TLR9 amplification in membrane-active AMP mutants, which suggests the existence of tradeoffs between membrane permeating activity and immunomodulatory activity in AMP sequences.

Prominin-1 Promotes Biliary Fibrosis Associated With Biliary Atresia.

In patients with biliary atresia (BA), the extent of intrahepatic biliary fibrosis negatively correlates with successful surgical bypass of the congenital cholangiopathy as well as subsequent transplant-free survival. We recently linked the expansion of a population of prominin-1 (Prom1)-expressing hepatic progenitor cells to biliary fibrogenesis. Herein, we hypothesized that Prom1-expressing progenitor cells play a role in BA-associated fibrosis. Rhesus rotavirus (RRV)-mediated experimental BA was induced in newborn mice homozygous for the transgene Prom1cre-ert2-nlacz , which was knocked in to the Prom1 gene locus, thus creating functional Prom1 knockout (KO) mice, and their wildtype (WT) littermates. Clinical data and tissue samples from BA infants from the Childhood Liver Disease Research Consortium were analyzed. Extrahepatic biliary obliteration was present in both WT and KO mice; there was no difference in serum total bilirubin (TBili) levels. The intrahepatic periportal expansion of the PROM1pos cell population, typically observed in RRV-induced BA, was absent in KO mice. RRV-treated KO mice demonstrated significantly fewer cytokeratin-19 (CK19)-positive ductular reactions (P = 0.0004) and significantly less periportal collagen deposition (P = 0.0001) compared with WT. RRV-treated KO mice expressed significantly less integrin-ß6, which encodes a key biliary-specific subunit of a transforming growth factor (TGF) ß activator (P = 0.0004). Infants with successful biliary drainage (Tbili ≤1.5 mg/dL within 3 months postoperatively), which is highly predictive of increased transplant-free survival, expressed significantly less hepatic PROM1, CK19, and COLLAGEN-1α compared with those with TBili >1.5 (P < 0.05). Conclusion: Prom1 plays an important role in biliary fibrogenesis, in part through integrin-mediated TGF pathway activation.