ObjectivesIdiopathic subglottic stenosis (iSGS) is characterized by progressive fibrosis and subglottic luminal narrowing. Currently, immune characterization has focused on T‐cells; however, macrophages remain largely unexplored. The goals of this study are to characterize the transcriptome of iSGS macrophages and the fibrogenic nature of identifed biomarkers.Study DesignBioinformatics and in vitro.MethodsHuman tracheal biopsies from iSGS scar (n = 4), and matched non‐scar (n = 4) regions were analyzed using single‐cell RNA‐seq (scRNA‐seq). Immunofluorescence (IF) was performed on rapidly processed autopsies (RPA) and iSGS tracheal resections (n = 4) to co‐localize S100A8/9 and CD11b. Collagen gene/protein expression was assessed in iSGS fibroblasts (n = 4) treated with protein S100A8/9 (1000 ng/ml). Macrophages were subclustered to identify distinct subpopulations.ResultsscRNA‐seq analysis revealed S100A8/S100A9 (fold change (FC) = 4.1/1.88, p < 0.001) as top differentially expressed genes in iSGS macrophages. IF exhibited increased CD11b+/S100A8/9+ cells in tracheal samples of iSGS versus RPA (26.75% ± 7.08 vs. 0.594% ± 0.974, n = 4, p = 0.029). iSGS fibroblasts treated with S100A8/9 demonstrated increased gene expression of COL1A1 (FC = 2.30 ± 0.45, p = 0.03, n = 4) and COL3A1 (FC = 2.44 ± 0.40, p = 0.03, n = 4). COL1A1 protein assays revealed an increase in the experimental group, albeit not significant, (p = 0.12, n = 4). Finally, macrophage sub clustering revealed one subpopulation as a predominant source of S100A8/S100A9 expression (FC = 7.94/5.47, p < 0.001).ConclusionsS100A8/9 is a key biomarker in iSGS macrophages. Although S100A8/9 demonstrates profibrotic nature in vitro, the role of S100A8/9+ macrophages in vivo warrants further investigation.Level of EvidenceNA Laryngoscope, 133:2308–2316, 2023
Introduction Burn injuries are well known to cause a state of immunosuppression in patients. This can result in wound infections, a common complication in burn injuries, that can lead to sepsis and increased mortality. Human immunodeficiency virus (HIV) is also known to cause immunosuppression in patients. The outcomes of burn patients with pre-existing HIV infections, however, are not yet completely understood. We conducted a systematic review and meta-analysis to compare the outcomes of burn patients with pre-existing HIV against those without this chronic infection. Methods We searched MEDLINE (Pubmed), Google Scholar, Scopus, and Embase for studies that compared outcomes and complications between burn patients with and without HIV. From this search, we screened 445 articles. Through our selection criteria, five articles focusing on HIV patients were selected for systematic review and meta-analysis. Data were analyzed using the Cochrane Review Manager (RevMan) Data Analysis package to produce pooled odds ratios and mean differences from the random effect model. Results Five studies observing a total of 24,419 burn patients, published between 2000 and 2017, were included. Of these, two are prospective studies and three are retrospective chart reviews. The primary outcome of mortality for HIV+ patients compared to HIV- patients had an odds ratio of 2.04 (CI= 0.46–9.14) in the random effects model. Secondary outcomes of sepsis and wound infection odds ratios were 1.47 (CI= 0.44–4.99) and 1.10 (CI= 0.28–4.25), respectively. The length of stay (LOS) between studies showed an overall mean difference of 0.95 (CI=-8.08–9.99). Most studies had a greater proportion of male patients. TBSA between studies ranged from 13.1% and 35%. Conclusions From our results, we concluded that HIV+ had a tendency toward greater mortality (OR=2.04) and sepsis (OR=1.47). However, mortality and sepsis had confidence intervals of [0.46–9.14] and [0.44–4.99], respectively. Therefore, we cannot definitively state that HIV infection is responsible for greater mortality or sepsis in burn patients. Additionally, LOS analysis also showed a wide confidence interval [-8.08–9.99], preventing us from making reliable deductions about this outcome. We believe further research is needed before universal conclusion or recommendations are appropriate.
Introduction This is a systematic review which seeks to establish if immediate/ultra-early excision (immediate: < 24 hours, ultra-early: 24 - 72 hours) and grafting is better or equivalent to early excision and grafting (early: 72 hours - 6 days) in adults with major burns. The concept of early excision and grafting, as opposed to late excision (late: >7 days), was introduced by Cope et al. and later popularized by Janzekovic in the 1970s when she introduced the concept of tangential excision. Delaying excision 24 to 48 hours has previously been thought to allow resuscitation and correction of physiologic derangements to optimize outcomes. However, timing for excision and grafting is subject to debate. The outcomes of interest include mortality, length of stay, complication rates, wound healing time, infection rates, physiologic demand, blood loss, and resting energy expenditure. Methods In this systematic review, we searched PubMed, Embase, CINAHL, Cochrane, Web of Science, and Scopus for studies that compared outcomes and complications between burn patients with ultra-early and early excisions. From this search, we screened 4235 articles. Through our selection criteria, five articles focusing on timing of burn excision were selected for systematic review. Results Five studies observing a total of 382 burn patients, published between 1995 and 2016, were included. All five studies are cohort studies, three were prospective studies while two were retrospective chart reviews. Two studies showed decreased length of stay with immediate/ultra-early excision (Still, Keshavarzi) and decreased time to healing with immediate/ultra-early excision (Guo, Lu). One study demonstrated decreased infection and mortality in ultra-early excision (Keshavarzi). One study demonstrated decreased resting energy expenditure in the ultra-early excision group (Gao). One study showed a decrease in blood transfusion in the immediate/ultra-early excision group (Guo). Both the Guo and Gao studies suggest that concerns over excision during the burn shock period may be unfounded provided that the patient is adequately resuscitated. Conclusions Studies investigating the immediate/ultra-early excision of burns tend to show improved outcomes for adults with major burns. It is difficult to attain conclusive data due to the lack in overlap of reported outcomes in modern studies. More studies are needed which compare outcomes in adults with major burns between immediate/ultra-early excision and early excision.
ObjectivesTo aim of the study was to characterize the molecular profile and functional phenotype of idiopathic subglottic stenosis (iSGS)‐scar epithelium.MethodsHuman tracheal biopsies from iSGS scar (n = 6) and matched non‐scar (n = 6) regions were analyzed using single‐cell RNA sequencing (scRNA‐seq). Separate specimens were used for epithelial cell expansion in vitro to assess average growth rate and functional capabilities using transepithelial‐electrical resistance (TEER), fluorescein isothiocyanate‐dextran flux permeability assay, ciliary coverage, and cilia beating frequency (CBF). Finally, epithelial tight junction protein expression of cultured cells was quantified using immunoblot assay (n = 4) and immunofluorescence (n = 6).ResultsscRNA‐seq analysis revealed a decrease in goblet, ciliated, and basal epithelial cells in the scar iSGS cohort. Furthermore, mRNA expression of proteins E‐cadherin, claudin‐3, claudin‐10, occludin, TJP1, and TJP2 was also reduced (p < 0.001) in scar epithelium. Functional assays demonstrated a decrease in TEER (paired 95% confidence interval [CI], 195.68–890.83 Ω × cm2, p < 0.05), an increase in permeability (paired 95% CI, −6116.00 to −1401.99 RFU, p < 0.05), and reduced epithelial coverage (paired 95% CI, 0.1814–1.766, fold change p < 0.05) in iSGS‐scar epithelium relative to normal controls. No difference in growth rate (p < 0.05) or CBF was found (paired 95% CI, −2.118 to 3.820 Hz, p > 0.05). Immunoblot assay (paired 95% CI, 0.0367–0.605, p < 0.05) and immunofluorescence (paired 95% CI, 13.748–59.191 mean grey value, p < 0.05) revealed E‐cadherin reduction in iSGS‐scar epithelium.ConclusioniSGS‐scar epithelium has a dysfunctional barrier and reduced structural protein expression. These results are consistent with dysfunctional epithelium seen in other airway pathology. Further studies are warranted to delineate the causality of epithelial dysfunction on the downstream fibroinflammatory cascade in iSGS.Level of EvidenceNA Laryngoscope, 2023
Introduction Effective management of chronic burn-induced neuropathy manifesting as pain and/or pruritus presents an ongoing challenge for clinicians. Standards of care are based on limited evidence and vary widely, especially for non-surgical neuropathies that are not associated with a specific nerve distribution. This study aims to quantify and qualify evidence for non-surgical treatments of chronic burn-induced neuropathy to define their efficacy. Methods PRISMA and Cochrane guidelines were implemented for review structure. PubMed, Science Direct, Embase, Cochrane Library, and Web of Science databases were searched for relevant studies. Inclusion criteria were patients age 18 years and older, with neuropathy lasting >6 months following burn injury. Studies for inclusion were comparative intervention studies for treatments of chronic burn-induced neuropathies. Mean differences (MD) between interventions eligible for meta-analysis were analyzed for neuropathy outcomes. Results Seventeen randomized controlled trials (RCTs) were identified for inclusion with a mean post-burn follow-up of 20.8±39.3 months. Nine studies reported pain and sixteen reported pruritus using patient reported visual analogue scales for 601 and 975 patients, respectively. Pain interventions included transcranial direct current stimulation (tDCS), extracorporeal shockwave therapy (EWST), massage therapy, carbon dioxide (CO2) laser, silicone gel, and pressure therapy. Pruritus interventions included tDCS, ESWT, massage, herbal cream, doxepin cream, enzymatic moisturizer, CO2 laser, silicone gel, and pressure therapy. CO2 laser showed no improvement over standard care for the treatment of pain or pruritus associated with hypertrophic scarring (pain: MD 0.26, 95%CI -0.04, 0.57; p=0.09; pruritus: MD -0.07, 95%CI -0.44, 0.30; p=0.72). ESWT showed no statistically significant improvement over standard care for the treatment of pruritus (MD -2.69, 95%CI -5.42, 0.04; p=0.05). Massage therapy was associated with significantly greater improvements in pruritus than standard care (MD -1.64, 95%CI -2.10, -1.09; p< 0.00001). Doxepin cream was not associated with greater improvements in pruritus than placebo or antihistamines (MD -0.84, 95%CI -3.61, 1.94; p=0.56). Conclusions Creative efforts have revealed massage therapy as a potential non-surgical intervention for treating chronic burn-induced neuropathy. Additional RCTs with innovative non-surgical interventions will provide further insights for this challenging condition.
Introduction Patients with homelessness in the setting of burns experience more complications and longer lengths of stay (LOS), resulting in higher costs of care and recidivism rates, making appropriate screening and documentation critical to improving outcomes. However, the prevalence of housing instability and its effect on outcomes has not yet been studied. This study sought to describe the prevalence of housing insecurity, or homelessness and housing instability, in patients admitted to an urban burn intensive care unit (BICU) and compare their outcomes to their housed counterparts. Methods This is a retrospective cohort study of all adult patients admitted to our BICU over 3 years. The degree of burn injury and LOS were collected. We used the World Health Organization definitions of housing insecurity to identify patients. Physician and case management notes were used to evaluate housing status. Results There were 881 patients observed. The prevalence of patients with homelessness was 2.9 per 100 patients. The prevalence of patients with housing instability was 10.3 per 100 patients. The median length of stay was 8 (IQR 4 – 11) days for patients with homelessness and 4.5 (IQR 2 – 12) days for patients with housing instability compared to 4 (IQR 1 – 8) days for housed patients (P < 0.001). Patients with housing insecurity had similar injuries to housed patients (P = 0.06). Physicians incorrectly documented housing status in 42.9% of patients with housing insecurity compared to case management, which correctly screened all patients (P < 0.01). The electronic medical record correctly screened less than 1% of the patients with housing insecurity (P < 0.01). Conclusions Housing insecurity is more prevalent than previously thought, with 13.2 per 100 patients experiencing either homelessness or housing instability. These patients have similar injuries to their housed counterparts, with longer stays and higher health care costs. Identifying and implementing appropriate screening tools can help provider teams connect patients with resources, reducing costs and improving outcomes. Applicability of Research to Practice Identifying patients at high risk earlier in their care can ensure that they are provided with the appropriate resources to avoid complications and worse outcomes.
Introduction Recent progress in pediatric burn care has reduced the mortality rate by 48.1% (Armstrong, 2020). Although it is well understood that mortality increases with increased number of systems involved, prior studies have not documented the effect of concomitant pediatric burn and craniomaxillofacial (CMF) trauma in pediatric patients. This retrospective cohort study is the first known to characterize presentation, management, and long-term outcomes of concomitant burns with CMF trauma in pediatric patients. Methods We performed a retrospective cohort study of all pediatrics patients who presented at a tertiary care center between the years 1990 to 2010 with CMF fractures and burns. Patient charts were reviewed for demographics, mechanism of injury, burn characteristics (TBSA %, location, and degree), imaging and interventions, involvement of child protective services, and long-term outcome. Data was analyzed using two-tailed Student’s t tests and chi square analysis. Results Of the 2,966 pediatric CMF trauma patients (64.0% boys; average age 7 ±4.7 years) that were identified, a total of 10 (0.34%) patients were identified to have concomitant burn injuries. Patients with concomitant burn and CMF injuries were less likely to have sustained blunt injuries (P < 0.0001) and had longer hospital lengths of stay (13 □ 18.6 vs 4 □ 6.2 days, P < 0.0001). Approximately 60% of CMF fractures were upper-third injuries. The CMF fractures of all 10 cases (100%) were managed non-operatively. 40% were due to child abuse, 40% due to motor vehicle collisions, and 20% due to house fires. Of the four patients who presented due to child abuse, CMF trauma was incidentally found on imaging. One (13 months, female) child-abuse case was found to have 32% TBSA 2nd and 3rd degree burns to bilateral lower extremities after being submerged in hot bathwater and had concomitant orbit/skull fractures. Two other child abuse cases presented with hand burns and concomitant nasal/skull fractures. All four child abuse patients presented in a delayed fashion. Conclusions Concomitant burns and CMF trauma is rare injury pattern in pediatric populations and is associated with longer hospital lengths of stay. Child abuse and motor vehicle accidents caused 80% of the cases.
Introduction Associations, institutions, and providers have made enormous efforts to educate the United States public on burn injury in the hopes of preventing burns. However, there are no reports to-date describing the level of public burn knowledge in the U.S. This study characterized the public knowledge of burn prevention and preparedness in the US. It also aimed to assess if our interactive quiz is an appropriate educational tool. Methods QualtricsTM surveys designed to test knowledge and educate about burns were crowdsourced to laypersons via Amazon MTurk. Demographics were self-reported. In section 1, respondents were presented six questions asking about causes and care for burns, in a quiz style with explanations provided immediately. In section 2, respondents self-reported personal experiences with burns, burn education, and knowledge of verified burn centers. In section 3, they reported attitudes towards burn care. Survey responses were analyzed using two-tailed Student’s t tests and chi square analyses. Results We received 402 completed survey responses, and 331 total were included for analysis; studies were excluded if they were completed in < 5 minutes or had incorrect attention check questions. The mean age was 39.4 ± 12.08, and 51% male. 1. Knowledge: The average quiz score was 51% ± 8; while 65% of respondents knew to run scald burns under cool water, only 41% knew the optimal time of more than 20 minutes. The majority of respondents (92%) reported the quiz improved their burn knowledge. Also, while majority (63%) of respondents had heard of verified burn centers, only 44% knew where the closest one was. 2. Experiences: 72% of respondents had personally experienced a burn, of which 62% were treated in the emergency room. 57% of respondents had witnessed a burn injury occur, of which 92% applied first aid using cool running water (26%), ice (18%), burn gel (17%), and gauze (11%). Only 61% of respondents have participated in burn precautions at home. 56% of respondents have received formal burn training, such as from CPR class (21.4%) and recent first aid training (32.9%). Informal sources include from friends and family (66%), personal burn experience (63%), or social media (47.4%). 3. Attitudes: The majority of respondents agreed there should be more public education on risks/prevention (85%) and treatment of burns (78.6%). Only 63% believe acute burn care should be covered by insurance. Conclusions Our study demonstrates that despite personal experiences with burns and formalized courses, there remain gaps in public burn knowledge in the US. Further studies are required to characterize more detailed knowledge gaps and intervention strategies.
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