bluuebunny/crossref_metadata_2025_split huggingface dataset:
37 Procedural Pain Management in Burn Patients (Phase II) - A Quality Improvement Project
Authors: Pedroza Albert , Fleishhacker Zack , Galet Colette , Wibbenmeyer Lucy 
Published: March 2022

Abstract

Introduction
This quality improvement project (QI) focused on reducing procedural pain. Phase I of this project demonstrated a need to improve our patients' and nurses’ satisfaction with pain control management during hydrotherapy. In this phase (Phase II), we educated the nursing staff on 1) appropriate dosing and timing of opioid administration (Oral and IV) and 2) need for more frequent midazolam administration before hydrotherapy. We also assessed the safety and potential benefits of ketamine for procedural pain control.

Methods
Patients undergoing wound cleaning procedures were surveyed for up to three hydrotherapy encounters. Nurses were educated on procedural pain control prior to this current phase. A convenience sample of patients underwent ketamine administration. Ketamine was administered per protocol starting at 0.3 or 0.4 mg/kg with intermittent boluses of 0.25 mg/kg as needed. Demographics, opioid (oral morphine equivalents, OME), midazolam, and ketamine doses and time of administration, and adverse events were collected. Patient pain scores (1-10) before and after hydrotherapy and patient and nurse satisfaction scores (1-10) after hydrotherapy were collected. Paired t-tests and one-way ANOVA were performed. P &lt; 0.05 was considered significant.

Results
During Phase II, 9 patients and 19 encounters were analyzed; of which ketamine was administered for 10 events. Compared to Phase I (28 Patients and 50 encounters), education of the nursing staff resulted in a significant improvement in giving midazolam prior to hydrotherapy (78.9% vs. 10%; p &lt; 0.001) and opioid administration (27.4 OME vs. 20.2 OME, p = 0.043). Timing of opioid administration did not improve when compared to Phase I (Outside the window of efficacy: 42.1% vs. 43.8%, p = 0.903). Both patient (8.7 ± 2.4 vs. 7.7 ± 2.1; p = 0.011) and nurse (8.2 ± 2.1 vs. 7.3 ± 1.9; p = 0.021) satisfaction scores regarding pain control improved. None of the patients who received ketamine experienced adverse effects. Notably, the use of ketamine improved nurse satisfaction scores with patient pain control (9.2 ± 0.8 vs. 7.1 ± 2.6; p = 0.035). While patients on ketamine were more satisfied with pain control, significance was not reached (9.4 ± 1.1 vs. 7.9 ± 3.2; p = 0.315).

Conclusions
Our data demonstrate that nurse education regarding medication administration was effective, but further education is needed to improve the timing of opioid administration. Ketamine offers additional benefits that deserve additional study.
44 Endothelial Monolayers Treated with Burn Patient Plasma Exhibit Differential Gene Expression Linked to Cytoskeletal Rearrangement
Authors: Kelly Edward J , Keyloun John W , Carney Bonnie C , Moffatt Lauren T , Shupp Jeffrey W 
Published: March 2022

Abstract

Introduction
Burn shock is one of the most serious and complex complications suffered by patients following thermal injury. Endothelial dysfunction may play a role in the pathogenesis of burn shock. However, the mechanisms underlying the contribution to pathophysiology are still largely unknown. Previous studies have shown a connection between the rearrangement of cytoskeletal elements leading to increased vascular permeability. The aim of this study was to examine the differential expression of genes involved in cytoskeletal arrangement in endothelial cell monolayers treated with plasma from burn patients.

Methods
Human umbilical vein endothelial cells (HUVECs) were seeded into transwell plates to form confluent monolayers. Plasma was collected from burn patients 4 hours post-admission. HUVEC cells were exposed to 10% multi-donor pooled healthy human plasma (HHP) or burn patient plasma. Monolayers were subsequently incubated with FIT-C Dextran (40,000 kD) for 2 hours. Monolayer permeability was measured with indices calculated by normalizing values to blank wells (transwell inserts) and HHP-treated monolayer FIT-C diffusion. RNA was isolated from these same cells that had increased monolayer permeability and PCR analysis was carried out using an 84 gene array of human cytoskeletal regulators (Qiagen). A Ct value of 35 was used to indicate expression and a fold change of 1.5 to indicate differential expression in the control vs. injured groups.

Results
Four burn patient plasma samples were utilized to create injuries. Patients were mostly male (75%) with a mean age of 50±20 years and mean %TBSA burn of 37±34%. Differential gene expression in burn vs. HHP was compared. Ten genes showed significant upregulation (ARHGDIB, AURKA, AURKB, CCNB2, CIT, IQGAP2, VASP, SSH2, MYLK and DIAPH1). Four genes showed significant downregulation in (FSCN2, ARHGAP6, CYFIP2, CCNA1). Monolayer permeability indices showed statistically significant increases when compared to controls ranging from 3-13.33% (p &lt; .05).

Conclusions
The interplay of burn shock and endothelial dysfunction remains a complex process of which much is unknown. However, RNA analyses of burn patient plasma reveals involvement of multiple cytoskeletal regulators. Furthermore, all these samples show a concurrent increase in permeability indices when compared to controls, further strengthening the association between cytoskeletal rearrangement and endotheliopathy. Future research to better understand the specifics of these pathways could help aid in the development of more targeted treatments of endotheliopathy and burn shock. Cytoskeletal rearrangement may be an interesting target for future work to understand this mechanistic interplay.
46 Bardoxolone-methyl Microparticles Ameliorate Immune Dysfunction Following Burn and Inhalation Injury Through the NRF2/KEAP1 Axis
Authors: Seim Roland F , Maile Rob , Hall Hannah R , Wallet Shannon , King Booker 
Published: March 2022

Abstract

Introduction
Severe burn injury leads to many systemic stresses that can seriously impact multiple systems throughout the body. These stresses are further exacerbated if there is a combined burn and inhalation injury, which leads to increased morbidity and mortality for many patients. Combined burn and inhalation injury causes an intense systemic inflammatory response and activation of the innate immune system which can lead to inflammatory complications, such as systemic inflammatory response syndrome and multiple organ failure. Nuclear Factor-Erythroid-2-Related Factor (NRF2) is a transcription factor that acts to downregulate overt damaging pro-inflammatory and oxidative responses and maintain immune homeostasis. This transcription factor remains bound to Kelch-like ECH-associated protein 1 (KEAP1) in the cytoplasm. Under oxidative stress, NRF2 dissociates from KEAP1 and translocates to the nucleus where it facilitates the transcription of anti-inflammatory and antioxidant genes. We hypothesized that NRF2 is a key regulator after burn and inhalation injury, and activation of NRF2 can limit the severity of burn and inhalation injury.

Methods
To test this, we have developed a mouse model of combined cutaneous burn and woodsmoke inhalation injury. After burn and inhalation injury, we found that NRF2-/- knockout mice have higher mortality compared to wild-type (WT) mice and suffer from increased vascular permeability and lung edema, suggesting that this transcription factor is important for controlling morbidity and mortality. In WT mice, NRF2 is activated following burn and inhalation injury, however, based on immunohistochemical staining, it is not sufficiently induced following this insult since it remains in the cytoplasm and is unable to transcribe anti-inflammatory genes. Therefore, we treated WT mice with an intraperitoneal injection of bardoxolone-methyl microparticles, a NRF2 activator that separates KEAP1 from NRF2 in the cytoplasm, immediately after burn and inhalation injury in WT mice

Results
We observed significant decreases in mortality as well as reduced concentrations of certain pro-inflammatory cytokines in the blood and bronchoalveolar-lavage fluid of these mice. In the lungs of these mice, there was an upregulation in numerous pathways involved in the management of inflammation and immune response compared to mice that did not receive bardoxolone-methyl microparticles.

Conclusions
In conclusion, treatment with bardoxolone-methyl microparticles immediately after burn and inhalation injury might be effective for reducing the severity of the inflammatory response and limiting inflammatory complications.
47 Successful Prevention of Secondary Burn Progressions Using Topical Tacrolimus and Infliximab Hydrogel
Authors: Kalmar Christopher L , White-Dzuro Colin G , Pollins Alonda , Burns Brady , Assi Patrick , Thomas Harrison , Jackson Kianna , Perdikis Galen , Bellan Lleon , Thayer Wesley 
Published: March 2022

Abstract

Introduction
The pathophysiology of partial- to full-thickness burn wound conversion remains poorly understood. Recent studies have demonstrated that an altered inflammatory response may play be implicated in this secondary conversion to deeper wounds. Therefore, reduction in early inflammation may decrease burn severity and morbidity.
Specifically, TNF-ɑ has been shown to detrimentally affect the healing process after injury through a variety of mechanisms. We hypothesized that microcapillary alginate hydrogel loaded with immunosuppressive medications applied to partial-thickness burns would reduce inflammation and prevent further progression to full-thickness burns.
The purpose of this study was to determine whether topical application of infliximab or tacrolimus could decrease burn wound depth.

Methods
Assembly of the microfluidic hydrogels was achieved by embedding microfibers within a hydrogel scaffold composed of an alginate blend. The treatment cohorts received either (1) infliximab loaded hydrogel or (2) tacrolimus skin ointment covered by hydrogel. The control cohort only received an occlusive dressing.
There were 12 young (2-4 months) and 12 old ( &gt;16 months) mice, which were separated into treatment and control cohorts. All mice were anesthetized and given partial thickness burns by a validated scalding protocol. Mice were euthanized on post-burn day 3, and skin samples were taken. Burn depth was evaluated using Vimentin immunostaining.

Results
In young mice, infliximab hydrogel (p=.002) and tacrolimus hydrogel (p=.002) significantly decreased burn depth compared to controls. In old mice, infliximab hydrogel (p=.005) and tacrolimus hydrogel (p&lt; .001) significantly decreased burn depth compared to controls.
In young mice, infliximab and tacrolimus were similarly efficacious (p &gt; .05). In old mice, tacrolimus significantly decreased burn depth compared to infliximab (p=.002).
In controls, old mice had deeper burn wound progression than young mice (p&lt; .001). Similarly, in those treated with infliximab, old mice had deeper burn wound progression than young mice (p=.002). Interestingly, tacrolimus was able to decrease burn wound depth in old mice such that their burn wound thickness was similar to young mice (p &gt;.05).

Conclusions
Application of a novel microcapillary alginate hydrogel infused with infliximab or topical tacrolimus reduced partial- to full-thickness burn wound conversion in mice. Application of immunosuppressive dressings may be a promising avenue for further clinical investigation to reduce morbidity and mortality associated with burn injuries.
48 Metformin Rescues the Aging-induced Failure of Post-burn White Adipose Browning
Authors: Barayan Dalia , Knuth Carly M , Jeschke Marc G 
Published: March 2022

Abstract

Introduction
Severe burns are responsible for an estimated 300,000 deaths per year worldwide. While modern burn care has markedly improved survival for pediatric and adult patients, this is sadly not the case for one population: the elderly. Despite being the fastest-growing demographic in North America, burn patients over the age of 60 years have the highest mortality and morbidity rates. Recent evidence suggests that progressive aging induces several structural and functional alterations which impair the capacity of older trauma patients to adequately respond to stress. Indeed, it was discovered that reduced survival in elderly burn patients is associated with the failure to initiate the browning of white adipose tissue (WAT) —a hallmark of the systemic response to injury commonly observed in adults. Interestingly, the widely used hypoglycemic drug metformin has been found to protect against aging-induced metabolic decline in various pathological conditions. Thus, we investigated the anti-aging effects of metformin on the metabolic deterioration of post-burn WAT responses in elderly patients and mice after injury.

Methods
Human WAT was obtained from elderly patients admitted to our burn center. Elderly (75-week) mice received a full-thickness scald burn and/or daily intraperitoneal injections of metformin (100 mg/kg) for 7 days. The inguinal WAT was harvested for histological analyses. Mitochondrial respiration was measured via Seahorse XF96. Gene and protein expression was assessed via RT-PCR and western blot, respectively.

Results
Post-burn metformin treatment restores the thermogenic activation of WAT in elderly patients and mice, reflected by the increased expression of key browning markers, UCP-1 and PGC-1α (p&lt; 0.05). This was accompanied by higher mitochondrial respiration, improved lipolysis (p&lt; 0.05) and increased fat wasting (p&lt; 0.01) relative to control counterparts. The anti-aging effects of metformin appeared to be mediated by AMPK, which consequently increased [NAD+] (p&lt; 0.01), thereby promoting activation of the longevity-specific enzyme Sirt-1 (p&lt; 0.05).

Conclusions
Here, we show that post-burn metformin treatment effectively rejuvenates adaptive metabolic responses in elderly WAT by targeting key longevity pathways which rescue the age-dependent loss of being back to youthful levels. Our findings support the potential of anti-aging modalities to improve care and outcomes in elderly burned patients.
54 Cost of Dakin’s Solution vs. Mafenide Soaks in Acute Burn Care
Authors: Hirsch Jason , DeHoff Deanna , Hollowed Kathleen , Halicki Elizabeth , Condeni Melanie S , Hink Ashley , Ozhathil Deepak , Kahn Steven A 
Published: March 2022

Abstract

Introduction
The cost of health care in the United States is extremely high, with burn care being no exception to this rule. A 2016 study found that burn care costs are twice as much as the cost of non-burn related inpatient admissions, necessitating the need for cost savings. As one such measure, the authors no longer routinely use mafenide solution for burn care, and now use 0.0125% Dakin’s as a default topical irrigant, due to lower cost and less cytotoxicity. The aim of this analysis is to investigate the cost savings from using Dakin’s Solution (0.125%, 0.25%, and 0.50% strengths) versus the theoretical cost of using an equivalent amount of 5% mafenide.

Methods
This study was a retrospective review that characterized a single cohort of burn patients treated with Dakin’s solution in the pre and post operative setting. Graft loss was recorded and defined as &gt;25% loss. As a default, 0.125% Dakin’s was used, and concentration was potentially escalated based on attending judgement of wound characteristics. We qualitatively compared length of stay (LOS) index to expected for length of stay index using 1.1 hospital days per %TBSA and using 2019 NBR statistics of 3 days per %TBSA for survivors. Using costs of $37.29 (0.0125%), $40.69 (0.25%), and $38.11 (0.5%) per liter of Dakin’s versus $165.05 per liter for 5% mafenide, we looked at potential savings per patient and for the entire cohort. Average cost, median cost, and total cost of both Dakin’s solution and Mafenide were calculated. Mann Whitney Test was used to compare costs of Dakin’s versus theoretical cost of mafenide.

Results
The total number of cases analyzed was 39 (n=39). The median burn size was 4% TBSA (IQR:1,6) and the median LOS was 3 days (IQR:2,8) The average cost for Dakins per patient was $721.61 versus $3172.98 had mafenide been used, p&lt; 0.001. When all of the Dakins use was amalgamated, this represents a potential cost savings of $2451.37 per patient and $95603.43 for the entire cohort. LOS index was 0.68 with the conservative measure and 0.25 using 2019 NBR data. Only 2 patients had unplanned readmissions within 30 days. None of the patients suffered graft loss.

Conclusions
Use of Dakin’s solution as an alternative to mafenide results in a significant potential cost savings compared to 5% mafenide. The patients treated with Dakins in this study spent less time in the hospital than expected compared to national averages. In addition to lower strength Dakin’s dilutions being well established as less cytotoxic, this study suggests it can save money for the burn center. Future studies should directly compare the two topicals to determine if true differences in infection, healing, or length of stay that might offset or augment cost savings emerge.
57 Understanding the Burden of Burn Injury in Latin America & the Caribbean
Authors: Collier Zachary J , Bourcier Alexandre J , Naidu Priyanka , Magee William P , Potokar Tom , Gillenwater Justin 
Published: March 2022

Abstract

Introduction
Burn injuries are a global health problem disproportionately affecting low- and middle-income countries, especially in Latin America and Caribbean (LAC) where cooking methods, dangerous work conditions, and minimal housing regulations place people at increased risk of burn injury. Until recently, there was limited global epidemiological data on burn injuries. Following publication of the 2017 Global Burden of Disease (GBD17) database, we obtained objective and comparable data on burn injuries while specifically focusing on LAC countries.

Methods
Data from all 35 LAC countries were collected from GBD17 for fire, heat, and hot substance-related injuries to calculate burn incidence, deaths, and Disability-Adjusted Life Years (DALYs) with respect to country, age, and gender from 1990 to 2017. Incidence and deaths were reported as rates per 100,000 persons. Mortality rate was reported as a percentage of deaths-to-incidence. DALYs were reported in years per 100,000 persons. Incidence, death, DALY, and mortality rate trends were assessed using age-standardized, age-stratified, and gender-specific cohorts. All statistical analyses were performed using Excel.

Results
Over 27 years, LAC’s rates for burn incidence (-19%), deaths (-63%), DALYs (-62%), and mortality (-54%) all decreased with the greatest improvements seen in Brazil and Paraguay. All indicators improved around 15% more than the global averages during the same period with LAC’s rates 30-40% below global rates by 2017. The highest burn incidence (227 cases/100,000) was in Southern Latin America (Argentina, Chile, Uruguay). The Caribbean had the worst DALYs (124 years/100,000). In 2017, LAC accounted for 7% of global burns, 5.5% of deaths, and 5.1% of DALYs with Central America contributing the greatest numbers. For 27 years, Chile had the highest burn incidence but Haiti had the greatest death, DALY, and mortality rates of all LAC. Children under 14 years of age and males were disproportionately affected compared to other regional and global cohorts.

Conclusions
Despite a relatively greater reduction in burn severity and lifelong disability within LAC compared to the world, certain regions and countries exhibited significantly higher rates of burn injury, morbidity, and mortality. Central America (e.g. Costa Rica, Belize, Mexico) and the Caribbean (e.g. Haiti, Cuba) were particularly affected, comprising the majority of cases, deaths, and DALYs. This study provides essential analyses for developing regional and country-specific strategies to reduce the burden of burns through targeted interventions for prevention, workforce, and capacity building efforts.
62 The Impact of ICD10 on the Incidence of Abuse in the National Burn Repository
Authors: Hodgman Erica , Wharton Kristin 
Published: March 2022

Abstract

Introduction
Previously, cases of abuse may only have been coded as such when the investigation was complete, thus skewing the data available in the National Burn Repository (NBR) toward more severe or obvious cases of abuse. The introduction of the ICD10 coding system in 2015 brought with it the concept of “confirmed” and “suspected” cases of abuse. We hypothesized that the creation of these two categories might shift our understanding of non-accidental pediatric burn injuries.

Methods
We queried the NBR, a retrospective database maintained by the American Burn Association (ABA) which contains data submitted by all ABA-verified burn centers as well as some non-verified centers, for all children under the age of 18. Data were cleaned using e-codes where appropriate. To create equal samples, we created two cohorts: the ICD-9 sample comprises all children treated from 2012-2014, and the ICD-10 sample includes all children treated from 2016 to 2018. Data from 2015 were omitted as the ICD-10 coding system was introduced part way through the year.

Results
A total of 34,456 patients are included in the sample, including 18,783 (54.5%) in the ICD-9 group and 15,673 in the ICD-10 group. The most common causes of injury in both eras was scald (48.7% in ICD-9 and 55.2% in ICD-10), followed by fire/ flame (20.3% in ICD-9 and 20.9% in ICD-10). The overall rate of abuse (including both suspected and confirmed abuse in the ICD-10 group) was higher in the ICD-9 era than the ICD-10 era (4.2 vs 3.2%, p&lt; 0.001). As seen in previous studies, children with injuries due to abuse were younger (median age 2.0 vs 3.0 years, p&lt; 0.001), had a larger median burn size (3.0 vs 5.0%, p&lt; 0.001), a longer hospital length of stay (2.0 vs 4.0 days, p&lt; 0.001), and a higher rate of mortality (0.8 vs 0.5%, p&lt; 0.001). In the ICD-10 cohort, only 17 cases were coded as “confirmed” abuse (0.1%) and 478 were coded as “suspected” (3.0%). In contrast, in the ICD-9 group, 789 patients (4.2%) were coded as being victims of abuse.

Conclusions
We expected that adoption of ICD-10, with its ability to yield increased data granularity, would yield a higher overall incidence of injury. Specifically, we expected more patients with smaller injuries to be included in the new “suspected” category, given the lower threshold to apply that diagnosis. However, this was not demonstrated in the NBR dataset, and in fact the overall incidence of abuse decreased. Given the added layers of complexity within the ICD-10 system, it is possible that the differences reflect challenges in coding cases of abuse rather than actual epidemiological changes.